Roberto Salerno

Systemic mastocytosis is a rare heterogeneous myeloproliferative neoplasm characterized by abnormal proliferation and activation of mast cells. We describe a large multicentre series of 460 adult patients with systemic mastocytosis, with a diagnosis based on WHO 2008 criteria, in a "real-life" setting of ten Italian centers with dedicated multidisciplinary programs. We included indolent forms with (n = 255) and without (n = 165) skin lesions, smouldering (n = 20), aggressive (n = 28), associated with other hematological diseases mastocytosis (n = 21) and mast cell leukemia (n = 1). This series was uniquely characterized by a substantial proportion of patients with low burden of neoplastic mast cells; notably, 38% of cases were diagnosed using only minor diagnostic criteria according to WHO 2008 classification, underlying the feasibility of early diagnosis where all diagnostic approaches are made available. This has particular clinical relevance for prevention of anaphylaxis manifestations, that were typically associated with indolent forms. In multivariate analysis, the most important features associated with shortened overall survival were disease subtype and age at diagnosis >60 years. Disease progression was correlated with mastocytosis subtype and thrombocytopenia. As many as 32% of patients with aggressive mastocytosis suffered from early evolution into acute leukemia. Overall, this study provides novel information about diagnostic approaches and current presentation of patients with SM and underlines the importance of networks and specialized centers to facilitate early diagnosis and prevent disease-associated manifestations. Am. J. Hematol. 91:692-699, 2016. © 2016 Wiley Periodicals, Inc.

The intraprostatic concentrations of testosterone (T) and dihydrotestosterone (DHT) have been measured in only a few men. We measured, in prostatic tissue obtained at surgery from seven men with benign prostatic hyperplasia, the effects of 3-month treatment with a long-acting GnRH agonist on 1) the intraprostatic concentrations of T, DHT, and 5α-androstan-3α,17β-diol (3α-diol); 2) prostatic 5α-reductase activity; and 3) the prostatic content of androgen receptors (AR). Plasma T, DHT, and 3α-diol levels also were measured. Prostatic tissue samples obtained at surgery from a group of untreated men with benign prostatic hyperplasia also were studied. The mean DHT and 3α-diol concentrations in the prostatic tissue of the treated men were about 10/ of those in untreated men (n = 19; P < 0.01 for DHT and P < 0.05 for 3α-diol), and the mean intraprostatic T concentration in the treated men was about 25/ of that in the control group (0.10 > P > 0.05). The mean in vitro formation of DHT by the prostatic tissue of the treated men was about 50/ lower (P < 0.05) than that by prostatic tissue of the untreated men (n = 9). The mean cytosolic AR content in the prostatic tissue of the treated men was significantly higher (P < 0.05), whereas the mean nuclear content of both salt-extractable and salt-resistant AR was significantly lower (P < 0.05) than that in the prostatic tissue of the untreated men (n = 8). The mean plasma T levels in treated men decreased from 4.77 ± 1.79 (sd) ng/mL (16.5 ± 6.2 nmol/L) to 0.27 ± 0.42 ng/mL (0.9 ± 1.5 nmol/L) after 1 month of therapy and remained in the castrate range thereafter. We conclude that pharmacological castration resulting from 3-month treatment with a long-acting GnRH agonist decreases the intraprostatic T concentration to about one fourth and those of DHT and 3α-diol to about one tenth of the levels in untreated men. Thus, GnRH agonist treatment may not completely abolish intraprostatic androgen concentrations in metastatic prostatic cancer patients. The decrease in prostatic 5a-reductase activity as well as the decrease in nuclear receptors are probably secondary to the decrease in plasma T concentrations.

Olfactory neurons and gonadotropin-releasing hormone (GnRH) neurons share a common origin during organogenesis. Kallmann's syndrome, clinically characterized by anosmia and hypogonadotropic hypogonadism, is due to an abnormality in the migration of olfactory and GnRH neurons. We recently characterized the human FNC-B4 cell line, which retains properties present <i>in vivo</i> in both olfactory and GnRH neurons. In this study, we found that FNC-B4 neurons expressed GnRH receptor and responded to GnRH with time- and dose-dependent increases in GnRH gene expression and protein release (up to 5-fold). In addition, GnRH and its analogs stimulated cAMP production and calcium mobilization, although at different biological thresholds (nanomolar for cAMP and micromolar concentrations for calcium). We also observed that GnRH triggered axon growth, actin cytoskeleton remodeling, and a dose-dependent increase in migration (up to 3–4-fold), whereas it down-regulated nestin expression. All these effects were blocked by a specific GnRH receptor antagonist, cetrorelix. We suggest that GnRH, secreted by olfactory neuroblasts, acts in an autocrine pattern to promote differentiation and migration of those cells that diverge from the olfactory sensory lineage and are committed to becoming GnRH neurons.

The result of a search at the LHC for heavy stable charged particles produced in pp collisions at $ \sqrt {s} = 7\;{\text{TeV}} $ is described. The data sample was collected with the CMS detector and corresponds to an integrated luminosity of 3.1 pb−1. Momentum and ionization-energy-loss measurements in the inner tracker detector are used to identify tracks compatible with heavy slow-moving particles. Additionally, tracks passing muon identification requirements are also analyzed for the same signature. In each case, no candidate passes the selection, with an expected background of less than 0.1 events. A lower limit at the 95% confidence level on the mass of a stable gluino is set at 398GeV/c 2, using a conventional model of nuclear interactions that allows charged hadrons containing this particle to reach the muon detectors. A lower limit of 311 GeV/c 2 is also set for a stable gluino in a conservative scenario of complete charge suppression, where any hadron containing this particle becomes neutral before reaching the muon detectors.

Hadronic event shapes have been measured in proton-proton collisions at sqrt(s)=7 TeV, with a data sample collected with the CMS detector at the LHC. The sample corresponds to an integrated luminosity of 3.2 inverse picobarns. Event-shape distributions, corrected for detector response, are compared with five models of QCD multijet production.

A measurement of the top-antitop production cross section in proton-proton collisions at a centre-of-mass energy of 7 TeV has been performed at the LHC with the CMS detector. The analysis uses a data sample corresponding to an integrated luminosity of 36 inverse picobarns and is based on the reconstruction of the final state with one isolated, high transverse-momentum electron or muon and three or more hadronic jets. The kinematic properties of the events are used to separate the top-antitop signal from W+jets and QCD multijet background events. The measured cross section is 173 + 39 - 32 (stat. + syst.) pb, consistent with standard model expectations.

The charge asymmetry in the production of top quark and antiquark pairs is measured in proton-proton collisions at a center-of-mass energy of 8 TeV. The data, corresponding to an integrated luminosity of 19.6 inverse femtobarns, were collected by the CMS experiment at the LHC. Events with a single isolated electron or muon, and four or more jets, at least one of which is likely to have originated from hadronization of a bottom quark, are selected. A template technique is used to measure the asymmetry in the distribution of differences in the top quark and antiquark absolute rapidities. The measured asymmetry is A[c,y] = [0.33 +/- 0.26 (stat) +/- 0.33 (syst)]%, which is the most precise result to date. The results are compared to calculations based on the standard model and on several beyond-the-standard-model scenarios.

This document summarises the talks and discussions happened during the VBSCan Split17 workshop, the first general meeting of the VBSCan COST Action network. This collaboration is aiming at a consistent and coordinated study of vector-boson scattering from the phenomenological and experimental point of view, for the best exploitation of the data that will be delivered by existing and future particle colliders.

Abstract BACKGROUND Prostate cancer is a worldwide significant health care problem, due to its high incidence and mortality. In particular, androgen‐independent tumors have the worst prognosis, because they are refractory to almost all kinds of available therapy. Hence, there is the need of new treatment opportunities targeting androgen‐independent, growth factor‐mediated, tumor signaling. One of these new promising opportunities is vitamin D 3 and its related analogues. METHODS We investigated the effect of a vitamin D 3 analogue, analogue (V), on proliferation of several human prostate cancer cells in basal condition and after treatment with KGF, one of the intraprostatic growth factors that might participate in the progression of prostate cancer. In addition, in the androgen‐independent cell line DU 145, we also studied the effect of analogue (V), KGF, and their mutual interaction on protein tyrosine phosphorylation, bcl ‐2 expression and apoptosis. RESULTS Overall, we found that analogue (V) dose‐dependently decreased basal and KGF‐induced prostate cancer cell growth, although to a different extent. Maximal effect was obtained in DU 145 cells. In these cells, KGF stimulated tyrosine phosphorylation of a protein corresponding to its receptor, induced bcl‐2 expression, and prolonged cell survival. Analogue (V) not only counteracted all these KGF‐mediated events, but also decreased basal bcl‐2 expression, therefore, allowing DU 145 cells to undergo an apoptotic program. CONCLUSIONS Our results indicated that in prostate cancer cells analogue (V) decreased basal and KGF‐induced cell proliferation. This effect, at least in DU 145 cells, is in part mediated by negative interactions with cell survival and KGF signaling. Prostate 50: 15–26, 2002. © 2002 Wiley‐Liss, Inc.

Abstract Two cortisol-chemiluminescent marker conjugates, cortisol-21-hemisuccinate-aminobutyl ethyl-iso-luminol (C-21-HS-ABEI) and cortisol-21-hemisuccinate-aminobutyl-isoluminol (C-21-HS-ABI), were synthesized and evaluated as potential labels for the development of an immunoassay for cortisol based on chemiluminescence. Both conjugates were able to compete with tritiated cortisol for the binding sites of an antibody raised against a cortisol-21-hemisuccinate-BSA and they showed higher affinity than unaltered cortisol. These conjugates produced light upon oxidation by a hydrogen peroxide-microperoxidase system. The chemiluminescent reaction was optimized in terms of pH, concentration of oxidant and enzyme. Under optimal conditions both conjugates were detectable at femtomolar levels. The detection limits of C-21-HS-ABEI and C-21-HS-ABI were respectively 0.2 fmol and 1.0 fmol. These results indicated that immunoassay procedures for cortisol based on monitoring chemiluminescence can be developed with these labels.

This article reports an isotope dilution mass spectrometric method for the simultaneous measurement of testosterone (T), dihydrotestosterone (DHT), and 5α‐androstan‐3α, 17β‐diol (3α‐diol) in human plasma and prostatic tissue. After addition of tri‐deuterated steroids as internal standards to prostatic tissue homogenates or plasma samples, extraction was performed with diethylether. The extracts were purified by two chromatographic steps (Sep‐Pak C 18 cartridge and Sephadex LH‐20) and injected into a gas chromatograph coupled with a mass spectrometer after derivatization with heptafluorobutyric acid. This method was highly specific and showed good precision, accuracy, reproducibility and sensitivity. T, DHT, and 3α‐diol were measured in human plasma and in prostatic tissue of seven patients with benign prostatic hyperplasia (BPH) treated for 3 months with a long acting GnRH analog before surgery. Plasma levels of T, DHT, and 3α‐diol were reduced by GnRH analog treatment to castrate levels. The tissue concentrations of the same steroids, compared with those obtained from 19 untreated patients, showed a mean reduction of about 90% for DHT and 3α‐diol, and about 75% for T. These results suggest that about 90% of prostatic DHT and 3α‐diol depend on testicular activity because they are dramatically reduced after pharmacologic castration.

In order to stimulate new engagement and trigger some concrete studies in areas where further work would be beneficial towards fully understanding the physics potential of an $e^+e^-$ Higgs / Top / Electroweak factory, we propose to define a set of focus topics. The general reasoning and the proposed topics are described in this document.

The effect of varying the length of the alkyl bridge linking the chemiluminescent label isoluminol to progesterone on the light yield and binding affinity of progesterone chemiluminescent-marker conjugates was investigated. For this purpose five different derivatives of isoluminol, aminoethyl isoluminol (AEI), aminoethylethyl isoluminol (AEEI), aminobutyl isoluminol (ABI), aminobutyl-ethyl isoluminol (ABEI) and aminoethyl-ethyl isoluminol (AHEI) were covalently linked through a peptide bond to progesterone-11 alpha -hemisuccinate (P-11-HS). The resulting progesterone chemiluminescent-marker conjugates were then evaluated as potential labels for the development of an immunoassay based on monitoring chemiluminescence. These conjugates were able to compete with tritiated progesterone for the binding sites of an antibody raised against progesterone-11 alpha-HS bovine serum albumin, and they showed higher affinity than unaltered progesterone. These conjugates produced light upon oxidation by a hydrogen peroxide-microperoxidase system. The chemiluminescent reaction was optimized in terms of pH, concentration of oxidant, catalyst and conjugate design. Under optimal conditions, all the conjugates were detectable at femtomolar levels. The lowest detection limit was obtained using P-11-HS-ABEI (0.1 fmol). These results indicated that immunoassay techniques based on chemiluminescence can be developed with these labels.

An immunoassay procedure for determination of cortisol in human plasma and in urine is described, which utilizes chcmiluminescence as the end point. The assay utilizes cortisol-21-hemisuccinate-aminobutyl-ethyl-isoluminol (C-21-HS-ABEI) as the chemiluminescent marker, and dextran coated charcoal is used for separation of bound and free forms of the ligand. The chemiluminescent assay for cortisol was validated in terms of sensitivity, specificity, linear range and precision. An assay procedure for measuring of plasma and urinary free cortisol was established and assay results were compared with radioimmunoassay, using the same antiserum with tritiated cortisol as the label. The two methods agreed well (r = 0.95 for plasma cortisol and r = 0.97 for urinary free cortisol). The proposed method takes full advantage of specificity and sensitivity that result from the use of an antibody, without employing an isotopically labelled ligand.

An immunoassay procedure for determination of progesterone in human plasma is described which utilizes chemiluminescence as the endpoint. The assay utilized progesterone-11-hemisuccinate-aminobutyl-ethyl-isoluminol (P-11-HS-ABEI) as the chemiluminescent marker conjugate and dextran coated charcoal for the separation of bound and free fractions of the ligand. An assay procedure for progesterone was established and validated in terms of sensitivity and precision, and assay results were compared with radioimmunoassay, using tritiated progesterone as the tracer. The two methods agreed well (n=35, r=0.96). The most important advantage of this assay is the elimination of problems inherent in the use of radioactive materials.

Prostate growth and differentiation is under the control of androgens not only during fetal life and childhood but also in adulthood, and it has been proposed that increased prostatic concentration of androgens, or increased androgen responsiveness, causes benign prostatic hyperplasia (BPH). However, different androgen ablation strategies such as treatment with GnRH agonists and finasteride resulted in a modest decrease of the hyperplastic prostate volume. In the last few years it became evident that both androgen-dependent and androgen-independent growth factors promote prostate enlargement by inducing cell proliferation or reducing apoptosis. Therefore, new therapeutic strategies, aimed at reducing intraprostatic growth factor signaling, are under investigation. In this study, we report further evidence that a non hypercalcemic-analogue of vitamin D3, analogue (V) decreases growth factor-induced human BPH cell proliferation and survival. We found that Des (1-3) insulin-like growth factor [Des (1-3) IGF-I], an IGF-I analogue, which does not bind to IGF-binding proteins, is a potent mitogen for BPH stromal cells via a dual mechanism: stimulation of cell growth and inhibition of apoptosis. Similar results were previously reported for another growth factor for BPH cells, keratinocyte growth factor (KGF). Accordingly, we speculate that both KGF and IGF might be involved in the pathogenesis of BPH. We also found analogue (V) not only inhibits the mitogenic activity of growth factors on BPH cells, but even decreased the basal expression of bcl-2, and induced apoptosis. Therefore, vitamin D3 analogues might be considered for the medical treatment of BPH.

Sarcopenia is the physiological age related decline in muscle mass and strength. It is a main cause of muscle weakness and reduced locomotory ability and its adverse effects contributes to a reduction in physical function and performance with decreased independence and quality of life. In fact, sarcopenia has been associated with disability and morbidity in the elderly population. Therefore, prevention and treatment of sarcopenia are areas of intense interest. The studies suggest that the pathogenesis of sarcopenia is multifactorial, but the decreased physical activity with aging appears to be a key factor involved in producing this pathology. We investigated the role of adapted physical activity on the adverse effects of the sarcopenia: we examined the effect of a specific resistance training program in twenty sedentary older men, 60-80 years old, with sarcopenia. The program was performed three days a week for 18 total weeks with isotonic machines; in particular the exercises effected with leg press, chest press and vertical row were monitored using a Globus-Tesys dynamometer with Real Power. The maximum repetition test (1RM) was used to calculate the percentage of work and formulate the methodology. Our results demonstrated that the proposed training can improve the dynamic characteristics of muscle strength. In particular, we showed that a medium-low intensity training, structured in series and repetitions with gradual increased workload, produced a time-dependent improvement of strength. Our training increased the muscle strength mainly in the lower limbs reducing the risk of falls which frequently occurs in the elderly. Therefore, a planned resistance training could be an effective countermeasure to prevent or reduce the adverse effects of the sarcopenia improving the quality of life. The physical activity should be personalized and adapted to subject's age and/or disability.

Autosomal dominant neurohypophyseal diabetes insipidus (adNDI) is caused by arginine vasopressin (AVP) deficiency resulting from mutations in the AVP-NPII gene encoding the AVP preprohormone.To describe the clinical and molecular features of Italian unrelated families with central diabetes insipidus.We analyzed AVP-NPII gene in 13 families in whom diabetes insipidus appeared to be segregating.Twenty-two patients were found to carry a pathogenic AVP-NPII gene mutation. Two novel c.173 G>C (p.Cys58Ser) and c.215 C>A (p.Ala72Glu) missense mutations and additional eight different mutations previously described were identified; nine were missense and one non-sense mutation. Most mutations (eight out of ten) occurred in the region encoding for the NPII moiety; two mutations were detected in exon 1. No mutations were found in exon 3. Median age of onset was 32.5 months with a variability within the same mutation (3 to 360 months). No clear genotype-phenotype correlation has been observed, except for the c.55 G>A (p.Ala19Thr) mutation, which led to a later onset of disease (median age 120 months). Brain magnetic resonance imaging (MRI) revealed the absence of posterior pituitary hyperintensity in 8 out of 15 subjects, hypointense signal in 4 and normal signal in 2. Follow-up MRI showed the disappearance of the posterior pituitary hyperintensity after 6 years in one case.adNDI is a progressive disease with a variable age of onset. Molecular diagnosis and counseling should be provided to avoid unnecessary investigations and to ensure an early and adequate treatment.

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.

5α-Dihydrotestosterone has been widely measured in human prostatic tissue using RIA since it is involved in the pathogenesis of human prostatic hyperplasia and seems to be the best index for the follow-up of patients affected by prostatic cancer under endocrine treatment. A GC-MS method for the simultaneou determination of testosterone (T), 5α-dihydrotestosterone (DHT) and 5α-androstan-3α, 17β-diol (3α-diol) in prostatic tissue based on the isotopic dilution technique was developed. Tri-deuterated internal standards of each compound were previously synthetized in our laboratory. After extraction and purification on Sep-Pak C 18 and Sephadex LH-20, T and its metabolites were measured as heptafluorobutyric ester (HFB) derivatives. Quantitative analysis was performed on a VG 7070 EQ mass spectromer equipped with a fused silica capillary column using the Selected Ion Monitoring technique. Steroid values (mean ± SD; ng/g tissue) found in nine human hypertrophic prostates were: T: 0.71 ± 0.43; DHT: 4.46 ± 1.41; 3α-diol: 0.34 ± 0.23. Preliminary results obtained from the detection of the three androgens in human prostatic hyperplasia treated for 3 months with GnRH before surgery seem to indicate that DHT concentration decreases more than 10 times. Values obtained (n = 1; ng/g tissue) were: T: 0.194; DHT: 0.255; 3α-diol: 0.015.

Prostate enlargement and function is under the dual control of androgens and intraprostatic growth factors. They regulate, in concert, prostate cell proliferation and apoptosis. An increased signaling of both growth factors and androgens are supposed to underlie benign prostate hyperplasia (BPH), one of the more common disorders of the aging male. Since, in clinical practice, androgen ablation resulted in a rather limited decrease in prostate volume, therapeutic strategies targeting intraprostatic growth factors are emerging. The activated form of vitamin D, vitamin D3, and some of its analogues have been described as potent regulators of cell growth and differentiation. In this study, we report the effects of one of these vitamin D3 analogues, 1,25-dihydroxy-16ene-23yne D3, or analogue (V), on the fate of isolated epithelial cells derived from patients with BPH. We essentially found that analogue (V), as well as vitamin D3, inhibited BPH cell proliferation and counteracted the mitogenic activity of a potent growth factor for BPH cells, such as keratinocyte growth factor (KGF). Moreover, analogue (V) induced bcl-2 protein expression, intracellular calcium mobilization, and apoptosis in both unstimulated and KGF-stimulated BPH cells. Since a short-term (5-min) incubation with analogue (V) reduced the KGF-induced tyrosine phosphorylation of a 120-kDA protein, corresponding to the KGF receptor, a rapid and direct cross-talk between these two molecules is suggested. Such a rapid effect of analogue (V), together with the transient induction of intracellular calcium waves, seems to indicate the partial involvement of a membrane, nongenomic receptor for vitamin D3. In conclusion, we demonstrated the antiproliferative and proapoptotic effect of analogue (V) in BPH cells and speculated on its possible use in the therapy of BPH.

A prospective study for the observability of heavy neutral Higgs bosons decaying into supersymmetric particles at the Large Hadron Collider with the CMS detector is presented. The analysis focuses on the decay of the Higgs bosons into a pair of next-to-lightest neutralinos χ02, followed by the cascade down to the lightest neutralino, χ02 → l+l−χ01. The final state is characterized by the presence of four isolated leptons and missing transverse energy. The parameter space of the minimal supergravity model is explored and favourable regions for the observation of the A0/H0 bosons are identified. The A0/H0 bosons could be discovered in the 2e2μ channel in the mass region 250 ≲ mA/H ≲ 400 GeV/c2 with an integrated luminosity of 30 fb−1.

An original method is described for the determination in human plasma of 4-hydroxy-4-androstene-3,17-dione (4-OHA), a potent aromatase inhibitor, by isotope dilution mass-spectrometry using 7,7-[2H2]-4-OHA as internal standard. This compound was synthesized starting from 7,7-[2H2]-4-androstene-3,17-dione. The procedure includes an extraction step using an Extrelut 1 column and a derivatization with N,o-bis(trimethylsilyl)trifluoroacetamide (BSTFA). The minimum detection level of the method is 0.650 pg and the coefficients of variation for the 0.5 ng/ml (plasma) and 5 ng/ml (plasma) concentrations are 3.2% (within assay) and 6.7% (between assay) and 1.86% (within assay) and 2.3% (between assay) respectively.

5 alpha-Dihydrotestosterone (DHT) has been widely measured in human prostatic tissue using RIA since it is found to be involved in pathogenesis of human prostatic hyperplasia (BHP) and to be the best index for the follow-up of patients affected by prostatic cancer under endocrine treatment. A GC/MS method for the simultaneous determination of testosterone (T), dihydrotestosterone (DHT), 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) in prostatic tissue was developed based on the isotopic dilution technique. Trideuterated internal standards of each compound were previously synthesized in our laboratory. After previous extraction and purification on Sep-Pak C-18 cartridges and Lipidex DEAP columns, T and its metabolites were measured as heptafluorobutyric esters (HFB). Quantitative analysis was performed on a VG 7070 EQ mass spectrometer equipped with a fused silica capillary column using the Selected Ion Monitoring technique. Steroid values (means +/- SD; ng/g tissue) found in 9 human hypertrophic prostates were: T, 0.71 +/- 0.43; DHT, 4.46 +/- 1.41; 3 alpha-diol, 0.34 +/- 0.23; 3 beta-diol, 0.14 +/- 0.32.

For the physics program of the CMS experiment at the LHC to be carried out successfully, excellent electromagnetic calorimetry is required. Given the thermal properties of CMS ECAL, keeping the constant term of the energy resolution below 0.5% needs its temperature to be stabilized at 18/spl deg/C within 0.05/spl deg/C. A prototype module of ECAL with the final cooling system has been tested at CERN to check its integration with the read-out electronics and verify that it complies with the severe thermal requirements. The thermal performance of the cooling system is reported here.

A prospective analysis is presented for the discovery of the Standard Model Higgs boson in the CMS experiment at the LHC collider. The analysis focuses on the pp → H + X → ZZ(*) + X → e+e−e+e− + X channel for Higgs boson masses in the range 120 ≲ mH ≲ 300 GeV/c2. It relies on a full simulation of the detector response and usage of new detailed electron reconstruction tools. Emphasis is put on realistic strategies for the evaluation of experimental systematics and control of physics background processes. For an integrated LHC luminosity of 30fb−1, a Standard Model Higgs boson would be observed in the e+e−e+e− channel with a significance above 3 standard deviations for masses mH in the range from about 130 to 160 GeV/c2 and above 180 GeV/c2. A discovery with a significance above 5 standard deviations is possible for this integrated luminosity around mH ≃ 150 GeV/c2 and in the range from about 190 to 300 GeV/c2. The mass (cross-section) of the Higgs boson can be determined with a precision better than 1% (30%).

A search is performed for the production of a massive W′ boson decaying to a top and a bottom quark. The data analysed correspond to an integrated luminosity of 19.7 fb−1 collected with the CMS detector at the LHC in proton-proton collisions at $$ \sqrt{s}=8 $$ TeV. The hadronic decay products of the top quark with high Lorentz boost from the W′ boson decay are detected as a single top flavoured jet. The use of jet substructure algorithms allows the top quark jet to be distinguished from standard model QCD background. Limits on the production cross section of a right-handed W′ boson are obtained, together with constraints on the left-handed and right-handed couplings of the W′ boson to quarks. The production of a right-handed W′ boson with a mass below 2.02 TeV decaying to a hadronic final state is excluded at 95% confidence level. This mass limit increases to 2.15 TeV when both hadronic and leptonic decays are considered, and is the most stringent lower mass limit to date in the tb decay mode.

The application of luminescence to the development of non-isotopic immunoassay methods for steroids and urinary steroid metabolites is reviewed. On-line computer analysis of the light emission is particularly useful, as it reveals the interfering effects of biological compounds on the reaction and this can improve the quality of luminescence immunoassay (LIA) methods. The main characteristics of chemiluminescent tracers are stability, safety, speed and sensitivity of detection, and reliability. Homogeneous methods, not requiring phase separation, have also been reported and validated. Heterogeneous methods which use dextran-coated charcoal or solid-phase techniques can be used for direct determination of urinary steroids in unextracted samples.

We interfaced a microcomputer on-line with a luminometer to acquire the light signal of chemiluminescent reactions from a photomultiplier and then compute significant parameters of light emission and kinetic "shape" indices. Using this system to study interferences from biological samples on the measurement of chemiluminescent reactions, we observed that such effects are usually associated with modifications of the shape of the light-emission kinetics. These results suggest that a simultaneous evaluation of the shape of a chemiluminescent reaction and the measurement of light emission can be combined to assess luminescent immunoassays as an internal control of the interferences in measurements of the chemiluminescent tracer. As an example of this approach, we developed and validated a luminescent immunoassay for free cortisol in diluted urine. Dextran-coated charcoal is used for bound-free separation.

Testosterone (T), 17-hydroxyprogesterone (17P) and Cortisol (F) plasma levels have been measured in two groups of prepubertal boys before and during surgery under general anaesthesia (Group 1) and epidural anaesthesia (Group 2) respectively. The mean plasma levels of T, 17P and F increased significantly (P < 0.05; P < 0.001; P < 0.005, respectively) during surgery in Group 1; in Group 2 the plasma levels of T and F did not show any significant variation, whereas 17P significantly increased (P < 0.05). However the mean level reached by 17P in Group 2 was significantly lower (P < 0.005) than that observed in Group 1. No significant variation of LH and FSH plasma levels was observed in either group. Our report suggests that the modifications of T and 17P plasma levels observed during surgery under general anaesthesia (GA) are probably due to the stress induced adrenal response. This response can be inhibited or reduced by epidural anaesthesia (EA).

It is widely accepted that polypeptide growth factors are involved in the growth and development of normal and neoplastic human prostate. It has been previously reported that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) receptors are present in the human hyperplastic prostate tissue (BPH). To add information on the mechanism of action of EGF and transforming growth factor-alpha (TGF alpha), a peptide correlated to EGF, and the EGF receptor (EGF-R) in the human prostate, we studied the expression and cellular localization of messenger ribonucleic acid (RNA) encoding EGF, EGF-R, and TGF alpha in BPH tissue. Reverse transcriptase-PCR of total RNA extracted from BPH tissues documented the presence of specific transcripts for EGF, EGF-R, and TGF alpha. In situ hybridization with specific RNA probes synthesized from the respective complementary DNA demonstrated that EGF, EGF-R, and TGF alpha messenger RNAs were mainly localized in the epithelial cells. Immunprecipitation and Western blot analysis showed that BPH tissue contained the corresponding proteins, EGF and TGF alpha. Our findings provide additional support for the idea that EGF and TGF alpha may be considered specialized symbols in the language of cell-cell interactions and for the hypothesis that in the human prostate they seem to act in an autocrine fashion.

Abstract We describe a mass-spectrometric method based on the fast atom bombardment ionization technique in the negative-ion mode for measuring pregnanediol-3 alpha-glucuronide in diluted urine from women. The procedure requires addition of testosterone-17 beta-D-glucuronide (2.5 micrograms/25 microL) to the urine sample as internal standard, and the sample is added directly to the fast atom bombardment target with no further manipulation. We have assessed and evaluated the method by the traditional criteria of reliability.

Abstract Background The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private surveillance systems and networks. Implementing and sustaining programs to detect emerging and re-emerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. Methods This study sought to gain an understanding of the role of federal government agencies in supporting such pathogen-agnostic testing of human specimens in the United States. A landscape analysis was conducted of federal agency websites for publicly accessible information on the availability and type of pathogen-agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by expert review of results with representatives from the federal agencies. Results Operating divisions within the Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing at scale. Metagenomic facilities supported by US agencies were not equally geographically distributed across the US. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal apparent collaboration across agencies. Conclusion Developing a national sentinel surveillance network with existing resources and infrastructure could potentially increase efficiency, accelerate identification of emerging biothreats, and support coordinated intervention strategies that reduce morbidity and mortality. Disclosures All Authors: No reported disclosures

Abstract The determination of the concentration of estrone‐3‐glucuronide and pregnanediol‐3α‐glucuronide has been performed by a chemiluminescent immunoassay in early morning urine samples of 14 normal menstruating women and 11 women affected by luteal phase defect. The early morning urine samples were daily collected for an entire menstrual cycle. We have employed a timed and measured volume collection procedure as correction factor. The integrated values of the hormonal data in definite time intervals were used to create a nomogram. By means of this method, it was possible to completely separate normal from luteal insufficiency subjects and to distinguish two different types of luteal phase defects. Moreover, the same approach was applied to the study of the role and the frequency of luteal phase defect in 15 patients affected by habitual abortion and in 17 premenopausal women who had undergone quadrantectomy for T1a No Mo breast cancer. A luteal phase defect was detected in nine of the aborting patients (60%) and in eight women affected by breast cancer (47%). Finally estrone‐3‐glucuronide was measured in early morning urine samples of 96 prepubertal and pubertal girls in different pubertal stages and in one patient affected by precocious puberty, before and during an agonist GnRH treatment. The urinary test of ovarian function seems to be suitable for diagnostic purposes and for clinical studies.

For many years, hypersecretion of estrogens has been suspected of being one of the major risk factors of breast cancer for premenopausal women. Seventeen premenopausal women, who had undergone lumpectomy because of breast cancer (T1a No Mo) 3 yr before entering the study, were compared to 9 normal women of similar age, parity and body weight. A chemiluminescent method was used for the determination of estrone-3-glucuronide (E1-3G) and pregnanediol-3-glucuronide (Pd-3G) in early morning urine samples collected for an entire menstrual cycle of each of the 26 subjects. During the follicular phase, no significant differences in E1-3G and/or Pd-3G excretion were found between the two groups. During the luteal phase the E1-3G/Pd-3G ratio in the early, middle and late luteal phase had significantly increased in the women with breast cancer, in spite of normal Pd-3G excretion. Therefore, the measurement of glucuronoconjugate metabolites of ovarian hormones in overnight urine might be conveniently applied to the study of ovarian function in subjects with breast cancer. Furthermore, the results of this study may indicate that an estrogen/progesterone imbalance is an additional risk factor for the premenopausal breast cancer patient.

Preserving high reconstruction efficiency and best four-momentum measurements down to low pT for electrons in CMS is a necessity for optimal discovery prospects in the ZZ* and WW* Higgs boson decay channels and in the leptonic decay of charginos and neutralinos. This is challenging in view of the material budget in front of the electromagnetic calorimeter ECAL and the presence of a strong magnetic field. The reconstruction for isolated electrons in CMS is described. The performances of electron identification, combining tracking and calorimetry information, are discussed.

Climate changes have never been as dramatically apparent in our everyday life as now. It is urgent to reduce greenhouse gas emissions and mitigate the consequences of climate changes both on the planet and on human health. The indiscriminate exploitation of natural resources and the lack of shared rules are among the major causes. Recently, some economists have called for a radical change in the present economic model towards a ‘social solidarity economy’ model. G.Giraud, a French economist, called for an ecological and social transition in order to reduce the ecological footprint and deal concretely with the problem of global warming. The good news is that the solutions are there and do not have to be punitive. Health consequences of climate changes have already caused serious draw backs on public health. Doctors and scientific institutions can and must contribute to help mitigate the effects of climate change through increasing commitment and support to goodenvironmental policies. Climate emergency requires the extension of ethics and medical practice beyond their traditional mission to involve the relationship between patients, doctors and society. We propose that medical scientific institutions quickly promote the birth of task forces dedicated to addressing this problem. (GCND_planet)

Annals of the New York Academy of SciencesVolume 595, Issue 1 p. 275-280 Measurement of Steroids in Human Plasma and Tissues by Isotope Dilution Mass Spectrometrya M. Serio, M. Serio Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorA. Guarna, A. Guarna Endocrinology Unit Department of Clinical Physiopathology Department of Organic Chemistry University of Florence 50134 Florence, ItalySearch for more papers by this authorR. Salerno, R. Salerno Endocrinology Unit Department of Clinical Physiopathology I.N.R.C.A. University of Florence 50134 Florence, ItalySearch for more papers by this authorC. Orlando, C. Orlando Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorM. Pazzagli, M. Pazzagli Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorE. Calabresi, E. Calabresi Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorG. Moneti, G. Moneti Endocrinology Unit Department of Clinical Physiopathology Mass Spectrometry Center University of Florence 50134 Florence, ItalySearch for more papers by this author M. Serio, M. Serio Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorA. Guarna, A. Guarna Endocrinology Unit Department of Clinical Physiopathology Department of Organic Chemistry University of Florence 50134 Florence, ItalySearch for more papers by this authorR. Salerno, R. Salerno Endocrinology Unit Department of Clinical Physiopathology I.N.R.C.A. University of Florence 50134 Florence, ItalySearch for more papers by this authorC. Orlando, C. Orlando Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorM. Pazzagli, M. Pazzagli Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorE. Calabresi, E. Calabresi Endocrinology Unit Department of Clinical Physiopathology Department of Pharmacology University of Florence 50134 Florence, ItalySearch for more papers by this authorG. Moneti, G. Moneti Endocrinology Unit Department of Clinical Physiopathology Mass Spectrometry Center University of Florence 50134 Florence, ItalySearch for more papers by this author First published: June 1990 https://doi.org/10.1111/j.1749-6632.1990.tb34301.xCitations: 2 a This paper was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC) e Consiglio Nazionale delle Ricerche (CNR), Progetto Finalizzato Oncologia (contracts: 88.00666.44 and 88.00.879.44). AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume595, Issue1Steroid Formation, Degradation, and Action in Peripheral TissuesJune 1990Pages 275-280 RelatedInformation

INTRODUCTION AND OBJECTIVE: To improve our ability of monitoring prostate gland in live animals and to study the molecular steps of prostate carcinogenesis, we developed a transgenic mouse model overexpressing luciferase (luc) gene in the prostate gland under the control of a human super prostate-specific antigen (sPSA) promoter (Yeung, et al. mc 275: 40846, 2000).This mouse model is used to study prostate development and to assess quantitatively the effect of androgen in stimulating prostate growth using a non-invasive imaging technique.This model will confirm the specificity of a human sPSA promoter for transgene delivery specifically to the prostate gland using murine models.METHODS: sPSA-Iuc transgenic mouse lines carrying the firefly luciferase gene driven by a 600 bp chimeric sPSA promoter were generated and maintained in pure FVB background.Expression of the luc reporter in living mice was analyzed using a whole-body optical cooled charged-coupled device (CCD) imaging system and confirmed by tissue luciferase enzymatic activity and immunohistochemical (IHC) assays.CCD imaging of sPSA-luc in male offspring between 2 and 52 weeks of age were conducted.This model was also used to assess prostate involution and androgen-induced prostate regeneration in vivo.RESULTS: Three sPSA-Iuc founder animals were identified by genotyping, Two female founders showed transmission of the transgene to their offspring by PCR screening; another male founder was infertile.CCD imaging of male offspring from one of the female founders showed extremely high level of bioluminescence photon counts in prostate lobes without any noticeable signals in 12 other organs.This result is consistent with luciferase enzymatic activity and IHC assays.Males of 2 to 4 weeks of age did not show significant bioluminescence image until sexual maturation while an almost constant, high level of signal was detected from 8 to 52 weeks of age.CCD imaging signal was decreased dramatically after castration and returned very rapidly to precastration levels after DHT (5mglkg) administration.CONCLUSIONS: Human sPSA promoter is superior to the full-length PSA, C-3 and MMTV promoters in conferring transgene expression only in mouse prostate.Imaging mouse prostate by bioluminescence of luc activity offers a non-invasive modality to follow prostate development, to assess prostate involution and regeneration.This model can be further developed to increase our understanding of prostate growth control.

A search for massive resonances decaying to a Z boson and a photon is performed in events with a hadronically decaying Z boson candidate, separately in light-quark and b quark decay modes, identified using jet substructure and advanced b tagging techniques. Results are based on samples of proton-proton collisions collected with the CMS detector at the LHC at center-of-mass energies of 8 and 13 TeV, corresponding to integrated luminosities of 19.7 and 2.7 inverse femtobarns, respectively. The results of the search are combined with those of a similar search in the leptonic decay modes of the Z boson, based on the same data sets. Spin-0 resonances with various widths and with masses in a range between 0.2 and 3.0 TeV are considered. No significant excess is observed either in the individual analyses or the combination. The results are presented in terms of upper limits on the production cross section of such resonances and constitute the most stringent limits to date for a wide range of masses.

Abstract Introduction: Systemic mastocytosis (SM) is an heterogeneous myeloproliferative neoplasm characterized by uncontrolled growth of cKIT mutated clonal mast cells, with clinical manifestations ranging from indolent forms (ISM) with only skin lesions and/or anaphylactic shock to smouldering SM (SSM) with evidence of organ involvement to aggressive forms (ASM) with extensive organ damage. SM with an associated hematological neoplasm (SM-AHN) is a subtype with adverse prognosis possibly related to the associated neoplasm rather than SM. Recent data indicate that mutations in genes associated to myeloid malignancies correlate with survival and disease progression but information are still scanty and not completely concordant, and mutations apparently did not correlate with disease manifestations; furthermore, most patients analyzed were SM-AHN, therefore the contribution of mutations associated with the non-mast cell clone could not be ascertained clearly. The aim of this study was to address the prognostic relevance of mutations at diagnosis in a series of 70 pts with SM, excluding SM-AHD. Methods: There were 58 ISM, 4 SSM, 7 ASM and 1 mast cell leukemia (MCL) pts. cKITD816V mutation was assessed by RTQ-PCR. Mutations in myeloid-neoplasm associated genes were assessed by next generation sequencing (NGS) with Ion Torrent PGM platform; analyzed genes included ASXL1, CBL, cKIT, ETNK1, EZH2, IDH1, IDH2, SRSF2, RUNX1, TET2. We also evaluated the cKITD816V variant allele frequency (VAF) by NGS. Kruskal-Wallis test and Chi-squared test were used for analysis of continuous and categorical variables, respectively. Cox regression model was used for survival analysis; variables included were WHO subgroup, cKITD816V &gt;2% VAF, mutations in additional genes, age at diagnosis &gt;60 years, serum tryptase &gt;200 ng/mL, alkaline phosphatase and white blood cells greater than upper normal limit. We did not considered as single entities the features included in B and/or C findings. Results: Median age at diagnosis was 45 years (y)(range 17-76) for ISM, 67 y (53-74) for SSM, 73 (41-81) for ASM (p&lt;0.001). At last follow up (median 2 years, range 0.2-14) 2 pts with ASM evolved to acute myeloid leukemia (AML, 2.8% of all series, 28% of ASM), 1 ISM pts developed organ damage and shifted to ASM; 4 pts died (4/70, 5.7%). Skin involvement was found in 80.6% of pts, 31.3% had history of anaphylaxis and 27.8% osteoporosis. Median serum tryptase levels were 28.7 ng/mL (range 3-192) for ISM, 190 (60-591) for SSM, 64 (23-300) for ASM and 2000 in MCL. All but 3 pts (2 ISM, 1 ASM) were cKITD816V mutated by RT-PCR in bone marrow aspirate (BM) or peripheral blood (PB) (in pts with punctio sicca). 54/67 (80%) had a cKITD816V mutation detectable in PB, underlying that even with high sensitivity methods PB cannot replace BM analysis for diagnosis. Median VAF was 0.34% (range 0.03-38.4) in ISM, 17.2% (0.3-45) in SSM, 26.7% (0.9-81.7) in ASM and 71.7% in MCL. Pts with at least 1 additional mutation were 6.9% (4/54) ISM, 50% (2/4) SSM and 57% (4/7) ASM(p&lt;0.001). Five pts (7%), 4 ASM (57%) and 1 MCL, had more than 1 additional mutations (p&lt;0.001). TET2 was the most frequent mutated gene, in 9/70 cases (12.9%), followed by ASXL1 and SRSF2 in 2 pts (2.9% each) and EZH2, IDH2, CBL and RUNX1 in 1 pts each (1.4%). No mutation was found in IDH1 and ETNK1. No recurrent mutation types were found. All pts with more than one additional mutations other than cKITD816V carried a TET2 mutation combined with ASXL1 and SRSF2 mutation in two cases each and CBL in one case. One pt had a third additional EZH2 mutation. Karyotype was normal in all the 58 pts evaluated, including 5 ASM and 3 SSM. In univariate analysis the following parameters were associated with shorter survival: one or more additional mutations (HR 19.2, CI 2-185, p&lt;0.001), TET2 mutation (HR 28, CI 2.9-271, p=0.004) (mutations in other single genes were not evaluated due to low number of cases) and ASM variant (HR 5.3, CI 1.7-16.1, p=0.003). Pts older than 60 y at diagnosis had higher frequency of additional mutations (35% versus 8% in pts &lt;60 y, p=0.005) and of cKITD816V VAF &gt;2% (68.8% versus 8.3%, P&lt;0.001). None of the analyzed molecular features correlated with anaphylaxis, osteoporosis or skin involvement. Conclusions: With the limitations due the small number of events recorded in this series, these data suggest that knowledge of molecular asset in pts with SM might provide prognostically relevant information. Disclosures Vannucchi: Novartis: Consultancy, Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Shire: Speakers Bureau.

The inelastic hadronic cross section in proton-lead collisions at a centre-of-mass energy per nucleon pair of 5.02 TeV is measured with the CMS detector at the LHC. The data sample, corresponding to an integrated luminosity of 12.6 +/- 0.4 inverse nanobarns, has been collected with an unbiased trigger for inclusive particle production. The cross section is obtained from the measured number of proton-lead collisions with hadronic activity produced in the pseudorapidity ranges 3<abs(eta)<5 and/or -5<abs(eta)<-3, corrected for photon-induced contributions, experimental acceptance, and other instrumental effects. The inelastic cross section is measured to be sigma[inel,pPb]=2061 +/- 3 (stat) +/- 34 (syst) +/- 72 (lum) mb. Various Monte Carlo generators, commonly used in heavy ion and cosmic ray physics, are found to reproduce the data within uncertainties. The value of sigma[inel,pPb] is compatible with that expected from the proton-proton cross section at 5.02 TeV scaled up within a simple Glauber approach to account for multiple scatterings in the lead nucleus, indicating that further net nuclear corrections are small.

During the last few years cities have increased widely their competences. Above all, from the point of view of the socio-economic policies we observe a growing activism from their side. This activism is very different from that one of the previous years. From the urban transformations to the cultural policies, the main players of the cities are now perceived, by the local communities, as the powerful ones. But what has brought this change? And how different are the cities that compete in order to attract more and more desirable resources? The growth machine and the entertainment machine are really so different? This essay goes back to the great oil crisis of 1973 which is considered the starting point of this great transformation, showing the narrowing down of the venues for discussion and, in particular, a clear centralization of the decision powers.

Results are summarized from searches for the standard model Higgs boson in pp collisions at sqrt(s) = 7 and 8 TeV in the CMS experiment at the LHC. The measurements of mass, cross section, and properties of the narrow resonance recently observed are presented. The searches beyond standard model Higgs boson, in the CMS experiment at the LHC, are highlighted.

Results are summarized from searches for the standard model Higgs boson in pp collisions at sqrt(s) = 7 and 8 TeV in the CMS experiment at the LHC. The measurements of mass, cross section, and properties of the narrow resonance recently observed are presented. The searches beyond standard model Higgs boson, in the CMS experiment at the LHC, are highlighted.

A measurement of the ttbar production cross section at sqrt(s)=13 TeV is presented using proton-proton collisions, corresponding to an integrated luminosity of 2.3 inverse femtobarns, collected with the CMS detector at the LHC. Final states with one isolated charged lepton (electron or muon) and at least one jet are selected and categorized according to the accompanying jet multiplicity. From a likelihood fit to the invariant mass distribution of the isolated lepton and a jet identified as coming from the hadronization of a bottom quark, the cross section is measured to be sigma(ttbar)= 835 +/- 3 (stat) +/- 23 (syst) +/- 23 (lum) pb, in agreement with the standard model prediction. Using the expected dependence of the cross section on the pole mass of the top quark (m[t]), the value of m[t] is found to be 172.7+2.4-2.7 GeV.

Preserving high reconstruction efficiency and best four-momentum measurements down to low pT for electrons in CMS is a necessity for optimal discovery prospects in the ZZ(∗) and WW(∗) Higgs boson decay channels and in the leptonic decay of charginos and neutralinos. This is challenging in view of the material budget in front of the electromagnetic calorimeter ECAL and the presence of a strong magnetic field. The reconstruction for isolated electrons in CMS is described. The performances of electron identification, combining tracking and calorimetry information, are discussed.

This document summarises the talks and discussions happened during the VBSCan Split17 workshop, the first general meeting of the VBSCan COST Action network. This collaboration is aiming at a consistent and coordinated study of vector-boson scattering from the phenomenological and experimental point of view, for the best exploitation of the data that will be delivered by existing and future particle colliders.

The latest results on Higgs boson physics obtained by ATLAS and CMS experiments using LHC proton-proton collisions at $\sqrt{s}=13$TeV are presented.

Progress in the simulaction and analysis of the Higgs decay to the 4 electrons via ZZ* intermediate state

New results in Higgs to ZZ* to 4 electron channel are reported with emphasis on electron reconstruction tools and framework for overall analysis

Status report of the work on detailed simulation of the Higgs decay to 4 electrons is given.

The COVID-19 pandemic has by-and-large prevented in-person meetings since March 2020. While the increasing deployment of effective vaccines around the world is a very positive development, the timeline and pathway to "normality" is uncertain and the "new normal" we will settle into is anyone's guess. Particle physics, like many other scientific fields, has more than a year of experience in holding virtual meetings, workshops, and conferences. A great deal of experimentation and innovation to explore how to execute these meetings effectively has occurred. Therefore, it is an appropriate time to take stock of what we as a community learned from running virtual meetings and discuss possible strategies for the future. Continuing to develop effective strategies for meetings with a virtual component is likely to be important for reducing the carbon footprint of our research activities, while also enabling greater diversity and inclusion for participation. This report summarizes a virtual two-day workshop on Virtual Meetings held May 5-6, 2021 which brought together experts from both inside and outside of high-energy physics to share their experiences and practices with organizing and executing virtual workshops, and to develop possible strategies for future meetings as we begin to emerge from the COVID-19 pandemic. This report outlines some of the practices and tools that have worked well which we hope will serve as a valuable resource for future virtual meeting organizers in all scientific fields.