Spinal or general anaesthesia for surgical repair of hip fracture and subsequent risk of mortality and morbidity: a database analysis using propensity score‐matching

Around 76,000 people fracture their hip annually in the UK at a considerable personal, social and financial cost. Despite longstanding debate, the optimal mode of anaesthesia (general or spinal) remains unclear. Our aim was to assess whether there is a significant difference in mortality and morbidity between patients undergoing spinal anaesthesia compared with general anaesthesia during hip fracture surgery. A secondary analysis examined whether a difference exists in mortality for patients with pre‐existing cardiovascular disease or chronic obstructive pulmonary disease. This was a clinical database analysis of patients treated for hip fracture in Nottingham, UK between 2004 and 2015. Propensity score‐matching was used to generate matched pairs of patients, one of whom underwent each mode of anaesthesia. Data were analysed using conditional logistic regression, with 7164 patients successfully matched. There was no difference in 30‐ or 90‐day mortality in patients who had spinal rather than general anaesthesia (OR [95%CI] 0.97 [0.8–1.15]; p = 0.764 and 0.93 [0.82–1.05]; p = 0.247 respectively). Patients who had a spinal anaesthetic had a lower‐risk of blood transfusion (OR [95%CI] 0.84 [0.75–0.94]; p = 0.003) and urinary tract infection (OR [95%CI] 0.72 [0.61–0.84]; p [less than] 0.001), but were more likely to develop a chest infection (OR [95%CI] 1.23 [1.07–1.42]; p = 0.004), deep vein thrombosis (OR [95%CI] 2.18 [1.07–4.45]; p = 0.032) or pulmonary embolism (OR [95%CI] 2.23 [1.16–4.29]; p = 0.016). The mode of anaesthesia for hip fracture surgery resulted in no significant difference in mortality, but there was a significant difference in several measures of postoperative morbidity

Nitric oxide sensing in plants is mediated by proteolytic control of group VII ERF transcription factors

Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants

Evidence for alterations in fixational eye movements in glaucoma

BACKGROUND: Fixation changes in glaucoma are generally overlooked, as they are not strikingly evident as in macular diseases. Fundus perimetry might give additional insights into this aspect, along with traditional perimetric measures. In this work we propose a novel method to quantify glaucomatous changes in fixation features as detected by fundus perimetry and relate them to the extent of glaucomatous damage. METHODS: We retrospectively analysed fixation data from 320 people (200 normal subjects and 120 with glaucoma) from the Preferred Retinal Locus (PRL) detection of a Compass perimeter. Fixation stability was measured as Bivariate Contour Ellipse Area (BCEA), and using two novel metrics: (1) Mean Euclidean Distance (MED) from the Preferred Retinal Locus, and (2) Sequential Euclidean Distance (SED) of sequential fixation locations. These measures were designed to capture the spread of fixation points, and the frequency of position changes during fixation, respectively. RESULTS: In the age corrected analysis, SED was significantly greater in glaucomatous subjects than controls (P = 0.002), but there was no difference in BCEA (P = 0.15) or MED (P = 0.054). Similarly, SED showed a significant association with Mean Deviation (P  0.14 for both). CONCLUSION: Changes in the scanning pattern detected by SED are better than traditional measures of fixation spread (BCEA) for describing the changes in fixation stability observed in glaucoma

Operational experience with the GEM detector assembly lines for the CMS forward muon upgrade

The CMS Collaboration has been developing large-area triple-gas electron multiplier (GEM) detectors to be installed in the muon Endcap regions of the CMS experiment in 2019 to maintain forward muon trigger and tracking performance at the High-Luminosity upgrade of the Large Hadron Collider (LHC); 10 preproduction detectors were built at CERN to commission the first assembly line and the quality controls (QCs). These were installed in the CMS detector in early 2017 and participated in the 2017 LHC run. The collaboration has prepared several additional assembly and QC lines for distributed mass production of 160 GEM detectors at various sites worldwide. In 2017, these additional production sites have optimized construction techniques and QC procedures and validated them against common specifications by constructing additional preproduction detectors. Using the specific experience from one production site as an example, we discuss how the QCs make use of independent hardware and trained personnel to ensure fast and reliable production. Preliminary results on the construction status of CMS GEM detectors are presented with details of the assembly sites involvement

Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition

Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumor-cell-intrinsic and microenvironmental features underpinning CPI sensitization. Here, we collated whole-exome and transcriptomic data for >1,000 CPI-treated patients across seven tumor types, utilizing standardized bioinformatics workflows and clinical outcome criteria to validate multivariable predictors of CPI sensitization. Clonal tumor mutation burden (TMB) was the strongest predictor of CPI response, followed by total TMB and CXCL9 expression. Subclonal TMB, somatic copy alteration burden, and histocompatibility leukocyte antigen (HLA) evolutionary divergence failed to attain pan-cancer significance. Dinucleotide variants were identified as a source of immunogenic epitopes associated with radical amino acid substitutions and enhanced peptide hydrophobicity/immunogenicity. Copy-number analysis revealed two additional determinants of CPI outcome supported by prior functional evidence: 9q34 (TRAF2) loss associated with response and CCND1 amplification associated with resistance. Finally, single-cell RNA sequencing (RNA-seq) of clonal neoantigen-reactive CD8 tumor-infiltrating lymphocytes (TILs), combined with bulk RNA-seq analysis of CPI-responding tumors, identified CCR5 and CXCL13 as T-cell-intrinsic markers of CPI sensitivity

Atividade física, qualidade de vida e depressão durante a gravidez

This study examines physical activity patterns among women, from pre-pregnancy to the second trimester of pregnancy, and the relationship between physical activity status based on physical activity guidelines and health-related quality of life (HRQoL) and depression over pregnancy. 56 healthy pregnant women self reported physical activity, HRQoL and depression at 10-15 and 19-24 weeks of pregnancy and physical activity before pregnancy. Whereas vigorous leisure physical activity decreased after conception, moderate leisure physical activity and work related physical activity remained stable over time. The prevalence of recommended physical activity was 39.3% and 12.5% in the 1st and 2nd trimesters of pregnancy respectively, and 14.3% pre-pregnancy. From the 1st to the 2nd pregnancy trimester, most physical HRQoL dimensions scores decreased and only mental component increased, independently of physical activity status. No changes in mean depression scores were observed. These data suggest that physical activity patterns change with pregnancy and that physical and mental components are differentially affected by pregnancy course, independently of physical activity status.Este estudo examina os padrões de atividade física antes da concepção até o segundo trimestre de gravidez e a relação entre o nível de atividade física, com base nas recomendações de atividade física, a qualidade de vida relacionada à saúde (QVRS) e depressão ao longo da gravidez. Cinquenta e seis grávidas saudáveis reportaram nível de atividade física, QVRS e depressão às 10-15 e 19-24 semanas de gravidez, além de atividade física antes da concepção. Enquanto a atividade física vigorosa no lazer diminuiu depois da concepção, as atividades físicas moderadas no lazer e no trabalho mantiveram-se estáveis. A prevalência de atividade fí- sica recomendada foi de 39,3%, 12,5% e 14,3% antes, no primeiro e no segundo trimestres de gravidez, respectivamente. Independentemente do estatuto de atividade física, a maior parte dos escores nas dimensões físicas da QVRS diminui do primeiro para o segundo trimestre de gestação, e apenas o componente mental aumenta. Não se verificaram alterações nos escores médios de depressão. Estes dados sugerem que, com a gravidez, há alteração nos padrões de atividade física; além disso, os componentes físico e mental são diferentemente afetados pelo curso da gestação, independentemente do nível de atividade física

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.