Biomarker proxies for reconstructing Quaternary climate and environmental change

To reconstruct past environmental changes, a range of indirect or proxy approaches can be applied to Quaternary archives. Here, we review the complementary and novel insights which have been provided by the analysis of chemical fossils (biomarkers). Biomarkers have a biological source that can be highly specific (e.g., produced by a small group of organisms) or more general. We show that biomarkers are able to quantify key climate variables (particularly water and air temperature) and can provide qualitative evidence for changes in hydrology, vegetation, human-environment interactions and biogeochemical cycling. In many settings, biomarker proxies provide the opportunity to simultaneously reconstruct multiple climate or environmental variables, alongside complementary and long-established approaches to palaeo-environmental reconstruction. Multi-proxy studies have provided rich sets of data to explore both the drivers and impacts of palaeo-environmental change. As new biomarker proxies continue to be developed and refined, there is further potential to answer emerging questions for Quaternary science and environmental change

Psychobiological, Clinical, and Sociocultural Factors That Influence Black Women Seeking Treatment for Infertility: A Mixed-methods Study

OBJECTIVE: To provide a comprehensive and multidimensional description and conceptualization of the experiences of Black women seeking treatment for infertility. DESIGN: Convergent parallel mixed-methods study combining retrospective chart review data and semistructured interview data. SETTING: Private infertility clinic. PATIENT(S): African American/Black women between 18 and 44 years of age who presented for an initial infertility evaluation with a male partner between January 2015 and September 2019 at an infertility clinic in the metropolitan Washington D.C. area. INTERVENTION(S): None MAIN OUTCOME(S): Treatment seeking. MEASURE(S): Psychobiological, clinical, and sociocultural factors. RESULT(S): Along with the psychobiological, clinical, and sociocultural domains, we understood that Black women who sought treatment for infertility were older and overweight, had complex gynecological diagnoses, and experienced infertility for long periods of time. The delay in seeking treatment was possibly because of a low perceived risk of infertility, poor understanding of treatment options, inadequate referral patterns of primary care providers, and limited social support. Further, Black women experienced delays in seeking treatment because they attempted lifestyle-based self-interventions before considering medical interventions. Facilitators to care included psychological distress, complex gynecological medical history, and finding culturally competent providers. CONCLUSION(S): The study findings show that Black women in the United States are vulnerable to disparities in healthcare delivery, especially within reproductive endocrinology. Our findings highlight areas where Black women are experiencing missed opportunities for teaching, early identification, and early referrals for infertility-related concerns. Future studies should seek to reduce barriers to infertility treatment at the clinical and policy levels

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder

Funding Information: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z). CG is supported by The Medical Research Council and The University of Edinburgh through the Precision Medicine Doctoral Training program. SRC is supported by the UK Medical Research Council [MR/R024065/1] and a National Institutes of Health (NIH) research grant R01AG054628. Acknowledgements The authors thank all of the STRADL and Generation Scotland participants for their time and effort taking part in this study. We would also like to thank all of the research assistants, clinicians and technicians for their help in the collecting this data.Peer reviewedPublisher PD

Optimising experimental design for MEG resting state functional connectivity measurement

The study of functional connectivity using magnetoencephalography (MEG) is an expanding area of neuroimaging, and adds an extra dimension to the more common assessments made using fMRI. The importance of such metrics is growing, with recent demonstrations of their utility in clinical research, however previous reports suggest that whilst group level resting state connectivity is robust, single session recordings lack repeatability. Such robustness is critical if MEG measures in individual subjects are to prove clinically valuable. In the present paper, we test how practical aspects of experimental design affect the intra-subject repeatability of MEG findings; specifically we assess the effect of co-registration method and data recording duration. We show that the use of a foam head-cast, which is known to improve co-registration accuracy, increased significantly the between session repeatability of both beamformer reconstruction and connectivity estimation. We also show that recording duration is a critical parameter, with large improvements in repeatability apparent when using ten minute, compared to five minute recordings. Further analyses suggest that the origin of this latter effect is not underpinned by technical aspects of source reconstruction, but rather by a genuine effect of brain state; short recordings are simply inefficient at capturing the canonical MEG network in a single subject. Our results provide important insights on experimental design and will prove valuable for future MEG connectivity studies

The CCP4 suite : integrative software for macromolecular crystallography

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570