Combined palaeolimnological and ecological approach provides added value for understanding the character and drivers of recent environmental change in Flow Country lakes

The Flow Country peatlands receive national and international recognition and protection as a highly valued habitat, and also provide a number of important ecosystem services. While there has been much research on the terrestrial peatland habitat of the Flow Country, the area’s many hundreds of natural water bodies have been largely unstudied. The first part of this study therefore focuses on establishing the contemporary conditions at 18 Flow Country lakes, examining between-lake heterogeneity in terms of physical structure, water chemistry and biological communities. Temporal change in these lakes is then considered by combining contemporary ecological and palaeolimnological approaches. We examine how the diatom and chironomid communities of Flow Country lakes have changed since a time prior to the mid-nineteenth century. Results show that the lake communities today are different to those present pre-1850, containing more taxa tolerant of increased acidity and nutrient availability. General linear modelling (GLM) analysis demonstrated a statistically significant association between the extent of change in diatom communities and both dissolved organic carbon (DOC) and nitrate. Community shifts, though considerable, are shown to be complex and idiosyncratic and no shift between trophic states is indicated. The extent and type of coarse-scale community change we observed points to widespread bottom-up drivers such as land management, afforestation and/or atmospheric deposition rather than more localised management practices such as fish stocking. The benefits of combining approaches is discussed and palaeolimnological methods by which land management, afforestation and atmospheric deposition could be further disentangled are identified

South African healthcare provider perspectives on transitioning adolescents into adult HIV care

Background. The first generation of South African (SA) children perinatally infected with HIV is entering adulthood, and there is now a pressing need for systematised transfer of these patients from paediatric to adult care.Objectives. Previous research has investigated the HIV healthcare transition in North America and Europe, yet none has been conducted in SA. Our study is the first to describe the perspectives of healthcare providers overseeing the transition in resource-limited settings.Methods. We approached healthcare providers working in government paediatric HIV clinics and hospitals in the Western Cape Province, SA. Seven physicians and counsellors in adolescent/paediatric care, representing five clinics, were  interviewed, and 43 completed a written survey. Interviews addressed the current state of the transition, barriers and facilitators, and model components. Interviews were assessed for major themes using framework analysis, while logistic regression was applied to survey responses to identify associations with measured covariates.Results. Analysis of interview transcripts revealed several overarching perspectives that were corroborated by survey responses. One barrier identified was the  healthcare providers’ difficulty in letting go of their relationships with the adolescent patients. Since healthcare providers regarded their patients as particularly  vulnerable, they felt a strong and protective attachment towards them. A second barrier identified was a lack of structure and effective communication between adult and paediatric providers; accordingly, healthcare providers feared that they were transferring their adolescents unprepared, to a judgemental, depersonalised and overburdened environment. All interviewees and a majority of survey respondents (>80%) agreed that the formation of adolescent support groups in adult care clinics as well as a later transition age would improve the transition process.Conclusion. This study highlights the need for a systematic healthcare transition for HIV-positive adolescents cared for in the Western Cape, while acknowledging the limitations of the current healthcare infrastructure. Several feasible   recommendations have been identified, including forming support groups and greater involvement of adolescent healthcare providers to facilitate the transition

Trait Sensitivity, Anxiety and Personality are predictive of Central Sensitisation Symptoms in Patients with Chronic Low Back Pain.

BACKGROUND:Sensitivity-related trait characteristics involving physical and emotional sensitivities and high trait anxiety personality types have been observed in individuals with non-specific chronic low back pain (NSCLBP). High trait sensitivity to sensory stimulation combined with interpretation biases based on personality type may contribute to the development of central sensitisation (CS) symptoms. To date there is limited research that has considered both sensitivity levels and personality type in NSCLBP with CS. The purpose of this study was to investigate 1) relationships between trait sensory profiles, trait anxiety and CS symptoms, and 2) the predictive capacity of sensory profiles, trait anxiety and personality types on CS symptoms, in people with NSCLBP. METHODS:This was a cross-sectional observational study using four self-report measures on adults (N = 165, mean age = 45 +-12 SD) from physiotherapy clinics in England, Ireland and New Zealand. Inclusion: NSCLBP > 6 months, aged 18-64, predominant CS pain presentation, no other pathology. Parametric and non-parametric correlation statistics and regression analyses were used. RESULTS:Positive correlations were found between central sensitisation inventory (CSI) scores and sensory hyper-sensitivity profiles and trait anxiety. CSI score increases could be predicted by: Sensory Sensitive, Low Registration profiles, trait anxiety scores and extreme defensive high anxious personality type. CONCLUSIONS:Trait sensory hyper- and/or hypo-sensitivity and high trait-anxiety related personality type characteristics predicts the extent of CS symptoms in people with NSCLBP. Further investigation is required to establish causality between these characteristics and CS symptoms. This article is protected by copyright. All rights reserved

Atlantic overturning in decline?

Global ocean circulation is an important factor in climate variability and change. In particular, changes in the strength of the Atlantic meridional overturning circulation (AMOC) have been implicated in ancient climate events, as well as in recent climate anomalies such as the rapid warming of the North Atlantic Ocean in the mid-1990s. A series of moored current meters and temperature sensors deployed in the Atlantic at 26° N known as the RAPID-MOCHA array has been used to monitor the strength of meridional overturning since 2004. The data indicate a decline in this strength over the period 2004–20123. Here, using additional observations and climate model simulations we suggest that this measured decline is not merely a short-term fluctuation, but is part of a substantial reduction in meridional overturning occurring on a decadal timescale

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms.

OBJECTIVES: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined (18)F-fludeoxyglucose ((18)F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. MATERIALS AND METHODS: Fifteen patients with asymptomatic AAA with diameter 46 ± 7 mm underwent PET-CT with (18)F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure (18)F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. RESULTS: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n = 70,345 voxels; r = .30; p < .0001). Although regions of increased (18)F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026-0.122). (18)F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. CONCLUSIONS: Both (18)F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.This research was supported by grants from the National Institutes of Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (11/20/03), the British Heart Foundation (PG/09/083) and the Evelyn Trust (09/22). Dr. McBride is supported by the Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine. Dr. Joshi is supported by Chief Scientist Office (ETM/160). Dr. van Beek is supported by the Scottish Imaging Network e a Platform of Scientific Excellence. The work of Dr. Rudd is part-supported by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation and the Wellcome Trust. Dr. Newby is supported by the British Heart Foundation (CH/09/002). The Wellcome Trust Clinical Research Facility and the Clinical Research Imaging Centre are supported by National Health Service Research Scotland through National Health Service Lothian.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ejvs.2015.12.01

A reversal of climatic trends in the North Atlantic since 2005

In the mid-1990s the North Atlantic subpolar gyre warmed rapidly, which had important climate impacts, such as increased hurricane numbers, and changes to rainfall over Africa, Europe and North America. Evidence suggests that the warming was largely due to a strengthening of the ocean circulation, particularly the Atlantic Meridional Overturning Circulation (AMOC). Since the mid-1990s direct and indirect measurements have suggested a decline in the strength of the ocean circulation, which is expected to lead to a reduction in northward heat transport. Here we show that since 2005 a large volume of the upper North Atlantic Ocean has cooled significantly by approximately -0.45C or 1.5x10^22 J, reversing the previous warming trend. By analysing observations and a state-of-the-art climate model, we show that this cooling is consistent with a reduction in the strength of the ocean circulation and heat transport, linked to record low densities in the deep Labrador Sea. The low density in the deep Labrador Sea is primarily due to deep ocean warming since 1995, but a long-term freshening also played a role. The observed upper ocean cooling since 2005 is not consistent with the hypothesis that anthropogenic aerosols directly drive Atlantic temperatures

Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide ( average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mgm(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mgm(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mgm(-2). The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Loss of endogenous thymosin β4 accelerates glomerular disease

Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4 in the kidney is unknown. We demonstrate that thymosin β4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β4 did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β4 in the migration of these cells. Thymosin β4 knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin β4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression