Performance of a Large-area GEM Detector Read Out with Wide Radial Zigzag Strips

A 1-meter-long trapezoidal Triple-GEM detector with wide readout strips was tested in hadron beams at the Fermilab Test Beam Facility in October 2013. The readout strips have a special zigzag geometry and run along the radial direction with an azimuthal pitch of 1.37 mrad to measure the azimuthal phi-coordinate of incident particles. The zigzag geometry of the readout reduces the required number of electronic channels by a factor of three compared to conventional straight readout strips while preserving good angular resolution. The average crosstalk between zigzag strips is measured to be an acceptable 5.5%. The detection efficiency of the detector is (98.4+-0.2)%. When the non-linearity of the zigzag-strip response is corrected with track information, the angular resolution is measured to be (193+-3) urad, which corresponds to 14% of the angular strip pitch. Multiple Coulomb scattering effects are fully taken into account in the data analysis with the help of a stand-alone Geant4 simulation that estimates interpolated track errors.Comment: 30 pages, 28 figures, submitted to NIM

Bayesian methods for complex data structures, with applications to precision medicine in women’s healthcare

This thesis explores novel Bayesian non-parametric regression techniques for data with complex structures, developed in response to challenges in women's health and obstetrics. Nearly all pregnancy-related research shares a key statistical issue: that most outcomes vary smoothly with gestational age. Models which reflect this smoothness aid in interpretability by aligning model choices with clinical knowledge; from a statistical perspective, smoothing can reduce variance without inflating bias. Existing models tend to smooth over all covariates, or require specification of parametric forms and interactions based on a priori knowledge of maternal and fetal covariates. Current literature does not provide an especially nuanced characterization of these functional forms. Chapter 1 frames these issues in the context of current statistical modeling practices in women's health and obstetrics. Chapter 2 introduces a model for estimating patient-specific stillbirth risk over the course of gestation, with the aim to help obstetricians prevent fetal mortality. In this chapter, we introduce BART with Targeted Smoothing (tsBART), a nonparametric regression model which extends the Bayesian Additive Regression Trees (BART) prior to introduce smoothness over a single target covariate t. TsBART extends BART by parameterizing each tree's terminal nodes with smooth functions of t, rather than independent scalars. Both BART and tsBART capture complex nonlinear relationships and interactions among the predictors, but tsBART guarantees that the response surface is smooth in the target covariate. This improves interpretability and helps regularize the estimate. After introducing and benchmarking the tsBART model, we apply it to pregnancy outcomes data from the National Center for Health Statistics. Our aim is to provide patient-specific estimates of stillbirth risk across gestational age (t), based on maternal and fetal risk factors (x). The results of our analysis show the clear superiority of the tsBART model for quantifying stillbirth risk, thereby providing patients and doctors with better information for managing the risk of fetal mortality. Chapter 3 extends these ideas into the causal inference setting to analyze a new clinical protocol for early medical abortion. We introduce Targeted Smooth Bayesian Causal Forests (tsBCF), a nonparametric Bayesian approach for estimating heterogeneous treatment effects which vary smoothly over a single covariate in the observational data setting. The tsBCF method also induces smoothness by parameterizing terminal tree nodes with smooth functions, and allows for separate regularization of treatment effects versus prognostic effect of control covariates. Smoothing parameters for prognostic and treatment effects can be chosen to reflect prior knowledge or tuned in a data-dependent way. Our aim is to assess the relative effectiveness of simultaneous versus interval administration of mifepristone and misoprostol over the first nine weeks of gestation. The model reflects our expectation that the relative effectiveness varies smoothly over gestation, but not necessarily over other covariates. We demonstrate the performance of the tsBCF method on benchmarking experiments. In Chapter 4, we aim to characterize the relationship between birth weight and maternal pre-eclampsia across gestation at a large maternity hospital in urban Uganda. Key scientific questions we investigate include: 1) how pre-eclampsia compares to other maternal-fetal covariates as a predictor of birth weight; and 2) whether the impact of pre-eclampsia on birthweight varies across gestation. We propose a nonparametric regression model called Projective Smooth BART (psBART), which addresses several key statistical challenges. First, our model correctly encodes the prior medical knowledge that birth weight should vary smoothly and monotonically with gestational age. It also avoids assumptions about functional forms and about how birth weight varies with other covariates. Finally, psBART accounts for the fact that a high proportion (83%) of birth weights in our dataset are rounded to the nearest 100 grams. Such extreme data coarsening is rare in maternity hospitals in high resource obstetrics settings but common for data sets collected in low and middle-income countries (LMICs); this introduces a substantial extra layer of uncertainty into the problem and is a major reason why we adopt a Bayesian approach. The results of our analysis show that pre-eclampsia is a dominant predictor of birth weight in this urban Ugandan setting and is therefore an important risk factor for perinatal mortality. Chapter 5 summarizes our contributions and describes directions for future research.Statistic

Correspondence

Presents letters to the editor referencing articles and topics discussed in previous issues. "Let Them Eat Stocks," which suggested that laid-off workers be given stock options in lieu of severance pay in the U.S.; "Huddled Excesses," which argued that immigration restriction laid the groundwork for labor's gains in 1920 to 1960 in the U.S.; "Econ 2," which offered views on the issue of minimum wage increase

Evaluating Digital Humanities Projects: Collaborative Course Assessment

Curatorial note from Digital Pedagogy in the Humanities: This assignment includes multiple measures, collaboration, integration of concepts outside the classroom, and modeling professional expectations. Students evaluate digital humanities projects and use digital markup tools to learn how to collaboratively evaluate and respond to digital work. This is an example of learning by doing: the form and content of the assignment and the assessment work together seamlessly. Students are assessed on how they mark up the digital work, how they work in a group collaboratively, and how they respond to digital work. The task models how they will be evaluated, and it is a precursor to how students will use technology in professional environments. The assessment design mimics professional work life, allowing students to perform and be evaluated in a more realistic context with professional stakes

Characterising timing and pattern of relapse following surgery for localised oesophagogastric adenocarcinoma: a retrospective study

Background: Oesophagogastric adenocarcinoma (OGA) has a poor prognosis, even for patients with operable disease. However, the optimal surveillance strategy following surgery is unknown. Methods: We performed a retrospective review of all patients with OGA who had undergone surgery with radical intent at the Royal Marsden between January 2001 and December 2010. Results: Of the 360 patients with OGA who underwent potentially curative surgery, 100/214 patients (47 %) with oesophageal/gastro-oesophageal junction (GOJ) adenocarcinoma and 47/146 patients (32 %) with gastric adenocarcinoma developed recurrent disease. 51, 79 and 92 % of relapses occurred within 1, 2 and 3 years respectively and the majority of patients relapsed at distant sites. Of the patients who relapsed, 67 % (67/100) with oesophageal/GOJ adenocarcinoma and 72 % of patients with gastric cancer (34/47) were symptomatic at the time of relapse. The majority of asymptomatic relapses were first detected by a rise in tumour markers. There was no difference in disease-free survival between asymptomatic and symptomatic patients, but asymptomatic patients were more likely to receive further treatment and had a longer survival beyond relapse. Conclusion: The majority of relapses occur within the first 3 years and at distant sites. Monitoring of tumour markers should be considered as part of a surveillance program

Perfil clínico-epidemiológico de pacientes com hanseníase atendidos em hospital universitário no Rio de Janeiro entre 2008 e 2017

Modelo do estudo: Estudo observacional, longitudinal, retrospectivo e descritivo de uma coorte de pacientes. Objetivo: Descrever o perfil clínico e epidemiológico dos pacientes com diagnóstico de hanseníase, atendidos em um centro de referência no estado do Rio de Janeiro. Metodologia: Foram incluídos todos os pacientes com diagnóstico de hanseníase atendidos no Hospital Universitário Gaffrée e Guinle entre os anos de 2008 a 2017. Os dados foram coletados através da revisão de prontuários e analisados através de estatística descritiva, utilizando-se o software SPSS 22.0 database . Resultados: Um total de 112 pacientes foi incluído no estudo, sendo que 54,5% eram do sexo masculino. A média de idade foi de 49,9 anos, 62,4% eram moradores do município do Rio de Janeiro e 69,9% apresentaram formas clínicas multibacilares da hanseníase. Foi possível avaliar o grau de incapacidade inicial de 36 (32,1%) dos pacientes incluídos. Desses, 25% apresentaram grau de incapacidade inicial II. Durante o tratamento poliquimioterápico, 21 (18,8%) pacientes apresentaram algum efeito colateral, sendo o mais comum a anemia relacionada à dapsona. Cinquenta e nove (52,7%) pacientes apresentaram algum tipo de estado reacional da hanseníase e 10 (8,9%) apresentaram complicações sistêmicas graves durante o acompanhamento. Conclusões: O presente estudo evidenciou um perfil clínico-epidemiológico diferente do descrito na literatura, com uma grande porcentagem de pacientes com grau de incapacidade inicial II, uma alta frequência de estados reacionais e de complicações advindas do curso clínico da doença ou dos tratamentos implementados.Introduction: This was an observational, longitudinal, retrospective and descriptive study of a cohort of patients. Objectives: To describe the clinical and epidemiological profile of the patients diagnosed with leprosy admitted to a reference medical center in the State of Rio de Janeiro. Methods: All leprosy patients admitted to the dermatology clinic from the Hospital Universitário Gaffrée and Guinle between 2008 and 2017 were included. Pertinent patients’ data were collected through medical charts review. Data were then analyzed through descriptive statistics using SPSS 22.0  software.  Results: a total of 112 patients were included in the study. Among them, 54.5% were male, the median age was 49.9 years old, 62.4% were residents in the city of Rio de Janeiro and 69.9% presented multibacillary leprosy clinical forms. We evaluated the initial disability grade of 36 from the 112 included patients,  and out of them,  25% had grade II disability. During multidrug therapy, 21 (18.8%) patients presented an adverse effect, which is the most common anemia related to Dapsone. Fifty-nine (52.7%) patients presented leprosy reaction and 10 (8.9%) patients presented severe systemic complications during the follow-up. Conclusions: In the present study, it was observed a distinctive clinical and epidemiological leprosy profile. There was a high frequency of grade II initial disability, leprosy reaction and severe clinical complications due to the progression of the disease or as adverse effects of leprosy treatment

LC-MS and NMR Based Structural Characterization and Isotopic Abundance Ratio Analysis of Magnesium Gluconate Treated with the Consciousness Energy Healing

Magnesium gluconate is widely used pharmaceutical/nutraceutical compound for the prevention and treatment of magnesium deficiency diseases. The present study was designed to explore the effect of The Trivedi Effect® - Energy of Consciousness Healing Treatment (Biofield Energy Healing Treatment) on magnesium gluconate for the change in the structural properties and isotopic abundance ratio (PM+1/PM and PM+2/PM) using LC-MS and NMR spectroscopy. Magnesium gluconate was divided into two parts – one part was control, and another part was treated with The Trivedi Effect® - Energy of Consciousness Healing Treatment remotely by twenty renowned Biofield Energy Healers and defined as The Trivedi Effect® treated sample. The LC-MS analysis of both the control and Biofield Energy Treated samples indicated the presence of mass of the protonated magnesium gluconate at m/z 415 at the retention time of 1.52 min and fragmentation pattern of both samples were almost identical. The relative peak intensities of the fragment ions were significantly altered in the treated sample compared to the control sample. The proton and carbon signals for CH, CH2 and CO groups in the proton and carbon NMR spectra of the control and treated samples were found same. The percentage change in the isotopic abundance ratio of PM+1/PM (2H/1H or 13C/12C or 17O/16O or 25Mg/24Mg) was significantly decreased in the treated sample by 48.87% compared to the control sample. Subsequently, the isotopic abundance ratio of PM+2/PM (18O/16O or 26Mg/24Mg) in the treated sample was significantly increased by 29.18% compared with the control sample. In summary, 13C, 2H, 17O, and 25Mg contributions from (C12H23MgO14)+ to m/z 416; 18O and 26Mg contributions from (C12H23MgO14)+ to m/z 417 in the treated sample were significantly altered compared with the control sample. Thus, The Trivedi Effect® Treated magnesium gluconate might be helpful to design the novel potent enzyme inhibitors using its kinetic isotope effects. Consequently, The Trivedi Effect® Treated magnesium gluconate would be valuable for designing better pharmaceutical and/or nutraceutical formulations through its altered physicochemical and thermal properties, which might be providing better therapeutic response against various diseases such as diabetes mellitus, allergy, aging, inflammatory diseases, immunological disorders, and other chronic infections. https://www.trivedieffect.com/science/lc-ms-and-nmr-based-structural-characterization-and-isotopic-abundance-ratio-analysis-of-magnesium-gluconate-treated-with-the-consciousness-energy-healing http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=216&paperId=1002165

Evaluation of the Physicochemical, Spectral, Thermal and Behavioral Properties of Sodium Selenate: Influence of the Energy of Consciousness Healing Treatment

Sodium selenate is an inorganic nutraceutical/pharmaceutical compound used for the prevention and treatment of several diseases. The current research article was aimed to explore the effect of The Trivedi Effect® - Energy of Consciousness Healing Treatment on the physicochemical, spectral, thermal, and behavioral properties of sodium selenate using PXRD, PSD, FT-IR, UV-vis, TGA, and DSC analysis. Sodium selenate was divided into two parts – one part was control, while another part was The Trivedi Effect® Treated sample which was received The Trivedi Effect® remotely by twenty renowned Biofield Energy Healers. A significant alteration of the crystallite size of the treated sample was observed in the range of -42.87% to 39.99% compared to the control sample. Consequently, the average crystallite size was significantly enhanced in the treated sample by 5.07% compared with the control sample. The particle size distribution of the treated sample at d10, d50, and d90 values were significantly reduced by 7.68%, 9.49%, and 4.08%, respectively compared with the control sample. Subsequently, the surface area of the treated sample was significantly increased by 8.16% compared with the control sample. The control and treated FT-IR spectra exhibited the sharp and strong vibration bands at 889 cm-1 and 888 cm-1, respectively for Se=O stretching. The control and treated samples displayed the maximum absorbance at 204.9 nm and 204.5 nm, respectively. A significant reduction of total weight loss by 6.11% in the treated sample indicated the improvement of the thermal stability of the treated sample compared with the control sample. The vaporization temperature of the treated sample (95.68°C) was higher with a significant reduced latent heat of vaporization by 60.80% compared to the control sample (95.29°C). Thus, The Trivedi Effect® - Energy of Consciousness Healing Treatment might produce a new polymorphic form of sodium selenate which would be more soluble, dissolution rate, bioavailable, and thermally stable compared with the untreated sample. The Trivedi Effect® treated sodium selenate would be very suitable to design improved nutraceutical and pharmaceutical formulations that might provide better therapeutic response against several diseases such as stress, aging, inflammatory diseases, immunological disorders, infectious diseases, cancer, etc. Source: https://www.trivedieffect.com/science/evaluation-of-the-physicochemical-spectral-thermal-and-behavioral-properties-of-sodium-selenate-influence-of-the-energy-of-consciousness-healing-treatment http://www.sciencepublishinggroup.com/journal/paperinfo?journalid=398&doi=10.11648/j.ajqcms.20170101.1

EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers.

Funder: FP7 People: Marie-Curie Actions; FundRef: http://dx.doi.org/10.13039/100011264; Grant(s): CIG 334261OBJECTIVE: Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome and EGFR copy number (CN) in pretreatment tissue and plasma cell-free DNA (cfDNA) of patients enrolled in a randomised first-line phase III clinical trial of chemotherapy or chemotherapy plus the anti-EGFR monoclonal antibody panitumumab in aGEA (NCT00824785). DESIGN: EGFR CN by either fluorescence in situ hybridisation (n=114) or digital-droplet PCR in tissues (n=250) and plasma cfDNAs (n=354) was available for 474 (86%) patients in the intention-to-treat (ITT) population. Tissue and plasma low-pass whole-genome sequencing was used to screen for coamplifications in receptor tyrosine kinases. Interaction between chemotherapy and EGFR inhibitors was modelled in patient-derived organoids (PDOs) from aGEA patients. RESULTS: EGFR amplification in cfDNA correlated with poor survival in the ITT population and similar trends were observed when the analysis was conducted in tissue and plasma by treatment arm. EGFR inhibition in combination with chemotherapy did not correlate with improved survival, even in patients with significant EGFR CN gains. Addition of anti-EGFR inhibitors to the chemotherapy agent epirubicin in PDOs, resulted in a paradoxical increase in viability and accelerated progression through the cell cycle, associated with p21 and cyclin B1 downregulation and cyclin E1 upregulation, selectively in organoids from EGFR-amplified aGEA. CONCLUSION: EGFR CN can be accurately measured in tissue and liquid biopsies and may be used for the selection of aGEA patients. EGFR inhibitors may antagonise the antitumour effect of anthracyclines with important implications for the design of future combinatorial trials