Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Dark matter lighter than 10  GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10  MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies

Quantificação de fatores de crescimento na pele de equinos tratada com plasma rico em plaquetas

O plasma rico em plaquetas (PRP) é um produto derivado da centrifugação do sangue total, sendo rico em fatores bioativos, como os de crescimento. Apesar da ampla utilização em processos cicatriciais, há controvérsia sobre a eficácia da terapia na cicatrização cutânea. O objetivo desse estudo foi quantificar e comparar a concentração dos fatores TGF-β1 e PDGF-BB no PRP, plasma sanguíneo e pele, durante diferentes fases do processo de cicatrização da pele tratada ou não com PRP. Foram utilizados sete equinos machos castrados, mestiços, hígidos, com idade entre 16 e 17 (16,14±0,63) anos. Três lesões em formato quadrangular (6,25cm²) foram produzidas cirurgicamente nas regiões glúteas direita e esquerda de todos os animais. Doze horas após indução das feridas, 0,5mL do PRP foi administrado em cada uma das quatro extremidades das feridas de uma das regiões glúteas (Grupo tratado = GT), escolhida aleatoriamente. A região contralateral foi utilizada como controle (GC). As feridas foram submetidas à limpeza diária com água Milli Q, e amostras foram obtidas mediante biópsias realizadas com Punch de 6mm. Foram obtidas seis biópsias de pele, sendo a primeira realizada logo após a produção da ferida (T0), e as demais com 1 (T1) 2 (T2) 7 (T3) e 14 (T4) dias após a indução da lesão. A sexta biópsia (T5) foi obtida após completo fechamento da pele, que ocorreu aproximadamente aos 37 dias (36,85±7,45, GC; 38,85±6,46, GT). Também foram obtidas amostras de sangue com EDTA em todos os tempos mencionados. A quantificação dos fatores de crescimento TGF-β1 e PDGF-BB na pele, PRP e plasma sanguíneo foi realizada pela técnica ELISA. Os dados foram analisados estatisticamente pelo teste t, correlação de Pearson e regressão, utilizando nível de significância de 5%. Não houve diferença entre os grupos, nos valores dos dois fatores de crescimento mensurados na pele, nos diferentes tempos. Também não houve correlação entre a quantidade dos fatores de crescimento presentes na pele e no plasma. Por outro lado, correlação positiva foi observada entre PRP e pele no grupo tratado, para os fatores de crescimento TGF-β1 (r=0,31) e PDGF-BB (r=0,38), bem como entre ambos os fatores de crescimento presentes no PRP (r=0,81). Considerando as concentrações dos fatores de crescimento no T0, os maiores valores cutâneos (p<0,05) do TGF-β1, em ambos os grupos, ocorreram nos tempos T3 e T5. Valores mais elevados (p<0,05) do PDGF-BB ocorreram no T4 (GT) e T5 (GC). No plasma não houve alteração nas concentrações desses fatores em relação ao T0, o que sugere que o PRP não acarreta efeito sistêmico, quando os procedimentos adotados na presente pesquisa são utilizados. A administração local de PRP no volume estudado, 12 h após indução cirúrgica de ferida cutânea na região glútea de equinos não ocasiona maiores concentrações dos fatores de crescimento TGF-β1 e PDGF-BB no plasma sanguíneo e pele, durante o processo de cicatrização

Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis

Background: We published a meta-analysis of the association between work as a motor vehicle mechanic and mesothelioma in 2004. Since then, several relevant studies on this topic have been published. Thus, to update the state-of-the-science on this issue, we conducted a new systematic review and meta-analysis. Methods: A comprehensive PubMed literature search through May 2014 was conducted to identify studies that reported relative risk estimates for mesothelioma among motor vehicle mechanics (in general), and those who were engaged in brake repair (specifically). Studies were scored and classified based on study characteristics. Random-effects meta-analyses generated summary relative risk estimates (SRREs) and corresponding 95% confidence intervals (CI). Heterogeneity of results was examined by calculating Q-test P-values (P-H) and I 2 estimates. Sub-group and sensitivity analyses were conducted for relevant study characteristics and quality measures. Results: Ten case-control studies, one cohort study, and five proportionate mortality ratio (PMR)/standardized mortality odds ratio (SMOR) studies were identified and included in the quantitative assessment. Most meta-analysis models produced SRREs below 1.0, and no statistically significant increases in mesothelioma were observed. The SRRE for all studies was 0.80 (95% CI: 0.61-1.05) with significant heterogeneity (P-H <0.001, I 2 = 62.90). A similar SRRE was observed among the five Tier 1 studies with the highest quality ratings (SRRE = 0.76, 95% CI: 0.46-1.25), with no heterogeneity among studies (P-H = 0.912, I 2 = 0.00). Meta-analysis of the Tier 2 (n = 5) and Tier 3 (n = 6) studies resulted in SRREs of 1.09 (95% CI: 0.76-1.58) and 0.73 (95% CI: 0.49-1.08), respectively. Restricting the analysis to Tiers 1 and 2 combined resulted in an SRRE of 0.92 (95% CI: 0.72-1.29). The SRRE specific to brake work (n = 4) was 0.64 (95% CI: 0.38-1.09). Conclusions: This meta-analysis of the epidemiologic studies provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma. \ua9 2015 The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society

Response to Kay Teschke. Re: Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis

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Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8⁺ T cells.

Tissue-resident memory CD8+ T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector. We found that CD8+ T cells of different specificities underwent antigen-dependent competition in the infected tissue, which shaped the composition of the local pool of TRM cells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, TRM cell development remained largely undisturbed by the presence of potential competitors when antigens expressed in the same tissue were segregated through infection with antigenically distinct viral quasispecies. Functionally, local cross-competition might serve as a gatekeeping mechanism to regulate access to the resident memory niche and to fine-tune the local repertoire of antiviral TRM cells

Predicition models for delayed graft function : External validation on the Dutch Prospective Renal Transplantation Registry

Background. Delayed graft function (DGF) is a common complication after kidney transplantation in the era of accepting an equal number of brain-and circulatory-death donor kidneys in the Netherlands. To identify those cases with an increased risk of developing DGF, various multivariable algorithms have been proposed. The objective was to validate the reproducibility of four predictive algorithms by Irish et al. (A risk prediction model for delayed graft function in the current era of deceased donor renal transplantation. Am J Transplant 2010;10:2279-2286) (USA), Jeldres et al. (Prediction of delayed graft function after renal transplantation. Can Urol Assoc J 2009;3:377-382) (Canada), Chapal et al. (A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors. Kidney Int 2014;86:1130-1139) (France) and Zaza et al. (Predictive model for delayed graft function based on easily available pre-renal transplant variables. Intern Emerg Med 2015;10:135-141) (Italy) according to a novel framework for external validation. Methods. We conducted a prospective observational study with data from the Dutch Organ Transplantation Registry (NOTR). Renal transplant recipients from all eight Dutch academic medical centers between 2002 and 2012 who received a deceased allograft were included (N= 3333). The four prediction algorithms were reconstructed from donor, recipient and transplantation data. Their predictive value for DGF was validated by cstatistics, calibration statistics and net benefit analysis. Casemix (un)relatedness was investigated with a membership model and mean and standard deviation of the linear predictor. Results. The prevalence of DGF was 37%. Despite a significantly different case-mix, the US algorithm by Irish was best reproducible, with a c-index of 0.761 (range 0.756-0.762), and well-calibrated over the complete range of predicted probabilities of having DGF. The US model had a net benefit of 0.242 at a threshold probability of 0.25, compared with 0.089 net benefit for the same threshold in the original study, equivalent to correctly identifying DGF in 24 cases per 100 patients (true positive results) without an increase in the number of false-positive results. Conclusions. The US model by Irish et al. was generalizable and best transportable to Dutch recipients with a deceased donor kidney. The algorithm detects an increased risk of DGF after allocation and enables us to improve individual patient management