The association of APOE genotype and cognitive decline in interaction with risk factors in a 65–69 year old community sample

<p>Abstract</p> <p>Background</p> <p>While the evidence of an association between the apolipoprotein E (<it>APOE</it>) <it>*E4 </it>allele and Alzheimer's disease is very strong, the effect of the <it>*E4 </it>allele on cognitive decline in the general population is more equivocal. A cross-sectional study on the lifespan effects of the <it>*E4 </it>allele <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> failed to find any effect of the <it>*E4 </it>allele on cognitive performance at ages 20–24, 40–44 or 60–64 years.</p> <p>Methods</p> <p>In this four year follow-up study, we reexamine the effect of <it>*E4 </it>in the sample of 2,021 individuals, now aged 65–69 years.</p> <p>Results</p> <p>Performance on the Mini-Mental State Examination (MMSE) was significantly poorer for <it>*E4 </it>homozygotes than heterozygotes or non-carriers. The effects of the <it>*E4 </it>genotype on cognitive decline over four years were found on the MMSE and Symbol-Digit Modalities test but only when controlling for risk factors such as head injury and education. Analyses were repeated with the exclusion of participants diagnosed with a mild cognitive disorder, with little change.</p> <p>Conclusion</p> <p>It is possible that <it>*E4 </it>carriers become vulnerable to greater cognitive decline in the presence of other risk factors at 65–69 years of age.</p

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Abstract: Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

A horizon scan of global biological conservation issues for 2024

We present the results of our 15th horizon scan of novel issues that could influence biological conservation in the future. From an initial list of 96 issues, our international panel of scientists and practitioners identified 15 that we consider important for societies worldwide to track and potentially respond to. Issues are novel within conservation or represent a substantial positive or negative step-change with global or regional extents. For example, new sources of hydrogen fuel and changes in deep-sea currents may have profound impacts on marine and terrestrial ecosystems. Technological advances that may be positive include benchtop DNA printers and the industrialisation of approaches that can create high-protein food from air, potentially reducing the pressure on land for food production

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

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Observation of electroweak production of two jets in association with an isolated photon and missing transverse momentum, and search for a Higgs boson decaying into invisible particles at 13 TeV with the ATLAS detector

This paper presents the measurement of the electroweak production of two jets in association with a $Z\gamma$ pair with the $Z$ boson decaying into two neutrinos. It also presents the search for invisible or partially invisible decays of a Higgs boson with a mass of 125 GeV produced through vector-boson fusion with a photon in the final state. These results use data from LHC proton-proton collisions at $\sqrt{s}$ = 13 TeV collected with the ATLAS detector corresponding to an integrated luminosity of 139 fb$^{-1}$. The event signature, shared by all benchmark processes considered for measurements and searches, is characterized by a significant amount of unbalanced transverse momentum and a photon in the final state, in addition to a pair of forward jets. For electroweak production of $Z\gamma$ in association with two jets, the background-only hypothesis is rejected with an observed (expected) significance of 5.2 (5.1) standard deviations. The measured fiducial cross-section for this process is 1.31$\pm$0.29 fb. Observed (expected) upper limit of 0.37 (0.34) at 95% confidence level is set on the branching ratio of a 125 GeV Higgs boson to invisible particles, assuming the Standard Model production cross-section. The signature is also interpreted in the context of decays of a Higgs boson to a photon and a dark photon. An observed (expected) 95% CL upper limit on the branching ratio for this decay is set at 0.018 (0.017), assuming the 125 GeV Standard Model Higgs boson production cross-section

The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2

The design and performance of the inner detector trigger for the high level trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-18 data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector recorded 35.6 fb$^{-1}$, 46.9 fb$^{-1}$, and 60.6 fb$^{-1}$ respectively of proton-proton collision data at a centre-of-mass energy of 13 TeV. In order to deal with the very high interaction multiplicities per bunch crossing expected with the 13 TeV collisions the inner detector trigger was redesigned during the long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of these developments is provided and the performance of the tracking in the trigger for the muon, electron, tau and $b$-jet signatures is discussed. The high performance of the inner detector trigger with these extreme interaction multiplicities demonstrates how the inner detector tracking continues to lie at the heart of the trigger performance and is essential in enabling the ATLAS physics programme

The ATLAS inner detector trigger performance in pp collisions at 13 TeV during LHC Run 2

The design and performance of the inner detector trigger for the high level trigger of the ATLAS experiment at the Large Hadron Collider during the 2016-18 data taking period is discussed. In 2016, 2017, and 2018 the ATLAS detector recorded 35.6 fb$^{-1}$, 46.9 fb$^{-1}$, and 60.6 fb$^{-1}$ respectively of proton-proton collision data at a centre-of-mass energy of 13 TeV. In order to deal with the very high interaction multiplicities per bunch crossing expected with the 13 TeV collisions the inner detector trigger was redesigned during the long shutdown of the Large Hadron Collider from 2013 until 2015. An overview of these developments is provided and the performance of the tracking in the trigger for the muon, electron, tau and $b$-jet signatures is discussed. The high performance of the inner detector trigger with these extreme interaction multiplicities demonstrates how the inner detector tracking continues to lie at the heart of the trigger performance and is essential in enabling the ATLAS physics programme