A. Rácz

Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart.Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor.Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7).Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

It has been unclear whether ischemic stroke induces neurogenesis or neuronal DNA rearrangements in the human neocortex. Using immunohistochemistry; transcriptome, genome and ploidy analyses; and determination of nuclear bomb test-derived (14)C concentration in neuronal DNA, we found neither to be the case. A large proportion of cortical neurons displayed DNA fragmentation and DNA repair a short time after stroke, whereas neurons at chronic stages after stroke showed DNA integrity, demonstrating the relevance of an intact genome for survival.

To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials.Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses.The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%.Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.

<h3>Background</h3> and Objectives The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in drug resistant epilepsy (DRE) patients was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. Methods MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), <i>responder rate (RR)</i>, health-related quality of life (Quality of Life in Epilepsy Inventory 31, QOLIE-31), depression, and safety outcomes. Results Of the 191 patients recruited 170 (mean (SD) age of 35.6 (10.7) years, 43% female) were implanted with DBS Therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (P&lt;0.0001) with 32.3% RR. In the subgroup of 47 patients that completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (P&lt;0.0001) with 53.2% RR. Factors influencing SF reduction included number of implants per center. In patients with cognitive impairment, the reduction in median monthly seizure frequency was 26.0% by two years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g. increased frequency/severity) in seizure (16%), memory impairment (patient reported complaint, 15%), depressive mood (patient reported complaint, 13%) and epilepsy (12%). One definite Sudden Death in Epilepsy (SUDEP) case was reported. Discussion The MORE registry supports the effectiveness and safety of ANT-DBS therapy in a real-world setting in the 2-years following implantation.

Generation of fast network oscillations in the hippocampus relies on interneurons, but the underlying specific synaptic mechanisms are not established. The excitatory recruitment of fast-spiking interneurons during hippocampal sharp waves has been suggested to be critical for the generation of 140-200 Hz ("ripple") oscillations in the CA1 area. To directly test this, we used genetically modified mice (PV-DeltaGluR-A) with reduced AMPA receptor-mediated excitation onto parvalbumin (PV)-positive interneurons and studied hippocampal oscillations in freely moving animals. In PV-DeltaGluR-A mice, ripple-amplitude and associated rhythmic modulation of pyramidal cells and fast-spiking interneurons were increased. These changes were not accompanied by concurrent alterations of firing rates. Neither theta nor gamma oscillations displayed marked alterations in the mutant. These results provide evidence that fast excitation from pyramidal cells to PV-positive interneurons differentially influences ripple and gamma oscillations in vivo.

<h3>Background and Objectives</h3> Limbic encephalitis (LE) is an autoimmune disease often associated with temporal lobe epilepsy and subacute memory deficits. It is categorized into serologic subgroups, which differ in clinical progress, therapy response, and prognosis. Using longitudinal MRI analysis, we hypothesized that mesiotemporal and cortical atrophy rates would reveal serotype-specific patterns and reflect disease severity. <h3>Methods</h3> In this longitudinal case-control study, all individuals with antibody-positive (glutamic acid decarboxylase 65 [GAD], leucine-rich glioma-inactivated protein 1 [LGI1], contactin-associated protein 2 [CASPR2], and <i>N</i>-methyl-d-aspartate receptor [NMDAR]) nonparaneoplastic LE according to Graus9 diagnostic criteria treated between 2005 and 2019 at the University Hospital Bonn were enrolled. A longitudinal healthy cohort was included as the control group. Subcortical segmentation and cortical reconstruction of T1-weighted MRI were performed using the longitudinal framework in FreeSurfer. We applied linear mixed models to examine mesiotemporal volumes and cortical thickness longitudinally. <h3>Results</h3> Two hundred fifty-seven MRI scans from 59 individuals with LE (34 female, age at disease onset [mean ± SD] 42.5 ± 20.4 years; GAD: n = 30, 135 scans; LGI1: n = 15, 55 scans; CASPR2: n = 9, 37 scans; and NMDAR: n = 5, 30 scans) were included. The healthy control group consisted of 128 scans from 41 individuals (22 female, age at first scan [mean ± SD] 37.7 ± 14.6 years). The amygdalar volume at disease onset was significantly higher in individuals with LE (<i>p</i><b>≤</b> 0.048 for all antibody subgroups) compared with that in healthy controls and decreased over time in all antibody subgroups, except in the GAD subgroup. We observed a significantly higher hippocampal atrophy rate in all antibody subgroups compared with that in healthy controls (all <i>p</i><b>≤</b> 0.002), except in the GAD subgroup. Cortical atrophy rates exceeded normal aging in individuals with impaired verbal memory, while those who were not impaired did not differ significantly from healthy controls. <h3>Discussion</h3> Our data depict higher mesiotemporal volumes in the early disease stage, most likely due to edematous swelling, followed by volume regression and atrophy/hippocampal sclerosis in the late disease stage. Our study reveals a continuous and pathophysiologically meaningful trajectory of mesiotemporal volumetry across all serogroups and provides evidence that LE should be considered a network disorder in which extratemporal involvement is an important determinant of disease severity.

Abstract Objective Medial temporal lobe epilepsy (MTLE) is a drug‐resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration. Methods We quantified the numbers of CD3 + T cells and CD8 + cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls. Results We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3 + as well as CD8 + T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T‐cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event. Significance We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity.

Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis, including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes mellitus, which has a strong genetic susceptibility conferred by human leukocyte antigen (HLA) and non-HLA genomic regions. We investigated the genetic predisposition in patients with anti-GAD65 AINS. We performed a genome-wide association study (GWAS) and an association analysis of the HLA region in a large German cohort of 1214 individuals. These included 167 patients with anti-GAD65 AINS, recruited by the German Network for Research on Autoimmune Encephalitis (GENERATE), and 1047 individuals without neurological or endocrine disease as population-based controls. Predictions of protein expression changes based on GWAS findings were further explored and validated in the CSF proteome of a virtually independent cohort of 10 patients with GAD65-AINS and 10 controls. Our GWAS identified 16 genome-wide significant (P < 5 × 10-8) loci for the susceptibility to anti-GAD65 AINS. The top variant, rs2535288 [P = 4.42 × 10-16, odds ratio (OR) = 0.26, 95% confidence interval (CI) = 0.187-0.358], localized to an intergenic segment in the middle of the HLA class I region. The great majority of variants in these loci (>90%) mapped to non-coding regions of the genome. Over 40% of the variants have known regulatory functions on the expression of 48 genes in disease relevant cells and tissues, mainly CD4+ T cells and the cerebral cortex. The annotation of epigenomic marks suggested specificity for neural and immune cells. A network analysis of the implicated protein-coding genes highlighted the role of protein kinase C beta (PRKCB) and identified an enrichment of numerous biological pathways participating in immunity and neural function. Analysis of the classical HLA alleles and haplotypes showed no genome-wide significant associations. The strongest associations were found for the DQA1*03:01-DQB1*03:02-DRB1*04:01HLA haplotype (P = 4.39 × 10-4, OR = 2.5, 95%CI = 1.499-4.157) and DRB1*04:01 allele (P = 8.3 × 10-5, OR = 2.4, 95%CI = 1.548-3.682) identified in our cohort. As predicted, the CSF proteome showed differential levels of five proteins (HLA-A/B, C4A, ATG4D and NEO1) of expression quantitative trait loci genes from our GWAS in the CSF proteome of anti-GAD65 AINS. These findings suggest a strong genetic predisposition with direct functional implications for immunity and neural function in anti-GAD65 AINS, mainly conferred by genomic regions outside the classical HLA alleles.

Fast ring imaging Cherenkov counters, with pad readout for unambiguous image reconstruction, are considered for use in a high luminosity environment. The quantum efficiency of several new photosensitive gases (TMA and DMA) are measured and compared to the known standard gases (TEA and TMAE). A solid CsI/TMAE reflective photocathode is also considered as an alternative fast and efficient photosensor. A detailed experimental investigation has been made of a multiwire photon detector with TEA as the photosensitive converter. This detector, designed as part of a RICH counter for a B factory electron-positron collider, may also be used at hadron colliders as well as at fixed target facilities. These tests allowed the optimization of relevant construction parameters to fulfill the requirements of speed (σt < 10 ns), cathode pad detection efficiency (ϵc > 0.98) and pixel error (σx < 1.5 mm) over the full surface of the detector. Its performance was used to tune the parameters of a general Monte Carlo simulation program in order to predict the response of a photodetector with various photoconverters and pad sizes.

OBJECTIVE Both pre- and postoperative seizures comprise common side effects that negatively impact patient quality of life in those suffering from intracranial meningioma. Therefore, seizure freedom represents an important outcome measure in meningioma surgery. In the current study the authors analyzed their institutional database to identify risk factors for postoperative seizure occurrence after surgical meningioma therapy in patients with preoperative symptomatic epilepsy. METHODS Between February 2009 and April 2017, 187 patients with preoperative seizures underwent resection of supratentorial meningioma at the authors’ institution. Seizure outcome was assessed retrospectively 12 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class I) versus unfavorable (ILAE classes II–VI). A univariate and multivariate analysis was performed to identify factors influencing seizure outcome. RESULTS Overall 169 (90%) of 187 patients with preoperative seizures achieved favorable outcome in terms of seizure freedom after meningioma resection. Multivariate analysis revealed peritumoral edema &gt; 1 cm in maximal diameter and WHO grade II and III tumors, as well as a low extent of resection (Simpson grades III–V) as independent predictors for postoperative unfavorable seizure outcome. CONCLUSIONS Surgery is highly effective in the treatment of seizures as common side effects of supratentorial meningioma. Furthermore, the present study identified several significant and independent risk factors for postoperative seizure occurrence, enabling one to select for high-risk patients that require special attention in clinical and surgical management.

Abstract Objective Neuropsychological impairments are major symptoms of autoimmune limbic encephalitis (LE) epilepsy patients. In LE epilepsy patients with an autoimmune response against intracellular antigens as well as in antibody-negative patients, the antibody findings and magnetic resonance imaging pathology correspond poorly to the clinical features. Here, we evaluated whether T- and B-cells are linked to cognitive impairment in these groups. Methods In this cross-sectional, observational, case–controlled study, we evaluated 106 patients with adult-onset epilepsies with a suspected autoimmune etiology. We assessed verbal and visual memory, executive function, and mood in relation to the presence or absence of known auto-antibodies, and regarding T- and B-cell activity as indicated by flow cytometry (fluorescence-activated cell sorting = FACS, peripheral blood = PB and cerebrospinal fluid = CSF). Results 56% of the patients were antibody-negative. In the other patients, auto-antibodies were directed against intracellular antigens (GAD65, paraneoplastic: 38%), or cellular surface antigens (LGI1/CASPR2/NMDA-R: 6%). Excluding LGI1/CASPR2/NMDA-R, the groups with and without antibodies did not differ in disease features, cognition, or mood. CD4+ T-cells and CD8+ T-cells in blood and CD4+ T-cells in CSF were prominent in the auto-antibody positive group. Regression analyses indicated the role education, drug load, amygdala and/or hippocampal pathology, and CD4+ T-cells play in verbal memory and executive function. Depressed mood revealed no relation to flow cytometry results. Conclusion Our results indicate a link between T- and B-cell activity and cognition in epilepsy patients with suspected limbic encephalitis, thus suggesting that flow cytometry results can provide an understanding of cognitive impairment in LE patients with autoantibodies against intracellular antigens.

Background: There is insufficient data in the literature regarding the real-life, daily clinical practice evaluation of patients with advanced Parkinson’s disease (APD). We are not sure what is the upper limit of dopaminergic medication, especially the levodopa (LD) dosage, and how it is influenced by access and suitability to the various add-on and device-aided therapies (DAT). Objective: This retrospective study explored the profile of APD patients that were considered and systematically evaluated regarding the suitability for DAT. Methods: We analyzed the data from 311 consecutive patients with APD hospitalized between 2011 and 2017 that 1) described at least 2 hrs/day off periods divided into at least two instances/day (except early morning akinesia), 2) were in stage 3 or above on the Hoehn and Yahr scale, 3) were with or without dyskinesia, and 4) received at least four levodopa doses/day combined with adjuvant therapy. Results: Of the 311 patients enrolled initially, 286 patients showed up for the second visit, of which in 125 cases we assessed that DAT would be necessary. Finally, 107 patients were tested in our clinic to confirm the efficacy of LCIG. Patients selected for DAT had significantly longer off periods, more frequent dyskinesia, early morning akinesia, and freezing despite having significantly higher LD doses than those with an improved conservative therapy. Conclusion: Patients with APD can have a variety of symptoms, and because symptoms and therapeutical efficacy can be manifested in many different combinations, it is not possible to decide using a single, rigid set of criteria which APD patient is eligible for DAT. Nevertheless, treating physicians should refer APD patients to a specialized movement disorder center when patients with an average daily dose of LD of at least 750–1000 mg and maximal complementary therapies present daily motor complications that significantly reduce the quality of life. Keywords: advanced Parkinson’s disease, motor complications, levodopa doses, levodopa-carbidopa intestinal gel

The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures.Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors' institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2-6).Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4-515.9).ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy. Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews. Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic–clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only. Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.

The CMS data acquisition system is made of two major subsystems: event building and event filter. The presented paper describes the architecture and design of the software that processes the data flow in the currently operating experiment. The central DAQ system relies on industry standard networks and processing equipment. Adopting a single software infrastructure in all subsystems of the experiment imposes, however, a number of different requirements. High efficiency and configuration flexibility are among the most important ones. The XDAQ software infrastructure has matured over an eight years development and testing period and has shown to be able to cope well with the requirements of the CMS experiment.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n = 15; CASPR2, n = 5) of 32 patients with LGI1 (n = 24) and CASPR2 (n = 8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Background: Artificial Intelligence (AI) has significantly improved diagnostic accuracy in many disorders. Advances have been most evident in the classification of medical images. A correct diagnosis, however, often involves localising pathological tissue, which may be crucial for a targeted treatment. The output of AI for such tasks differs from human diagnosis in the clinical setting, and both are not natively comparable. Here, we aimed to create common ground between technical and medical domains and lay the foundation for AI's systematic and beneficial usage as computer-aided detection (CADe) tools using Focal Cortical Dysplasia (FCD) as a paradigmatic example.Methods: We evaluated the detection performance of twenty-eight human raters and three state-of-the-art AI models in 180 subjects, 146 diagnosed with FCD.Findings: Our analysis suggests a misalignment between clinical practice and computer vision standards: The average overlap between human predictions and ground-truth lesion masks and the inter-rater agreement were far below what is commonly acceptable. We adjusted our evaluation criteria to reproduce known diagnostic yields for human raters and allow a direct comparison between human raters and AI models. While current models did not outperform expert raters, even the performance of non-expert raters paired with AI could improve above the specialist level. We identified a possible interaction between raters and models and analysed when raters should trust their localisation or adopt a model's prediction. All raters could benefit from AI, especially when a lesion did not exhibit specific MRI features or a rater showed low confidence in their prediction.Interpretation: AI-based lesion detection can be evaluated regarding its clinical relevance, and rules for including AI in a lesion detection diagnostic workup should be derived based on human-AI interaction. This study paves the way for successfully translating AI-based CADe into clinical practice.Funding: No external funding.Declaration of Interest: AR has received fees as a speaker from UCB Pharma, and travel support from the Elisabeth und Helmut Uhl Stiftung. UA has received fees as a speaker for Siemens Healthineers and as clinical consultant for Bayer. CEE has received fees from UCB, Desitin, Bial. H.U. has received fees from Eisai, Biogen, and MBits and is on the advisory board of Biogen. AR lectures for Guerbet and Bayer, and is part of the Advisory Board for GE, Bracco, and Guerbet. RS has received personal fees as speaker or for serving on advisory boards from Angelini, Arvelle, Bial, Desitin, Eisai, Jazz Pharmaceuticals Germany GmbH, Janssen-Cilag GmbH, LivaNova, LivAssured B.V., Novartis, Precisis GmbH, Rapport Therapeutics, Tabuk Pharmaceuticals, UCB Pharma, UNEEG, and Zogenix. TR has received fees as a speaker from Eisai. None of the previously mentioned activities were related to the content of this manuscript. The remaining authors have nothing to declare.Ethical Approval: The University of Bonn Ethics Committee approved the study (452-19). All raters and people with epilepsy and FCD as well as people without epilepsy provided written informed consent.

Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied.We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen.Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed.This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

The CMS data acquisition (DAQ) is implemented as a service-oriented architecture where DAQ applications, as well as general applications such as monitoring and error reporting, are run as self-contained services. The task of deployment and operation of services is achieved by using several heterogeneous facilities, custom configuration data and scripts in several languages. In this work, we restructure the existing system into a homogeneous, scalable cloud architecture adopting a uniform paradigm, where all applications are orchestrated in a uniform environment with standardized facilities. In this new paradigm DAQ applications are organized as groups of containers and the required software is packaged into container images. Automation of all aspects of coordinating and managing containers is provided by the Kubernetes environment, where a set of physical and virtual machines is unified in a single pool of compute resources. We demonstrate that a container-based cloud architecture provides an acrossthe-board solution that can be applied for DAQ in CMS. We show strengths and advantages of running DAQ applications in a container infrastructure as compared to a traditional application model.

The Online Monitoring System (OMS) at the Compact Muon Solenoid experiment (CMS) at CERN aggregates and integrates different sources of information into a central place and allows users to view, compare and correlate information. It displays real-time and historical information. The tool is heavily used by run coordinators, trigger experts and shift crews, to ensure the quality and efficiency of data taking. It provides aggregated information for many use cases including data certification. OMS is the successor of Web Based Monitoring (WBM), which was in use during Run 1 and Run 2 of the LHC. WBM started as a small tool and grew substantially over the years so that maintenance became challenging. OMS was developed from scratch following several design ideas: to strictly separate the presentation layer from the data aggregation layer, to use a well-defined standard for the communication between presentation layer and aggregation layer, and to employ widely used frameworks from outside the HEP community. A report on the experience from the operation of OMS for the first year of data taking of Run 3 in 2022 is presented.

The data acquisition (DAQ) of the Compact Muon Solenoid (CMS) experiment at CERN, collects data for events accepted by the Level-1 Trigger from the different detector systems and assembles them in an event builder prior to making them available for further selection in the High Level Trigger, and finally storing the selected events for offline analysis. In addition to the central DAQ providing global acquisition functionality, several separate, so-called “MiniDAQ” setups allow operating independent data acquisition runs using an arbitrary subset of the CMS subdetectors. During Run 2 of the LHC, MiniDAQ setups were running their event builder and High Level Trigger applications on dedicated resources, separate from those used for the central DAQ. This cleanly separated MiniDAQ setups from the central DAQ system, but also meant limited throughput and a fixed number of possible MiniDAQ setups. In Run 3, MiniDAQ-3 setups share production resources with the new central DAQ system, allowing each setup to operate at the maximum Level-1 rate thanks to the reuse of the resources and network bandwidth. Configuration management tools had to be significantly extended to support the synchronization of the DAQ configurations needed for the various setups. We report on the new configuration management features and on the first year of operational experience with the new MiniDAQ-3 system.

The Compact Muon Solenoid (CMS) experiment at CERN incorporates one of the highest throughput data acquisition systems in the world and is expected to increase its throughput by more than a factor of ten for High-Luminosity phase of Large Hadron Collider (HL-LHC). To achieve this goal, the system will be upgraded in most of its components. Among them, the event builder software, in charge of assembling all the data read out from the different sub-detectors, is planned to be modified from a single event builder to an orbit builder that assembles multiple events at the same time. The throughput of the event builder will be increased from the current 1.6 Tb/s to 51 Tb/s for the HL-LHC orbit builder. This paper presents preliminary network transfer studies in preparation for the upgrade. The key conceptual characteristics are discussed, concerning differences between the CMS event builder in Run 3 and the CMS Orbit Builder for the HL-LHC. For the feasibility studies, a pipestream benchmark, mimicking event-builder-like traffic has been developed. Preliminary performance tests and results are discussed.

Abstract This paper describes recent progress on the design of the DAQ and Timing Hub, or DTH, an ATCA (Advanced Telecommunications Computing Architecture) hub board intended for the phase-2 upgrade of the CMS experiment. Prototyping was originally divided into multiple feature lines, spanning all different aspects of the DTH functionality. The second DTH prototype merges all R&amp;D and prototyping lines into a single board, which is intended to be the production candidate. Emphasis is on the process and experience in going from the first to the second DTH prototype, which included a change of the chosen FPGA as well as the integration of a commercial networking solution.

The age at epilepsy onset in patients with inborn or very early acquired brain lesions depends on the epileptogenic potential of the lesion and the patients' individual "susceptibility" to epileptic seizures. To gain insight into these determinants, we analysed the case history of patients with focal cortical dysplasias (FCDs) and neuroglial tumours.In a systematic, retrospective analysis comprised of 233 patients who underwent surgery (116 with FCDs and 117 with neuroglial tumours), we evaluated the age at epilepsy onset according to histopathologic subgroups, lesion location and family history.Epilepsy onset was significantly earlier in patients with FCD than for those with neuroglial tumours (FCDs: 8.06 ± 0.74 years, gangliogliomas: 15.86 ± 1.24 years, dysembryoplastic neuroepithelial tumours (DNTs): 19.18 ± 2.47 years; p < 0.00001). FCDs were most frequently located in the frontal, whereas neuroglial tumours most frequently in the temporal lobe. For FCD patients, the age at epilepsy onset was not dependent on lesion location, whereas DNTs in a temporal location were associated with a later epilepsy onset than gangliogliomas and extratemporal DNTs. A positive family history for epilepsy or epileptic seizures was found more frequently among patients with FCDs (FCDs: 20.4%, neuroglial tumours: 8.1%; p = 0.013).We postulate that the age difference at epilepsy onset between patients with FCDs and neuroglial tumours can be attributed - at least partially - to unidentified genetic factors underlying the epileptogenic potential of the brain tissue. Additionally, the large variance in the age at epilepsy onset is possibly also genetically determined.

Abstract: Introduction: The motor and non-motor complications of Parkinson’s disease impair the patients’ quality of life and limit therapeutical options. There are no clear criteria for ‘advanced’ Parkinson’s disease or for the optimal moment for invasive therapies. There is little evidence regarding the upper limits of levodopa doses, and how these may be influenced by the availability of device-aided therapies. Aim: To analyze substitution therapy in patients with advanced Parkinson’s disease. Method: In our retrospective study, we analyzed the data from all patients with advanced Parkinson’s disease hospitalized between 1st June 2011 and 31st May 2017, receiving combined levodopa treatment at least 4×/day, reporting a minimum of 2 hours off periods, with or without dyskinesia. We analyzed levodopa therapy for patients who were recommended either device-aided or conservative therapy. Results: Out of 311 patients with advanced Parkinson’s disease, for 125 we proposed device-aided therapies whereas in 42 patients we increased the levodopa dose. The average levodopa doses and the administration rate were higher for the 107 patients tested for levodopa-carbidopa intestinal gel. Disease duration, mean levodopa doses and frequency of dosing were all higher in patients proposed for device-aided therapies versus patients with continued conservative treatment. Conclusion: Our patients were on lower levodopa doses (compared to literature), but the combinations were used more often. Device-aided therapies should be considered in patients with severe motor complications who receive at least 750–1000 mg levodopa daily, divided minimum 5×/day. These patients need to be tested in specialized centers by multidisciplinary teams in order to make the best decision for further action. Orv Hetil. 2019; 160(17): 662–669.

The data-acquisition system of the CMS experiment at the LHC performs the read-out and assembly of events accepted by the first level hardware trigger. Assembled events are made available to the high-level trigger which selects interesting events for offline storage and analysis. The system is designed to handle a maximum input rate of 100 kHz and an aggregated throughput of 100GB/s originating from approximately 500 sources. An overview of the architecture and design of the hardware and software of the DAQ system is given. We discuss the performance and operational experience from the first months of LHC physics data taking.

The data acquisition (DAQ) system of the CMS experiment at the CERN Large Hadron Collider assembles events at a rate of 100 kHz, transporting event data at an aggregate throughput of 100 GB/s to the high level trigger (HLT) farm. The HLT farm selects interesting events for storage and offline analysis at a rate of around 1 kHz. The DAQ system has been redesigned during the accelerator shutdown in 2013/14. The motivation is twofold: Firstly, the current compute nodes, networking, and storage infrastructure will have reached the end of their lifetime by the time the LHC restarts. Secondly, in order to handle higher LHC luminosities and event pileup, a number of sub-detectors will be upgraded, increasing the number of readout channels and replacing the off-detector readout electronics with a <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\mu {\hbox {TCA}}$</tex></formula> implementation. The new DAQ architecture will take advantage of the latest developments in the computing industry. For data concentration, 10/40 Gb/s Ethernet technologies will be used, as well as an implementation of a reduced TCP/IP in FPGA for a reliable transport between custom electronics and commercial computing hardware. A Clos network based on 56 Gb/s FDR Infiniband has been chosen for the event builder with a throughput of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\sim 4~\hbox{Tb/s}$</tex> </formula> . The HLT processing is entirely file based. This allows the DAQ and HLT systems to be independent, and to use the HLT software in the same way as for the offline processing. The fully built events are sent to the HLT with 1/10/40 Gb/s Ethernet via network file systems. Hierarchical collection of HLT accepted events and monitoring meta-data are stored into a global file system. This paper presents the requirements, technical choices, and performance of the new system.

To determine whether semiological similarity of electrically induced seizures (EIS) and spontaneously occurring habitual seizures (SHS) is associated with postsurgical seizure outcome in patients undergoing invasive video-EEG monitoring (VEM) before resective epilepsy surgery. Data of patients undergoing invasive VEM were retrospectively reviewed and included if at least one EIS and SHS during VEM occurred and the brain region in which EIS were elicited was resected. Seizure outcome was evaluated at three follow-up (FU) visits after surgery (1, 2 years and last available FU) according to the classification by Engel and the International League Against Epilepsy (ILAE). The level of semiological similarity of EIS and SHS was rated blinded to the surgical outcome. Statistics were done using Fisher’s exact test and a mixed linear-logistic regression model. 65 patients were included. Postsurgical seizure freedom was achieved in 51% (ILAE class 1) and 58% (Engel class I) at last FU (median 36 months). Patients with identical EIS and SHS displayed significantly better postsurgical seizure outcomes (ILAE class 1 at last FU: 76% vs. 31%, p < 0.001; Engel class I: 83% vs. 39%, p < 0.001). EIS are useful to confirm the location of the epileptogenic zone. A high level of similarity between EIS and SHS is associated with a favorable postsurgical seizure outcome. EIS may be used as an additional predictor of postsurgical outcome when counselling patients to proceed to resective epilepsy surgery.

The CMS data acquisition system is designed to build and filter events originating from 476 detector data sources at a maximum trigger rate of 100 kHz. Different architectures and switch technologies have been evaluated to accomplish this purpose. Events will be built in two stages: the first stage will be a set of event builders called front-end driver (FED) builders. These will be based on Myrinet technology and will pre-assemble groups of about eight data sources. The second stage will be a set of event builders called readout builders. These will perform the building of full events. A single readout builder will build events from about 60 sources of 16 kB fragments at a rate of 12.5 kHz. In this paper, we present the design of a readout builder based on TCP/IP over Gigabit Ethernet and the refinement that was required to achieve the design throughput. This refinement includes architecture of the readout builder, the setup of TCP/IP, and hardware selection.

The DAQ system of the CMS experiment at CERN collects data from more than 600 custom detector Front-End Drivers (FEDs). During 2013 and 2014 the CMS DAQ system will undergo a major upgrade to address the obsolescence of current hardware and the requirements posed by the upgrade of the LHC accelerator and various detector components. For a loss-less data collection from the FEDs a new FPGA based card implementing the TCP/IP protocol suite over 10Gbps Ethernet has been developed. To limit the TCP hardware implementation complexity the DAQ group developed a simplified and unidirectional but RFC 793 compliant version of the TCP protocol. This allows to use a PC with the standard Linux TCP/IP stack as a receiver. We present the challenges and protocol modifications made to TCP in order to simplify its FPGA implementation. We also describe the interaction between the simplified TCP and Linux TCP/IP stack including the performance measurements.

For the upgrade of the DAQ of the CMS experiment in 2013/2014 an interface between the custom detector Front End Drivers (FEDs) and the new DAQ eventbuilder network has to be designed. For a loss-less data collection from more then 600 FEDs a new FPGA based card implementing the TCP/IP protocol suite over 10Gbps Ethernet has been developed. We present the hardware challenges and protocol modifications made to TCP in order to simplify its FPGA implementation together with a set of performance measurements which were carried out with the current prototype.

Absztrakt: Bevezetés: Parkinson-kórban gastrointestinalis zavarok a betegség minden stádiumában előfordulnak, gyakran évekkel a diagnózis felállítása előtt. Jelentőségük előrehaladott Parkinson-kórban nagy, mert az életminőséget tovább rontják, és korlátozhatják mind a hagyományos, mind az eszközös terápiás lehetőségeket. Célkitűzés: Előrehaladott Parkinson-kórban szenvedő betegeknél jelentkező gastrointestinalis zavarok felmérése. Módszer: Retrospektív tanulmányunkban 6 éves periódusban minden olyan, levodopára reagáló Parkinson-kóros beteg adatait elemeztük, akinél legalább napi 2 óra off állapot bizonyítható, az on állapot súlyossága a Hoehn–Yahr-skálán mérve legalább 3 pont, és legalább napi négyszer kapott levodopát különböző kombinációkban. A gastrointestinalis panaszokat a következő célzott kérdésekre adott igen-nem válaszok segítségével azonosítottuk: volt-e nyelészavar, étvágytalanság, gyomortáji diszkomfort, puffadás, korai jóllakottság, émelygés, hányás, székrekedés. Eredmények: A 286 beteget két csoportra osztottuk a gastrointestinalis panaszok jelenléte, illetve hiánya szerint. A legalább egy gastrointestinalis tünetre panaszkodó 181 beteg esetében szignifikánsan hosszabb volt a kórtartam (10,13 ± 4,03 vs. 7,4 ± 2,42 év), illetve súlyosabb a klinikai kép (hosszabb off periódusok: 4,03 ± 1,32 vs. 2,91 ± 1,02 óra, tartósabbak a dyskinesisek: 2,76 ± 0,91 vs. 1,83 ± 0,61 óra, magasabb a Hoehn–Yahr-pontszám). Ezek a betegek nagyobb levodopaadagokat kaptak nagyobb adagolási frekvenciával. A gastrointestinalis panaszok közül a székrekedés (59%) és a meteorismus (32,5%) volt a leggyakoribb. A panaszok nagy többsége szignifikánsan gyakrabban fordult elő a dyskinesises betegeknél. Következtetés: A tápcsatorna működésére vonatkozó panaszok gyakoriak előrehaladott Parkinson-kórban. Ezek felmérése a rutinvizsgálat szerves része kell, hogy legyen. Meg kellene határozni a betegek gastrointestinalis profilját, interdiszciplináris megközelítésben, a megfelelő klinikai és paraklinikai módszerekkel. A gastroparesis és a dyskinesisek közötti kapcsolat fontos láncszem lehet az előrehaladott Parkinson-kór patomechanizmusában, ennek tisztázására további vizsgálatok szükségesek. Orv Hetil. 2020; 161(39): 1681–1687.

The objective of this study was to compare complications, seizures, and neuropsychological outcomes after resective epilepsy surgery in patients ≥ 60 years of age who underwent operations to younger and matched controls.Charts of 2243 patients were screened for operated patients in the authors' center between 2000 and 2015. Patients with available postsurgical follow-up data who were operated on at the age of 60 years or older and matched (by gender, histopathology, and side of surgery) controls who were between 20 and 40 years of age at the time of surgery were included. Outcomes regarding postoperative seizure control were scored according to the Engel classification and group comparisons were performed by using chi-square statistics.Data of 20 older patients were compared to those of 60 younger controls. Postoperative seizure control was favorable in the majority of the elderly patients (Engel classes I and II: 75% at 12 months, 65% at last follow-up), but the proportion of patients with favorable outcome tended to be larger in the control group (Engel classes I and II: 90% at 12 months, p = 0.092; 87% at last follow-up, p = 0.032, chi-square test). The surgical complication rate was higher in the elderly population (65% vs 27%, p = 0.002), but relevant persistent deficits occurred in 2 patients of each group only. Neuropsychological and behavioral assessments displayed considerable preoperative impairment and additional postoperative worsening, particularly of verbal skills, memory (p < 0.05), and mood in the elderly.The overall favorable postsurgical outcome regarding seizure control and the moderate risk of disabling persistent neurological deficits in elderly patients supports the view that advanced age should not be a barrier per se for resective epilepsy surgery and underscores the importance of an adequate presurgical evaluation and of referral of elderly patients to presurgical assessment.

The CMS Phase-2 upgrade for the HL-LHC aims at preserving and expanding the current physics capability of the experiment under extreme pileup conditions. A new tracking system incorporates a track finder processor, providing tracks to the Level-1 (L1) trigger. A new high-granularity calorimeter provides fine-grained energy deposition information in the endcap region. New front-end and back-end electronics feed the L1 trigger with high-resolution information from the barrel calorimeter and the muon systems. The upgraded L1 will be based primarily on the Xilinx Ultrascale Plus series of FPGAs, capable of sophisticated feature searches with resolution often similar to the offline reconstruction. The L1 Data Scouting system (L1DS) will capture L1 intermediate data produced by the trigger processors at the beam-crossing rate of 40 MHz, and carry out online analyses based on these limited-resolution data. The L1DS will provide fast and virtually unlimited statistics for detector diagnostics, alternative luminosity measurements, and, in some cases, calibrations. It also has the potential to enable the study of otherwise inaccessible signatures, either too common to fit in the L1 trigger accept budget or with requirements that are orthogonal to “mainstream” physics. The requirements and architecture of the L1DS system are presented, as well as some of the potential physics opportunities under study. The first results from the assembly and commissioning of a demonstrator currently being installed for LHC Run-3 are also presented. The demonstrator collects data from the Global Muon Trigger, the Layer-2 Calorimeter Trigger, the Barrel Muon Track Finder, and the Global Trigger systems of the current CMS L1. This demonstrator, as a data acquisition (DAQ) system operating at the LHC bunch-crossing rate, faces many of the challenges of the Phase-2 system, albeit with scaled-down connectivity, reduced data throughput and physics capabilities, providing a testing ground for new techniques of online data reduction and processing.

Ictal single photon emission computed tomography (SPECT) can be used as an advanced diagnostic modality to detect the seizure onset zone in the presurgical evaluation of people with epilepsy. In addition to visual assessment (VSA) of ictal and interictal SPECT images, postprocessing methods such as ictal-interictal SPECT analysis using SPM (ISAS) can visualize regional ictal blood flow differences. We aimed to evaluate and differentiate the diagnostic value of VSA and ISAS in the Bonn cohort.We included 161 people with epilepsy who underwent presurgical evaluation at the University Hospital Bonn between 2008 and 2020 and received ictal and interictal SPECT and ISAS. We retrospectively assigned SPECT findings to one of five categories according to their degree of concordance with the clinical focus hypothesis.Seizure onset zones could be identified more likely on a sublobar concordance level by ISAS than by VSA (31% vs. 19% of cases; OR = 1.88; 95% Cl [1.04, 3.42]; P = 0.03). Both VSA and ISAS more often localized a temporal seizure onset zone than an extratemporal one. Neither VSA nor ISAS findings were predicted by the latency between seizure onset and tracer injection (P = 0.75). In people who underwent successful epilepsy surgery, VSA and ISAS indicated the correct resection site in 54% of individuals, while MRI and EEG showed the correct resection localization in 96% and 33% of individuals, respectively. It was more likely to become seizure-free after epilepsy surgery if ISAS or VSA had been successful. There was no MR-negative case with successful surgery, indicating that ictal SPECT is more useful for confirmation than for localization.The results of the most extensive clinical study of ictal SPECT to date allow an assessment of the diagnostic value of this elaborate examination and emphasize the importance of postprocessing routines.

Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry-based tool that enables point-wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point-wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age- and gender-matched healthy subjects. FreeSurfer-based segmentations of hippocampal subfields in 3T-MRI were subjected to a geometry-based analysis that resulted in a coordinate system of the hippocampal mid-surface and allowed for point-wise measurements of hippocampal thickness and other features. Using point-wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS-mTLE). In the contralateral hippocampus of HS-mTLE and the affected hippocampus of MRI-negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS-mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni-corrected p < .05). We show that point-wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.

The Compact Muon Solenoid (CMS) experiment operating at the CERN (European Laboratory for Nuclear Physics) Large Hadron Collider (LHC) is in the process of upgrading several of its detector systems. Adding more individual detector components brings the need to test and commission those components separately from existing ones so as not to compromise physics data-taking. The CMS Trigger, Timing and Control (TTC) system had reached its limits in terms of the number of separate elements (partitions) that could be supported. A new Timing and Control Distribution System (TCDS) has been designed, built and commissioned in order to overcome this limit. It also brings additional functionality to facilitate parallel commissioning of new detector elements. The new TCDS system and its components will be described and results from the first operational experience with the TCDS in CMS will be shown.

Tick-borne encephalitis (TBE) is a central nervous system (CNS) disease caused by the neurotropic, positive-sense RNA virus, tick-borne encephalitis virus (TBEV). A possible association between predisposition to TBE in a Russian population and two polymorphisms, a 32 bp deletion in the coding region of the chemokine receptor CCR5 gene and the rs3775291 single nucleotide polymorphism (SNP) (G/A, Leu412Phe) in exon 4 of the toll-like receptor TLR3 gene, was investigated. The genotypic and allelic frequencies of these polymorphisms were analyzed in 137 non-immunized TBE patients with different clinical manifestations, including fever (35), meningitis (62), and severe CNS disease (40), as well as in a control population (269 randomly selected Novosibirsk citizens). The frequencies of the TLR3 G allele and G/G homozygotes were significantly higher among the patients with TBE compared with the control group (P = 0.029 and 0.037, respectively), especially among patients with severe disease (P = 0.018 and 0.017, respectively). These results indicate that the G allele (within the G/G homozygous genotype) of the TLR3 rs3775291 SNP is associated with predisposition to TBE in the Russian population.

Abstract Our goal was to assess the interrater agreement (IRA) of photoparoxysmal response (PPR) using the classification proposed by a task force of the International League Against Epilepsy (ILAE), and a simplified classification system proposed by our group. In addition, we evaluated IRA of epileptiform discharges (EDs) and the diagnostic significance of the electroencephalographic (EEG) abnormalities. We used EEG recordings from the European Reference Network (EpiCARE) and Standardized Computer‐based Organized Reporting of EEG (SCORE). Six raters independently scored EEG recordings from 30 patients. We calculated the agreement coefficient (AC) for each feature. IRA of PPR using the classification proposed by the ILAE task force was only fair (AC = 0.38). This improved to a moderate agreement by using the simplified classification (AC = 0.56; P = .004). IRA of EDs was almost perfect (AC = 0.98), and IRA of scoring the diagnostic significance was moderate (AC = 0.51). Our results suggest that the simplified classification of the PPR is suitable for implementation in clinical practice.

A fast integrated electronic chain is presented to read out the cathode pad array of a multiwire photon detector for a fast RICH counter. Two VLSI circuits have been designed and produced. An analog eight-channel, low-noise, fast, bi-polar current preamplifier-amplifier and discriminator chip serves as the front-end detection electronics. It has an rms equivalent noise current of 10 nA, 50 MHz bandwidth with 10 mW of power consumption per channel. Two analog chips are coupled to a digital sixteen-channel CMOS readout chip, operating at 20 MHz with a power consumption of 6 mW per channel. Readout of a 4000 pad sector requires 2–3 μs, depending on the number of hit pads. The full RICH counter is made up of many such sectors, read out in parallel. The minimum time needed to separate successive hits on the same pad is 70 ns. The conception of the digital chip and its properties are fully presented in this report. The analog chip is described in less detail since it will be fully covered in a forthcoming paper.

The CMS experiment at the LHC at CERN will start taking data in 2008. To configure, control and monitor the experiment during data-taking the Run Control system was developed. This paper describes the architecture and the technology used to implement the Run Control system, as well as the deployment and commissioning strategy of this important component of the online software for the CMS experiment.

The Data Acquisition System of the Compact Muon Solenoid experiment at the Large Hadron Collider reads out event fragments of an average size of 2 kB from around 650 detector front-ends at a rate of up to 100 kHz. The first stage of event-building is performed by the Super-Fragment Builder employing custom-built electronics and a Myrinet optical network. It reduces the number of fragments by one order of magnitude, thereby greatly decreasing the requirements for the subsequent event-assembly stage. Back-pressure from the down-stream event-processing or variations in the size and rate of events may give rise to buffer overflows in the subdetector's front-end electronics, which would result in data corruption and would require a time-consuming re-sync procedure to recover. The Trigger-Throttling System protects against these buffer overflows. It provides fast feedback from any of the subdetector front-ends to the trigger so that the trigger can be throttled before buffers overflow. This paper reports on new performance measurements and on the recent successful integration of a scaled-down setup of the described system with the trigger and with front-ends of all major subdetectors. The on-going commissioning of the full-scale system is discussed.

The CMS data acquisition system comprises O(20000) interdependent services that need to be monitored in near real-time. The ability to monitor a large number of distributed applications accurately and effectively is of paramount importance for robust operations. Application monitoring entails the collection of a large number of simple and composed values made available by the software components and hardware devices. A key aspect is that detection of deviations from a specified behaviour is supported in a timely manner, which is a prerequisite in order to take corrective actions efficiently. Given the size and time constraints of the CMS data acquisition system, efficient application monitoring is an interesting research problem. We propose an approach that uses the emerging paradigm of Web-service based eventing systems in combination with hierarchical data collection and load balancing. Scalability and efficiency are achieved by a decentralized architecture, splitting up data collections into regions of collections. An implementation following this scheme is deployed as the monitoring infrastructure of the CMS experiment at the Large Hadron Collider. All services in this distributed data acquisition system are providing standard web service interfaces via XML, SOAP and HTTP [15,22]. Continuing on this path we adopted WS-* standards implementing a monitoring system layered on top of the W3C standards stack. We designed a load-balanced publisher/subscriber system with the ability to include high-speed protocols [10,12] for efficient data transmission [11,13,14] and serving data in multiple data formats.

The CMS event builder assembles events accepted by the first level trigger and makes them available to the high-level trigger. The event builder needs to handle a maximum input rate of 100 kHz and an aggregated throughput of 100 GB/s originating from approximately 500 sources. This paper presents the chosen hardware and software architecture. The system consists of 2 stages: an initial pre-assembly reducing the number of fragments by one order of magnitude and a final assembly by several independent readout builder (RU-builder) slices. The RU-builder is based on 3 separate services: the buffering of event fragments during the assembly, the event assembly, and the data flow manager. A further component is responsible for handling events accepted by the high-level trigger: the storage manager (SM) temporarily stores the events on disk at a peak rate of 2 GB/s until they are permanently archived offline. In addition, events and data-quality histograms are served by the SM to online monitoring clients. We discuss the operational experience from the first months of reading out cosmic ray data with the complete CMS detector.

The CMS experiment at the LHC features a two-level trigger system. Events accepted by the first level trigger, at a maximum rate of 100 kHz, are read out by the Data Acquisition system (DAQ), and subsequently assembled in memory in a farm of computers running a software high-level trigger (HLT), which selects interesting events for offline storage and analysis at a rate of order few hundred Hz. The HLT algorithms consist of sequences of offline-style reconstruction and filtering modules, executed on a farm of 0(10000) CPU cores built from commodity hardware. Experience from the operation of the HLT system in the collider run 2010/2011 is reported. The current architecture of the CMS HLT, its integration with the CMS reconstruction framework and the CMS DAQ, are discussed in the light of future development. The possible short- and medium-term evolution of the HLT software infrastructure to support extensions of the HLT computing power, and to address remaining performance and maintenance issues, are discussed.

As part of the CMS upgrade during CERN's shutdown period (LS1), the CMS data acquisition system is incorporating Infiniband FDR technology to boost event-building performance for operation from 2015 onwards.Infiniband promises to provide substantial increase in data transmission speeds compared to the older 1GE network used during the 2009-2013 LHC run.Several options exist to end user developers when choosing a foundation for software upgrades, including the uDAPL (DAT Collaborative) and Infiniband verbs libraries (OFED).Due to advances in technology, the CMS data acquisition system will be able to achieve the required throughput of 100 kHz with increased event sizes while downsizing the number of nodes by using a combination of 10GE, 40GE and 56 Gb Infiniband FDR.This paper presents the analysis and results of a comparison between GE and Infiniband solutions as well as a look at how they integrate into an event building architecture, while preserving the scalability, efficiency and deterministic latency expected in a high end data acquisition network.

The DAQ and Timing Hub is an ATCA hub board designed for the Phase-2 upgrade of the CMS experiment.In addition to providing high-speed Ethernet connectivity to all back-end boards, it forms the bridge between the sub-detector electronics and the central DAQ, timing, and trigger control systems.One important requirement is the distribution of several high-precision, phasestable, and LHC-synchronous clock signals for use by the timing detectors.The current paper presents first measurements performed on the initial prototype, with a focus on clock quality.It is demonstrated that the current design provides adequate clock quality to satisfy the requirements of the Phase-2 CMS timing detectors.

Összefoglaló. Bevezetés: Az előrehaladott Parkinson-kór bizonyos fázisában a motoros komplikációk már nem befolyásolhatók hatékonyan a hagyományos orális, illetve transdermalis gyógyszerekkel. Ilyenkor meg kell fontolni, komplex felmérési és döntési folyamatot követően, az invazív eszközös terápiák bevezetését. Célkitűzés: A döntéshozatal és a fontosabb klinikai paraméterek elemzése levodopa-karbidopa intestinalis géllel kezelt betegeinknél az elfogadás időtartamának függvényében. Módszer: Retrospektíven vizsgáltuk azon betegeink adatait, akiknél a marosvásárhelyi 2. Sz. Ideggyógyászati Klinikán 2011. június 1. és 2019. december 31. között vezettük be a levodopa-karbidopa intestinalis géllel történő terápiát. A kezelés elfogadásához szükséges időintervallum szerint két csoportot alkottunk: egy hónap vagy annál rövidebb, illetve egy hónapnál több idő az első, célzott kivizsgálás és a tesztelés megkezdése között. Eredmények: A vizsgált időszakban 163 betegnél teszteltük orrszondán a kezelés hatékonyságát, közülük 127 esetben történt meg a terápia véglegesítése. A döntéshozatal 56 betegnél egy hónap vagy annál rövidebb időt, míg 71 betegnél egy hónapnál több időt igényelt. A dyskinesisek átlagos időtartamának szempontjából szignifikáns különbséget találtunk a két csoport között (3,1 ± 0,7 vs. 2,8 ± 0,8 óra, p = 0,02). Az eszközös terápia bevezetése előtti levodopa-átlagadag 821,5 ± 246,6 mg volt, naponta átlagosan 5-ször adagolva. A kiegészítő terápiák alkalmazási arányai: a dopaminagonisták 80,3%-ban, a katechol-O-metiltranszferáz-gátlók 62,2%-ban, illetve a monoaminoxidáz-B-gátlók 68,5%-ban. Az átlagos off időtartam 4,7 ± 1,1 óra volt, és 85 betegünknél tapasztaltunk 2,9 ± 0,8 óra átlag-időtartamú dyskinesist. Következtetés: Hamarabb fogadják el az eszközös terápiát azok az előrehaladott Parkinson-kóros betegek, akiknek hosszabb időtartamú a napi dyskinesisük, illetve régebbi a betegségük. A terápiás irányelvek gyakorlatba ültetésekor figyelembe kell venni a helyi sajátosságokat: a kiegészítő gyógyszerekhez, illetve az eszközös terápiákhoz való hozzáférést. Orv Hetil. 2021; 162(21): 839–847. Summary. Introduction: In advanced stages of Parkinson’s disease, motor complications cannot be effectively controlled with conventional therapies. In such cases, the complex assessment and decision-making process that leads to device-aided therapies should be considered. Objective: To analyze the decision-making and key clinical parameters, as a function of duration of acceptance, patients treated with levodopa-carbidopa intestinal gel. Method: We retrospectively examined the data of patients who started levodopa-carbidopa intestinal gel therapy at the 2nd Department of Neurology Târgu Mureş, between 1 June 2011 and 31 December 2019. Two groups were formed: less than one month and more than one month between the first targeted examination and the start of testing. Results: Therapeutic efficiency was tested with nasal tube on 163 patients, out of whom 127 patients remained on treatment. Decision-making took one month or less for 56 patients and more than a month for 71 patients. Duration of dyskinesias was significantly different between the two groups (3.1 ± 0.7 vs 2.8 ± 0.8 hours, p = 0.02). Mean dose of levodopa prior to the introduction of device-aided therapy was 821.5 ± 246.6 mg, administered 5 times daily. Dopamine agonists were used in 80.3%, catechol-O-methyltransferase inhibitors in 62.2%, and monoamine oxidase-B inhibitors in 68.5% of cases. The mean off -time was 4.7±1.1 hours and data from 85 patients showed 2.9 ± 0.8 hours of dyskinesia. Conclusion: Device-aided therapy is adopted sooner by patients with advanced Parkinson’s disease with longer disease duration and more dyskinesias. Local specificities, such as access to add-on medication and device-aided therapies, must be taken into account when implementing therapeutic guidelines. Orv Hetil. 2021; 162(21): 839–847.

The High Luminosity LHC (HL-LHC) will start operating in 2027 after the third Long Shutdown (LS3), and is designed to provide an ultimate instantaneous luminosity of 7:5 × 10 34 cm −2 s −1 , at the price of extreme pileup of up to 200 interactions per crossing. The number of overlapping interactions in HL-LHC collisions, their density, and the resulting intense radiation environment, warrant an almost complete upgrade of the CMS detector. The upgraded CMS detector will be read out by approximately fifty thousand highspeed front-end optical links at an unprecedented data rate of up to 80 Tb/s, for an average expected total event size of approximately 8 − 10 MB. Following the present established design, the CMS trigger and data acquisition system will continue to feature two trigger levels, with only one synchronous hardware-based Level-1 Trigger (L1), consisting of custom electronic boards and operating on dedicated data streams, and a second level, the High Level Trigger (HLT), using software algorithms running asynchronously on standard processors and making use of the full detector data to select events for offline storage and analysis. The upgraded CMS data acquisition system will collect data fragments for Level-1 accepted events from the detector back-end modules at a rate up to 750 kHz, aggregate fragments corresponding to individual Level- 1 accepts into events, and distribute them to the HLT processors where they will be filtered further. Events accepted by the HLT will be stored permanently at a rate of up to 7.5 kHz. This paper describes the baseline design of the DAQ and HLT systems for the Phase-2 of CMS.

We developed a complete GPU based data processing for cone-beam micro CT application which performs not only the reconstruction but also all the correction of the projection images on-the-fly. Test measurements were performed and processing times was compared on different hardware setups. The performance of the GPU together with our modified algorithm allow to process all the calculations within the shortest exposure time of the system for the highest reconstructed volume size thus makes possible the complete data processing in real-time.

This paper outlines a software architecture where zero-copy operations are used comprehensively at every processing point from the Application layer to the Physical layer. The proposed architecture is being used during feasibility studies on advanced networking technologies for the CMS experiment at CERN. The design relies on a homogeneous peer-to-peer message passing system, which is built around memory pool caches allowing efficient and deterministic latency handling of messages of any size through the different software layers. In this scheme portable distributed applications can be programmed to process input to output operations by mere pointer arithmetic and DMA operations only. The approach combined with the open fabric protocol stack (OFED) allows one to attain near wire-speed message transfer at application level. The architecture supports full portability of user applications by encapsulating the protocol details and network into modular peer transport services whereas a transparent replacement of the underlying protocol facilitates deployment of several network technologies like Gigabit Ethernet, Myrinet, Infiniband, etc. Therefore, this solution provides a protocol-independent communication framework and prevents having to deal with potentially difficult couplings when the underlying communication infrastructure is changed. We demonstrate the feasibility of this approach by giving efficiency and performance measurements of the software in the context of the CMS distributed event building studies.

We discuss the first test results, obtained with cosmic rays, of a full-scale Fast-RICH Prototype with proximity-focused 10 mm thick LiF (CaF2) solid radiators, TEA as photosensor in CH4, and readout of 12 × 103 cathode pads (5.334 × 6.604 mm2) using dedicated VLSI electronics we have developed. The number of detected photoelectrons is 7.7 (6.9) for the CaF2 (LiF) radiator, very near to the expected values 6.4 (7.5) from Monte Carlo simulations. The single-photon Cherenkov angle resolution σθ = 19.1 (15.2) mrad for the CaF2 (LiF) radiator, to be compared with 19.3 (13.2) mrad predicted by the Monte Carlo calculations. These first results have shown that the Fast-RICH Prototype works well and that the technique is well-suited for the next generation of high luminosity e+e− or hadron colliders.

A neutron noise based method is proposed for the detection of impacting of detector tubes in BWRs. The basic idea relies on the assumption that non-stationary transients (e.g. fuel box vibrations) may be induced at impacting. Such short-lived transients are difficult to detect by spectral analysis methods. However, their presence in the detector signal can be detected by wavelet analysis. A simple wavelet technique, the so-called Haar transform, is suggested for the detection of impacting. Tests of the proposed method have been performed with success on both simulated data with controlled impacting as well as with real measurement data. The simulation model as well as the rsults of the wavelet analysis are reported in this paper. The source codes written in MATLAB® are available at a public ftp site. The necessary information to reproduce the simulation results is also reported.

Abstract In the present paper we critically review the bank of Kalman filter method for reactivity estimation originally suggested by D'Attellis and Cortina. It is pointed out that the procedure can not be applied reliably in the form proposed by the authors, because of the invalid interpretation of the decision rule as well as the presence of the filter divergence. An improved method based on D'Attellis' and Cortina's idea, free from divergence problems, is presented. The procedure is applied for estimation of small reactivity changes occurring after a long critical operation of the reactor.

The data acquisition system for the CMS experiment at the Large Hadron Collider (LHC) will require a large and high performance event building network. Several switch technologies are currently being evaluated in order to compare different architectures for the event builder. One candidate is Myrinet. This paper describes the demonstrator which has been set up to study a small-scale (8/spl times/8) event builder based on a Myrinet switch. Measurements are presented on throughput, overhead and scaling for various traffic conditions. Results are shown on event building with a push architecture.

V. Brigljevic, G. Bruno, E. Cano, S. Cittolin, A. Csilling, D. Gigi, F. Glege, R. Gomez-Reino, M. Gulmini, J. Gutleber, C. Jacobs, M. Kozlovszky, H. Larsen, I. Magrans, F. Meijers, E. Meschi, S. Murray, A. Oh, L. Orsini, L. Pollet, A. Racz, D. Samyn, P. Scharff-Hansen, C. Schwick, P. Sphicas CERN, European Organization for Nuclear Research, Geneva, Switzerland Also at INFN, Laboratori Nazionali di Legnaro, Legnaro, Italy Also at University of Athens, Greece L. Berti, G. Maron, G. Rorato, N. Toniolo, L. Zangrando INFN, Laboratori Nazionali di Legnaro, Legnaro, Italy M. Bellato, S. Ventura INFN, Sezione di Padova, Padova, Italy S. Erhan University of California, Los Angeles, California, USA

Run control systems of modern high-energy particle physics experiments have requirements similar to those of today's Internet applications. The Compact Muon Solenoid (CMS) collaboration at CERN's Large Hadron Collider (LHC) therefore decided to build the run control system for its detector based on web technologies. The system is composed of Java Web Applications distributed over a set of Apache Tomcat servlet containers that connect to a database back-end. Users interact with the system through a web browser. The present paper reports on the successful scaling of the system from a small test setup to the production data acquisition system that comprises around 10.000 applications running on a cluster of about 1600 hosts. We report on operational aspects during the first phase of operation with colliding beams including performance, stability, integration with the CMS Detector Control System and tools to guide the operator.

The DAQ system of the CMS experiment at the LHC is upgraded during the accelerator shutdown in 2013/14. To reduce the interdependency of the DAQ system and the high-level trigger (HLT), we investigate the feasibility of using a file-system-based HLT. Events of ~1 MB size are built at the level-1 trigger rate of 100 kHz. The events are assembled by ~50 builder units (BUs). Each BU writes the raw events at ~2GB/s to a local file system shared with Q(10) filter-unit machines (FUs) running the HLT code. The FUs read the raw data from the file system, select Q(1%) of the events, and write the selected events together with monitoring meta-data back to a disk. This data is then aggregated over several steps and made available for offline reconstruction and online monitoring. We present the challenges, technical choices, and performance figures from the prototyping phase. In addition, the steps to the final system implementation will be discussed.

A flexible monitoring system has been designed for the CMS File-based Filter Farm making use of modern data mining and analytics components. All the metadata and monitoring information concerning data flow and execution of the HLT are generated locally in the form of small documents using the JSON encoding. These documents are indexed into a hierarchy of elasticsearch (es) clusters along with process and system log information. Elasticsearch is a search server based on Apache Lucene. It provides a distributed, multitenant-capable search and aggregation engine. Since es is schema-free, any new information can be added seamlessly and the unstructured information can be queried in non-predetermined ways. The leaf es clusters consist of the very same nodes that form the Filter Farm thus providing natural horizontal scaling. A separate central" es cluster is used to collect and index aggregated information. The fine-grained information, all the way to individual processes, remains available in the leaf clusters. The central es cluster provides quasi-real-time high-level monitoring information to any kind of client. Historical data can be retrieved to analyse past problems or correlate them with external information. We discuss the design and performance of this system in the context of the CMS DAQ commissioning for LHC Run 2.

A fast integrated electronic chain is presented to read out the cathode pad array of a multiwire photon detector for a fast RICH counter. Two VLSI circuits have been designed and produced. An analog eight channel, low noise, fast, bipolar, current preamplifier and discriminator chip serves as front-end electronics. It has an rms equivalent noise current of 10 nA (2000 e−), 50 MHz bandwidth with 10 mW of power consumption per channel. Two analogue chips are coupled to a digital 16 channels CMOS readout chip, operating at 20 MHz, that provides a pipelined delay of 1.3 μs and zero suppression with a power consumption of about 6 mW per channel. Readout of a 4000 pad sector requires 3–4 μs depending on the number of hit pads. The full RICH counter is made up of many of such sectors (the prototype has three fully equipped sectors), read out in parallel [1,2]. The minimum time to separate successive hits on the same pad is about 70 ns. The time skew of the full chain is about 15 ns.

The CMS data acquisition (DAQ) system relies on a purely software driven high level trigger (HLT) to reduce the full Level 1 accept rate of 100 kHz to approximately 100 Hz for archiving and later offline analysis. The HLT operates on the full information of events assembled by an event builder collecting detector data from the CMS front-end systems. The HLT software consists of a sequence of reconstruction and filtering modules executed on a farm of O(1000) CPUs built from commodity hardware. This paper presents the architecture of the CMS HLT, which integrates the CMS reconstruction framework in the online environment. The mechanisms to configure, control, and monitor the filter farm and the procedures to validate the filtering code within the DAQ environment are described.

The Compact Muon Solenoid (CMS) is a CERN multi-purpose experiment that exploits the physics of the Large Hadron Collider (LHC). The Detector Control System (DCS) is responsible for ensuring the safe, correct and efficient operation of the experiment, and has contributed to the recording of high quality physics data. The DCS is programmed to automatically react to the LHC operational mode. CMS sub-detectors' bias voltages are set depending on the machine mode and particle beam conditions. An operator provided with a small set of screens supervises the system status summarized from the approximately 6M monitored parameters. Using the experience of nearly two years of operation with beam the DCS automation software has been enhanced to increase the system efficiency by minimizing the time required by sub-detectors to prepare for physics data taking. From the infrastructure point of view the DCS will be subject to extensive modifications in 2012. The current rack mounted control PCs will be replaced by a redundant pair of DELL Blade systems. These blade servers are a high-density modular solution that incorporates servers and networking into a single chassis that provides shared power, cooling and management. This infrastructure modification associated with the migration to blade servers will challenge the DCS software and hardware factorization capabilities. The on-going studies for this migration together with the latest modifications are discussed in the paper.

The CMS experiment will be upgraded for operation at the HighLuminosity LHC to maintain and extend its physics performance under extreme pileup conditions. Upgrades will include an entirely new tracking system, supplemented by a track finder processor providing tracks at Level-1, as well as a high-granularity calorimeter in the endcap region. New front-end and back-end electronics will also provide the Level-1 trigger with high-resolution information from the barrel calorimeter and the muon systems. The upgraded Level-1 processors, based on powerful FPGAs, will be able to carry out sophisticated feature searches with resolutions often similar to the offline ones, while keeping pileup effects under control. In this paper, we discuss the feasibility of a system capturing Level-1 intermediate data at the beam-crossing rate of 40 MHz and carrying out online analyzes based on these limited-resolution data. This 40 MHz scouting system would provide fast and virtually unlimited statistics for detector diagnostics, alternative luminosity measurements and, in some cases, calibrations. It has the potential to enable the study of otherwise inaccessible signatures, either too common to fit in the Level-1 accept budget, or with requirements which are orthogonal to “mainstream” physics, such as long-lived particles. We discuss the requirements and possible architecture of a 40 MHz scouting system, as well as some of the physics potential, and results from a demonstrator operated at the end of Run-2 using the Global Muon Trigger data from CMS. Plans for further demonstrators envisaged for Run-3 are also discussed.

The identification and distinction of the pathological conditions underlying acute psychosis are often challenging. We present the case of a 35-year-old ranger who had no history of acute or chronic infectious disease or any previous neuropsychiatric symptoms. He arrived at the Psychiatry Clinic and was admitted as an emergency case, displaying bizarre behavior, hallucinations, paranoid ideation, and delusional faults. These symptoms had first appeared 7 days earlier. An objective examination revealed abnormalities of behavior, anxiety, visual hallucinations, choreiform, and tic-like facial movements. After the administration of neuroleptic and antidepressant treatment, he showed an initial improvement, but on day 10 entered into a severe catatonic state with signs of meningeal irritation and was transferred to the intensive care unit. An electroencephalogram showed diffuse irritative changes, raising the possibility of encephalitis. Taking into consideration the overt occupational risk, Borrelia antibody tests were prescribed and highly positive immunoglobulin (Ig)M and IgG titers were obtained from serum, along with IgG and antibody index positivity in cerebrospinal fluid. In parallel, anti-N-methyl-D-aspartate receptor antibodies and a whole battery of other autoimmune encephalitis markers showed negative. A complex program of treatment was applied, including antibiotics, beginning with ceftazidime and ciprofloxacin - for suspected aspiration bronchopneumonia - and thereafter with ceftriaxone. A gradual improvement was noticed and the treatment continued at the Infectious Disease Clinic. Finally, the patient was discharged with a doxycycline, antidepressant, and anxiolytic maintenance treatment. On his first and second control (days 44 and 122 from the disease onset), the patient was stable with no major complaints, Borrelia seropositivity was confirmed both for IgM and IgG while the cerebrospinal fluid also showed reactivity for IgG on immunoblot. On the basis of the putative occupational risk, acute psychotic episode, and the success of antibiotic therapy, we registered this case as a late neuroborreliosis with atypical appearance.

The data acquisition system (DAQ) of the CMS experiment at the CERN Large Hadron Collider (LHC) assembles events at a rate of 100 kHz, transporting event data at an aggregate throughput of more than 100GB/s to the Highlevel Trigger (HLT) farm. The HLT farm selects and classifies interesting events for storage and offline analysis at an output rate of around 1 kHz. The DAQ system has been redesigned during the accelerator shutdown in 2013-2014. The motivation for this upgrade was twofold. Firstly, the compute nodes, networking and storage infrastructure were reaching the end of their lifetimes. Secondly, in order to maintain physics performance with higher LHC luminosities and increasing event pileup, a number of sub-detectors are being upgraded, increasing the number of readout channels as well as the required throughput, and replacing the off-detector readout electronics with a MicroTCA-based DAQ interface. The new DAQ architecture takes advantage of the latest developments in the computing industry. For data concentration 10/40 Gbit/s Ethernet technologies are used, and a 56Gbit/s Infiniband FDR CLOS network (total throughput ≈ 4Tbit/s) has been chosen for the event builder. The upgraded DAQ - HLT interface is entirely file-based, essentially decoupling the DAQ and HLT systems. The fully-built events are transported to the HLT over 10/40 Gbit/s Ethernet via a network file system. The collection of events accepted by the HLT and the corresponding metadata are buffered on a global file system before being transferred off-site. The monitoring of the HLT farm and the data-taking performance is based on the Elasticsearch analytics tool. This paper presents the requirements, implementation, and performance of the system. Experience is reported on the first year of operation with LHC proton-proton runs as well as with the heavy ion lead-lead runs in 2015.

OBJECTIVE Traditionally, patients who underwent elective craniotomy for epilepsy surgery are monitored postoperatively in an intensive care unit (ICU) overnight in order to sufficiently respond to potential early postoperative complications. In the present study, the authors investigated the frequency of early postoperative events that entailed ICU monitoring in patients who had undergone elective craniotomy for epilepsy surgery. In a second step, they aimed at identifying pre- and intraoperative risk factors for the development of unfavorable events to distinguish those patients with the need for postoperative ICU monitoring at the earliest possible stage. METHODS The authors performed a retrospective observational cohort study assessing patients with medically intractable epilepsy (n = 266) who had undergone elective craniotomy for epilepsy surgery between 2012 and 2019 at a tertiary care epilepsy center, excluding those patients who had undergone invasive diagnostic approaches and functional hemispherectomy. Postoperative complications were defined as any unfavorable postoperative surgical and/or anesthesiological event that required further ICU therapy within 48 hours following surgery. A multivariate analysis was performed to reveal preoperatively identifiable risk factors for postoperative adverse events requiring an ICU setting. RESULTS Thirteen (4.9%) of 266 patients developed early postoperative adverse events that required further postoperative ICU care. The most prevalent event was a return to the operating room because of relevant postoperative intracranial hematoma (5 of 266 patients). Multivariate analysis revealed intraoperative blood loss ≥ 325 ml (OR 6.2, p = 0.012) and diabetes mellitus (OR 9.2, p = 0.029) as risk factors for unfavorable postoperative events requiring ICU therapy. CONCLUSIONS The present study revealed routinely collectable risk factors that would allow the identification of patients with an elevated risk of postsurgical complications requiring a postoperative ICU stay following epilepsy surgery. These findings may offer guidance for a stepdown unit admission policy following epilepsy surgical interventions after an external validation of the results.

Limbic encephalitis is an increasingly recognized cause of medial temporal lobe epilepsy (mTLE) and associated cognitive deficits, potentially resulting in hippocampal sclerosis (HS). For several reasons, these patients usually do not undergo epilepsy surgery. Thus, histopathologic examinations in surgical specimens of clearly diagnosed limbic encephalitis are scarce. The purpose of this study was a detailed histopathologic analysis of surgical tissue alterations, including neurodegenerative markers, in patients with limbic encephalitis undergoing epilepsy surgery.We investigated the surgical specimens of six patients operated on with mTLE related to limbic encephalitis (among them four patients were with GAD65 and one with Ma1/2 antibodies), and compared the findings to a control group with six patients matched according to age at the time of surgery without limbic encephalitis and without early inciting events.Histopathologic analysis in the group with limbic encephalitis revealed HS in four patients, while three of them also displayed signs of an active inflammatory reaction with lymphocytes. In one of the patients with GAD65-encephalitis who was suffering from a late-onset mTLE and a long disease course, neurodegenerative protein markers (β-amyloid and hyperphosphorylated tau) were found coexisting with inflammatory reactions and HS. Investigations in the control group did not reveal any inflammatory reaction or neurodegenerative marker.Our findings suggest a possible link between long-lasting immune reactions in the medial temporal lobe, HS, and further toward the development of neurodegenerative diseases. Presently, however, a causal relationship between these entities cannot yet be established. Furthermore, our results suggest that an immunological etiology should always be considered in late onset (> 18 years) mTLE, also in cases of long disease duration and the presence of HS.

Recently, we showed that resection of at least 27% of the temporal part of piriform cortex (PiC) strongly correlated with seizure freedom 1 year following selective amygdalo-hippocampectomy (tsSAHE) in patients with mesial temporal lobe epilepsy (mTLE). However, the impact of PiC resection on long-term seizure outcome following tsSAHE is currently unknown. The aim of this study was to evaluate the impact of PiC resection on long-term seizure outcome in patients with mTLE treated with tsSAHE.Between 2012 and 2017, 64 patients were included in the retrospective analysis. Long-term follow-up (FU) was defined as at least 2 years postoperatively. Seizure outcome was assessed according to the International League against Epilepsy (ILAE). The resected proportions of hippocampus, amygdala, and PiC were volumetrically assessed.The mean FU duration was 3.75 ± 1.61 years. Patients with ILAE class 1 revealed a significantly larger median proportion of resected PiC compared to patients with ILAE class 2-6 [46% (IQR 31-57) vs. 16% (IQR 6-38), p = 0.001]. Resected proportions of hippocampus and amygdala did not significantly differ for these groups. Among those patients with at least 27% resected proportion of PiC, there were significantly more patients with seizure freedom compared to the patients with <27% resected proportion of PiC (83% vs. 39%, p = 0.0007).Our results show a strong impact of the extent of PiC resection on long-term seizure outcome following tsSAHE in mTLE. The authors suggest the PiC to constitute a key target volume in tsSAHE to achieve seizure freedom in the long term.

The data acquisition system for the CMS experiment at the Large Hadron Collider (LHC) will require a large and high performance event building network. Several switch technologies are currently being evaluated in order to compare different architectures for the event builder. One candidate is Myrinet. This paper describes the demonstrator which has been setup to study a small-scale (16×16) event builder based on PCs running Linux connected to Myrinet and Ethernet switches. A detailed study of the Myrinet switch performance has been performed for various traffic conditions, including the behaviour of composite switches. Results from event building studies are presented, including measurements on throughput, overhead and scaling. Traffic shaping techniques have been implemented and the effect on the event building performance has been investigated. The paper reports on performances and maximum event rate obtainable using custom software, not described, for the Myrinet control program and the low-level communication layer, implemented in a driver for Linux. A high performance sender is emulated by creating a dummy buffer that remains resident in the network interface and moving from the host only the first 64 bytes used by the event building protocol. An approximate scaling in N is presented assuming a balanced system where each source sends on average data to all destinations with the same rate.

The Run Control and Monitor System (RCMS) of the CMS experiment is the set of hardware and software components responsible for controlling and monitoring the experiment during data-taking. It provides users with a "virtual counting room", enabling them to operate the experiment and to monitor detector status and data quality from any point in the world. This paper describes the architecture of the RCMS with particular emphasis on its scalability through a distributed collection of nodes arranged in a tree-based hierarchy. The current implementation of the architecture in a prototype RCMS used in test beam setups, detector validations and DAQ demonstrators is documented. A discussion of the key technologies used, including Web Services, and the results of tests performed with a 128-node system are presented.

The CMS experiment at the CERN Large Hadron Collider is currently being commissioned and is scheduled to collect the first pp collision data in 2008. CMS features a two-level trigger system. The Level-1 trigger, based on custom hardware, is designed to reduce the collision rate of 40 MHz to approximately 100 kHz. Data for events accepted by the Level-1 trigger are read out and assembled by an Event Builder. The High Level Trigger (HLT) employs a set of sophisticated software algorithms, to analyze the complete event information, and further reduce the accepted event rate for permanent storage and analysis. This paper describes the design and implementation of the HLT Configuration Management system. First experiences with commissioning of the HLT system are also reported.

The Data Acquisition system of the Compact Muon Solenoid experiment at CERN assembles events at a rate of 100 kHz, transporting event data at an aggregate throughput of 100 GByte/s. We are presenting the design of the 2nd generation DAQ system, including studies of the event builder based on advanced networking technologies such as 10 and 40 Gbit/s Ethernet and 56 Gbit/s FDR Infiniband and exploitation of multicore CPU architectures. By the time the LHC restarts after the 2013/14 shutdown, the current compute nodes, networking, and storage infrastructure will have reached the end of their lifetime. In order to handle higher LHC luminosities and event pileup, a number of sub-detectors will be upgraded, increase the number of readout channels and replace the off-detector readout electronics with a μTCA implementation. The second generation DAQ system, foreseen for 2014, will need to accommodate the readout of both existing and new off-detector electronics and provide an increased throughput capacity. Advances in storage technology could make it feasible to write the output of the event builder to (RAM or SSD) disks and implement the HLT processing entirely file based.

The data-acquisition (DAQ) system of the CMS experiment at the LHC performs the read-out and assembly of events accepted by the first level hardware trigger. Assembled events are made available to the high-level trigger (HLT), which selects interesting events for offline storage and analysis. The system is designed to handle a maximum input rate of 100 kHz and an aggregated throughput of 100 GB/s originating from approximately 500 sources and 10^8 electronic channels. An overview of the architecture and design of the hardware and software of the DAQ system is given. We report on the performance and operational experience of the DAQ and its Run Control System in the first two years of collider runs of the LHC, both in proton-proton and Pb-Pb collisions. We present an analysis of the current performance, its limitations, and the most common failure modes and discuss the ongoing evolution of the HLT capability needed to match the luminosity ramp-up of the LHC.

We present the automation mechanisms that have been added to the Data Acquisition and Run Control systems of the Compact Muon Solenoid (CMS) experiment during Run 1 of the LHC, ranging from the automation of routine tasks to automatic error recovery and context-sensitive guidance to the operator. These mechanisms helped CMS to maintain a data taking efficiency above 90% and to even improve it to 95% towards the end of Run 1, despite an increase in the occurrence of single-event upsets in sub-detector electronics at high LHC luminosity.

The CMS online cluster consists of more than 2000 computers running about 10000 application instances. These applications implement the control of the experiment, the event building, the high level trigger, the online database and the control of the buffering and transferring of data to the Central Data Recording at CERN. In this paper the IT solutions employed to fulfil the requirements of such a large cluster are revised. Details are given on the chosen network structure, configuration management system, monitoring infrastructure and on the implementation of the high availability for the services and infrastructure.

The upgraded High Luminosity LHC, after the third Long Shutdown (LS3), will provide an instantaneous luminosity of 7.5 × 1034 cm−2s−1 (levelled), at the price of extreme pileup of up to 200 interactions per crossing. In LS3, the CMS Detector will also undergo a major upgrade to prepare for the phase-2 of the LHC physics program, starting around 2025. The upgraded detector will be read out at an unprecedented data rate of up to 50 Tb/s and an event rate of 750 kHz. Complete events will be analysed by software algorithms running on standard processing nodes, and selected events will be stored permanently at a rate of up to 10 kHz for offline processing and analysis.

TCP and the socket abstraction have barely changed over the last two decades, but at the network layer there has been a giant leap from a few megabits to 100 gigabits in bandwidth. At the same time, CPU architectures have evolved into the multi-core era and applications are expected to make full use of all available resources. Applications in the data acquisition domain based on the standard socket library running in a Non-Uniform Memory Access (NUMA) architecture are unable to reach full efficiency and scalability without the software being adequately aware about the IRQ (Interrupt Request), CPU and memory affinities. During the first long shutdown of LHC, the CMS DAQ system is going to be upgraded for operation from 2015 onwards and a new software component has been designed and developed in the CMS online framework for transferring data with sockets. This software attempts to wrap the low-level socket library to ease higher-level programming with an API based on an asynchronous event driven model similar to the DAT uDAPL API. It is an event-based application with NUMA optimizations, that allows for a high throughput of data across a large distributed system. This paper describes the architecture, the technologies involved and the performance measurements of the software in the context of the CMS distributed event building.

During the LHC Long Shutdown 1, the CMS Data Acquisition (DAQ) system underwent a partial redesign to replace obsolete network equipment, use more homogeneous switching technologies, and support new detector back-end electronics. The software and hardware infrastructure to provide input, execute the High Level Trigger (HLT) algorithms and deal with output data transport and storage has also been redesigned to be completely file- based. All the metadata needed for bookkeeping are stored in files as well, in the form of small documents using the JSON encoding. The Storage and Transfer System (STS) is responsible for aggregating these files produced by the HLT, storing them temporarily and transferring them to the T0 facility at CERN for subsequent offline processing. The STS merger service aggregates the output files from the HLT from ∼62 sources produced with an aggregate rate of ∼2GB/s. An estimated bandwidth of 7GB/s in concurrent read/write mode is needed. Furthermore, the STS has to be able to store several days of continuous running, so an estimated of 250TB of total usable disk space is required. In this article we present the various technological and implementation choices of the three components of the STS: the distributed file system, the merger service and the transfer system.

A general framework for the detectin of gradually developing changes in a noise generating system is presented. The procedure is based on a new learning algorithm developed for neural networks with dynamically building architecture. The method has been tested by using almost a thousand noise spectra recorded from different detector types and from different detector positions. This work is part of a larger project, aimed at developing a noise diagnostic expert system.

The CMS Data Acquisition System is designed to build and Alter events originating from 476 detector data sources at a maximum trigger rate of 100 KHz. Different architectures and switch technologies have been evaluated to accomplish this purpose. Events will be built in two stages: the first stage will be a set of event builders called FED Builders. These will be based on Myrinet technology and will pre-assemble groups of about 8 data sources. The second stage will be a set of event builders called Readout Builders. These will perform the building of full events. A single Readout Builder will build events from 72 sources of 16 KB fragments at a rate of 12.5 KHz. In this paper we present the design of a Readout Builder based on TCP/IP over Gigabit Ethernet and the optimization that was required to achieve the design throughput. This optimization includes architecture of the Readout Builder, the setup of TCP/IP, and hardware selection.

The Data Acquisition system of the Compact Muon Solenoid experiment at CERN assembles events at a rate of 100 kHz, transporting event data at an aggregate throughput of 100 GByte/s. We are presenting the design of the 2nd generation DAQ system, including studies of the event builder based on advanced networking technologies such as 10 and 40 Gbit/s Ethernet and 56 Gbit/s FDR Infiniband and exploitation of multicore CPU architectures. By the time the LHC restarts after the 2013/14 shutdown, the current compute nodes, networking, and storage infrastructure will have reached the end of their lifetime. In order to handle higher LHC luminosities and event pileup, a number of sub-detectors will be upgraded, increase the number of readout channels and replace the off-detector readout electronics with a μTCA implementation. The second generation DAQ system, foreseen for 2014, will need to accommodate the readout of both existing and new off-detector electronics and provide an increased throughput capacity. Advances in storage technology could make it feasible to write the output of the event builder to (RAM or SSD) disks and implement the HLT processing entirely file based.

The supervisory level of the Detector Control System (DCS) of the CMS experiment is implemented using Finite State Machines (FSM), which model the behaviours and control the operations of all the sub-detectors and support services. The FSM tree of the whole CMS experiment consists of more than 30.000 nodes. An analysis of a system of such size is a complex task but is a crucial step towards the improvement of the overall performance of the FSM system. This paper presents the analysis of the CMS FSM system using the micro Common Representation Language 2 (mcrl2) methodology. Individual mCRL2 models are obtained for the FSM systems of the CMS sub-detectors using the ASF+SDF automated translation tool. Different mCRL2 operations are applied to the mCRL2 models. A mCRL2 simulation tool is used to closer examine the system. Visualization of a system based on the exploration of its state space is enabled with a mCRL2 tool. Requirements such as command and state propagation are expressed using modal mu-calculus and checked using a model checking algorithm. For checking local requirements such as endless loop freedom, the Bounded Model Checking technique is applied. This paper discusses these analysis techniques and presents the results of their application on the CMS FSM system.

The CMS detector control system (DCS) is responsible for controlling and monitoring the detector status and for the operation of all CMS sub detectors and infrastructure. This is required to ensure safe and efficient data taking so that high quality physics data can be recorded. The current system architecture is composed of more than 100 servers in order to provide the required processing resources. An optimization of the system software and hardware architecture is under development to ensure redundancy of all the controlled subsystems and to reduce any downtime due to hardware or software failures. The new optimized structure is based mainly on powerful and highly reliable blade servers and makes use of a fully redundant approach, guaranteeing high availability and reliability. The analysis of the requirements, the challenges, the improvements and the optimized system architecture as well as its specific hardware and software solutions are presented.

Summary form only given. The data acquisition system (DAQ) of the CMS experiment at the CERN Large Hadron Collider assembles events at a rate of 100 kHz, transporting event data at an aggregate throughput of 100 GB/s to the high level trigger (HLT) farm. The HLT farm selects interesting events for storage and offline analysis at a rate of around 1 kHz. The DAQ system has been redesigned during the accelerator shutdown in 2013/14. The motivation is twofold: Firstly, the current compute nodes, networking, and storage infrastructure will have reached the end of their lifetime by the time the LHC restarts. Secondly, in order to handle higher LHC luminosities and event pileup, a number of sub-detectors will be upgraded, increasing the number of readout channels and replacing the off-detector readout electronics with a μTCA implementation. The new DAQ architecture will take advantage of the latest developments in the computing industry. For data concentration, 10/40 Gb/s Ethernet technologies will be used, as well as an implementation of a reduced TCP/IP in FPGA for a reliable transport between custom electronics and commercial computing hardware. A 56 Gb/s Infiniband FDR Clos network has been chosen for the event builder with a throughput of ~4 Tb/s. The HLT processing is entirely file based. This allows the DAQ and HLT systems to be independent, and to use the HLT software in the same way as for the offline processing. The fully built events are sent to the HLT with 1/10/40 Gb/s Ethernet via network file systems. Hierarchical collection of HLT accepted events and monitoring meta-data are stored into a global file system. This paper presents the requirements, technical choices, and performance of the new system.

The CMS detector will undergo a major upgrade for the Phase-2 of theLHC program the High-Luminosity LHC.The upgraded CMS detector willbe read out at an unprecedented data rate exceed-ing50 Tb/s, with a Level-1 trigger selecting eventsat a rate of 750 kHz, and an average event size reaching8.5MB.The Phase-2 CMS back-end electronics will bebased on the ATCA standard, with node boards receiving the detectordata from the front-ends via custom, radiation-tolerant, opticallinks.The CMS Phase-2 data acquisition (DAQ) design tightens the integrationbetween trigger control and data flow, extending the synchronousregime of the DAQ system.At the core of the design is the DAQ andTiming Hub, a custom ATCA hub card forming the bridge between thedifferent, detectorspecific, control and readout electronics and thecommon timing, trigger, and control systems.The overall synchronisation and data flow of the experiment is handledby the Trigger and Timing Control and Distribution System (TCDS).Forincreased flexibility during commissioning and calibration runs, thePhase-2 architecture breaks with the traditional distribution tree, infavour of a configurable network connecting multiple independentcontrol units to all off-detector endpoints.This paper describes the overall Phase-2 TCDS architecture, andbriefly compares it to previous CMS implementations.It then discussesthe design and prototyping experience of the DTH, and concludes withthe convergence of this prototyping process into the (pre)productionphase, starting in early 2023.

Abstract The European cultural landscape and its traditional values represent a significant condition for recreation and tourism. However, we are aware of the negative consequences of human activity in the past years in rural areas and pay more attention to protecting these values. Modern rural recreation and tourism must be built on scientific background. That is why the presented contribution brings an innovative integrated approach to sustainable rural recreation and tourism model by applying landscape ecological planning methodology with a combination of ecological stability and landscape character assessment. It deals with the qualitative evaluation of the landscape potential of the foothill village of Podkonice in Slovakia and the possibilities of its use in sustainable rural tourism. Determining the potential in confrontation with different forms of tourism activities can help achieve a sustainable tourism concept. The main result of the presented research is the final optimal selection of activities and use of the landscape with regard to the development of tourism. Such a proposal can be used in spatial planning and strategic decision-making processes not only in the study area, but it can be applied in the European context.

Manna ash (Fraxinus ornus L.) is a Mediterranean shrub or a small tree with the northern limit of its natural range in central Europe. At the same time, it is also a tree species which, due to its considerable tolerance to high temperatures and lack of moisture, as well as some expansive properties, could be expected to increase its range in the coming decades as a result of the changing climate and the associated spontaneous spread. The paper summarizes the results of several years of our research, during which we evaluated the following growth and reproductive characteristics: (1) phenological traits and the length of the growing season, (2) the intensity and evenness of fruiting, and (3) the numbers of individuals and stems according to the height categories. In addition, the species composition of vegetation cover was analysed on the sites with the occurrence of manna ash. Observations were made in two autochthonous populations of manna ash in Southern Slovakia and one allochthonous population in its central region. The onset of spring vegetative and generative phenophases showed a noticeable latitudinal trend during our observations (2015‒2019). In Central Slovakia, flowering and leafing of manna ash occurred on average more than two weeks later than in its southernmost region. The “Central Slovakian” population of manna ash was also characterised by the earliest onset of autumn vegetative phenophases and the lowest total length of the growing season. Despite these trends, flowering and fruiting in this population were relatively regular ‒ in contrast to the other two sites, it was observed every year. In this locality, we also observed the highest total numbers of individuals and stems in all the height categories and the markedly decreased occurrence of competing species. The achieved results point out to the considerable vigour and high reproductive ability of the allochthonous population of manna ash outside its natural range and the natural range of its most important competitors.

Abstract A significant phenomenon of sacral complexes in a landscape is their cultural heritage dimension. They are part of historical landscape structures, representing a type of cultural landscape. In addition, they are often perceived as important landscape landmarks and symbols. In Slovakia (Central Europe), most such complexes are abandoned and deteriorated. In this context presented paper deals with the assessment and possible future human use of Calvary in Hliník nad Hronom (Slovakia) in order to preserve it for future generations. A central aspect of our research work presented in this contribution is to elaborate a sustainable and feasible concept for the Calvary following the integrated approach of its revitalization. Firstly, we analyzed Calvary´s historical and regional setting with the help of a thorough review of literature, historical maps, and pictures. Then we evaluated architectural, landscape, and vegetation values, as well as landscape structure changes using relevant methodologies. Based on this evaluation, much fieldwork, and social survey we were able to identify the current problems of the place connected with abandonment and use, evaluated values, socio-economic factors, and preservation policies. Subsequently, we prepared a future concept for the Calvary following the selected criteria and distinguishing features and looking at the Calvary as a result of collective work. Finally, recommendations were formulated for legal framework and spatial planning procedures in order to enforce better preservation of values of sacral complexes in the country.