North Atlantic natural variability modulates emergence of widespread Greenland melt in a warming climate

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 45 (2018): 9171-9178, doi:10.1029/2018GL079682.Record‐breaking melt over Greenland in recent decades is linked not only to climate change but also to natural variability, including persistent atmospheric high‐pressure conditions in the negative phase of the North Atlantic Oscillation and warm North Atlantic Ocean temperatures during the positive phase of the Atlantic Multidecadal Oscillation. However, the relative importance of natural variability for Greenland melt under varying degrees of greenhouse forcing is still unclear. Using reanalysis data and a large ensemble of climate model simulations, we find that a negative North Atlantic Oscillation and positive Atlantic Multidecadal Oscillation consistently promote heightened summer melt under various forcing conditions. Moreover, timing of widespread 21st century Greenland melt varies considerably between ensemble members due to different phasing of these modes of natural variability. These results indicate the importance of natural modes of variability across a range of external forcing conditions for interannual melt variability and the emergence of widespread Greenland melt.U.S. National Science Foundation Grant Number: ANS‐1736738; Woods Hole Oceanographic Institution Summer Student Fellow program Grant Number: AGS‐13553392019-03-1

Importance of Orography for Greenland cloud and melt response to atmospheric blocking

Author Posting. © American Meteorological Society, 2020. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Hahn, L. C., Storelvmo, T., Hofer, S., Parfitt, R., & Ummenhofer, C. C. Importance of Orography for Greenland cloud and melt response to atmospheric blocking. Journal of Climate, 33(10), (2020): 4187-4206, doi:10.1175/JCLI-D-19-0527.1.More frequent high pressure conditions associated with atmospheric blocking episodes over Greenland in recent decades have been suggested to enhance melt through large-scale subsidence and cloud dissipation, which allows more solar radiation to reach the ice sheet surface. Here we investigate mechanisms linking high pressure circulation anomalies to Greenland cloud changes and resulting cloud radiative effects, with a focus on the previously neglected role of topography. Using reanalysis and satellite data in addition to a regional climate model, we show that anticyclonic circulation anomalies over Greenland during recent extreme blocking summers produce cloud changes dependent on orographic lift and descent. The resulting increased cloud cover over northern Greenland promotes surface longwave warming, while reduced cloud cover in southern and marginal Greenland favors surface shortwave warming. Comparison with an idealized model simulation with flattened topography reveals that orographic effects were necessary to produce area-averaged decreasing cloud cover since the mid-1990s and the extreme melt observed in the summer of 2012. This demonstrates a key role for Greenland topography in mediating the cloud and melt response to large-scale circulation variability. These results suggest that future melt will depend on the pattern of circulation anomalies as well as the shape of the Greenland Ice Sheet.This research was supported by the Woods Hole Oceanographic Institution Summer Student Fellow program, by the U.S. National Science Foundation under AGS-1355339 to C.C.U., and by the European Research Council through Grant 758005

The landscape of extreme genomic variation in the highly adaptable Atlantic killifish

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Genome Biology and Evolution 9 (2017): 659-676, doi:10.1093/gbe/evx023.Understanding and predicting the fate of populations in changing environments require knowledge about the mechanisms that support phenotypic plasticity and the adaptive value and evolutionary fate of genetic variation within populations. Atlantic killifish (Fundulus heteroclitus) exhibit extensive phenotypic plasticity that supports large population sizes in highly fluctuating estuarine environments. Populations have also evolved diverse local adaptations. To yield insights into the genomic variation that supports their adaptability, we sequenced a reference genome and 48 additional whole genomes from a wild population. Evolution of genes associated with cell cycle regulation and apoptosis is accelerated along the killifish lineage, which is likely tied to adaptations for life in highly variable estuarine environments. Genome-wide standing genetic variation, including nucleotide diversity and copy number variation, is extremely high. The highest diversity genes are those associated with immune function and olfaction, whereas genes under greatest evolutionary constraint are those associated with neurological, developmental, and cytoskeletal functions. Reduced genetic variation is detected for tight junction proteins, which in killifish regulate paracellular permeability that supports their extreme physiological flexibility. Low-diversity genes engage in more regulatory interactions than high-diversity genes, consistent with the influence of pleiotropic constraint on molecular evolution. High genetic variation is crucial for continued persistence of species given the pace of contemporary environmental change. Killifish populations harbor among the highest levels of nucleotide diversity yet reported for a vertebrate species, and thus may serve as a useful model system for studying evolutionary potential in variable and changing environments.This work was primarily supported by a grant from the National Science Foundation (collaborative research grants DEB-1265282, DEB-1120512, DEB-1120013, DEB-1120263, DEB-1120333, DEB-1120398 to J.K.C., D.L.C., M.E.H., S.I.K., M.F.O., J.R.S., W.W., and A.W.). Further support was provided by the National Institute of Environmental Health Sciences (1R01ES021934-01 to A.W., P42ES7373 to T.H.H., P42ES007381 to M.E.H., and R01ES019324 to J.R.S.), the National Institute of General Medical Sciences (P20GM103423 and P20GM104318 to B.L.K.), and the National Science Foundation (DBI-0640462 and XSEDE-MCB100147 to D.G.)

Patient-reported outcome measures for monitoring primary care patients with depression: the PROMDEP cluster RCT and economic evaluation

Background: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes.// Objective: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback.// Design: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control.// Setting: UK primary care (141 group general practices in England and Wales).// Inclusion criteria: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations.// Exclusions: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide.// Intervention: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10–35 days later, compared with usual care.// Primary outcome: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks.// Secondary outcomes: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events.// Sample size: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure.// Randomisation: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location.// Blinding: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation.// Analysis: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks.// Qualitative interviews: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework.// Results: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference –0.46, 95% confidence interval –2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval –0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (–£163, 95% confidence interval –£349 to £28). Cost-effectiveness and cost–utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming.// Conclusions: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients’ quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment

Chimpanzee APOBEC3 proteins deter SIVs from any monkey business

Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee's main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4(+) T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1–3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science

The pipeline project: Pre-publication independent replications of a single laboratory's research pipeline

This crowdsourced project introduces a collaborative approach to improving the reproducibility of scientific research, in which findings are replicated in qualified independent laboratories before (rather than after) they are published. Our goal is to establish a non-adversarial replication process with highly informative final results. To illustrate the Pre-Publication Independent Replication (PPIR) approach, 25 research groups conducted replications of all ten moral judgment effects which the last author and his collaborators had “in the pipeline” as of August 2014. Six findings replicated according to all replication criteria, one finding replicated but with a significantly smaller effect size than the original, one finding replicated consistently in the original culture but not outside of it, and two findings failed to find support. In total, 40% of the original findings failed at least one major replication criterion. Potential ways to implement and incentivize pre-publication independent replication on a large scale are discussed

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Data from a pre-publication independent replication initiative examining ten moral judgement effects

We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory's research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science.Link_to_subscribed_fulltex