Atmospherically produced beryllium-10 in annually laminated late-glacial sediments of the North American Varve Chronology

We attempt to synchronize the North American Varve Chronology (NAVC) with ice core and calendar year timescales by comparing records of atmospherically produced 10Be fallout in the NAVC and in ice cores. The North American Varve Chronology (NAVC) is a sequence of 5659 varves deposited in a series of proglacial lakes adjacent to the southeast margin of the retreating Laurentide Ice Sheet between approximately 18 200 and 12 500 years before present. Because properties of NAVC varves are related to climate, the NAVC is also a climate proxy record with annual resolution, and our overall goal is to place the NAVC and ice core records on the same timescale to facilitate high-resolution correlation of climate proxy variations in both. Total 10Be concentrations in NAVC sediments are within the range of those observed in other lacustrine records of 10Be fallout, but 9Be and 10Be concentrations considered together show that the majority of 10Be is present in glacial sediment when it enters the lake, and only a minority of total 10Be derives from atmospheric fallout at the time of sediment deposition. Because of this, an initial experiment to determine whether or not 10Be fallout variations were recorded in NAVC sediments by attempting to observe the characteristic 11-year solar cycle in short varve sections sampled at high resolution was inconclusive: short-period variations at the expected magnitude of this cycle were not distinguishable from measurement scatter. On the other hand, longer varve sequences sampled at decadal resolution display centennial-period variations in reconstructed 10Be fallout that have similar properties as coeval 10Be fallout variations recorded in ice core records. These are most prominent in glacial sections of the NAVC that were deposited in proglacial lakes and are suppressed in paraglacial sections of the NAVC that were deposited in lakes lacking direct glacial sediment input. We attribute this difference to the fact that buffering of 10Be fallout by soil adsorption can filter out short-period variations in an entirely deglaciated watershed, but such buffering cannot occur in the ablation zone of an ice sheet. This implies that proglacial lakes whose watershed is mostly glacial may effectively record 10Be fallout variations. We attempted to match centennial-period variations in reconstructed 10Be fallout flux from two segments of the NAVC with ice core fallout records. For both records, it is possible to obtain matches that result in acceptable correlation between NAVC and ice core 10Be fallout records, but the best-fitting matches for the two segments disagree, and only one of them is consistent with independent calendar year calibrations of the NAVC and therefore potentially valid. This leaves several remaining ambiguities in whether or not 10Be fallout variations can, in fact, be used for synchronizing NAVC and ice core timescales, but these could most likely be resolved by higher-resolution and replicate 10Be measurements on targeted sections of the NAVC

Making sense of the evolving nature of depression narratives and their inherent conflicts

Originally a psychiatric diagnosis fashioned by Western psychiatry in the 20th Century, depression evolved to encompass varying lineages of discourse and care. This article elucidates some of the current challenges – as well as emerging discourses – influencing the category of depression. Depression-like experiences are shaped by (at times conflicting) subjectivities, claims to knowledge, material realities, social contexts and access to resources. With no unified understanding of the category of ‘depression’ available, lay people, social and neuro scientists, GPs, psychiatrists, talking therapists and pharmaceutical companies all attempt to shape narratives of depression. The current paper focuses on patient narratives about depression – in the context of these wider debates – to better elucidate the ways in which depression discourses are publically developing along varying lines. In conclusion, the paper suggests that we could better conceptualise the resulting ‘depression(s)’ with concepts such as ‘society of mind’ and notions of subjectivity unbounded by individuals

CD4+ T Cell Effects on CD8+ T Cell Location Defined Using Bioluminescence

T lymphocytes of the CD8+ class are critical in delivering cytotoxic function and in controlling viral and intracellular infections. These cells are “helped” by T lymphocytes of the CD4+ class, which facilitate their activation, clonal expansion, full differentiation and the persistence of memory. In this study we investigated the impact of CD4+ T cells on the location of CD8+ T cells, using antibody-mediated CD4+ T cell depletion and imaging the antigen-driven redistribution of bioluminescent CD8+ T cells in living mice. We documented that CD4+ T cells influence the biodistribution of CD8+ T cells, favoring their localization to abdominal lymph nodes. Flow cytometric analysis revealed that this was associated with an increase in the expression of specific integrins. The presence of CD4+ T cells at the time of initial CD8+ T cell activation also influences their biodistribution in the memory phase. Based on these results, we propose the model that one of the functions of CD4+ T cell “help” is to program the homing potential of CD8+ T cells

DCE-MRI perfusion and permeability parameters as predictors of tumor response to CCRT in patients with locally advanced NSCLC

In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and permeability parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp) were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with V e and its standard variation V e-SD and positively correlated with K trans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve-SD, MTT, BV-SD and MTT-SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. © 2016 The Author(s)

How do we improve men’s mental health via primary care? An evaluation of the Atlas Men’s Well-being Pilot Programme for stressed/distressed men

Background Over three-quarters of all suicides are men (England and Wales), this is despite higher levels of anxiety and depression being reported by women. This disparity may in part be explained by atypical presentations of distress in men, and gendered issues around help-seeking. Consequently, the Atlas Men’s Well-being Programme was designed to engage stressed/distressed men who were patients at a London-based GP surgery. Atlas encouraged GPs to identify and refer men for counselling and/or acupuncture by raising their awareness of men’s distress. The aim of this pilot study was to evaluate Atlas in terms of patients’ characteristics, service utilisation, patient outcomes and cost implications. Methods All patients using the Programme were asked to complete a questionnaire before and after their Atlas sessions. Outcome measures included the Hospital Anxiety and Depression scale, Perceived Stress Scale, Warwick-Edinburgh Mental Well-being Scale, a 11-point scale measuring physical health, and the Psychological Outcome Profiles (PSYCHLOPS), a patient-generated outcome measure. Additionally, for cost calculations, participants were asked about their employment, number of days off work due to illness, and their health and social care service use. Results 102 participants were recruited, 82 completed pre- and post-treatment questionnaires. Comparisons pre- and post-treatment revealed a statistically significant improvement in anxious mood (p <0.001), perceived stress (p < 0.001), positive well-being (p = <0.001), PSYCHLOPS (p = <0.001) and physical health (p = 0.001), though not depressed mood (p = 0.660). Additionally, reductions in costs related to lost employment and health and social care use, exceeded the cost of Atlas counselling and acupuncture sessions, with an average saving of nearly £700 per patient. Conclusions Atlas attendance was associated with improvements in patients’ mental and physical health, and demonstrated likely cost savings. It is now important to understand patient and stakeholder perspectives. Further research could compare usual care with the Atlas approach, and investigate full cost-effectiveness

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

We are grateful to the families and individuals who took part in the GS:SFHS and UKB studies, and to all those involved in participant recruitment, data collection, sample processing and QC, including academic researchers, clinical staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/ 14/Z. We acknowledge with gratitude the financial support received from the Dr Mortimer and Theresa Sackler Foundation. This research has been conducted using the GS:SFHS and UK Biobank (project #4844) resources. GS:SFHS received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. UKB was established using funding from the Wellcome Trust, Medical Research Council, the Scottish Government Department of Health, and the Northwest Regional Development Agency. DJP, IJD, TCR and AMM are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). TCR is supported by Alzheimer's Scotland, through the Marjorie MacBeath bequest. Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. We are grateful for the use of summary data from the International Genomics of Alzheimer's Project and the Major Depressive Disorder working group of the Psychiatric Genomics Consortium.Peer reviewedPublisher PD

CD4+ T Cell-Derived IL-2 Signals during Early Priming Advances Primary CD8+ T Cell Responses

Stimulating naïve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansion and effector functions. In this study, we show that the activation and differentiation of CD8+ T cells require IL-2 provided by activated CD4+ T cells at the initial priming stage within 0–2.5 hours after stimulation. This critical IL-2 signal from CD4+ cells is mediated through the IL-2Rβγ of CD8+ cells, which is independent of IL-2Rα. The activation of IL-2 signaling advances the restriction point of the cell cycle, and thereby expedites the entry of antigen-stimulated CD8+ T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNγ and granzyme B produced by CD8+ T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8+ T-cell response is elicited by a critical temporal function of IL-2 released from CD4+ T cells, providing mechanistic insights into the regulation of CD8+ T cell activation and differentiation

A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization

Is it feasible and effective to provide osteopathy and acupuncture for patients with musculoskeletal problems in a GP setting? A service evaluation

<p>Abstract</p> <p>Background</p> <p>Spinal manipulation and acupuncture can be helpful in reducing the symptoms of musculoskeletal (MSK) pain. Both approaches are currently recommended by NICE as treatment options for patients with persistent low back pain. However, there has been no previous evaluation of a GP service using them together for MSK pain. The purpose of this study was to evaluate acceptability and outcomes for an osteopathy and acupuncture service (delivered by complementary therapy practitioners) for patients with MSK problems provided within a General Practice.</p> <p>Methods</p> <p>Patients were asked to complete a questionnaire before and after their course of treatment. Outcome measures included the Bournemouth Questionnaire (measuring MSK problems), EuroQoL-5D (measuring quality of life), medication use, physical activity and general well-being. Non-parametric tests were used to compare pre- and post- treatment variables. Qualitative data, regarding participants' views on the service, were collected from patients via a service survey and healthcare professionals via interviews. Qualitative data were analysed using thematic analysis.</p> <p>Results</p> <p>123 adults with MSK problems were referred into the service (79 female and 44 male, mean age 49 years). Complete patient questionnaire data sets (pre- and post- treatment) were available for 102 participants; 91 completed a service survey. All healthcare professionals involved in the service participated in interviews including all seven GPs and the administration manager at the practice, as well as the three acupuncture/osteopathy practitioners.</p> <p>Patient outcomes: comparisons between pre and post-treatment revealed a statistically significant improvement in MSK pain (p < 0.0001) and quality of life (p < 0.0001), and a statistically significant reduction in medication use (p < 0.0001). Qualitative analysis found that patients reported improvements in their MSK pain, mobility, other physical health conditions, well-being and self-management of their MSK problem.</p> <p>Acceptability of the service: overall patients and healthcare professionals were satisfied with the service and its provision within the Practice. Patients reported wanting increased appointment availability and flexibility, and more sessions. Complementary therapy practitioners reported finding the high number of referrals of chronic patients challenging, and wanting increased communication with GPs.</p> <p>Conclusions</p> <p>Provision of acupuncture and osteopathy for MSK pain is achievable in General Practice. A GP surgery can quickly adapt to incorporate complementary therapy provided key principles are followed.</p