Quantifying the Thermal Fatigue of CPV Modules

A method is presented to quantify thermal fatigue in the CPV die-attach from meteorological data. A comparative study between cities demonstrates a significant difference in the accumulated damage. These differences are most sensitive to the number of larger (ΔT) thermal cycles experienced for a location. High frequency data (\u3c1/min) may be required to most accurately employ this method

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

On the Effect of Ramp Rate in Damage Accumulation of the CPV Die-Attach Preprint On The Effect of Ramp Rate in Damage Accumulation of the CPV Die-Attach

Abstract-It is commonly understood that thermal cycling at high temperature ramp rates may activate unrepresentative failure mechanisms. Increasing the temperature ramp rate of thermal cycling, however, could dramatically reduce the test time required to achieve an equivalent amount of thermal fatigue damage, thereby reducing overall test time. Therefore, the effect of temperature ramp rate on physical damage in the CPV die-attach is investigated. Finite Element Model (FEM) simulations of thermal fatigue and thermal cycling experiments are made to determine if the amount of damage calculated results in a corresponding amount of physical damage measured to the die-attach for a variety of fast temperature ramp rates. Preliminary experimental results are in good agreement with simulations and reinforce the potential of increasing temperature ramp rates. Characterization of the microstructure and resulting fatigue crack in the die-attach suggest a similar failure mechanism across all ramp rates tested

Equality in maternal and newborn health: modelling geographic disparities in utilisation of care in five East African countries

Background: Geographic accessibility to health facilities represents a fundamental barrier to utilisation of maternal and newborn health (MNH) services, driving historically hidden spatial pockets of localized inequalities. Here, we examine utilisation of MNH care as an emergent property of accessibility, highlighting high-resolution spatial heterogeneity and sub-national inequalities in receiving care before, during, and after delivery throughout five East African countries.Methods: We calculated a geographic inaccessibility score to the nearest health facility at 300 x 300 m using a dataset of 9,314 facilities throughout Burundi, Kenya, Rwanda, Tanzania and Uganda. Using Demographic and Health Surveys data, we utilised hierarchical mixed effects logistic regression to examine the odds of: 1) skilled birth attendance, 2) receiving 4+ antenatal care visits at time of delivery, and 3) receiving a postnatal health check-up within 48 hours of delivery. We applied model results onto the accessibility surface to visualise the probabilities of obtaining MNH care at both high-resolution and sub-national levels after adjusting for live births in 2015.Results: Across all outcomes, decreasing wealth and education levels were associated with lower odds of obtaining MNH care. Increasing geographic inaccessibility scores were associated with the strongest effect in lowering odds of obtaining care observed across outcomes, with the widest disparities observed among skilled birth attendance. Specifically, for each increase in the inaccessibility score to the nearest health facility, the odds of having skilled birth attendance at delivery was reduced by over 75% (0.24; CI: 0.19–0.3), while the odds of receiving antenatal care decreased by nearly 25% (0.74; CI: 0.61–0.89) and 40% for obtaining postnatal care (0.58; CI: 0.45–0.75).Conclusions: Overall, these results suggest decreasing accessibility to the nearest health facility significantly deterred utilisation of all maternal health care services. These results demonstrate how spatial approaches can inform policy efforts and promote evidence-based decision-making, and are particularly pertinent as the world shifts into the Sustainable Goals Development era, where sub-national applications will become increasingly useful in identifying and reducing persistent inequalities