Isothermal annealing of radiation defects in bulk material of diodes from 8" silicon wafers

The high luminosity upgrade of the LHC will provide unique physics opportunities, such as the observation of rare processes and precision measurements. However, the accompanying harsh radiation environment will also pose unprecedented challenged to the detector performance and hardware. In this paper, we study the radiation induced damage and its macroscopic isothermal annealing behaviour of the bulk material from new 8" silicon wafers using diode test structures. The sensor properties are determined through measurements of the diode capacitance and leakage current for three thicknesses, two material types, and neutron fluences from $6.5\cdot 10^{14}$ to $10^{16}\,\mathrm{neq/cm^2}$.Comment: 15 pages, 11 Figure

Isothermal annealing of radiation defects in silicon bulk material of diodes from 8” silicon wafers

The high luminosity upgrade of the LHC will provide unique physics opportunities, such as the observation of rare processes and precision measurements. However, the accompanying harsh radiation environment will also pose unprecedented challenged to the detector performance and hardware. In this paper, we study the radiation induced damage and its macroscopic isothermal annealing behaviour of the bulk material from new 8" silicon wafers using diode test structures. The sensor properties are determined through measurements of the diode capacitance and leakage current for three thicknesses, two material types, and neutron fluences from 6.5 · 10$^{14}$ to 1 · 10$^{16}$ n$_{eq}$/cm$^2$

Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung Cancer

In recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC

The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells

Interleukin (IL) 6 is a proinflammtory cytokine produced by antigen-presenting cells and nonhematopoietic cells in response to external stimuli. It was initially identified as a B cell growth factor and inducer of plasma cell differentiation in vitro and plays an important role in antibody production and class switching in vivo. However, it is not clear whether IL-6 directly affects B cells or acts through other mechanisms. We show that IL-6 is sufficient and necessary to induce IL-21 production by naive and memory CD4+ T cells upon T cell receptor stimulation. IL-21 production by CD4+ T cells is required for IL-6 to promote B cell antibody production in vitro. Moreover, administration of IL-6 with inactive influenza virus enhances virus-specific antibody production, and importantly, this effect is dependent on IL-21. Thus, IL-6 promotes antibody production by promoting the B cell helper capabilities of CD4+ T cells through increased IL-21 production. IL-6 could therefore be a potential coadjuvant to enhance humoral immunity

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

Socio-economic inequalities in body mass index among preschool children: do sports programs in early childhood education and care centers make a difference?

BackgroundOverweight in childhood is considered to be one of the most serious public health challenges. Many studies have investigated individual-level determinants of children's body mass index (BMI), yet studies exploring determinants at the meso-level are sparse. The aim of our study was to examine how a sports focus at early childhood education and care (ECEC) centers moderates the effect of parental socio-economic position (SEP) on children's BMI.MethodsWe used data from the German National Educational Panel Study and included 1,891 children (955 boys and 936 girls) from 224 ECEC centers in our analysis. Linear multilevel regressions were used to estimate the main effects of family SEP and the ECEC center sports focus, as well as their interaction, on children's BMI. All analyses were stratified by sex and adjusted for age, migration background, number of siblings, and employment status of parents.ResultsOur analysis confirmed the wellknown health inequalities in childhood overweight with a social gradient toward a higher BMI for children from lower SEP families. An interactive effect between family SEP and ECEC center sports focus was found. Boys with low family SEP not attending a sports-focused ECEC center had the highest BMI among all boys. In contrast, boys with low family SEP attending a sports-focused ECEC center had the lowest BMI. For girls, no association regarding ECEC center focus or interactive effects emerged. Girls with a high SEP had the lowest BMI, independent of the ECEC center focus.ConclusionWe provided evidence for the gender-specific relevance of sports-focused ECEC centers for the prevention of overweight. Especially boys from low SEP families benefited from a sports focus, whereas for girls the family's SEP was more relevant. As a consequence, gender differences in determinants for BMI at different levels and their interaction should be considered in further research and preventive measures. Our research indicates that ECEC centers may decrease health inequalities by providing opportunities for physical activity

Two Lensed Lyman-alpha Emitting Galaxies at z~5

We present observations of two strongly lensed $z\sim5$ Lyman-$\alpha$ Emitting (LAE) galaxies that were discovered in the Sloan Giant Arcs Survey (SGAS). We identify the two sources as SGAS J091541+382655, at $z=5.200$, and SGAS J134331+415455 at $z=4.994$. We measure their AB magnitudes at $(i,z)=(23.34\pm0.09,23.29\pm0.13$) mags and $(i,z)=(23.78\pm0.18,24.24^{+0.18}_{-0.16}$) mags, and the rest-frame equivalent widths of the Lyman-$\alpha$ emission at $25.3\pm4.1$\AA~and $135.6\pm20.3$\AA~for SGAS J091541+382655 and SGAS J134331+415455, respectively. Each source is strongly lensed by a massive galaxy cluster in the foreground, and the magnifications due to gravitational lensing are recovered from strong lens modeling of the foreground lensing potentials. We use the magnification to calculate the intrinsic, unlensed Lyman-$\alpha$ and UV continuum luminosities for both sources, as well as the implied star formation rates (SFR). We find SGAS J091541+382655 and SGAS J134341+415455 to be galaxies with (L$_{Ly-\alpha}$, L$_{UV})\leq(0.6$L$_{Ly-\alpha}^{*}, 2$L$_{UV}^{*}$) and (L$_{Ly-\alpha}$, L$_{UV})=(0.5$L$_{Ly-\alpha}^{*}, 0.9$L$_{UV}^{*}$), respectively. Comparison of the spectral energy distributions (SEDs) of both sources against stellar population models produces estimates of the mass in young stars in each galaxy: we report an upper limit of M$_{stars} \leq 7.9^{+3.7}_{-2.5} \times 10^{7}$ M_{\sun} h_{0.7}^{-1} for SGAS J091531+382655, and a range of viable masses for SGAS J134331+415455 of $2\times10^{8}$ M_{\sun} h_{0.7}^{-1} < M$_{stars} < 6\times10^{9}$ M_{\sun} h_{0.7}^{-1}.Comment: 10 pages, 8 figures, emulate apj format, Accepted to Ap

No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

We evaluated the genetic contribution of the T cell-erestricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated

Power and rights in the community: paralegals as leaders in women's legal empowerment in Tanzania

What can an analysis of power in local communities contribute to debates on women’s legal empowerment and the role of paralegals in Africa? Drawing upon theories of power and rights, and research on legal empowerment in African plural legal systems, this article explores the challenges for paralegals in facilitating women’s access to justice in Tanzania, which gave statutory recognition to paralegals in the Legal Aid Act 2017. Land conflicts represent the single-biggest source of local legal disputes in Tanzania and are often embedded in gendered land tenure relations. This article argues that paralegals can be effective actors in women’s legal empowerment where they are able to work as leaders, negotiating power relations and resisting the forms of violence that women encounter as obstacles to justice. Paralegals’ authority will be realised when their role is situated within community leadership structures, confirming their authority while preserving their independence