Benjamin Fischer

Our prospective study tested the hypothesis that the 30-day clinical outcome of elective percutaneous catheter intervention (PCI) differs between strata defined by quartiles of platelet aggregation after loading with 600 mg clopidogrel.Platelet responses after loading with clopidogrel are highly variable. The impact of this variability on the peri-interventional risk of patients undergoing PCI has not been investigated prospectively.Our study included 802 consecutive patients undergoing elective coronary stent placement. Before PCI, patients received a loading dose of 600 mg clopidogrel followed by 75 mg daily. Primary end point was the 30-day composite of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]). Platelet aggregation was assessed immediately before PCI by optical aggregometry (5 micromol/l adenosine diphosphate).During 30-day follow-up, 15 patients (1.9%) incurred MACE (3 deaths, 8 myocardial infarctions, 8 target lesion revascularizations). Quartiles of platelet aggregation were <4%, 4% to 14%, 15% to 32%, and >32%. Thirty-day MACE differed significantly (p = 0.034) between quartiles of platelet aggregation. It was 0.5% in the first quartile, 0.5% in the second, 3.1% in the third, and 3.5% in the fourth. Platelet aggregation above the median carried a 6.7-fold risk (95% confidence interval 1.52 to 29.41; p = 0.003) of 30-day MACE. Multivariable logistic regression analysis, including pertinent covariables, confirmed platelet aggregation as a significant independent predictor of 30-day MACE (adjusted odds ratio per 10% increase in platelet aggregation 1.32, 95% confidence interval 1.04 to 1.61; p = 0.026).The level of platelet aggregation immediately before elective coronary stenting in patients pre-treated with a high loading dose of clopidogrel is correlated with early outcome after the procedure.

Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel.Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 micromol/L ADP was 51+/-14% when catheterization was performed at <1 hour, 41+/-14% at 1 to <2 hours, 37+/-15% at 2 to <4 hours, 36+/-13% at 4 to <6 hours, and 35+/-14% at > or =6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (P>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (P=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point.After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.

The neurodegenerative aspects of chronic progressive multiple sclerosis (MS) have received increasing attention in recent years, since anti-inflammatory and immunosuppressive treatment strategies have largely failed. However, successful neuroprotection and/or neuroregeneration in MS have not been demonstrated yet. Encouraged by the multifaceted neuroprotective effects of recombinant human erythropoietin (rhEPO) in experimental models, we performed an investigator-driven, exploratory open label study (phase I/IIa) in patients with chronic progressive MS. Main study objectives were (i) evaluating safety of long-term high-dose intravenous rhEPO treatment in MS, and (ii) collecting first evidence of potential efficacy on clinical outcome parameters.

Strong low-energy collective transitions in the deformed nuclei 156,158,160Gd have been observed with nuclear resonance fluorescence techniques utilizing 3.5 MeV bremsstrahlung and a high-resolution Ge(Li) detector. It is most probable that a new collective M1 mode, predicted by several theoretical models of deformed nuclei and discovered recently in 156,158Gd(e, e′) experiments, has been observed. The Gd(γ, γ′) measurements reveal a strong coupling of the levels to the first rotational 2+ state as expected in the IBA-2 model. If all the transitions reported are due to M1 excitations, a fragmentation of strength is present in 158,160Gd and the sums of B(M1)↑ values amount to 1.5 ± 0.3, 2.3 ± 0.5, and 2.3 ± 0.6 μ02 for 156,158,160Gd, respectively.

Drosophila larvae combine a numerically simple brain, a correspondingly moderate behavioral complexity, and the availability of a rich toolbox for transgenic manipulation. This makes them attractive as a study case when trying to achieve a circuit-level understanding of behavior organization. From a series of behavioral experiments, we suggest a circuitry of chemosensory processing, odor-tastant memory trace formation, and the "decision" process to behaviorally express these memory traces--or not. The model incorporates statements about the neuronal organization of innate vs. conditioned chemosensory behavior, and the types of interaction between olfactory and gustatory pathways during the establishment as well as the behavioral expression of odor-tastant memory traces. It in particular suggests that innate olfactory behavior is responsive in nature, whereas conditioned olfactory behavior is captured better when seen as an action in pursuit of its outcome. It incorporates the available neuroanatomical and behavioral data and thus should be useful as scaffold for the ongoing investigations of the chemo-behavioral system in larval Drosophila.

The surface charge of a biomaterial represents a promising tool to direct cellular behavior, which is crucial for therapeutic approaches in regenerative medicine. To expand the understanding of how the material surface charge affects protein adsorption and mesenchymal stem cell behavior, differently charged surfaces with zeta potentials spanning from -25 mV to +15 mV were fabricated by the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that the increase of the biomaterials surface charge resulted in enhanced quantities of biologically available, surface-attached proteins. Since different surface charges were equalized after protein adsorption, mesenchymal stem cells interacted rather with diverse protein compositions instead of different surface features. Besides an enhanced cell attachment to increasingly positively charged surfaces, the cell spreading area and the expression of adhesion-related genes integrin α5 and tensin 1 were found to be increased after adhesion. Moreover, first results indicate a potential impact of the surface charge on mesenchymal stem cell differentiation towards bone and fat cells. The improved understanding of surface charge-related cell behavior has significant impact on the design of biomedical devices and artificial organs.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in downstream applications, either as monolayers or spheroids.

To date, there have been no studies describing the characteristics of posteromedial fragment in the posterior malleolus fracture. The aim was to investigate the variability of posteromedial fracture fragments to enable better surgical planning.All Mason and Molloy type 2B fractures, defined as fracture of both the posterolateral and the posteromedial fragments of the posterior malleolus, from our database were identified to analyze the preoperative computed tomography scan. The posteromedial fragment was investigated in 47 cases (mean age, 46.6 years; 11 male, 36 female).Morphologically, the fracture could be divided into 2 subtypes: (1) a large pilon intra-articular fragment (mean of X axis: 33.0 mm, Y: 30.7 mm, Z: 31.7 mm) presented in 29 cases with mean interfragmentary angle of 32.1 and back of tibia angle of 32.7 degrees (this was seen in 25 of 27 cases with supination injury pattern); and (2) a small extra-articular avulsion fragment (mean of X axis: 9.6 mm, Y: 13.2 mm, Z: 11.5 mm) present in 18 cases with a mean interfragmentary angle of 11.0 and back of tibia angle of 10.1 degrees. It was seen in 80% of pronation injuries.The avulsion type of the posteromedial fragment of posterior malleolus fracture was more common in pronation injuries, likely the result of traction by the intermalleolar ligament, and the pilon type was more common in supination injuries, likely the result of the rotating talus impaction. Because of the intra-articular involvement, we believe the pilon type should undergo fixation to achieve articular congruity, unlike the avulsion type which may only function as a secondary syndesmotic stabilizer.Level III, retrospective comparative series.

Results from high resolution inelastic electron scattering and nuclear resonance fluorescence experiments on 156Gd are combined to yield information on the distribution of orbital magnetic dipole strength. The magnetic dipole strength connected with the new M1 mode is closely centered in five Jπ = 1+ states around 3 MeV excitation energy.

Abstract Despite accumulating evidence of inter and intraindividual variability in response to theta burst stimulation, it is widely believed that in therapeutic applications, repeated sessions can have a “build‐up” effect that increases the response over and above that seen in a single session. However, strong evidence for this is lacking. Therefore, we examined whether daily administration of intermittent theta burst stimulation ( iTBS ) over the primary motor cortex induces cumulative changes in transcranial magnetic stimulation measures of cortical excitability, above the changes induced by sham stimulation. Over five consecutive days, 20 healthy participants received either active iTBS or sham stimulation. Each day, baseline measures of cortical excitability were assessed before and up to 30 min after the intervention. There was no significant difference in the rate of response between iTBS and sham stimulation on any of the 5 days. There was no iTBS specific cumulative increase of corticospinal excitability. The likelihood that an individual would remain a responder from day‐to‐day was low in both groups, implying high within‐subject variability of both active and sham iTBS after‐effects. In contrast, we found a high within‐subject repeatability of resting and active motor threshold, and baseline motor‐evoked potential amplitude. In summary, sham stimulation has similar effect to active iTBS on corticospinal excitability, even when applied repeatedly for 5 days. Our results might be relevant to research and clinical applications of theta burst stimulation protocols.

Nowadays, modern approaches in tissue engineering include the combination of therapeutic relevant cells with high quality, biocompatible biomaterials. The resulting cellularized scaffolds are of great interest for several pharmaceutical applications such as drug screening/discovery, disease modeling, and toxicity testing. In addition, the introduction of human-induced pluripotent stem cells (hiPSCs) further increased the importance and the potential of tissue engineering not only for the pharmaceutical industry, but also for future therapeutic applications. Artificial microenvironments of hiPSCs comprise combinations of adhesive proteins and are particularly influenced by mechanical properties of the growth surface. The increasing focus on mechanical properties and the ability to adjust them propose alginate hydrogels as suitable candidates for engineered scaffolds. Ultra-pure alginates, however, are bioinert and require modifications for bioactivation. In this study, we present two modifications of alginate hydrogels based on direct covalent coupling of collagen I and coupling of a special linker molecule with subsequent Matrigel coating. We were able to demonstrate the successful adhesion and proliferation of hiPSCs on these linker-modified alginates. The developed modifications are particularly applicable for planar as well as spherical hydrogel surfaces. In this context, a scalable adherent suspension culture on alginate microcarriers could be established. Our data further indicate that larger alginate microcarriers modified with collagen I is less susceptible for agglomeration compared to small microcarriers. The obtained results indicate these modifications as suitable for both adhesion and cultivation of human stem cells such as human mesenchymal stem cells or hiPSCs.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) represent a valuable tool for in vitro modeling of the cardiac niche and possess great potential in tissue engineering applications. However, conventional polystyrene-based cell culture substrates have adverse effects on cardiomyocytes in vitro due to the stress applied by a stiff substrate on contractile cells. Ultra-high viscosity alginates offer a unique versatility as tunable substrates for cardiac cell cultures due to their biocompatibility, flexible biofunctionalization, and stability. In this work, we analyzed the effect of alginate substrates on hPSC-CM maturity and functionality. Alginate substrates in high-throughput compatible culture formats fostered a more mature gene expression and enabled the simultaneous assessment of chronotropic and inotropic effects upon beta-adrenergic stimulation. Furthermore, we produced 3D-printed alginate scaffolds with differing mechanical properties and plated hPSC-CMs on the surface of these to create Heart Patches for tissue engineering applications. These exhibited synchronous macro-contractions in concert with more mature gene expression patterns and extensive intracellular alignment of sarcomeric structures. In conclusion, the combination of biofunctionalized alginates and human cardiomyocytes represents a valuable tool for both in vitro modeling and regenerative medicine, due to its beneficial effects on cardiomyocyte physiology, the possibility to analyze cardiac contractility, and its applicability as Heart Patches.

The direct measurement of the top quark-Higgs coupling is one of the important questions in understanding the Higgs boson. The coupling can be obtained through measurement of the top quark pair-associated Higgs boson production cross-section. Of the multiple challenges arising in this cross-section measurement, we investigate the reconstruction of the partons originating from the hard scattering process using the measured jets in simulated tH events. The task corresponds to an assignment challenge of m objects (jets) to n other objects (partons), where m≥ n. We compare several methods with emphasis on a concept based on deep learning techniques which yields the best results with more than 50% of correct jet-parton assignments.

Abstract Breast cancer in men is relatively rare but outcome from the disease is worse than in women. Although 87% breast cancers in men are Estrogen Receptor-positive (ER+), anti-estrogen therapy is less efficacious in men compared to women with similar breast cancer subtype. Recent genomic analysis of breast tumors in men and women have identified overlapping as well as unique genomic aberrations in breast tumors of men. It is unclear whether genomic aberrations enriched in breast cancers of men uniquely affect the biology and thus alter response to antiestrogen therapy. This lack of knowledge is mainly due to scarcity of model systems. To overcome this limitation, we collected ultrasound guided breast biopsies of healthy men and characterized breast epithelial cells grown from these biopsies. Biopsies were also subjected to single nuclei sequencing. Single nuclei breast atlas of men is currently being superimposed on single nuclei breast atlas generated from breast biopsies of healthy women to determine whether distinct cell types exist in men and to distinguish ductal and lobular breast epithelial cells. Breast epithelial cells of men expressed higher levels of ER compared to similarly propagated breast epithelial cells of women. Expression of ER in a subpopulation of cultured breast epithelial cells was confirmed by immunofluorescence. Among the pioneer factors that determine genome wide binding pattern of ER, TBX3 is expressed at a higher level but FOXA1 is expressed at a lower level in breast epithelial cells of men compared to women. Comparative RNA-seq analysis of breast epithelial cells of men and women revealed elevated non-genomic ER signaling in men compared to women, which could be responsible for limited response of breast tumors of men to anti-estrogen therapy. Additional pathways uniquely upregulated in breast epithelial cells of men include non-canonical Wnt, HIF1A, JUN, NF-kB, TGFb, and FOXO1 signaling. Expectedly, breast epithelial cells of men expressed 15 Y chromosome associated genes including the epigenetic regulators KDM5D and UTY, which have recently been shown to be responsible for sex-specific differences in outcome from other cancer types and loss of Y chromosome could be driver event in certain cancer types. We have created immortalized and transformed variants of breast epithelial cells of men to further aid in mechanistic investigation and drug discovery. Furthermore, our tissue bank currently has breast biopsies of ~30 healthy men to be used as controls for breast cancer studies in men. To our knowledge, this is the first model system to study breast cancer in men starting with breast tissues of healthy men. Citation Format: Poornima Bhat-Nakshatri, Benjamin Fischer, Aditi Khatpe, Adedeji Adebayo, Hongyu Gao, Yunlong Liu, Michele Cote, Harikrishna Nakshatri. Deciphering biological differences between normal breast tissues in men and women using single cell sequencing and in vitro modeling [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-11.

Molecular mechanisms underlying bipolar affective disorders are unknown. Difficulties arise from genetic and phenotypic heterogeneity of patients and the lack of animal models. Thus, we focused on only one patient (n = 1) with an extreme form of rapid cycling. Ribonucleic acid (RNA) from peripheral blood mononuclear cells (PBMC) was analyzed in a three-tiered approach under widely standardized conditions. Firstly, RNA was extracted from PBMC of eight blood samples, obtained on two consecutive days within one particular episode, including two different consecutive depressive and two different consecutive manic episodes, and submitted to (1) screening by microarray hybridizations, followed by (2) detailed bioinformatic analysis, and (3) confirmation of episode-specific regulation of genes by quantitative real-time polymerase chain reaction (qRT-PCR). Secondly, results were validated in additional blood samples obtained one to two years later. Among gene transcripts elevated in depressed episodes were prostaglandin D synthetase (PTGDS) and prostaglandin D2 11-ketoreductase (AKR1C3), both involved in hibernation. We hypothesized them to account for some of the rapid cycling symptoms. A subsequent treatment approach over 5 months applying the cyclooxygenase inhibitor celecoxib (2 × 200 mg daily) resulted in reduced severity rating of both depressed and manic episodes. This case suggests that rapid cycling is a systemic disease, resembling hibernation, with prostaglandins playing a mediator role.

A novel wingless gene was isolated from the marine colonial hydroid Hydractinia echinata. Alignments and Bayesian inference analysis clearly assign the gene to the Wnt5A group. In line with data found for the brachyury ortholog of Hydractinia, He-wnt5A is expressed during metamorphosis in the posterior tip of the spindle-shaped planula larva, suggesting that the tip functions as a putative organizer during metamorphosis. Additionally, the outermost cells of the posterior tip are omitted from apoptosis during metamorphosis. In order to investigate this putative organizer function, we transplanted the posterior tip of metamorphosing animals into non-induced larvae and into primary polyps 24 h and 48 h of age. In larvae, the tip induced formation of a secondary axis. In polyps the building of ectopic head structures was induced. Based on our data on axis formation, on gene expression similar to the organizers of other species, and the absence of regular apoptosis, we conclude that the posterior tip of the Hydractinia larva has organizing activity during metamorphosis.

Upon contact with a biomaterial, cells and surrounding tissues respond in a manner dictated by the physicochemical and mechanical properties of the material. Traditionally, cellular responses are monitored using invasive analytical methods that report the expression of genes or proteins. These analytical methods involve assessing commonly used markers for a predefined readout, masking the actual situation induced in the cells. Hence, a broader expression profile of the cellular response should be envisioned, which technically limits up scaling to higher throughput systems. However, it is increasingly recognized that morphometric readouts, obtained non-invasively, are related to gene expression patterns. Here, we introduced distinct surface roughness to three PLA surfaces, by exposure to oxygen plasma of different duration times. The response of mesenchymal stromal cells was compared to smooth untreated PLA surfaces without the addition of differentiation agents. Morphological and genome wide expression profiles revealed underlying cellular changes which was hidden for the commonly used gene markers for osteo-, chondro- and adipogenesis. Using 3 morphometric parameters, obtained by high content imaging, we were able to build a classifier and discriminate between oxygen plasma-induced modified sheets and non-modified PLA sheets where evaluating classical candidates missed this effect. This approach shows the feasibility to use noninvasive morphometric data in high-throughput systems to screen biomaterial surfaces indicating the underlying genetic biomaterial-induced changes.

Gaussian processes are powerful tools since they can model non-linear dependencies between inputs, while remaining analytically tractable. A Gaussian process is characterized by a mean function and a covariance function (kernel), which are determined by a model selection criterion. The functions to be compared do not just differ in their parametrization but in their fundamental structure. It is often not clear which function structure to choose, for instance to decide between a squared exponential and a rational quadratic kernel. Based on the principle of posterior agreement, we develop a general framework for model selection to rank kernels for Gaussian process regression and compare it with maximum evidence (also called marginal likelihood) and leave-one-out cross-validation. Given the disagreement between current state-of-the-art methods in our experiments, we show the difficulty of model selection and the need for an information-theoretic approach.

People unfamiliar with Chinese characters show poorer visual working memory (VWM) performance for Chinese characters than do literates in Chinese. In a series of experiments, we investigated the reasons for this expertise advantage. Experiments 1 and 2 showed that the advantage of Chinese literates does not transfer to novel material. Experts had similar resolution as novices for material outside of their field of expertise, and the memory of novices and experts did not differ when detecting a big change; e.g., when a character's color was changed. Memorizing appears to function as a rather abstract representation of word forms because memory for characters' fonts was poor independently of expertise (Experiment 3), though still visual. Distractors that were highly similar conceptually did not increase memory errors, but visually similar distractors impaired memory (Experiment 4). We hypothesized that literates in Chinese represent characters in VWM as tokens of visual word forms made available by long-term memory. In Experiment 5, we provided novices with visual word form knowledge. Participants subsequently performed a change detection task with trained and novel characters in a functional magnetic resonance experiment. We analyzed set size and training dependent effects in the intraparietal sulcus (IPS) and the visual word form area. VWM for trained characters was better than for novel characters. Neural activity increased with set size and at a slower rate for trained than for novel characters. All conditions approached the same maximum, but novel characters reached the maximum at a smaller set size than trained characters. The time course of the bold response depended on set size and knowledge status. Starting from the same initial maximum, neural activity at small set sizes returned to baseline more quickly for trained characters than for novel characters. Additionally, high performers showed generally more neural activity in the IPS than low performers. We conclude that experts' better performance in WM is caused by the availability of visual long-term representations (word form types) that allow a sparse representation of the perceived stimuli and make even small changes big because they cause a type change that is easily detected.

The energy calibration of the analyzing magnet at the high-current 4 MV Dynamitron accelerator in Stuttgart has been carried out at proton beam energies Ep=0.99–4.23 MeV with a precision of ΔE/E=5×10−4. The beam energy resolution was found to be constant (δE=1.4 keV) over this energy range and to arise predominantly from the 120 kHz frequency of the oscillator. The energy stability was observed to be better than 85 eV over a running period of 3.5 h.

Nonhuman primates constitute an indispensable model system for studying higher brain functions at the neurophysiological level. Studies involving these animals elucidated the neuronal mechanisms of various cognitive and executive functions, such as visual attention, working memory, and decision-making. Positive reinforcement training (PRT) constitutes the gold standard for training animals on the cognitive tasks employed in these studies. In the laboratory, PRT is usually based on application of a liquid reward as the reinforcer to strengthen the desired behavior and absence of the reward if the animal’s response is wrong. By trial and error, the monkey may adapt its behavior and successfully reduce the number of error trials, and eventually learn even very sophisticated tasks. However, progress and success of the training strongly depend on reasonable error rates. If errors get too frequent, they may cause a drop in the animal’s motivation to cooperate or its adaptation to high error rates and poor overall performance. We introduce in this report an alternative training regime to minimize errors and base the critical information for learning on graded rewarding. For every new task rule, the feedback to the animal is provided by different amounts of reward to distinguish the desired, optimal behavior from less optimal behavior. We applied this regime in different situations during training of visual attention tasks and analyzed behavioral performance and reaction times to evaluate its effectiveness. For both simple and complex behaviors, graded rewarding was found to constitute a powerful technique allowing for effective training without trade-off in accessible task difficulty or task performance. NEW &amp; NOTEWORTHY Laboratory training of monkeys usually builds on providing a fixed amount of reward for the desired behavior, and no reward otherwise. We present a nonbinary, graded reward schedule to emphasize the positive, desired behavior and to keep errors on a moderate level. Using data from typical training situations, we demonstrate that graded rewards help to effectively guide the animal by success rather than errors and provide a powerful new tool for positive reinforcement training.

The aim of this study was to evaluate the influence of the introduction of online podcasts as part of the main lecture series in orthopaedics on the number of lecture attendees, the examination results and the assessment of teaching by the students. Additionally, we evaluated the use of other media for examination preparation.At the beginning and end of the lecture series questionnaires were handed out to the students to evaluate their attitudes towards attending lectures, the use of video podcasts and examination preparation. In addition, the number of lecture attendees and podcast usage during the semester were counted and the statements of the students in the evaluation assessments of orthopaedic teaching were evaluated. The examination results were correlated in a statistical analysis with the learning materials provided by the students for examination preparation.At the end of the lecture series, 284 students stated that they used the lecture podcast about twice as often as attending lectures; however, for the majority of the students the provision of a video podcast was no reason not to attend the lecture. For example, 37.2% stated that they never and 26.8% stated that they rarely had not attended the lecture by providing the podcasts. Of the students 91-95% considered the availability of lecture podcasts to be a rather meaningful or very meaningful supplement to the lecture visit. Students increasingly used digital media to prepare for examinations instead of using traditional analogue methods. None of the learning methods or materials examined showed a statistically significant advantage in examination results.Students in the age of digitalization use a variety of learning materials and are no longer bound to classical analog teaching methods. The use of online podcasts had no negative impact on examination performance. Most students perceived lecture podcasts as a useful supplement to lecture attendance. The students praised the expansion of the teaching curriculum to include additional digital offers with positive comments in the evaluations, but without achieving an improvement in these student evaluations.ZIELSETZUNG: Ziel dieser Untersuchung war es, den Einfluss der Einführung von Online-Podcasts im Rahmen der Hauptvorlesungsreihe der Orthopädie auf die Anzahl an Vorlesungsbesuchern, die Prüfungsergebnisse oder die Bewertung der Lehre durch die Studierenden zu evaluieren. Zusätzlich wurde die Nutzung anderer Lehrmedien zur Prüfungsvorbereitung evaluiert.Zu Beginn und zum Ende der Vorlesungsreihe wurden Fragebögen an die Studierenden ausgegeben, um deren Einstellung zum Vorlesungsbesuch, zur Nutzung von Video-Podcasts und zur Prüfungsvorbereitung zu evaluieren. Des Weiteren wurden die Vorlesungsbesucher und Podcast-Nutzungen während des Semesters gezählt und die Aussagen der Studierenden in den Evaluationsbewertungen der Lehre in der Orthopädie evaluiert. Die Prüfungsergebnisse wurde in einer statistischen Analyse mit den von den Studierenden angegeben Lernmaterialien zur Prüfungsvorbereitung korreliert.Am Ende der Vorlesungsreihe gaben 284 Studierende an, die Vorlesungs-Podcasts etwa doppelt so häufig genutzt zu haben wie die Möglichkeit zum Vorlesungsbesuch. Jedoch war die Bereitstellung eines Video-Podcasts für den Großteil der Studierenden kein Grund, die Vorlesung nicht zu besuchen. So gaben 37,2 % an „nie“ und 26,8 % „selten“ durch die Bereitstellung der Podcasts auf den Vorlesungsbesuch verzichtet zu haben. Für eine „eher sinnvolle“ oder „sehr sinnvolle“ Ergänzung zum Vorlesungsbesuch hielten 91–95 % der Studierenden die Verfügbarkeit von Vorlesungs-Podcasts. Die Studierenden verwendeten zur Prüfungsvorbereitung vermehrt digitale Medien anstatt klassischer analoger Methoden. Keine der überprüften Lernmethoden oder -materialien zeigte einen statistisch signifikanten Vorteil in der Prüfungsvorbereitung.Studierende im Zeitalter der Digitalisierung benutzen eine Vielzahl von Lernmaterialen und sind nicht mehr an klassische analoge Lehrmethoden gebunden. Der Einsatz von Online-Podcasts hatte keinen negativen Einfluss auf die Prüfungsleistung. Die meisten Studierenden empfinden Vorlesungs-Podcasts als eine sinnvolle Ergänzung zum Vorlesungsbesuch. Die Studierenden honorierten die Erweiterung des Lehrcurriculums um digitale Zusatzangebote mit positiven Kommentaren in den Evaluationen, allerdings ohne eine Verbesserung dieser studentischen Bewertungen zu erreichen.

Abstract In the run-up to biomechanical testing, fresh human tissue samples are often frozen in order to inhibit initial decomposition processes and to achieve a temporal independence of tissue acquisition from biomechanical testing. The aim of this study was to compare the mechanical properties of fresh tissue samples of the human iliotibial tract (IT) to fresh-frozen samples taken from the same IT and those modified with different concentrations of Dimethylsulfoxide (DMSO) prior to freezing. All samples were partial plastinated and destructive tensile tests were conducted with a uniaxial tensile test setup. A plastination technique already established in the laboratory was modified to improve the clamping behaviour of the samples. Material failure was caused by a gradual rupture of the load-bearing collagen fibre bundles. Contrary to our expectations, no significant difference was found between the tensile strength of fresh and fresh frozen specimens. The addition of 1 wt% DMSO did not increase the tensile strength compared to fresh-frozen samples; an addition of 10 wt% DMSO even resulted in a decrease. Based on our findings, the use of simple fresh-frozen specimens to determine the tensile strength is viable; however fresh specimens should be used to generate a complete property profile.

Neurogenin 2 encodes a neural-specific transcription factor (NGN2) able to drive neuronal fate on somatic and stem cells. NGN2 is expressed in neural progenitors within the developing central and peripheral nervous systems. Overexpression of NGN2 in human induced pluripotent stem cells (hiPSCs) or human embryonic stem cells has been shown to efficiently trigger conversion to neurons. Here we describe two gene-edited hiPSC lines harbouring a doxycycline (DOX)-inducible cassette in the AAVS1 locus driving expression of NGN2 (BIONi010-C-13) or NGN2-T2A-GFP (BIONi010-C-15). By introducing NGN2-expressing cassette, we reduce variability associated with conventional over-expression methods such as viral transduction, making these lines amenable for scale-up production and screening processes. DOX-treated hiPSCs convert to neural phenotype within one week and display the expression of structural neuronal markers such as Beta-III tubulin and tau. We performed functional characterization of NGN2-neurons co-cultured with hiPSC-derived astrocytes in a “fully-humanized” set up. Passive properties of NGN2-neurons were indistinguishable from mouse primary cells while displaying variable activity in extracellular recordings performed in multi-electrode arrays (MEAs). We demonstrate that hiPSC-derived astrocytes and neurons can be co-cultured and display functional properties comparable to the gold standard used in electrophysiology. Both lines are globally available via EBiSC repository at https://cells.ebisc.org/.

Background End artefacts play a major role in uniaxial compression tests with cancellous bone specimens. They lead to misinterpretation of mechanical parameters of bones due to uncontrolled introduction of bending moments into the free ends of trabeculae. This work aims to simplify current methods preventing end-artefacts and furthermore to investigate the influence of end artefacts on plateau stress. Methods 176 cylindrical cancellous bone specimens were taken from human femoral condyles and tested in uniaxial compression. The specimens were divided into 2 groups (direct, end-cap) and compressive modulus, maximum stress, plateau stress, energy absorbtion as well as apparent density were evaluated. Density values are from separate specimens which are immediately adjacent to the mechanical specimen. Findings All mechanical parameters were significantly higher in the end-cap specimens than in the direct ones by about 30 – 40 %, thus reaching similar differences as the previous studies. Greatest differences between groups were determined for compressive modulus (45 %) and plateau stress (35 %). Energy absorbtion can be explained with great accuracy by plateau stress (P < 0.001; R2 = 0.95). Among all parameters plateau stress can be best explained by apparent density using an exponential function (P < 0.001; R2 = 0.38). Interpretation The end-cap method used here to prevent end artefacts showed variations consistent with the literature when compared to the direct method. Additionally it was shown that the way in which the force is applied to the specimen has a major influence on the failure progression behavior, which was characterized using the plateau stress.

The derivation of neuronal lineage cells from human induced pluripotent stem cells (hiPSCs) marked a milestone in brain research. Since their first advent, protocols have been continuously optimized and are now widely used in research and drug development. However, the very long duration of these conventional differentiation and maturation protocols and the increasing demand for high-quality hiPSCs and their neural derivatives raise the need for the adoption, optimization, and standardization of these protocols to large-scale production. This work presents a fast and efficient protocol for the differentiation of genetically modified, doxycycline-inducible neurogenin 2 (iNGN2)-expressing hiPSCs into neurons using a benchtop three-dimensional (3D) suspension bioreactor. In brief, single-cell suspensions of iNGN2-hiPSCs were allowed to form aggregates within 24 h, and neuronal lineage commitment was induced by the addition of doxycycline. Aggregates were dissociated after 2 days of induction and cells were either cryopreserved or replated for terminal maturation. The generated iNGN2 neurons expressed classical neuronal markers early on and formed complex neuritic networks within 1 week after replating, indicating an increasing maturity of neuronal cultures. In summary, a detailed step-by-step protocol for the fast generation of hiPSC-derived neurons in a 3D environment is provided that holds great potential as a starting point for disease modeling, phenotypic high-throughput drug screenings, and large-scale toxicity testing.

Abstract The development of an LHC physics analysis involves numerous investigations that require the repeated processing of terabytes of data. Thus, a rapid completion of each of these analysis cycles is central to mastering the science project. We present a solution to efficiently handle and accelerate physics analyses on small-size institute clusters. Our solution uses three key concepts: vectorized processing of collision events, the “MapReduce” paradigm for scaling out on computing clusters, and efficiently utilized SSD caching to reduce latencies in IO operations. This work focuses on the latter key concept, its underlying mechanism, and its implementation. Using simulations from a Higgs pair production physics analysis as an example, we achieve an improvement factor of 6.3 in the runtime for reading all input data after one cycle and even an overall speedup of a factor of 14.9 after 10 cycles, reducing the runtime from hours to minutes.

Complex proximal humerus fractures place high demands on osteosynthetic treatment. In some cases, double plating has already been used to increase primary stability of the osteosynthesis. This approach was advanced in the present study by developing an additive plate for the sulcus bicipitalis. To demonstrate the superior primary stability of the newly developed plate osteosynthesis, a biomechanical comparison against a conventional locking plate with an additional calcar screw was performed.Ten pairs of cadaveric humeri were treated proximally with a locking plate (PENTA plate small fragment, INTERCUS). Each had a two-part fracture model with a fracture gap of 10 mm. All right humeri were treated with an additive novel plate that extends along the bicipital sulcus and encircles the lesser tuberosity proximally. First, the specimens were loaded sinusoidally at 250 N in 20° abduction for 5000 cycles. Afterwards quasi-static loading until failure was applied.The movement at the fracture gap due to the cyclic loading occurred mainly as rotation around the z-axis, corresponding to a tilt medially and distally. The double plate osteosynthesis reduces the rotation by approximately 39%. For all load cycles observed, except 5000 cycles, medial and distal rotation of the head was significantly reduced by the double plate. The failure loads showed no significant differences between the groups.In the tested scenario under cyclic loading, the novel double plate osteosynthesis showed a significant superiority of primary stability over the conventional treatment with one locking plate. Furthermore, the study showed the advantages of cyclic load application over quasi-static load application until failure.

Knowledge about the cause of differential structural damages following the occurrence of hazardous hydro-meteorological events can inform more effective risk management and spatial planning solutions. While studies have been previously conducted to describe relationships between physical vulnerability and features about building properties, the immediate environment and event intensity proxies, several key challenges remain. In particular, observations, especially those associated with high magnitude events, and studies designed to evaluate a comprehensive range of predictive features are both limited. To build upon previous developments, we described a workflow to support the continued development and assessment of empirical, multivariate physical vulnerability functions based on predictive accuracy. Within this workflow, we evaluated several statistical approaches, namely generalized linear models and their more complex alternatives. A series of models were built 1) to explicitly consider the effects of dimension reduction, 2) to evaluate the inclusion of interaction effects between and among predictors, 3) to evaluate an ensemble prediction method for applications where data observations are sparse, 4) to describe how model results can inform about the relative importance of predictors to explain variance in expected damages and 5) to assess the predictive accuracy of the models based on prescribed metrics. The utility of the workflow was demonstrated on data with characteristics of what is commonly acquired in ex-post field assessments. The workflow and recommendations from this study aim to provide guidance to researchers and practitioners in the natural hazards community.

Recordings of epidural field potentials (EFPs) allow neuronal activity to be acquired over a large region of cortical tissue with minimal invasiveness. Because electrodes are placed on top of the dura and do not enter the neuronal tissue, EFPs offer intriguing options for both clinical and basic science research. On the other hand, EFPs represent the integrated activity of larger neuronal populations and possess a higher trial-by-trial variability and a reduced signal-to-noise ratio due the additional barrier of the dura. It is thus unclear whether and to what extent EFPs have sufficient spatial selectivity to allow for conclusions about the underlying functional cortical architecture, and whether single EFP trials provide enough information on the short timescales relevant for many clinical and basic neuroscience purposes. We used the high spatial resolution of primary visual cortex to address these issues and investigated the extent to which very short EFP traces allow reliable decoding of spatial information. We briefly presented different visual objects at one of nine closely adjacent locations and recorded neuronal activity with a high-density epidural multielectrode array in three macaque monkeys. With the use of receiver operating characteristics (ROC) to identify the most informative data, machine-learning algorithms provided close-to-perfect classification rates for all 27 stimulus conditions. A binary classifier applying a simple max function on ROC-selected data further showed that single trials might be classified with 100% performance even without advanced offline classifiers. Thus, although highly variable, EFPs constitute an extremely valuable source of information and offer new perspectives for minimally invasive recording of large-scale networks.NEW & NOTEWORTHY Epidural field potential (EFP) recordings provide a minimally invasive approach to investigate large-scale neural networks, but little is known about whether they possess the required specificity for basic and clinical neuroscience. By making use of the spatial selectivity of primary visual cortex, we show that single-trial information can be decoded with close-to-perfect performance, even without using advanced classifiers and based on very few data. This labels EFPs as a highly attractive and widely usable signal.

Abstract There is great hope in 3D printing techniques to create patient specific scaffolds for therapeutic applications. The majority of these approaches rely on materials that both give support to cells and effectively mimic a tissue specific microenvironment. Hydrogels provide an exceptional support for cells but their physicochemical properties are not suited for conventional additive layer manufacturing. Their low viscosity and resulting fluidic nature inhibit voluminous 3D deposition and lead to crude printing accuracy. To enhance mechanical features, hydrogels are often chemically modified and/or mixed with additives; however it is not clear whether these changes induce effects on cellular behavior or if in vivo applications are at risk. Certainly it increases the complexity of scaffold systems. To circumvent these obstacles, we aimed for a 3D printing technique which is capable of creating scaffolds out of unmodified, pure hydrogels. Here we present a new method to produce alginate scaffolds in a viscosity- independent manner with high spatial resolution. This is achieved by printing in a sub-zero environment which leads to fast freezing of the hydrogels, thus preserving the printed shape and circumventing any viscosity dependent flows. This enables the user to create scaffolds which are able to reflect soft or stiff cell niches.

Abstract Time distributions of fission fragments from subbarrier photofission of 238U have been measured using a pulsed bremsstrahlung beam (EBS = 3.9–4.3 MeV). The observed half-life of 238mU (T1/2 = 155±33 ns) is in good agreement with previous results obtained at higher photon energies. The measured yield ratio of isomeric to prompt fission (Yiso/Ypr ≳1) directly demonstrates for the first time the overwhelming contribution of the isomeric fission in the energy range of the so-called “isomeric shelf”. The results are compared with the most recent calculations.

Measurements of the analyzing power Ay of elastic n-3He scattering in the energy range from 3.7 to 22 MeV are reported. These data improve considerably the precision of the data around 3 MeV. Recent results in the range 8 to 17 MeV are supplemented. The data at 22 MeV are not in agreement with a previous experiment which caused problems in phase-shift analyses. A comparison of the new data with n-3H, p-3H and p-3He analyzing powers shows only small Coulomb effects but strong dependence on the isospin structure of the intermediate A = 4 system.

Sesamoid bone disorders are a rare cause of metatarsal pain and can be difficult to diagnose. This article describes an atypical case of avascular necrosis of the fibular sesamoid in a 62-year-old male. Avascular necrosis of the sesamoid is an infrequent and incompletely defined process. The case described in this report is somewhat atypical as this condition is usually associated with female sex, adolescence, or a precipitating factor of minor trauma. Level of Clinical Evidence: 4. Sesamoid bone disorders are a rare cause of metatarsal pain and can be difficult to diagnose. This article describes an atypical case of avascular necrosis of the fibular sesamoid in a 62-year-old male. Avascular necrosis of the sesamoid is an infrequent and incompletely defined process. The case described in this report is somewhat atypical as this condition is usually associated with female sex, adolescence, or a precipitating factor of minor trauma. Level of Clinical Evidence: 4.

Osteoarthritis of the first metatarsophalangeal joint (hallux rigidus) leads to pain and poor function and mobility. Arthrodesis is the gold standard treatment for end-stage disease. Total joint arthroplasties have been attempted, but early loosening has been attributed to dorsally directed shear forces on the metatarsal component. Metallic proximal phalangeal hemiarthroplasty theoretically avoids this. Whilst early results are promising, no comparative trials exist comparing this to arthrodesis. The primary objectives are to determine the range of outcome scores between the two treatment arms (to inform a power calculation). Outcome measures will include the MOXFQ, AOFAS-Hallux and EuroQol EQ-5D-5 L. Secondary objectives are to determine the accrual rate, dropout rate and trial acceptability to both patients and surgeons. These data will allow the development of a larger trial with longer follow-up. This is a prospective randomised controlled single-centre study comparing proximal phalanx hemiarthroplasty (AnaToemic, Arthrex Ltd., Sheffield, UK) with arthrodesis (15 patients in each arm). Randomisation will be performed using a 1:1 allocation ratio in blocks of six. Patients meeting the eligibility criteria will be recruited from three foot and ankle consultant surgeon’s clinics (East Lancashire Hospitals NHS Trust). If agreeable, informed consent will be obtained before patients are randomised. The outcome measure scores will be completed pre-operatively and repeated at 6 weeks, 3 months and 12 months. A radiological review will be performed at 6 weeks and 12 months to determine rates of loosening (hemiarthroplasty) and union (arthrodesis). Data on length of stay, return to work, complications and re-operation rates will also be collected. The analysis will compare the change in outcome scores between treatment groups at all follow-up time points. Scores will be compared using a Student t-test, adjusting for scores at baseline. This study will be conducted in accordance with the current revision of the Declaration of Helsinki (1996) and the ICH-GCP Guideline (International Conference on Harmonisation, Good Clinical Practice, E6(R1), 1996). This study has been approved by the sponsor, the Trust Research & Development office. Ethical approval has been received from the National Research Ethics Service (North East: 12/NE/0385 for protocol version 5.3 dated 3 June 2013). Current Controlled Trials ISRCTN88273654

Intraoperative proximal femoral fractures (IPFF) represent a rare but challenging complication of total hip arthroplasties. They usually occur as a longitudinal split. This pilot trial aimed to compare the biomechanical primary stability of different fixation techniques for IPFF. Standardised longitudinal medial split fractures of the proximal femur (type II, Modified Mallory Classification) were created in artificial osteoporotic and non-osteoporotic composite femora after implantation of a cementless femoral stem. Five different fixation techniques were compared: cerclage band, cerclage wiring with one or two wires, and lag screw fixation with one or two lag screws. A quasi-static loading protocol was applied and failure loads were evaluated. The observed median failure loads were 4192N (3982N – 5189N) for one cerclage band, 4450N (3577N – 4927N) for one cerclage wire, 5016N (4175N – 5685N) for two cerclage wires, 6085N (5000N – 8907N) for one lag screw, and 4774N (4509N – 8502N) for two lag screws. Due to the wide range of failure loads within the experimental groups, there were no observable differences between the groups. All fixation techniques provided sufficient primary stability in osteoporotic and non-osteoporotic composite bones. Further cadaveric studies with larger sample sizes may be needed to confirm the results presented here.

Abstract: The usability of flexible electrodes in moving environment is limited due to different mechanical characteristics of their metallic and polymeric components. To achieve structure compatible electrodes, all used materials need to have similar Young’s moduli as the surrounding tissue. This paper describes the characterization of macroscopic as well as miniaturized electrodes entirely made out of modified silicone (PDMS). Electrochemical, mechanical, biological, optical, and applicative methods were used. It could be shown, that PDMS electrodes are capable to be used for recording electrocardiograms with similar form and amplitude as with standard electrodes.

<h2>Abstract</h2><h3>Background</h3> The femoral head is of central importance for the force transmission from the suprapelvic body mass to the lower extremity. However, the condition of the subcortical bone and its mechanical properties in case of pathological changes due to coxarthrosis or femoral head necrosis differ from the healthy condition. <h3>Methods</h3> Fresh femoral heads were gathered during hip total endoprosthesis surgeries and cylindrical cancellous bone samples were extracted with a hollow drill. By means of a uniaxial tensile-compression test system, the compressive strength was determined for two different specimen types (fresh and 24 h storage in acetone). Exemplary tests on an exceptionally large femoral head were performed to compare properties of fresh, fresh-deep-frozen and acetone-stored samples. <h3>Findings</h3> The deformation behaviour and the material parameters determined were very heterogeneous. For most of the specimens, a destructive material test was successfully carried out, i.e. the compressive strength was determined. The average strength of fresh specimens was slightly higher than that of acetone specimens. On the other hand, the average Young's modulus of the acetone specimens was higher than that of the fresh specimens. <h3>Interpretation</h3> The lower Young's moodulus of the fresh samples compared to the acetone samples could indicate a causal effect of the degreasing influence of the acetone. The partly considerable individual differences in compressive strength and failure compression can have patient-specific influencing factors such as constitution and physical fitness as well as causes in the initial pathological condition.

Gaussian processes are powerful, yet analytically tractable models for supervised learning. A Gaussian process is characterized by a mean function and a covariance function (kernel), which are determined by a model selection criterion. The functions to be compared do not just differ in their parametrization but in their fundamental structure. It is often not clear which function structure to choose, for instance to decide between a squared exponential and a rational quadratic kernel. Based on the principle of approximation set coding, we develop a framework for model selection to rank kernels for Gaussian process regression. In our experiments approximation set coding shows promise to become a model selection criterion competitive with maximum evidence (also called marginal likelihood) and leave-one-out cross-validation.

Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000-7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA).The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8-1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA).A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher-but not significant-mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible.The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group.

Abstract Variable-dependent scale factors are commonly used in HEP to improve shape agreement of data and simulation. The choice of the underlying model is of great importance, but often requires a lot of manual tuning e.g. of bin sizes or fitted functions. This can be alleviated through the use of neural networks and their inherent powerful data modeling capabilities. We present a novel and generalized method for producing scale factors using an adversarial neural network. This method is investigated in the context of the bottom-quark jet-tagging algorithms within the CMS experiment. The primary network uses the jet variables as inputs to derive the scale factor for a single jet. It is trained through the use of a second network, the adversary, which aims to differentiate between the data and rescaled simulation.

VISPA provides a graphical front-end to computing infrastructures giving its users all functionality needed for working conditions comparable to a personal computer. It is a framework that can be extended with custom applications to support individual needs, e.g. graphical interfaces for experiment-specific software. By design, VISPA serves as a multipurpose platform for many disciplines and experiments as demonstrated in the following different use-cases. A GUI to the analysis framework OFFLINE of the Pierre Auger collaboration, submission and monitoring of computing jobs, university teaching of hundreds of students, and outreach activity, especially in CERN's open data initiative. Serving heterogeneous user groups and applications gave us lots of experience. This helps us in maturing the system, i.e. improving the robustness and responsiveness, and the interplay of the components. Among the lessons learned are the choice of a file system, the implementation of websockets, efficient load balancing, and the fine-tuning of existing technologies like the RPC over SSH. We present in detail the improved server setup and report on the performance, the user acceptance and the realized applications of the system.

Gaussian processes are powerful, yet analytically tractable models for supervised learning. A Gaussian process is characterized by a mean function and a covariance function (kernel), which are determined by a model selection criterion. The functions to be compared do not just differ in their parametrization but in their fundamental structure. It is often not clear which function structure to choose, for instance to decide between a squared exponential and a rational quadratic kernel. Based on the principle of approximation set coding, we develop a framework for model selection to rank kernels for Gaussian process regression. In our experiments approximation set coding shows promise to become a model selection criterion competitive with maximum evidence (also called marginal likelihood) and leave-one-out cross-validation.

Abstract Many particle physics analyses are adopting the concept of vectorised computing, often making them increasingly performant and resource-efficient. While a variety of computing steps can be vectorised directly, some calculations are challenging to implement. One of these is the analytical neutrino reconstruction which involves fitting that naturally varies between events. We show a vectorised implementation of the analytical neutrino reconstruction using a graph computing model. It uses established deep learning software libraries and is natively portable to local and external hardware accelerators such as GPUs. Using the example of ttH events with a semi-leptonic final state, we present performance studies for our implementation.

Abstract We present a specialised layer for generative modeling of LHC events with generative adversarial networks. We use Lorentz boosts, rotations, momentum and energy conservation to build a network cell generating a 2-body particle decay. This cell is stacked consecutively in order to model two staged decays, respecting the symmetries across the decay chain. We allow for modifications of the resulting four-vectors in order to model higher order and detector effects. We give an evaluation of the generator quality in a Higgs decay into two Z bosons, further decaying into a muon pair each.

Abstract Fast turnaround times for LHC physics analyses are essential for scientific success. The ability to quickly perform optimizations and consolidation studies is critical. At the same time, computing demands and complexities are rising with the upcoming data taking periods and new technologies, such as deep learning. We present a show-case of the HH→bbWW analysis at the CMS experiment, where we process 𝒪(1 − 10)TB of data on 100 threads in a few hours. This analysis is based on the columnar NanoAOD data format, makes use of the NumPy ecosystem and HEP specific tools, in particular Coffea and Dask. Data locality, especially IO latency, is optimized by employing a multi-level caching structure using local file storage and on-worker SSD caches. We process thousands of events simultaneously within a single thread, thus enabling straightforward use of vectorized operations. Resource intensive computing tasks, such as GPU accelerated DNN inference and histogram aggregation in the 𝒪(10)GB regime, are offloaded to dedicated workers. The analysis consists of hundreds of distinctly different workloads and is steered through a workflow management tool ensuring reproducibility throughout the development process up to journal publication.

Sampling-based motion planning algorithms have been continuously developed for more than two decades. Apart from mobile robots, they are also widely used in manipulator motion planning. Hence, these methods play a key role in collaborative and shared workspaces. Despite numerous improvements, their performance can highly vary depending on the chosen parameter setting. The optimal parameters depend on numerous factors such as the start state, the goal state and the complexity of the environment. Practitioners usually choose these values using their experience and tedious trial and error experiments. To address this problem, recent works combine hyperparameter optimization methods with motion planning. They show that tuning the planner's parameters can lead to shorter planning times and lower costs. It is not clear, however, how well such approaches generalize to a diverse set of planning problems that include narrow passages as well as barely cluttered environments. In this work, we analyze optimized planner settings for a large set of diverse planning problems. We then provide insights into the connection between the characteristics of the planning problem and the optimal parameters. As a result, we provide a list of recommended parameters for various use-cases. Our experiments are based on a novel motion planning benchmark for manipulators which we provide at https://mytuc.org/rybj.

Abstract With the development of web information technology, recommendation systems are widely used in social media networks, news delivery, and shopping platforms. Collaborative filtering (CF) is one of the main methods in recommendation systems. In recent years, the graph convolutional neural network (GCN) has emerged as the hottest research method in the current recommendation system due to its powerful ability to learn embedding representations on graph structures. Although graph convolutional neural networks have been recognized as having significant advantages in recommendation tasks, the proposed GCN-based recommendation models have generally neglected two aspects. The graph convolution layer of most models does not take full advantage of the covariance signals of higher order neighbors. For example, GCMC only uses the signal update node inlay of the 1st order neighborhood. The graph convolution layer of existing models pays little attention to the impact of different user opinions on the recommendation results when propagating and aggregating synergistic signals. In the recommendation scenario, the rating represents the user's opinion. To address these problems, this paper proposes an enhanced collaborative filtering algorithm for graph neural networks based on meta-paths (MPECFG). The study exploits the synergistic signals of 2nd order neighbors and user's view to improve the accuracy of graph convolutional neural networks in learning node embedding. In particular, we first construct bipartite graphs of users and items, embed their historical interactions into feature vectors, and then obtain higher-order representations of users and items by multi-layer propagation of the neural network. We experimented on public datasets and compared them with traditional algorithms to verify the effectiveness of our model.

Sampling-based motion planning algorithms have been continuously developed for more than two decades. Apart from mobile robots, they are also widely used in manipulator motion planning. Hence, these methods play a key role in collaborative and shared workspaces. Despite numerous improvements, their performance can highly vary depending on the chosen parameter setting. The optimal parameters depend on numerous factors such as the start state, the goal state and the complexity of the environment. Practitioners usually choose these values using their experience and tedious trial and error experiments. To address this problem, recent works combine hyperparameter optimization methods with motion planning. They show that tuning the planner's parameters can lead to shorter planning times and lower costs. It is not clear, however, how well such approaches generalize to a diverse set of planning problems that include narrow passages as well as barely cluttered environments. In this work, we analyze optimized planner settings for a large set of diverse planning problems. We then provide insights into the connection between the characteristics of the planning problem and the optimal parameters. As a result, we provide a list of recommended parameters for various use-cases. Our experiments are based on a novel motion planning benchmark for manipulators which we provide at https://mytuc.org/rybj.

Background Atraumatic femoral head necrosis is a rare pathological change of the femoral head. It is characterized by local necrosis of the cancellous bone as a result of reduced blood supply to the bone. Even today it remains unclear how to assess the hardness of the necrosis, whether it is soft tissue that is easily removed, or hard tissue that is difficult to resect. Methods Femoral heads with primary coxarthrosis were selected as a comparison group. For this purpose, 49 femoral heads obtained during total hip arthroplasty surgery with either condition (23 femoral head necrosis, 26 coxarthrosis) were transferred to the testing laboratory in fresh condition. Cylindrical specimens were obtained using a tenon cutter along the main trabecular load direction in the subchondral region of the femoral head. Additionally, thin bone slices were extracted proximal and distal to the specimens for density measurements. Brass plates were glued to the circular surfaces of the specimens. After curing of the adhesive, the specimens were mounted in the testing machine and destructive uniaxial compression tests were conducted. Findings The recorded mean compressive strengths and elastic moduli were almost identical for both groups, but the necrosis group showed significantly higher data scattering and range regarding the elastic modulus. The mean density of the coxarthrosis specimens was significantly higher than that of the necrotic specimens. Interpretation The mechanical properties of cancellous bone vary considerably in the presence of femoral head necrosis. The existence of hard necrosis implies a potential challenge regarding the clinical resection of these tissues.

Given the urgency to reduce fossil fuel energy production to make climate tipping points less likely, we call for resource-aware knowledge gain in the research areas on Universe and Matter with emphasis on the digital transformation. A portfolio of measures is described in detail and then summarized according to the timescales required for their implementation. The measures will both contribute to sustainable research and accelerate scientific progress through increased awareness of resource usage. This work is based on a three-days workshop on sustainability in digital transformation held in May 2023.

Das Becken stellt eine Ringstruktur, bestehend aus 3 primären knöchernen Segmenten, dar. Dorsal mit kräftigen Ligamenten verspannt, bildet es die Verbindung der Wirbelsäule mit den unteren Extremitäten. Dabei erfüllt das Becken im Zusammenspiel mit seinen kräftigen Bändern, den knorpeligen und muskulären Strukturen eine zentrale Rolle in der Lastübertragung vom Rumpf auf die unteren Extremitäten und vice versa. Darüber hinaus bildet der Beckenring einen essenziellen mechanischen Schutz für die darin liegenden Weichteile.

The Visual Physics Analysis (VISPA) project defines a toolbox for accessing software via the web. It is based on latest web technologies and provides a powerful extension mechanism that enables to interface a wide range of applications. Beyond basic applications such as a code editor, a file browser, or a terminal, it meets the demands of sophisticated experiment-specific use cases that focus on physics data analyses and typically require a high degree of interactivity. As an example, we developed a data inspector that is capable of browsing interactively through event content of several data formats, e.g., MiniAOD which is utilized by the CMS collaboration. The VISPA extension mechanism can also be used to embed external web-based applications that benefit from dynamic allocation of user-defined computing resources via SSH. For example, by wrapping the JSROOT project, ROOT files located on any remote machine can be inspected directly through a VISPA server instance. We introduced domains that combine groups of users and role-based permissions. Thereby, tailored projects are enabled, e.g. for teaching where access to student's homework is restricted to a team of tutors, or for experiment-specific data that may only be accessible for members of the collaboration. We present the extension mechanism including corresponding applications and give an outlook onto the new permission system.

Latest developments in many research fields indicate that deep learning methods have the potential to significantly improve physics analyses. They not only enhance the performance of existing algorithms but also pave the way for new measurement techniques that are not possible with conventional methods. As the computation is highly resource-intensive both dedicated hardware and software are required to obtain results in a reasonable time which poses a substantial entry barrier. We provide direct access to this technology after a revision of the internet platform VISPA to serve the needs of researches as well as students. VISPA equips its users with working conditions on remote computing resources comparable to a local computer through a standard web browser. For providing the required hardware resources for deep learning applications we extend the CPU infrastructure with a GPU cluster consisting of 10 nodes with each 2 GeForce GTX 1080 cards. Direct access through VISPA, preinstalled analysis software and a workload management system allowed us on one hand to support more than 100 participants in a workshop on deep learning and in corresponding university classes, and on the other hand to achieve significant progress in particle and astroparticle research. We present the setup of the system and report on the performance and achievements in the above mentioned usecases.

VISPA (Visual Physics Analysis) is a web-platform that enables users to work on any secure shell (SSH) reachable resource using just their webbrowser. It is used successfully in research and education for HEP data analysis. The emerging JupyterLab is an ideal choice for a comprehensive, browser-based, and extensible work environment and we seek to unify it with the efforts of the VISPA-project. The primary objective is to provide the user with the freedom to access any external resources at their disposal, while maintaining a smooth integration of preconfigured ones including their access permissions. Additionally, specialized HEP tools, such as native format data browsers (ROOT, PXL), are being migrated from VISPA- to JupyterLab-extensions as well. We present these concepts and their implementation progress.

The objective of this study was to evaluate the intrinsic preload of the sacrotuberous ligament. Preload measurements and anatomical experiments were performed on 20 specimens from 10 human cadavers and assessed to consider the thesis of the ligamentous tension band system as a possible load distribution. The result was an unexpectedly high preload force with an overall average of 118 N ± 74 N. Age has been significantly different between females and males in the cohort (median 94 vs. 77 years). Nevertheless, there is preliminary evidence of the sex-dependent sacrotuberous ligament preload force with an average value of approximately 65 N for the 10 female cadaver specimens and 172 N for the 10 male cadaver specimens. The assessment of further influencing factors and their statistical evaluation also showed a dependence of the sacrotuberous ligament preload force on body height, age and elastin content. Thus, the sacrotuberous ligament is more preloaded in the cadaver than previously assumed in the literature. Therefore, and contrary to most assumptions, it could possibly also be more preloaded in a living person in an upright position under a muscular load. This leads to the hypothesis that pelvic stability is more dependent on ligamentous preload than previously thought. These considerations should be taken more into account in numerical simulations of sacroiliac joint function.

JOHN MILTON’s oft-analysed sonnet 19 has primarily been read autobiographically, exploring ways in which Milton uses Jesus’ parable of the talents to explore anxieties about fulfilling his poetic vocation with his degenerated vision around 1651.1 Most recently, Margaret Thickstun has re-situated the poem within the genre of devotional lyric, citing the contemporary feature of the intrusive voice.2 I argue that the intrusive, preventing voice of patience in Sonnet 19 belongs in a sense to the apostolic church father Clement of Rome. Milton borrows from and poetically translates a section of Clement’s letter to the Corinthians for the theological argument of his poem. In the most common reading of the poem, the speaker stands in for Milton as he wrestles with the fact of blindness and an unfulfilled sense of vocation. Alluding to the parable of the talents in Matthew 25, the speaker grows anxious at his accountability to God due to concerns about his stewardship. The Maker will return and settle accounts with the labourers—all those to whom a talent has been entrusted—and he will ask for the increase. In this reading, the speaker’s complaint in the octave is that blindness has come upon him before he could ‘make use’, or invest and bring profit from, his talent. The speaker’s mistrust of the Maker’s kindness aligns him with the slothful servant in the parable who was given a single talent. Traditionally this has been read as Milton’s literary talent, given to fulfil his calling to write the great English epic. Now blind, he wrestles with the anxiety of stewardship, concerned that he has squandered his gift. With such circumstances, ‘Doth God exact day-labour?’ the speaker asks, immediately acknowledging the fondness or foolishness of the question.

The paper comprises a simulative analysis of a modern security control lane for passengers and hand luggage as will apply at Berlin-Brandenburg Airport Willy Brandt.After a description of the procedures of a security control, a detailed model will be built utilizing the simulation software, CAST Terminal, and using real passenger parameters and process times to analyze the capacity of the control lane and locate a possible bottleneck.Due to purposive staff changes in the second hand luggage control, capacitive effects could be studied in consideration of different alarm rates of the baggage screening system.With an increasing alarm rate the capacitive bottleneck moves from luggage pick-up to second hand luggage control, which makes it necessary to employ a second security inspector.

For the single ended Stuttgart Dynamitron accelerator a pulsing system has been developed which switches the electron beam in the gun. A pulsed light beam is transmitted to the high voltage terminal where a special high voltage amplifier triggers the gun. High intensity electron beam pulses can be produced with widths larger than 100 ns at high duty cycles (⩽ 1 : 5).

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey detailed and reliable information about constituent features of activating stimuli.

In the first few decades of the nineteenth century, the experience of missionaries among peoples as diverse as the ancient civilizations of India, the highly organized Zulu kingdoms, and the cannibal tribes of the South Seas had sparked a national debate concerning whether or not the “civilization of the heathen” was necessary before they could be converted, or whether Christianity would be the best means of civilizing them. Unresolved as far as public policy was concerned, this question entered discussions of the 1835 Select Committee on Aboriginal Tribes (British Settlements), a committee convened to address problems arising between British settlers and indigenous communities, including important trade sites in Australia, New Zealand, and the islands of the Pacific. As with several other areas where significant British imperial pressure never took the form of direct colonial rule, the trade ports in China fell outside the committee's explicit considerations. Along with forbidding foreign settlements, Chinese culture did not fit the terms or assumptions of the committee's conversation. Since the first Jesuit mission to China in the late sixteenth century, there had been little doubt in Europe that Chinese civilization was far advanced. As a tightly controlled bureaucratic state confident of its own position as the Middle Kingdom of the world, China simply did not work within the discourse of civilization. This essay explores one attempt to adjust the terms of that British discourse in order to accommodate a civilized China.

The Visual Physics Analysis (VISPA) software is a toolbox for accessing analysis software via the web. It is based on latest web technologies and provides a powerful extension mechanism that enables to interface a wide range of applications. It especially meets the demands of sophisticated experiment-specific use cases that focus on physics data analyses and typically require a high degree of interactivity. As an example, we developed a data inspector which is capable of browsing interactively through event content of several data formats, e.g., MiniAOD which is utilized by the CMS collaboration. Visual control of a chain of user analysis modules as well as visualization of user specific workflows support users in rather complex analyses at the level of ttH cross section measurements. The VISPA extension mechanism is also used to embed external web-based applications which benefit from dynamic allocation of user-defined computing resources via SSH. For example, by wrapping the JSROOT project, ROOT files located on any remote machine can be inspected directly through a VISPA server instance. We present the techniques of the extension mechanism and corresponding applications.

The influence of G. K. Chesterton on the outlook and work of C. S. Lewis has long been a passing note for critics of Lewis. While some have admired Lewis’s adaptation of Chestertonian insights, others have made his mimesis the grounds for a general dismissal. None of these critics, however, have directly examined the nature of this influence itself. This essay addresses this critical omission by establishing the ways in which Lewis purposefully imitated his predecessor’s particular way of being a Christian who writes. From Chesterton, Lewis borrowed an approach to literary influence that not only rejects originality as an ultimate measure but also elevates deliberate literary imitation of earlier insights as necessary to Christian writing. In doing so, both writers drew on a common tradition, reworking and rearticulating it, and thereby contributed their own voices and insights to it.

Abstract Born in Oregon City to a middle‐class Baptist family, Latourette was early on encouraged in the two pursuits that characterized his life: faith and learning. As an Orientalist, missiologist, and historian of Christianity's expansion, he became, according to Norwegian missiologist O. G. Myklebust (1955: 13), “the greatest missionary scholar that America has produced.”

‘Their annual increase is counted by thousands; and they form a distinct people in the empire, having their peculiar laws and manners, a hierarchy, a costume, and even a physiognomy of their own’, wrote Robert Southey for the Quarterly Review in 1810, opening a balanced critique of what he called ‘the Evangelical Sects’. Leaders of the Evangelical Revival had taught in pulpit, pamphlet and periodical that to be truly Christian meant radical difference from others in society, even others professing faith; or, as Charles Simeon, the model and mentor for hundreds of Cambridge-educated evangelical ministers, stated it, ‘Christians are either nominal or real’. Following William Wilberforce’s urging in his Practical View of the Prevailing Religious System of Professed Christians… Contrasted with Real Christianity , Evangelicals strove in their separate spheres to accomplish a social revolution by which the mores, values and social practices received from the eighteenth century would be overturned by normalizing evangelical values in society. While working in their individual vocations, Evangelicals were also cooperating, ‘linked in a single, if multiform, social and religious phenomenon’. As Southey’s comments indicate, even by 1810 their revolution was proving noticeably effective.

Diese Arbeit handelt von der Grundlagenproblematik der Rektionsphonologie in zwei Bedeutungen des Wortes. Erstens im Sinne der Rechtfertigung, und zweitens im Sinne von grundlegenden Eigenschaften. Kapitel 2 dieser Abhandlung prasentiert die Theorie der Rektionsphonologie. Es wird gezeigt, dass sich sinnvoll unterscheiden lasst zwischen einem reprasentationellen Modell, das die Basis fur den empirischen Inhalt der Theorie darstellt, und dem grundlegenderen theoretischen Hintergrund, der die Gestaltung des Modells anleiten, aber nicht endgultig bestimmen kann. Das dritte Kapitel handelt von der Generativen Grammatik im Allgemeinen, wobei zwischen einer fruhen Form und spaten Form unterschieden wird. Kapitel 4 reagiert auf die methodologische Diskussion innerhalb der Rektionsphonologie, und lehnt die Vorstellung ab, dass eine Methodologie auf rein logischen Grundlagen gestellt sein kann. Es wird gezeigt, dass eine methodologische Theorie stattdessen einen konventionellen und zielgerichteten Charakter hat. Die negativen Konsequenzen fur die Praxis des Theorievergleichs und der Kritik im allgemeinen werden diskutiert, und fur ungefahrlich fur den Status der Generativen Grammatik als wissenschaftliche Aktivitat eingestuft. Das funfte und letzte Kapitel prasentiert vorlaufige Beobachtung uber die metaphysische Dimension der Wissenschaftstheorie. Das Ziel dieses Kapitels ist, zu zeigen, dass metaphysische Annahmen formativ auf methodologische und theoretische Annahmen wirken. Zusammenfassend ist zu sagen, dass diese Arbeit ein alternatives Verstandnis der Wissenschaftstheorie fordert. Eines, das weniger mit der Bestimmung einer idealen Methodologie beschaftigt ist, sondern um die Klarheit und Eindeutigkeit der theoretisches Diskussion bemuht ist.

Abstract Non-human primates constitute an indispensable model system for studying higher brain functions at the neurophysiological level. They can be trained on highly demanding cognitive tasks, and studies involving these animals elucidated the neuronal mechanisms of various cognitive and executive functions, such as visual attention, working memory, and decision-making. The training of behavioral tasks used to study these processes builds on reinforcement learning and involves many discrete stages. It may takes several months, but frequently lasts a year or longer. The training is usually based on applying a liquid reward as the reinforcer to strengthen the desired behavior, and absence of the reward if the animal’s response was wrong. We here propose an alternative, non-binary rewarding scheme that aims to minimize unrewarded behavior. We show the potential of this alternative scheme to significantly speed up the training of an animal at various stages, without trade-off in accessible task difficulty or task performance.

In high-energy particle physics, workflow management systems are primarily used as tailored solutions in dedicated areas such as Monte Carlo production. However, physicists performing data analyses are usually required to steer their individual workflows manually which is time-consuming and often leads to undocumented relations between particular workloads. We present a generic analysis design pattern that copes with the sophisticated demands of end-to-end HEP analyses and provides a make-like execution system. It is based on the open-source pipelining package Luigi which was developed at Spotify and enables the definition of arbitrary workloads, so-called Tasks, and the dependencies between them in a lightweight and scalable structure. Further features are multi-user support, automated dependency resolution and error handling, central scheduling, and status visualization in the web. In addition to already built-in features for remote jobs and file systems like Hadoop and HDFS, we added support for WLCG infrastructure such as LSF and CREAM job submission, as well as remote file access through the Grid File Access Library. Furthermore, we implemented automated resubmission functionality, software sandboxing, and a command line interface with auto-completion for a convenient working environment. For the implementation of a $t\bar{t}H$ cross section measurement, we created a generic Python interface that provides programmatic access to all external information such as datasets, physics processes, statistical models, and additional files and values. In summary, the setup enables the execution of the entire analysis in a parallelized and distributed fashion with a single command.

Jüdische und nicht-jüdische Jugendliche, Schulen und Organisationen sowie Bundeswehrsoldaten standen für diesen Band im Dialog. Die Ergebnisse eines bundesweiten Bildungsprojekts aus den Jahren 2008/2009 zum Thema "Jüdische Soldaten in deutschen Armeen" sind in dieses Buch eingeflossen. Erstmals wird in einer Gesamtschau aus unterschiedlichsten Perspektiven die Vergangenheit sowie Gegenwart betrachtet als auch ein Ausblick in die Zukunft gewagt. Der Band bietet religionsphilosophische Betrachtungen des Judentums, Beschreibungen jüdischer Identität, Betrachtungen zum Konflikt um das oft ausgrenzende deutsche Nationalbewusstsein, kulturhistorische Betrachtungen, medienpolitische Analysen, kultursoziologische Untersuchungen sowie eine Befragung jüdischer Jugendlicher. Die vielfältigen Beiträge verdichten sich zu einem Gesamtbild: Die gemeinsame Zukunft kann nach dem Holocaust nur in einem multiethnischen und multireligiösen Nationalstaatsverständnis liegen. Die Bundeswehr, selber Ziel antisemitischer Angriffe, bietet mit ihrer Organisationsphilosophie der "Inneren Führung" Lösungsansätze in einer zunehmend multireligiöseren und -ethnischeren Welt.

In the early decades of the nineteenth century, British missionaries disrupted the century-old tea-trade triangle by their insistence on penetrating the closed Chinese empire. Their cultural knowledge made these missionaries attractive potential allies for merchants while also giving accounts of their mission a literary appeal. Although missionary writing was intended for specifically Evangelical audiences, the influence of these works extended to popular culture and into the crafting of foreign policy for the Opium War as the political situation in China intensified due to opium trafficking. The first chapter traces the scholarly traditions on mission and imperialism, and the missionary movement in China. It also shows that two differing perspectives on mission and empire derive from competing subcultures in early-nineteenth-century Britain: middle-class popular culture and the growing Evangelical subculture. The second chapter adapts the notions of “imagined communities” and an “imperial archive” for considering ways in which Evangelicals created literatureI¢âÂan “Evangelical ArchiveI¢âÂthat formulated and maintained their conceptual unity both at home and with their missionaries and converts abroad. Aimed at recruiting missionaries, encouraging believers, providing ethnology, and garnering support, mission narratives first emerged from the difficult mission context of China. The third chapter contrasts Evangelical representations of China with those by Thomas DeQuincey, Jesuit missionaries, and travel writers. Encoding spiritual terms for both spiritual and material subjects of attention, mission narratives assisted in coloring China as dark and depraved in opposition to Christianity’s enlightening brightness. The fourth chapter examines the work of Charles Gutzlaff, Journal of Three Voyages, and demonstrates a shift in the Evangelical approach to both British culture and foreign peoples, and thus a refiguring of the relationship between mission and empire. The chapter also shows how the distribution of the Gospel in China and the circulation of Gutzlaff’s writing in Britain provided justifications for the Opium War, while at the same time they revealed a growing division of opinion among Evangelicals regarding cooperation with commerce and government. The dissertation argues that the mission in China represents a shift in British thinking about mission and empire, which reflects the achievement of Evangelical hegemony in British culture.

Category: Trauma; Ankle Introduction/Purpose: Diaphyseal tibial fractures account for approximately 1.9% of all adult fractures. A recent registry review in Finland found an annual incidence of 15.6 per 100,000 person-years in males and 11.5 per 100,000 person-years in women. There are several studies which have demonstrated a high proportion of diaphyseal tibial fractures have ipsilateral occult posterior malleolus fractures, this ranges from 22-92.3%. Recent work by Hendrickx et al has highlighted distal third and spiral tibial shaft fracture patterns as independent predictors of occult posterior malleolus fracture. Methods: Objectives Our primary outcome in this study was to identify any factors that could predict articular extension in tibial shaft fractures. Study Design &amp; Methods A retrospective review of a prospectively collected database was performed at Liverpool University Hospitals NH Foundation Trust between 1/1/2013 and 9/11/2020. The inclusion criteria were patients over the age of 16, with a diaphyseal tibial fracture and who underwent a CT of the affected lower limb. The articular fracture extension was categorised into either posterior malleolar (PM) or other fracture. Results: 764 diaphyseal tibial fractures were analysed, of these 300 had a CT and could be included. There were 127 intra- articular fractures. Of these, 83 (65.4%) cases were PM and 44 were other fractures. On univariate analysis, the PM fractures were associated with fibular spiral (p=-016) fractures and no fracture of the fibular (p=.003), lateral direction of the tibial fracture (p=.04), female gender (p=.002), AO classification 42B1 (p=.033) and an increasing angle of tibial fracture. However, on multivariate regression analysis the only significant factor was a high angle of tibia fracture. Other distal tibia fracture extensions were associated with no fracture of the fibular (p=.002), medial direction of tibia fracture (p=.004), female gender (p=.000), and AO classification 42A1 (p=.004), 42A2 (p=.029), 42B3 (p=035) and 42C2 (p=.032). On multivariate analysis. the lateral direction of tibia fracture, and AO classification 42A1 and 42A2 were significant factors. Conclusion: Distal tibia articular extension occurs in almost half of tibial shaft fractures. A number of factors were associated with the extension, however multivariate analysis did not create a suitable prediction model. Nevertheless, rotational tibia fractures with a high angle of fracture should have a low threshold of further investigation with a CT prior to surgical intervention.

Category: Trauma; Ankle Introduction/Purpose: Diaphyseal tibial fractures account for approximately 1.9% of all adult fractures. A recent registry review in Finland found an annual incidence of 15.6 in males and 11.5 per 100,000 person-years in women. There are several studies which have demonstrated a high proportion of diaphyseal tibial fractures have ipsilateral occult posterior malleolus fractures, this ranges from 22-92.3%. Recent work by Hendrickx et al has highlighted distal third and spiral tibial shaft fracture patterns as independent predictors of occult posterior malleolus fracture. We hypothesize that this rotational element will be highlighted in the Mason &amp; Molloy Classification of occult posterior malleolus fractures seen in tibial shaft fractures. Methods: Objectives Our primary outcome in this study was to identify any extension of tibial fractures to the posterior malleolus and describe its morphology. Study Design &amp; Methods A retrospective review of a prospectively collected database was performed at Liverpool University Hospitals NHS Foundation Trust between 1/1/2013 and 9/11/2020. The inclusion criteria were patients over the age of 16, with a diaphyseal tibial fracture and who underwent a CT of the affected lower limb. The Mason and Molloy posterior malleolus fracture classification system was used to describe the morphology of the fracture Results: 764 diaphyseal tibial fractures were analysed, of these 300 had a CT and could be included. There were 127 intra- articular fractures. A total of 83 (27.7%) cases were classifiable using the Mason and Molloy classification. There were 8 type 1 (9.6%), 43 type 2 (51.8%), 5 type 2B (6.0%) and 27 type 3 (32.5%). The majority of the posterior malleolar fractures (n=75, 90.4%) were undisplaced pre-surgical intervention. The majority of PM fractures occurred in type 42A1 (65 of 142 tibia fractures) and 42B1 (11 of 16). Conclusion: The majority of the PM fractures associated with tibial fractures occur as a consequence of a rotational mechanism. Unlike, the PM fractures of the ankle, the majority of PM fractures associated with tibia fractures are undisplaced. We theorise that unlike the force transmission in ankle fractures where the rotational force is in the axial plane in a distal-proximal direction, in the PM fractures related to fractures of the tibia, the rotational force in the axial plane progresses from proximal-distal. Therefore, the force transmission which exits posteriorly, finally dissipates the force and thus unlikely to displace.

The development of an LHC physics analysis involves numerous investigations that require the repeated processing of terabytes of data. Thus, a rapid completion of each of these analysis cycles is central to mastering the science project. We present a solution to efficiently handle and accelerate physics analyses on small-size institute clusters. Our solution is based on three key concepts: Vectorized processing of collision events, the "MapReduce" paradigm for scaling out on computing clusters, and efficiently utilized SSD caching to reduce latencies in IO operations. Using simulations from a Higgs pair production physics analysis as an example, we achieve an improvement factor of $6.3$ in runtime after one cycle and even an overall speedup of a factor of $14.9$ after $10$ cycles.

Die Angiogenese ist sowohl für das lokale Wachstum als auch für die Metastasierung solider Tumoren von zentraler pathogenetischer Bedeutung. PTK787/ZK 222584 (PTK/ZK) ist ein neu entwickelter, oral verfügbarer, antiangiogenetischer Tyrosinkinase-Inhibitor (small molecule compound), der gegen die aktuell bekannten VEGFR (vascular endothelial growth factor receptor) – Tyrosinkinasen 1–3 sowie gegen die Tyrosinkinasen PDGFR-ß und c-KIT gerichtet ist.

Molecular mechanisms underlying bipolar affective disorders, in particular rapid cycling, are unknown. We analyzed peripheral blood mononuclear cells (PBMC) of one individual patient with rapid cycling syndrome under widely standardized conditions. RNA was extracted from PBMC of eight blood samples, obtained on two consecutive days (8.00 am, overnight fast) within one particular phase, including two different consecutive depressive and manic phases, and submitted to screening by microarray hybridizations, followed by detailed bioinformatic analysis. Phase-specific regulation of genes was confirmed by quantitative RT-PCR, and validated in additional blood samples obtained over one year later. Among the phase-specific differentially expressed genes were genes involved in the regulation of the innate immune response by different mechanisms, neurodevelopmentally important genes, genes involved in prostaglandin metabolism and genes encoding the hemoglobins A and B. This case demonstrates a consistent phase-dependent alteration in PBMC gene expression in rapid cycling which might partly explain some of the concomitant clinical features, like allergic diathesis. Whether phase-specific regulation of neurodevelopmental genes in PBMC reflects parallel regulation of these genes in the brain remains open.

Die Qualitatsuberwachung in Unternehmen ist heute von groster Bedeutung. Fehler konnen in der gesamten Fertigung vom Rohmaterial bis zum fertigen Produkt auftreten. Je spater ein Fehler erkannt wird, desto hoher sind die Kosten fur Nacharbeit oder Ausschuss. Eine Moglichkeit um Fehler bereits fruhzeitig zu erkennen, sind Monitoring-Systeme, die die Bearbeitung von Werkstucken uberwachen. Kosten fur Nacharbeit und Ausschuss konnen so minimiert werden. Ziel dieser Veroffentlichung ist die Untersuchung der Eignung maschineninterner Signale (vor allem Sercos-Antriebssignale) zur Fehlstellendetektierung in Bauteilen wahrend des Zerspanungsprozesses. Die induzierten Fehlstellen, sowie der Verschleis, konnen in den Graphen der Auswertung nachgewiesen werden. Ebenfalls zeigt sich, dass nur bestimmte Signale fur eine Detektion infrage kommen.

Im Forschungsprojekt Landscaping untersuchte das Wuppertal Institut die fur Nordrhein-Westfalen aus heutiger Sicht denkbaren Technologieansatze, die dafur notigen politischen Rahmenbedingungen sowie mogliche Innovationen entlang der Wertschopfungsketten. Bestandteil des Berichts sind Steckbriefe, in denen die moglichen Technologien fur treibhausgasneutrale Industrieprozesse samt offener Forschungsfragen und Infrastrukturbedarfe dargestellt sind. Das Projekt entstand im Auftrag des Ministeriums fur Wirtschaft, Innovation, Digitalisierung und Energie des Landes Nordrhein-Westfalen.

Abstract Recordings of epidural field potentials (EFPs) allow to acquire neuronal activity over a large region of cortical tissue with minimal invasiveness. Because electrodes are placed on top of the dura and do not enter the neuronal tissue, EFPs offer intriguing options for both clinical and basic science research. On the other hand, EFPs represent the integrated activity of larger neuronal populations, possess a higher trial-by-trial variability, and a reduced signal-to-noise ratio due the additional barrier of the dura. It is thus unclear whether and to what extent EFPs have sufficient spatial selectivity to allow for conclusions about the underlying functional cortical architecture, and whether single EFP trials provide enough information on the short time scales relevant for many clinical and basic neuroscience purposes. We here use the high spatial resolution of primary visual cortex to address these issues and investigate the extent to which very short EFP traces allow reliable decoding of spatial information. We briefly presented different visual objects at one out of nine closely adjacent locations and recorded neuronal activity with a high-density, epidural multi-electrode array in three macaque monkeys. Using receiver-operating characteristics to identify most-informative data, machine-learning algorithms provided close-to-perfect classification rates for all 27 stimulus conditions. A binary classifier applying a simple max function on ROC-selected data further showed that single trials might be classified with 100% performance even without advanced offline classifiers. Thus, although highly variable, EFPs constitute an extremely valuable source of information and offer new perspectives for minimally invasive recording of large-scale networks.

Category: Ankle, Trauma Introduction/Purpose: To date, there have been no studies describing the characteristics of posteromedial fragment in the posterior malleolus fracture. The aim of this study was to investigate the variability of posteromedial fracture fragments in trimalleolar fractures to enable better surgical planning. Methods: In our department, data on all ankle fractures treated surgically are prospectively collected on our internal database. We collated data from August 2014 to October 2018 for this study. All Mason and Molloy type 2B fractures from our database were identified to analyse the preoperative computed tomography scan. The morphology of the fracture fragment was categorized on whether the fracture appeared to be an intraarticular pilon fragment (i.e. caused by impaction of the talus) or an avulsion extraarticular fracture (i.e. caused by the pull of a ligament). The fracture fragment characteristics were analysed for both the posteromedial and posterolateral fragments. Results: The fracture patterns of the posteromedial fragment were investigated in 47 cases (mean age, 46.6; 11 male, 36 female). Morphologically, the fracture could be divided into 2 subtypes, 1) a large pilon type intra-articular fragment (mean of X axis: 32.97 mm, Y: 30.69 mm, Z: 31.74 mm) present in 29 cases with mean Interfragmentary angle of 32.09 and back of tibia angle of 32.66 degrees. This was seen in 25 out of 27 cases with supination injury pattern. 2) A small extra-articular avulsion fragment (mean of X axis: 9.56 mm, Y: 13.22 mm, Z: 11.53 mm) present in 18 cases with mean Interfragmentary angle of 10.97 and back tibia angle of 10.06 degrees. It was seen in 80% of pronation injuries. Conclusion: The posteromedial fragment of posterior malleolus fracture can be morphologically subtyped into an avulsion type and pilon type variants. The avulsion type is more common in pronation injuries, likely the result of the pull of the inter-malleolar ligament, and the pilon type is more common in supination injuries, likely the result of the rotating talus impaction. Due to the intra-articular involvement, the pilon type should undergo fixation to achieve articular congruity, unlike the avulsion type whose function is only a secondary syndesmotic stabiliser.

Abstract Deep learning architectures in particle physics are often strongly dependent on the order of their input variables. We present a two-stage deep learning architecture consisting of a network for sorting input objects and a subsequent network for data analysis. The sorting network (agent) is trained through reinforcement learning using feedback from the analysis network (environment). The optimal order depends on the environment and is learned by the agent in an unsupervised approach. Thus, the two-stage system can choose an optimal solution which is not known to the physicist in advance. We present the new approach and its application to the signal and background separation in top-quark pair associated Higgs boson production.