Verifying likelihoods for low template DNA profiles using multiple replicates

AbstractTo date there is no generally accepted method to test the validity of algorithms used to compute likelihood ratios (LR) evaluating forensic DNA profiles from low-template and/or degraded samples. An upper bound on the LR is provided by the inverse of the match probability, which is the usual measure of weight of evidence for standard DNA profiles not subject to the stochastic effects that are the hallmark of low-template profiles. However, even for low-template profiles the LR in favour of a true prosecution hypothesis should approach this bound as the number of profiling replicates increases, provided that the queried contributor is the major contributor. Moreover, for sufficiently many replicates the standard LR for mixtures is often surpassed by the low-template LR. It follows that multiple LTDNA replicates can provide stronger evidence for a contributor to a mixture than a standard analysis of a good-quality profile. Here, we examine the performance of the likeLTD software for up to eight replicate profiling runs. We consider simulated and laboratory-generated replicates as well as resampling replicates from a real crime case. We show that LRs generated by likeLTD usually do exceed the mixture LR given sufficient replicates, are bounded above by the inverse match probability and do approach this bound closely when this is expected. We also show good performance of likeLTD even when a large majority of alleles are designated as uncertain, and suggest that there can be advantages to using different profiling sensitivities for different replicates. Overall, our results support both the validity of the underlying mathematical model and its correct implementation in the likeLTD software

The influence of barefoot and barefoot inspired footwear on the kinetics and kinematics of running in comparison to conventional running shoes.

Barefoot running has experienced a resurgence in footwear biomechanics literature, based on the supposition that it serves to reduce the occurrence of overuse injuries in comparison to conventional shoe models. This consensus has lead footwear manufacturers to develop shoes which aim to mimic the mechanics of barefoot locomotion. This study compared the impact kinetics and 3-D joint angular kinematics observed whilst running: barefoot, in conventional cushioned running shoes and in shoes designed to integrate the perceived benefits of barefoot locomotion. The aim of the current investigation was therefore to determine whether differences in impact kinetics exist between the footwear conditions and whether shoes which aim to simulate barefoot movement patterns can closely mimic the 3-D kinematics of barefoot running. Twelve participants ran at 4.0 m.s-1±5% in each footwear condition. Angular joint kinematics from the hip, knee and ankle in the sagittal, coronal and transverse planes were measured using an eight camera motion analysis system. In addition simultaneous tibial acceleration and ground reaction forces were obtained. Impact parameters and joint kinematics were subsequently compared using repeated measures ANOVAs. The kinematic analysis indicates that in comparison to the conventional and barefoot inspired shoes that running barefoot was associated significantly greater plantar-flexion at footstrike and range of motion to peak dorsiflexion. Furthermore, the kinetic analysis revealed that compared to the conventional footwear impact parameters were significantly greater in the barefoot condition. Therefore this study suggests that barefoot running is associated with impact kinetics linked to an increased risk of overuse injury, when compared to conventional shod running. Furthermore, the mechanics of the shoes which aim to simulate barefoot movement patterns do not appear to closely mimic the kinematics of barefoot locomotion

Suppressors of cytokine signaling: Relevance to gastrointestinal function and disease

AbstractBackground & Aims: The suppressor of cytokine signaling (SOCS) proteins are a family of Src homology 2 domain-containing proteins. Currently, there are 8 members of the SOCS family, of which a number have been implicated strongly in the negative regulation of cytokine signal transduction pathways. Methods: This review focuses on recent discoveries about 4 SOCS family members, SOCS-1, -2, and -3, and cytokine-inducible SH2-domain containing (CIS), and provides more limited information about other SOCS family members. Results: A large number of cytokines and growth factors are now known to induce SOCS proteins. In turn, SOCS inhibit the actions of a growing number of cytokines and growth factors in vitro or in vivo. SOCS proteins exert their inhibitory effects at the level of activation of janus kinases (JAKs) or by competing with transcription factors for binding sites on activated cytokine receptors. SOCS proteins also may mediate the ubiquitination and subsequent degradation of the SOCS protein and its bound signaling complex. Genetic modification of SOCS genes in mice has revealed crucial roles in the negative regulation of a number of important physiologic parameters including interferon γ activity, growth, blood cell production, and placental development. Conclusions: Information about SOCS action in gastrointestinal function and disease is only just emerging, but available data indicate a role in growth of gastrointestinal tissues, inflammatory bowel disease, and cancer.GASTROENTEROLOGY 2002;123:2064-208

Financial incentives for large-scale wetland restoration: beyond markets to common asset trusts

Wetlands provide $47.4 trillion/year worth of ecosystem services globally and support immense biodiversity, yet face widespread drainage and pollution, and large-scale wetlands restoration is urgently needed. Payment for ecosystem service (PES) schemes provide a viable avenue for funding large-scale wetland restoration. However, schemes around the globe differ substantially in their goals, structure, challenges, and effectiveness in supporting large-scale wetland restoration. Here, we suggest wetland-based PES schemes use common asset trusts (CATs) to build investment portfolios of wetlands across landscapes that sustain and enhance overall provision of multiple ecosystem services. CATs can meet the needs of multiple investors, permit bundled payments, and provide flexibility to invest in the restoration of numerous services/values, all using a coordinated, highly collaborative, prioritized, and transparent process. CATs would support financial viability, facilitate efficiency to reduce administrative burdens, and enable credibility and social licence building to restore wetland values and services globally

Experiences of Self-Management Support Following a Stroke: A Meta-Review of Qualitative Systematic Reviews

Abstract Backgroun

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

Design Thinking for Social Innovation in Health Care

Design has a potential to envision alternative futures for health care through new forms of innovation. In this paper, we propose a strategic framework for fostering a culture of design thinking for social innovation in health care. Drawing upon the theory of design (and its thinking), in conjunction with global and national health care strategies and policies, we critically reflect on pedagogical approaches for enhancing the curriculum in design as a means of discussing the need for new thinking in health. Findings to date suggest that new mechanisms of knowledge acquisition, application, and exploration are needed to address the complex challenges facing social and health care. Referring to the national health care strategies, connections are made with design thinking, social innovation, health and social care to facilitate a transition from applying design as a process to applying design as a strategy for cultural transformation

Design and evaluation of virtual human mediated tasks for assessment of depression and anxiety

Virtual human technologies are now being widely explored as therapy tools for mental health disorders including depression and anxiety. These technologies leverage the ability of the virtual agents to engage in naturalistic social interactions with a user to elicit behavioural expressions which are indicative of depression and anxiety. Research efforts have focused on optimising the human-like expressive capabilities of the virtual human, but less attention has been given to investigating the effect of virtual human mediation on the expressivity of the user. In addition, it is still not clear what an optimal task is or what task characteristics are likely to sustain long term user engagement. To this end, this paper describes the design and evaluation of virtual human-mediated tasks in a user study of 56 participants. Half the participants complete tasks guided by a virtual human, while the other half are guided by text on screen. Self-reported PHQ9 scores, biosignals and participants' ratings of tasks are collected. Findings show that virtual-human mediation influences behavioural expressiveness and this observation differs for different depression severity levels. It further shows that virtual human mediation improves users' disposition towards tasks

Experiences of Self-Management Support Following a Stroke: A Meta-Review of Qualitative Systematic Reviews

Supporting self-management in stroke patients improves psychological and functional outcomes but evidence on how to achieve this is sparse. We aimed to synthesise evidence from systematic reviews of qualitative studies in an overarching meta-review to inform the delivery and development of self-management support interventions.We systematically searched eight electronic databases including MEDLINE, EMBASE and CINAHL for qualitative systematic reviews (published January 1993 to June 2012). We included studies exploring patients', carers' or health care professionals' experiences relevant to self-management support following a stroke, including studies describing the lived experience of surviving a stroke. We meta-synthesised the included review findings using a meta-ethnographic framework.Seven reviews, reporting 130 unique studies, were included. Themes emerging from the reviews were pertinent, consistent and showed data saturation; though explicit mention of self-management support was rare. Our meta-review highlighted the devastating impact of stroke on patients' self-image; the varying needs for self-management support across the trajectory of recovery; the need for psychological and emotional support throughout recovery particularly when physical recovery plateaus; the considerable information needs of patients and carers which also vary across the trajectory of recovery; the importance of good patient-professional communication; the potential benefits of goal-setting and action-planning; and the need for social support which might be met by groups for stroke survivors.The observed data saturation suggests that, currently, no further qualitative research simply describing the lived experience of stroke is needed; we propose that it would be more useful to focus on qualitative research informing self-management support interventions and their implementation. Our findings demonstrate both the on-going importance of self-management support and the evolving priorities throughout the stages of recovery following a stroke. The challenge now is to ensure these findings inform routine practice and the development of interventions to support self-management amongst stroke survivors

A systematic review of tests for lymph node status in primary endometrial cancer

<p>Abstract</p> <p>Background</p> <p>The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer.</p> <p>Methods</p> <p>Relevant articles were identified form MEDLINE (1966–2006), EMBASE (1980–2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests.</p> <p>Results</p> <p>MRI (pooled positive LR 26.7, 95% CI 10.6 – 67.6 and negative LR 0.29 95% CI 0.17 – 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 – 53.2 and negative LR 0.22, 95% CI 0.1 – 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 – 7.3 and negative LR of 0.62, 95% CI 0.45 – 0.86. There was only one study that reported the use of ultrasound scanning.</p> <p>Conclusion</p> <p>MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.</p