On the Relationship Between the Madden‐Julian Oscillation and the Hadley and Walker Circulations

This study investigates: (i) how the local meridional (Hadley) and zonal (Walker) circulations change in each phase of the Madden‐Julian Oscillation (MJO); and (ii) the effect of enhanced and suppressed MJO‐related convection on the poleward extent of the local Hadley circulations and, thus, the strengths and positions of the subtropical jets. We examine these effects in ERA‐Interim reanalysis by decomposing the vertical mass flux into zonal and meridional components. We show for the first time, that as the envelope of enhanced convection moves eastwards from Africa to the Central Pacific the local Hadley circulation is enhanced. The regional Walker circulation in the Pacific is strengthened when the envelope of active MJO convection is located over the Maritime Continent and weakened when the region of suppressed convection is located there. In regions of anomalous upper‐level divergence the subtropical jet is enhanced. The core of the subtropical jet over Asia shifts eastwards with the progression of the MJO and shifts farther poleward in regions of anomalous upper‐level divergence linked with enhanced convection. The region of either enhanced or suppressed convection over the Maritime Continent strengthens or weakens the local Hadley circulation, producing disturbances in the subtropical jet. These disturbances then force midlatitude Rossby waves that propagate across the Pacific Ocean in both hemispheres

The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors

Experiences of current UK service provision for co-occurring parental domestic violence and abuse, mental ill-health, and substance misuse: a reflexive thematic analysis

This is the author accepted manuscript.Domestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) are inter-related public health problems negatively impacting families. Improved support requires an understanding of key stakeholders’ perspectives and experiences of current UK service provision. We conducted a qualitative research study to explore service users’, service providers’, and senior leadership/commissioners’ experiences of service provision for responding to parental DVA, MH, and SU in one locality. Six service users participated in individual, semi-structured interviews and ten service providers and senior leadership/commissioners attended two separate focus groups. We analysed data using reflexive thematic analysis. Five themes captured participants’ experiences: ‘it’s hard to get the support I need, when I need it’; ‘almost all services come together around a family’; ‘it’s all about the right relationships’; ‘addressing upstream drivers’; and ‘it’s difficult providing support for multiple needs’. These highlighted the importance of: early support; a relational response; and addressing needs beyond parental DVA, MH, and SU. They also emphasised the barriers presented by siloed specialisms and overwhelmed practitioners. Our study is one of the first to consider multiple stakeholders’ perspectives on current UK service provision for co-occurring parental DVA, MH, and SU. It highlights key challenges for working at the intersection of these problems and suggests system-level change is needed to create the conditions to support families with multiple needs.National Institute for Health and Care Research (NIHR

Local Expansion of Donation After Circulatory Death Kidney Transplant Activity Improves Waitlisted Outcomes and Addresses Inequities of Access to Transplantation

In the United Kingdom, donation after circulatory death (DCD) kidney transplant activity has increased rapidly, but marked regional variation persists. We report how increased DCD kidney transplant activity influenced waitlisted outcomes for a single center. Between 2002–2003 and 2011–2012, 430 (54%) DCD and 361 (46%) donation after brain death (DBD) kidney-only transplants were performed at the Cambridge Transplant Centre, with a higher proportion of DCD donors fulfilling expanded criteria status (41% DCD vs. 32% DBD; p = 0.01). Compared with U.K. outcomes, for which the proportion of DCD:DBD kidney transplants performed is lower (25%; p 65 years; waiting time 730 vs. 1357 days nationally; p < 0.001), who received predominantly DCD kidneys from older donors (mean donor age 64 years), whereas younger recipients received equal proportions of living donor, DBD and DCD kidney transplants. Death-censored kidney graft survival was nevertheless comparable for younger and older recipients, although transplantation conferred a survival benefit from listing for only younger recipients. Local expansion in DCD kidney transplant activity improves survival outcomes for younger patients and addresses inequity of access to transplantation for older recipients

Trends in the local Hadley and local Walker circulations

The linear trend in the local Hadley and Walker circulations from 1979 to 2009 is calculated. These local circulations are defined through a decomposition of the vertical mass flux into its zonal and meridional components. Defining the local circulation this way ensures that the two orthogonal circulations (the local Hadley and Walker circulations) sum to the original circulation even after averaging the circulations regionally. Large regional differences in changes in the local Hadley and Walker circulations over a 31 year period are found. For example, the local Hadley circulation has shifted southward over Africa, the Maritime Continent, and the western and central Pacific by about 1°. Over the Americas and the Atlantic the local Hadley circulation has strengthened by about 1-5%. The zonal component of the vertical mass flux has increased by about 10-20% in the tropics over all continents and decreased over the adjacent oceans by about 10-20%. Although the local Walker circulations in the Indian Ocean and the Atlantic have weakened, the circulation in the Pacific has changed little (about 1-2%). The local Walker circulations in all ocean basins have shifted westward by about 1-2°on average

Development and validation of a LC-MS/MS method for the quantification of the checkpoint kinase 1 inhibitor SRA737 in human plasma.

Aim SRA737 is an orally active small-molecule inhibitor of checkpoint kinase 1 being investigated in an oncology setting. A HPLC-MS/MS method for quantifying plasma concentrations of SRA737 was validated.Methods & results Sample preparation involved protein precipitation with acetonitrile following addition of 13C15N-deuterated SRA737 as internal standard. A rapid and selective method was fully validated across a range of 5-20,000 ng/ml, exhibiting good sensitivity, overall precision (expressed as coefficient of variation) ≤8.0% and accuracy 96-102%. Consistently high recovery was observed, with no matrix effect and a lower limit of quantitation of 5 ng/ml.Conclusion A novel method for analyzing SRA737 in human plasma has been validated and is now being utilized for quantification of SRA737 in a Phase I trial

Variable Baseline Papio cynocephalus Endogenous Retrovirus (PcEV) Expression Is Upregulated in Acutely SIV-Infected Macaques and Correlated to STAT1 Expression in the Spleen

Retroviral replication leaves a DNA copy in the host cell chromosome, which over millions of years of infection of germline cells has led to 5% of the human genome sequence being comprised of endogenous retroviruses (ERVs), distributed throughout an estimated 100,000 loci. Over time these loci have accrued mutations such as premature stop codons that prevent continued replication. However, many loci remain both transcriptionally and translationally active and ERVs have been implicated in interacting with the host immune system. Using archived plasma and tissue samples from past macaque studies, experimentally infected with simian immunodeficiency virus (SIV), the expression of one macaque ERV in response to acute viral infection was explored together with a measure of the innate immune response. Specifically, RNA levels were determined for (a) Papio cynocephalus Endogenous Retrovirus (PcEV), an ERV (b) STAT1, a key gene in the interferon signaling pathway, and (c) SIV, an exogenous pathogen. Bioinformatic analysis of DNA sequences of the PcEV loci within the macaque reference genome revealed the presence of open reading frames (ORFs) consistent with potential protein expression but not ERV replication. Quantitative RT-PCR analysis of DNase-treated RNA extracts from plasma derived from acute SIV-infection detected PcEV RNA at low levels in 7 of 22 macaques. PcEV RNA levels were significantly elevated in PBMC and spleen samples recovered during acute SIV infection, but not in the thymus and lymph nodes. A strong positive correlation was identified between PcEV and STAT1 RNA levels in spleen samples recovered from SIV-positive macaques. One possibility is that SIV infection induces PcEV expression in infected lymphoid tissue that contributes to induction of an antiviral response

The six-minute walk test in community dwelling elderly: influence of health status.

BACKGROUND: The 6 minutes walk test (6MWT) is a useful assessment instrument for the exercise capacity of elderly persons. The impact of the health status on the 6MWT-distance in elderly, however, remains unclear, reducing its value in clinical settings. The objective of this study was to investigate to what extent the 6MWT-distance in community dwelling elderly is determined by health conditions. METHODS: One hundred and fifty-six community dwelling elderly people (53 male, 103 female) were assessed for health status and performed the 6MWT. After clinical evaluation, electrocardiography and laboratory examination participants were categorized into a stratified six-level classification system according to their health status, going from A (completely healthy) to D (signs of active disease at the moment of examination). RESULTS: The mean 6MWT-distance was 603 m (SD = 178). The 6MWT-distance decreased significantly with increasing age (ANOVA p = 0.0001) and with worsening health status (ANCOVA, corrected for age p < 0.001). A multiple linear regression model with health status, age and gender as independent variables explained 31% of the 6MWT-distance variability. Anthropometrical measures (stature, weight and BMI) did not significantly improve the prediction model. A significant relationship between 6MWT-distance and stature was only present in category A (completely healthy). CONCLUSIONS: Significant differences in 6MWT-distance are observed according to health status in community-dwelling elderly persons. The proposed health categorizing system for elderly people is able to distinguish persons with lower physical exercise capacity and can be useful when advising physical trainers for seniors