Diagnostic Challenges in Sepsis.

Purpose of Review: Sepsis is a leading cause of death worldwide. Groundbreaking international collaborative efforts have culminated in the widely accepted surviving sepsis guidelines, with iterative improvements in management strategies and definitions providing important advances in care for patients. Key to the diagnosis of sepsis is identification of infection, and whilst the diagnostic criteria for sepsis is now clear, the diagnosis of infection remains a challenge and there is often discordance between clinician assessments for infection. Recent Findings: We review the utility of common biochemical, microbiological and radiological tools employed by clinicians to diagnose infection and explore the difficulty of making a diagnosis of infection in severe inflammatory states through illustrative case reports. Finally, we discuss some of the novel and emerging approaches in diagnosis of infection and sepsis. Summary: While prompt diagnosis and treatment of sepsis is essential to improve outcomes in sepsis, there remains no single tool to reliably identify or exclude infection. This contributes to unnecessary antimicrobial use that is harmful to individuals and populations. There is therefore a pressing need for novel solutions. Machine learning approaches using multiple diagnostic and clinical inputs may offer a potential solution but as yet these approaches remain experimental

The use of biomedicine, complementary and alternative medicine, and ethnomedicine for the treatment of epilepsy among people of South Asian origin in the UK

Studies have shown that a significant proportion of people with epilepsy use complementary and alternative medicine (CAM). CAM use is known to vary between different ethnic groups and cultural contexts; however, little attention has been devoted to inter-ethnic differences within the UK population. We studied the use of biomedicine, complementary and alternative medicine, and ethnomedicine in a sample of people with epilepsy of South Asian origin living in the north of England. Interviews were conducted with 30 people of South Asian origin and 16 carers drawn from a sampling frame of patients over 18 years old with epilepsy, compiled from epilepsy registers and hospital databases. All interviews were tape-recorded, translated if required and transcribed. A framework approach was adopted to analyse the data. All those interviewed were taking conventional anti-epileptic drugs. Most had also sought help from traditional South Asian practitioners, but only two people had tried conventional CAM. Decisions to consult a traditional healer were taken by families rather than by individuals with epilepsy. Those who made the decision to consult a traditional healer were usually older family members and their motivations and perceptions of safety and efficacy often differed from those of the recipients of the treatment. No-one had discussed the use of traditional therapies with their doctor. The patterns observed in the UK mirrored those reported among people with epilepsy in India and Pakistan. The health care-seeking behaviour of study participants, although mainly confined within the ethnomedicine sector, shared much in common with that of people who use global CAM. The appeal of traditional therapies lay in their religious and moral legitimacy within the South Asian community, especially to the older generation who were disproportionately influential in the determination of treatment choices. As a second generation made up of people of Pakistani origin born in the UK reach the age when they are the influential decision makers in their families, resort to traditional therapies may decline. People had long experience of navigating plural systems of health care and avoided potential conflict by maintaining strict separation between different sectors. Health care practitioners need to approach these issues with sensitivity and to regard traditional healers as potential allies, rather than competitors or quacks

Cooperation and Contagion in Web-Based, Networked Public Goods Experiments

A longstanding idea in the literature on human cooperation is that cooperation should be reinforced when conditional cooperators are more likely to interact. In the context of social networks, this idea implies that cooperation should fare better in highly clustered networks such as cliques than in networks with low clustering such as random networks. To test this hypothesis, we conducted a series of web-based experiments, in which 24 individuals played a local public goods game arranged on one of five network topologies that varied between disconnected cliques and a random regular graph. In contrast with previous theoretical work, we found that network topology had no significant effect on average contributions. This result implies either that individuals are not conditional cooperators, or else that cooperation does not benefit from positive reinforcement between connected neighbors. We then tested both of these possibilities in two subsequent series of experiments in which artificial seed players were introduced, making either full or zero contributions. First, we found that although players did generally behave like conditional cooperators, they were as likely to decrease their contributions in response to low contributing neighbors as they were to increase their contributions in response to high contributing neighbors. Second, we found that positive effects of cooperation were contagious only to direct neighbors in the network. In total we report on 113 human subjects experiments, highlighting the speed, flexibility, and cost-effectiveness of web-based experiments over those conducted in physical labs

Gender difference in symptomatic radiographic knee osteoarthritis in the Knee Clinical Assessment – CAS(K): A prospective study in the general population

<p>Abstract</p> <p>Background</p> <p>A recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis (knee ROA) in symptomatic males compared to females. This was independent of age, BMI and other clinical signs and symptoms. Since this finding contradicts many previous studies, our objective was to explore four possible explanations for this gender difference: X-ray views, selection, occupation and non-articular conditions.</p> <p>Methods</p> <p>A community-based prospective study. 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal questionnaires to a research clinic involving plain radiography (weight-bearing posteroanterior semiflexed, supine skyline and lateral views), clinical interview and physical examination. Any knee ROA, ROA severity, tibiofemoral joint osteoarthritis (TJOA) and patellofemoral joint osteoarthritis (PJOA) were defined using all three radiographic views. Occupational class was derived from current or last job title. Proportions of each gender with symptomatic knee ROA were expressed as percentages, stratified by age; differences between genders were expressed as percentage differences with 95% confidence intervals.</p> <p>Results</p> <p>745 symptomatic participants were eligible and had complete X-ray data. Males had a higher occurrence (77%) of any knee ROA than females (61%). In 50–64 year olds, the excess in men was mild knee OA (particularly PJOA); in ≥65 year olds, the excess was both mild and moderate/severe knee OA (particularly combined TJOA/PJOA). This male excess persisted when using the posteroanterior view only (64% vs. 52%). The lowest level of participation in the clinic was symptomatic females aged 65+. Within each occupational class there were more males with symptomatic knee ROA than females. In those aged 50–64 years, non-articular conditions were equally common in both genders although, in those aged 65+, they occurred more frequently in symptomatic females (41%) than males (31%).</p> <p>Conclusion</p> <p>The excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views. Although prior occupational exposures and the presence of non-articular conditions cannot be fully excluded, selective non-participation bias seems the most likely explanation. This has implications for future study design.</p

Improving the sensitivity of Higgs boson searches in the golden channel

Leptonic decays of the Higgs boson in the ZZ* channel yield what is known as the golden channel due to its clean signature and good total invariant mass resolution. In addition, the full kinematic distribution of the decay products can be reconstructed, which, nonetheless, is not taken into account in traditional search strategy relying only on measurements of the total invariant mass. In this work we implement a type of multivariate analysis known as the matrix element method, which exploits differences in the full production and decay matrix elements between the Higgs boson and the dominant irreducible background from q bar{q} -> ZZ*. Analytic expressions of the differential distributions for both the signal and the background are also presented. We perform a study for the Large Hadron Collider at sqrt{s}=7 TeV for Higgs masses between 175 and 350 GeV. We find that, with an integrated luminosity of 2.5 fb^-1 or higher, improvements in the order of 10 - 20 % could be obtained for both discovery significance and exclusion limits in the high mass region, where the differences in the angular correlations between signal and background are most pronounced.Comment: 31 pages, 8 figures. v2: Minus signs in definitions of angles corrected. Typos fixed. Reference added. Cosmetic changes to Figure 4. Additional sentence added for clarificatio

The Law of Society: Governance Through Contract

This paper focuses on contract law as a central field in contemporary regulatory practice. In recent years, governance by contract has emerged as the central concept in the context of domestic privatization, domestic and transnational commercial relations and law-and-development projects. Meanwhile, as a result of the neo-formalist attack on contract law, governance of contract through contract adjudication, consumer protection law and judicial intervention into private law relations has come under severe pressure. Building on early historical critique of the formalist foundations of an allegedly private law of the market, the paper assesses the current justifications for contractual governance and posits that only an expanded legal realist perspective can adequately explain the complex nature of contractual agreements in contemporary practice. The paper argues for an understanding of contracts as complex societal arrangements that visibilize and negotiate conflicting rationalities and interests. Institutionally, contractual governance has been unfolding in a complex, historically grown and ideologically continually contested regulatory field. Governance through contract, then, denotes a wide field of conflicting concepts, ideas and symbols, that are themselves deeply entrenched in theories of society, market and the state. From this perspective, we are well advised to study contracts in their socio-economic, historical and cultural context. A careful reading of scholars such as Henry Sumner Maine, Morris Cohen, Robert Hale, Karl Llewellyn, Stewart Macaulay and Ian Macneil offers a deeper understanding of the institutional and normative dimensions of contractual governance. Their analysis is particularly helpful in assessing currently ongoing shifts away from a welfare state based regulation (governance) of contractual relations. Such shifts are occurring on two levels. First, they take place against the backdrop of a neo-liberal critique of government interference into allegedly private relations. Secondly, the increasingly influential return to formalism in contract law, which privileges a functionalist, purportedly technical and autonomous design and execution of contractual agreements over the view of regulated contracts, is linked to a particular concept of sovereignty. The ensuing revival of freedom of contract occurs in remarkable neglect of the experiences of welfare state adjudication of private law adjudication and a continuing contestation of the political in private relationships. The paper takes up the Legal Realists\u27 search for the \u27basis of contract\u27, but seeks to redirect the focus from the traditional perspective on state vs. market to a disembedded understanding of contractual governance as delineating multipolar and multirational regulatory regimes. Where Globalization has led to a fragmentation, disembeddedness and transnationalization of contexts and, thus, has been challenging traditional understanding of embeddedness, the task should no longer be to try applying a largely nation-state oriented Legal Realist perspective and critique to the sphere of contemporary contractual governance, but - rather - to translate its aims into a more reflexive set of instruments of legal critique. Even if Globalization has led to a dramatic denationalization of many regulatory fields and functions, it is still not clear, whether and how Globalization replaces, complements or aggravates transformations of societal governance, with and through contract

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

Peer reviewedPublisher PD