A case cluster demonstrating the relationship between HLA concordance and virologic and disease outcomes in human immunodeficiency virus infection

AbstractWe present a detailed analysis of sexual HIV transmission from one source partner to two recipients. The HLA haplotypes between the source partner and one recipient were very similar with 7 out of 8 HLA alleles from four loci (HLA A, B, C and DRB) shared, while the other recipient shared only one allele. The immunologic outcomes between the two recipients differed dramatically, despite the absence of apparent virologic differences in their inoculums. We suggest that non-viral factors, which might be related to differences in the HLA profile, played a role in determining different CD4+ T-cells dynamics for these two recipients

Cognitive, behavioural and psychological barriers to the prevention of severe hypoglycaemia: A qualitative study of adults with type 1 diabetes

Objectives: Severe hypoglycaemia affects approximately one in three people with type 1 diabetes and is the most serious side effect of insulin therapy. Our aim was to explore individualistic drivers of severe hypoglycaemia events. Methods: In-depth semi-structured interviews were conducted with a purposive sample of 17 adults with type 1 diabetes and a history of recurrent severe hypoglycaemia, to elicit experiences of hypoglycaemia (symptoms/awareness, progression from mild to severe and strategies for prevention/treatment). Interviews were analysed using an adapted grounded theory approach. Results: Three main themes emerged: hypoglycaemia-induced cognitive impairment, behavioural factors and psychological factors. Despite experiencing early hypoglycaemic symptoms, individuals often delayed intervention due to impaired/distracted attention, inaccurate risk assessment, embarrassment, worry about rebound hyperglycaemia or unavailability of preferred glucose source. Delay coupled with use of a slow-acting glucose source compromised prevention of severe hypoglycaemia. Conclusion: Our qualitative data highlight the multifaceted, idiosyncratic nature of severe hypoglycaemia and confirm that individuals with a history of recurrent severe hypoglycaemia may have specific thought and behaviour risk profiles. Individualised prevention plans are required, emphasising both the need to attend actively to mild hypoglycaemic symptoms and to intervene promptly with an appropriate, patient-preferred glucose source to prevent progression to severe hypoglycaemia

Effect of nearest neighbor repulsion on the low frequency phase diagram of a quarter-filled Hubbard-Holstein chain

We have studied the influence of nearest-neighbor (NN) repulsion on the low frequency phase diagram of a quarter-filled Hubbard-Holstein chain. The NN repulsion term induces the apparition of two new long range ordered phases (one $4k_F$ CDW for positive $U_{eff} = U-2g^2/\omega$ and one $2k_F$ CDW for negative $U_{eff}$) that did not exist in the V=0 phase diagram. These results are put into perspective with the newly observed charge ordered phases in organic conductors and an interpretation of their origin in terms of electron-molecular vibration coupling is suggested.Comment: 10 pages, 10 figure

Exploring the nature of resilience in paramedic practice: A psycho-social study

Previous research has identified that paramedics experience high levels of stress and sickness rates which have escalated in recent years due to changes to workforce restructuring. While a number of studies have investigated resilience among healthcare professionals, there is little research exploring how paramedics address work challenges and how they become resilient. Using psychosocial methodology, seven paramedics participated in Free Association Narrative interviewing; all were based at one regional centre. In line with the study design, data analysis adopted a psycho-social approach that generated four themes and 10 sub-themes which, characterised participants’ experiences. Coping and resilience was impacted upon via formal methods of support including management, debriefing and referral to outside agencies. Alongside this, more informal methods aided resilience. Informal methods included peer support, support from family and friends and the use of humour. Uniquely, this study uncovered how detachment is used to manage emotions. The study has implications for the services need to support the emotional needs of paramedics

The prognostic significance of low-frequency somatic mutations in metastatic cutaneous melanoma

Background: Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance. Methods: After limiting our DNA sequencing analysis to MM samples (n = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF). We performed Cox analysis on 53 genes that were mutated in ≥3% of samples, and had ≥50% difference in incidence of mutations in deceased subjects versus alive subjects. Results: Four genes were potentially prognostic [RAC1, FGFR1, CARD11, CIITA; false discovery rate (FDR) 75% of the samples that exhibited corresponding DNA mutations. The low frequency, UV signature type and RNA expression of the 22 genes in MM samples were confirmed in a separate multi-institution validation cohort (n = 413). An underpowered analysis within a subset of this validation cohort with available patient follow-up (n = 224) showed that somatic mutations in SPEN and RAC1 reached borderline prognostic significance [log-rank favorable (p = 0.09) and adverse (p = 0.07), respectively]. Somatic mutations in SPEN, and to a lesser extent RAC1, were not associated with definite gene copy number or RNA expression alterations. High (>2+) nuclear plus cytoplasmic expression intensity for SPEN was associated with longer melanoma-specific overall survival (OS) compared to lower (≤ 2+) nuclear intensity (p = 0.048). We conclude that expressed somatic mutations in infrequently mutated genes beyond the well-characterized ones (e.g., BRAF, RAS, CDKN2A, PTEN, TP53), such as RAC1 and SPEN, may have prognostic significance in MM

Certify Sustainable Aquaculture?

Aquaculture, the farming of aquatic organisms, provides close to 50% of the world's supply of seafood, with a value of U.S. $125 billion. It makes up 13% of the world's animal-source protein (excluding eggs and dairy) and employs an estimated 24 million people (1). With capture (i.e., wild) fisheries production stagnating, aquaculture may help close the forecast global deficit in fish protein by 2020 (2). This so-called “blue revolution” requires addressing a range of environmental and social problems, including water pollution, degradation of ecosystems, and violation of labor standards

Stress testing and non-invasive coronary angiography in patients with suspected coronary artery disease: time for a new paradigm

Diagnosis and management of coronary artery disease represents major challenges to our health care system, affecting millions of patients each year. Until recently, the diagnosis of coronary artery disease was possible only through cardiac catheterization and invasive coronary angiography. To avoid the risks of an invasive procedure, stress testing is often employed for an initial assessment of patients with suspected coronary artery disease, serving as a gatekeeper for cardiac catheterization. With the emergence of non-invasive coronary angiography, the question arises if such a strategy is still sensible, particularly, in view of only a modest agreement between stress testing results and the presence of coronary artery disease established by cardiac catheterization. Much data in support of the diagnostic accuracy and prognostic value of non-invasive coronary angiography by computed tomography have emerged within the last few years. These data challenge the role of stress testing as the initial imaging modality in patients with suspected coronary artery disease. This article reviews the clinical utility, limitations, as well as the hazards of stress testing compared with non-invasive coronary artery imaging by computed tomography. Finally, the implications of this review are discussed in relation to clinical practice