Climate versus emission drivers of methane lifetime against loss by tropospheric OH from 1860–2100

With a more-than-doubling in the atmospheric abundance of the potent greenhouse gas methane (CH₄) since preindustrial times, and indications of renewed growth following a leveling off in recent years, questions arise as to future trends and resulting climate and public health impacts from continued growth without mitigation. Changes in atmospheric methane lifetime are determined by factors which regulate the abundance of OH, the primary methane removal mechanism, including changes in CH₄ itself. We investigate the role of emissions of short-lived species and climate in determining the evolution of methane lifetime against loss by tropospheric OH, (τCH₄_OH), in a suite of historical (1860–2005) and future Representative Concentration Pathway (RCP) simulations (2006–2100), conducted with the Geophysical Fluid Dynamics Laboratory (GFDL) fully coupled chemistry-climate model (CM3). From preindustrial to present, CM3 simulates an overall 5% increase in τCH₄_OH due to a doubling of the methane burden which offsets coincident increases in nitrogen oxide (NOx emissions. Over the last two decades, however, the τCH₄_OH declines steadily, coinciding with the most rapid climate warming and observed slow-down in CH₄ growth rates, reflecting a possible negative feedback through the CH₄ sink. Sensitivity simulations with CM3 suggest that the aerosol indirect effect (aerosol-cloud interactions) plays a significant role in cooling the CM3 climate. The projected decline in aerosols under all RCPs contributes to climate warming over the 21st century, which influences the future evolution of OH concentration and τCH₄_OH. Projected changes in τCH₄_OH from 2006 to 2100 range from −13% to +4%. The only projected increase occurs in the most extreme warming case (RCP8.5) due to the near-doubling of the CH₄ abundance, reflecting a positive feedback on the climate system. The largest decrease occurs in the RCP4.5 scenario due to changes in short-lived climate forcing agents which reinforce climate warming and enhance OH. This decrease is more-than-halved in a sensitivity simulation in which only well-mixed greenhouse gas radiative forcing changes along the RCP4.5 scenario (5% vs. 13%)

Innovative and rapid antimicrobial susceptibility testing systems

Antimicrobial resistance (AMR) is a major threat to human health worldwide, and the rapid detection and quantification of resistance, combined with antimicrobial stewardship, are key interventions to combat the spread and emergence of AMR. Antimicrobial susceptibility testing (AST) systems are the collective set of diagnostic processes that facilitate the phenotypic and genotypic assessment of AMR and antibiotic susceptibility. Over the past 30 years, only a few high-throughput AST methods have been developed and widely implemented. By contrast, several studies have established proof of principle for various innovative AST methods, including both molecular-based and genome-based methods, which await clinical trials and regulatory review. In this Review, we discuss the current state of AST systems in the broadest technical, translational and implementation-related scope

The fairness, predictive validity and acceptability of multiple mini interview in an internationally diverse student population--a mixed methods study

BACKGROUND: International medical students, those attending medical school outside of their country of citizenship, account for a growing proportion of medical undergraduates worldwide. This study aimed to establish the fairness, predictive validity and acceptability of Multiple Mini Interview (MMI) in an internationally diverse student population. METHODS: This was an explanatory sequential, mixed methods study. All students in First Year Medicine, National University of Ireland Galway 2012 were eligible to sit a previously validated 10 station MMI. Quantitative data comprised: demographics, selection tool scores and First Year Assessment scores. Qualitative data comprised separate focus groups with MMI Assessors, EU and Non-EU students. RESULTS: 109 students participated (45% of class). Of this 41.3% (n = 45) were Non-EU and 35.8% (n = 39) did not have English as first language. Age, gender and socioeconomic class did not impact on MMI scores. Non-EU students and those for whom English was not a first language achieved significantly lower scores on MMI than their EU and English speaking counterparts (difference in mean 11.9% and 12.2% respectively, P<0.001). MMI score was associated with English language proficiency (IELTS) (r = 0.5, P<0.01). Correlations emerged between First Year results and IELTS (r = 0.44; p = 0.006; n = 38) and EU school exit exam (r = 0.52; p<0.001; n = 56). MMI predicted EU student OSCE performance (r = 0.27; p = 0.03; n = 64). In the analysis of focus group data two overarching themes emerged: Authenticity and Cultural Awareness. MMI was considered a highly authentic assessment that offered a deeper understanding of the applicant than traditional tools, with an immediate relevance to clinical practice. Cultural specificity of some stations and English language proficiency were seen to disadvantage international students. Recommendations included cultural awareness training for MMI assessors, designing and piloting culturally neutral stations, lengthening station duration and providing high quality advance information to candidates. CONCLUSION: MMI is a welcome addition to assessment armamentarium for selection, particularly with regard to stakeholder acceptability. Understanding the mediating and moderating influences for differences in performance of international candidates is essential to ensure that MMI complies with the metrics of good assessment practice and principles of both distributive and procedural justice for all applicants, irrespective of nationality and cultural background

Systemic RALA/iNOS nanoparticles; a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment

This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [CMV]-driven or transcriptionally regulated human osteocalcin [hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-luc-D3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. Keywords: nonviral gene therapy, nitric oxide, nanoparticle, breast cancer, metastasi

Contemplative Practices and Mental Training: Prospects for American Education

This article draws on research in neuroscience, cognitive science, developmental psychology, and education, as well as scholarship from contemplative traditions concerning the cultivation of positive development, to highlight a set of mental skills and socioemotional dispositions that are central to the aims of education in the 21st century. These include self‐regulatory skills associated with emotion and attention, self‐representations, and prosocial dispositions such as empathy and compassion. It should be possible to strengthen these positive qualities and dispositions through systematic contemplative practices, which induce plastic changes in brain function and structure, supporting prosocial behavior and academic success in young people. These putative beneficial consequences call for focused programmatic research to better characterize which forms and frequencies of practice are most effective for which types of children and adolescents. Results from such research may help refine training programs to maximize their effectiveness at different ages and to document the changes in neural function and structure that might be induced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92125/1/cdep240.pd