Short communication: NKG2C+ NK cells contribute to increases in CD16+CD56- cells in HIV type 1+ individuals with high plasma viral load.

Chronic HIV-1 infection results in the expansion of both NKG2C+ and CD16+CD56- human natural killer cells. NKG2C+ cells proliferate in response to human cytomegalovirus (HCMV) and expansion of the dysfunctional CD56-CD16+ natural killer (NK) cells is associated with HIV-1 viremia. Here we report an association between increased proportions of CD56-CD16+ NK cells in viremic HIV-1+ individuals and an increased contribution of NKG2C+ cells to this subset. These data, in addition to anti-HCMV IgG serology, indicate a potential contribution of both HCMV and HIV-1 to NK cell dysfunction in HIV-1-infected individuals

Personal construct similarity and friendship

Two sets of literature are reviewed: firstly, a detailed review isgiven of ideas and indices derived from Kelly's Personal Construct Theory and of their use in research on interpersonal relationships and secondly, a more selective review of the interpersonal attraction literature is presented. Duck's (1973;1977) filter model of friendship, which forms the focus of this research, is then discussed. Five studies are reported. All were concerned with the relationship between friendship and similarity of personal construct content. The positions, within the proposed filter sequence, of similarity of personal construct organisation and structure, were also of primary interest. Other concerns were to investigate the relative importance in friendship of construct similarity, attitude and value similarity, and the meaning-fulness of others' constructs; to compare superordinate and subordinate construct similarity; to assess the effects of using different measures of content similarity; and to investigate sex and age differences. Friends were generally found to he relatively similar in terms of construct content, organisation and structure hut their constructs were not more meaningful and nor was there any evidence of friends having similar attitudes or values. It is suggested, on the basis of the findings relating construct content similarity to friendship, that the strength and nature of this relationship depends on the nature of the group e.g. on its homogeneity and centrality in the lives of its members. Superordinate similarity was found to he more strongly associated with established friendship than subordinate similarity. Some sex differences were found e.g. in the type of content similarity associated with friendship. The last chapter discusses the problems of specifying the filter sequence, the filter model from a Kellian perspective, and the importance of the social context of relationships. Suggestions for future research are made which emphasise the need to tap people's constructs of relationships.<p

Patent Foramen Ovale, Ischemic Stroke and Migraine: Systematic Review and Stratified Meta-Analysis of Association Studies

BACKGROUND: Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. METHODS: Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. RESULTS: We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9–2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0–2.5; 2 studies; OR 1.3; 95% CI 0.9–1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6–1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. CONCLUSIONS: The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect

HIV-1 viral load is elevated in individuals with reverse transcriptase mutation M184V/I during virological failure of first line antiretroviral therapy and is associated with compensatory mutation L74I

Background: M184V/I cause high-level lamivudine (3TC) and emtricitabine (FTC) resistance, and increased tenofovir (TDF) susceptibility. Nonetheless, 3TC and FTC (collectively referred to as XTC) appear to retain modest activity against HIV-1 with these mutations possibly as a result of reduced replication capacity. Here we determined how M184V/I impacts virus load (VL) in patients failing therapy on a TDF/XTC plus nonnucleoside RT inhibitor (NNRTI)-containing regimen. Methods: We compared VL in absence and presence M184V/I across studies using random effects meta-analysis. The effect of mutations on virus RT activity and infectiousness was analysed in vitro. Results: M184I/V was present in 817 (56.5%) of 1445 individuals with VF. VL was similar in individuals with or without M184I/V (difference in log10VL 0.18, 95% CI 0.05-0.31). CD4 count was lower both at initiation of ART and at VF in participants who went on to develop M184V/I. L74I was present in 10.2% of persons with M184V/I but absent in persons without M184V/I (p<0.0001). In vitro, L74I compensated for defective replication of M184V mutated virus. Conclusion: Virus loads were similar in persons with and without M184V/I during VF on a TDF/XTC/NNRTI-containing regimen. We therefore do not find evidence for a benefit of XTC in the context of first line failure on this combination

Teaching English to Young Learners. International TEYL Research Papers : 2016

This 2016 edition of TEYL research papers contains reports on small-scale classroom-based action research undertaken by post-graduate students for completion of their Master of Arts degree in Teaching English to Young Learners, from the University of York. In this edition, four papers are presented, focussing on: the impact of assessment descriptors on 12-14 year-old English language learners’ written work through increased self-awareness undertaken in Portugal (Diana England); teaching active listening skills to 14-16 year-old Spanish learners of English (John Lavery); the value of songs in the classroom to enhance vocabulary retention with very young learners in Greece (Soultana Papaioannou); the use of DARTs (analysis-directed activities related to text) to develop reading comprehension in 12-13 ESL year-old learners in a South-East Asian science classroom (Mark Anthony Steacy). This edition has been compiled and edited by Kate Gregson from the MATEYL supervisory team at the University of York

Natural character in Northland: application of the River Values Assessment System (RiVAS)

The River Values Assessment System (RiVAS) was applied by a River Expert Panel to eight resource attributes to assess 57 river units in the Northland Region for their natural character. The method was applied to differentiate rivers of high natural character (n=10), moderate natural character (n=34), and low natural character (n=13). Few data were available, so the Expert Panel relied on their own assessments for most attributes.This work was funded by Northland Regional Council and we gratefully acknowledge their support. Thanks to Northland Regional Council staff who assisted with this assessment: Andrew Macdonald, GIS Officer (GIS support); Dale Hansen, Water Resources/Hydrology Programme Manager (flow regime data); and Gail Townsend, Biosecurity Officer – Aquatic Pests, who reviewed scores for the ‘absence of exotic flora and fauna’ indicator

International patterns of dual antiplatelet therapy duration after acute coronary syndromes

Objective To describe international patterns of dual antiplatelet therapy (DAPT) duration after acute coronary syndrome (ACS), and explore its determinants and correlation with clinical events. Methods EPICOR (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients) is a prospective, international, observational study of 10 568 ACS hospital survivors enrolled in 555 centres from 20 countries across Europe and Latin America between 2010 and 2011, with telephone follow-up at quarterly intervals up to 24 months to assess treatment continuation and clinical events. Results Of 8593 patients discharged on DAPT, 4859 (57\%) remained on uninterrupted DAPT at end of follow-up. There were minor differences in rates of DAPT discontinuation according to age, gender, risk factors, therapeutic strategy or region, but major differences between countries. By study end, 555 of evaluable patients (5.7\%) died, 727 (10.0\%) experienced new cardiovascular (CV) events, 496 new coronary events (6.82\%) and 154 (2.11\%) clinically relevant bleeding (14 (6.7\%) fatal). Most CV events and deaths (85\%) occurred while on DAPT. DAPT interruption was associated with increased risk of CV events in the following week (HR 2.29; 95\% CI 1.08 to 4.84) but not specifically with time to first coronary event or mortality. Conclusions Despite guideline recommendations, most patients with ACS in Europe and Latin America remained on DAPT beyond 12 months, country being the most important determinant of DAPT duration. Increase in short-term CV risk was seen after switching from DAPT to less medication, as compared with continued DAPT, with no long-term effect on coronary or mortality risk.The EPICOR study was funded by AstraZeneca.S

Gene Expression Profiling of Bronchoalveolar Lavage Cells Preceding a Clinical Diagnosis of Chronic Lung Allograft Dysfunction.

BackgroundChronic Lung Allograft Dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Although CLAD is usually not responsive to treatment, earlier identification may improve treatment prospects.MethodsIn a nested case control study, 1-year post transplant surveillance bronchoalveolar lavage (BAL) fluid samples were obtained from incipient CLAD (n = 9) and CLAD free (n = 8) lung transplant recipients. Incipient CLAD cases were diagnosed with CLAD within 2 years, while controls were free from CLAD for at least 4 years following bronchoscopy. Transcription profiles in the BAL cell pellets were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression analysis, based on an absolute fold change (incipient CLAD vs no CLAD) &gt;2.0 and an unadjusted p-value ≤0.05, generated a candidate list containing 55 differentially expressed probe sets (51 up-regulated, 4 down-regulated).ResultsThe cell pellets in incipient CLAD cases were skewed toward immune response pathways, dominated by genes related to recruitment, retention, activation and proliferation of cytotoxic lymphocytes (CD8+ T-cells and natural killer cells). Both hierarchical clustering and a supervised machine learning tool were able to correctly categorize most samples (82.3% and 94.1% respectively) into incipient CLAD and CLAD-free categories.ConclusionsThese findings suggest that a pathobiology, similar to AR, precedes a clinical diagnosis of CLAD. A larger prospective investigation of the BAL cell pellet transcriptome as a biomarker for CLAD risk stratification is warranted

Efficacy of pulmonary artery pressure monitoring in patients with chronic heart failure:a meta-analysis of three randomized controlled trials

Aims Adjustment of treatment based on remote monitoring of pulmonary artery (PA) pressure may reduce the risk of hospital admission for heart failure (HF). We have conducted a meta-analysis of large randomized trials investigating this question. Methods A systematic literature search was performed for randomized clinical trials with PA pressure monitoring devices in patients and results with HF. The primary outcome of interest was the total number of HF hospitalizations. Other outcomes assessed were urgent visits leading to treatment with intravenous diuretics, all-cause mortality, and composites. Treatment effects are expressed as hazard ratios, and pooled effect estimates were obtained applying random effects meta-analyses. Three eligible randomized clinical trials were identified that included 1898 outpatients in New York Heart Association functional classes II–IV, either hospitalized for HF in the prior 12 months or with elevated plasma NT-proBNP concentrations. The mean followup was 14.7 months, 67.8% of the patients were men, and 65.8% had an ejection fraction ≤40%. Compared to patients in the control group, the hazard ratio (95% confidence interval) for total HF hospitalizations in those randomized to PA pressure monitoring was 0.70 (0.58–0.86) (P = .0005). The corresponding hazard ratio for the composite of total HF hospitalizations, urgent visits and all-cause mortality was 0.75 (0.61–0.91; P = .0037) and for all-cause mortality 0.92 (0.73–1.16). Subgroup analyses, including ejection fraction phenotype, revealed no evidence of heterogeneity in the treatment effect. Conclusion The use of remote PA pressure monitoring to guide treatment of patients with HF reduces episodes of worsening HF and subsequent hospitalizations.</p