The mean state and variability of the North Atlantic circulation: a perspective from ocean reanalyses

The observational network around the North Atlantic has improved significantly over the last few decades with subsurface profiling floats and satellite observations, and the recent efforts to monitor the Atlantic Meridional Overturning Circulation (AMOC). These have shown decadal timescale changes across the North Atlantic including in heat content, heat transport and the circulation. However there are still significant gaps in the observational coverage. Ocean reanalyses integrate the observations with a dynamically consistent ocean model and can be used to understand the observed changes. However the ability of the reanalyses to represent the dynamics must also be assessed. We use an ensemble of global ocean reanalyses to examine the time mean state and interannual‐decadal variability of the North Atlantic ocean since 1993. We assess how well the reanalyses are able to capture processes and whether any understanding can be gained. In particular we examine aspects of the circulation including convection, AMOC and gyre strengths, and transports. We find that reanalyses show some consistency, in particular showing a weakening of the subpolar gyre and AMOC at 50oN from the mid‐90s until at least 2009 (related to decadal variability in previous studies), a strengthening and then weakening of the AMOC at 26.5oN since 2000, and impacts of circulation changes on transports. These results agree with model studies and the AMOC observations at 26.5oN since 2005. We also see less spread across the ensemble in AMOC strength and mixed layer depth, suggesting improvements as the observational coverage has improved

Applying an automated method of classifying lip morphological traits

Objective: To apply an automated computerised method to categorise and determine the prevalence of different types of lip traits, and to explore associations between lip traits and sex differences. Design: Observational descriptive study utilising an automated method of facial assessment. Setting and participants: A total of 4747 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who each had 3D facial scans carried out at 15 years of age. Methods: Each of the participants was automatically categorised regarding predetermined lip morphological traits. Descriptive statistics were applied to report the prevalence of the different types of each trait, and chi-square tests were used to investigate sex differences and associations between traits. Results: A total of 4730 individuals were assessed (47% male, 53% female). Eight predetermined lip traits have been reported previously. There were differences in prevalence for all lip traits in male and female patients (all P ⩽ 0.0002), with differences between the sexes described for each trait. For example, a deeply grooved philtrum of average width was more prevalent in boys, and an indentation near the upper vermilion border was more prevalent in girls. Each of the traits was significantly associated with the other traits (all P < 0.0001), with particularly strong associations seen between traits in the same region (e.g. upper lip). Individual associations between traits are reported; for example, a straight lip contour was found to be associated with no true vermilion border in both the upper and lower lip regions. Conclusion: The automated computerised method described is an invaluable tool for the categorisation of lip morphological traits. The prevalence of various types of traits has been described. Sexual dimorphism exists for all the lip traits assessed. Generally, each of the traits are associated with all other traits, with individual associations reported

The effect of maternal smoking and alcohol consumption on lip morphology

Objective: To determine whether maternal smoking and/or alcohol consumption has an influence on lip morphology. Maternal smoking is a known risk factor for orofacial clefts; however, its influence on normal lip variation is unknown. Recent research regarding normal lip morphology has been contradictory. Design: Retrospective cohort study. Setting and participants: A total of 4747 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) who each had 3D facial scans carried out at 15 years of age were included in the study. Methods: Each of the participants was automatically categorised regarding predetermined lip morphological traits. Questionnaires completed by their mothers identified smoking and alcohol habits during pregnancy. Logistic regression analyses were applied to determine the effect of maternal smoking and alcohol consumption on lip morphology. Results: Maternal smoking has significant effects on upper and lower lip contours, Cupid’s bow, lower lip-chin shape and lower lip tone (all P 6 units of alcohol are consumed per week (P = 0.0149, 32 weeks). Overall results suggest a deeply grooved philtrum is more likely if alcohol is consumed. Investigating the combined effect of smoking and alcohol consumption, lower lip contour (P = 0.00923) and lower lip-chin shape (P = 0.0171) are statistically significant, with lower lip contour more likely to be narrow in the midline, and lower lip-chin shape more likely to be an angular concavity. Conclusion: Maternal smoking influences a number of lip traits, including a possible epigenetic effect on upper lip contour. Maternal alcohol consumption, particularly at a high level, influences philtrum shape. Maternal smoking and alcohol consumption have a combined effect on lower lip contour and lower lip-chin shape

HIV Rapid Diagnostic Test Inventories in Zambézia Province, Mozambique: A Tale of 2 Test Kits

Background: The first pillar of the UNAIDS 90-90-90 goal seeks to accurately identify persons living with HIV (PLHIV), a process that is predicated on facilities having the necessary HIV tests available to perform the task. In many rural settings, the identification of PLHIV is accomplished through a two-step process involving the sequential use of 2 separate rapid diagnostic tests (RDTs). Inadequate inventory of either test has ramifications for the success of HIV-related programs. The purpose of this study was to evaluate the inventory levels of HIV RDT kits at specific healthcare facilities in Zambézia province, Mozambique.Methods: Using facility-level pharmacy stock surveillance data from October 2015 through September 2016, we assessed the inventory levels of HIV RDTs at 75 health facilities in 8 districts within Zambézia province, Mozambique. Using programmatically established categories (good, sufficient, threatened, or stockout), defined in conjunction with the provincial health authorities, descriptive statistics were performed to determine inventory control of HIV RDTs at the district and health facility levels. Monthly proportions of adequate (good + sufficient) inventory were calculated for each district to identify inventory trends over the evaluation period. To assess whether the proportion of inadequate stocks differed between RDT, a mixed-effects logistic regression was conducted, with inadequate inventory status as the outcome of interest.Results: When viewed as a whole, the inventory of each test kit was reported as being at adequate levels more than 89% of the time across the 75 facilities. However, disaggregated analysis revealed significant variability in the inventory levels of HIV RDTs at the district level. Specifically, the districts of Inhassunge, Namacurra, and Pebane reported inadequate inventory levels (threatened + stockout), of one or both test kits, for more than 10% of the study period. In addition, a disparity between inventory levels of each test kit was identified, with the odds of reporting inadequate inventory levels of the confirmatory test (Uni-Gold™) being approximately 1.8-fold greater than the initial test (Determine™) (odds ratio: 1.82, 95% CI: 1.40-2.38). Conclusion: As Test and Treat programs evolve, a significant emphasis should be placed on the “test” component of the strategy, beginning with assurances that health facilities have the adequate inventory of RDT necessary to meet the needs of their community. As national policy-makers rely predominantly on data from the upstream arm of the supply chain, it is unlikely the disparity between inventory levels of HIV RDTs identified at individual districts and specific health facilities would have been recognized. Moving forward, our findings point to a need for (1) renewed efforts reinforcing appropriate downstream forecasting of essential medicines and diagnostic tests in general and for Uni-Gold™ test kits specifically, and (2) simple metrics that may be routinely collected at all health facilities and which may then easily and quickly flow upstream so that policy-makers may optimally allocate resources

Genome Wide Analysis of Acute Myeloid Leukemia Reveal Leukemia Specific Methylome and Subtype Specific Hypomethylation of Repeats

Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R2 = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Atlantic Meridional Overturning Circulation: Observed Transport and Variability

The Atlantic Meridional Overturning Circulation (AMOC) extends from the Southern Ocean to the northern North Atlantic, transporting heat northwards throughout the South and North Atlantic, and sinking carbon and nutrients into the deep ocean. Climate models indicate that changes to the AMOC both herald and drive climate shifts. Intensive trans-basin AMOC observational systems have been put in place to continuously monitor meridional volume transport variability, and in some cases, heat, freshwater and carbon transport. These observational programs have been used to diagnose the magnitude and origins of transport variability, and to investigate impacts of variability on essential climate variables such as sea surface temperature, ocean heat content and coastal sea level. AMOC observing approaches vary between the different systems, ranging from trans-basin arrays (OSNAP, RAPID 26°N, 11°S, SAMBA 34.5°S) to arrays concentrating on western boundaries (e.g., RAPID WAVE, MOVE 16°N). In this paper, we outline the different approaches (aims, strengths and limitations) and summarize the key results to date. We also discuss alternate approaches for capturing AMOC variability including direct estimates (e.g., using sea level, bottom pressure, and hydrography from autonomous profiling floats), indirect estimates applying budgetary approaches, state estimates or ocean reanalyses, and proxies. Based on the existing observations and their results, and the potential of new observational and formal synthesis approaches, we make suggestions as to how to evaluate a comprehensive, future-proof observational network of the AMOC to deepen our understanding of the AMOC and its role in global climate

The past, present, and future of the Brain Imaging Data Structure (BIDS)

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown