Skin- and gut-homing molecules on human circulating gamma delta T cells and their dysregulation in inflammatory bowel disease

Changes in phenotype and function of γδ T cells have been reported in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Dysregulation of lymphocyte migration plays a key role in IBD pathogenesis; however, data on migratory properties of γδ T cells are scarce. Human circulating γδ T cells from healthy controls (n = 27), patients with active CD (n = 15), active UC (n = 14) or cutaneous manifestations of IBD (n = 2) were characterized by flow cytometry. Circulating γδ T cells in healthy controls were CD3(hi) and expressed CD45RO. They expressed gut-homing molecule β7 but not gut-homing molecule corresponding chemokine receptors (CCR)9, or skin-homing molecules cutaneous lymphocyte-associated antigen (CLA) and CCR4, despite conventional T cells containing populations expressing these molecules. CCR9 expression was increased on γδ T cells in CD and UC, while skin-homing CLA was expressed aberrantly on γδ T cells in patients with cutaneous manifestations of IBD. Lower levels of CD3 expression were found on γδ T cells in CD but not in UC, and a lower proportion of γδ T cells expressed CD45RO in CD and UC. Enhanced expression of gut-homing molecules on circulating γδ T cells in IBD and skin-homing molecules in cutaneous manifestations of IBD may be of clinical relevance

Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

Developing culturally safe education practices in optometry schools across Australia and Aotearoa New Zealand

Access to culturally safe health services is a basic human right, however through the lasting effects of colonisation, oppression, and systemic racism, the individual and community health of Indigenous peoples in Australia and Aotearoa New Zealand have been severely impacted. The Aboriginal and Torres Strait Islander Health and Cultural Safety Strategy of the Australian Health Practitioners Regulation Agency, and the Standards of Cultural Competence and Cultural Safety of the Optometrists and Dispensing Opticians Board of New Zealand, recognise the importance of access to safe health care for Aboriginal, Torres Strait Islander and Māori patients, which encompasses both clinical competency and cultural safety. Universities have an ongoing responsibility to ensure their learning and teaching activities result in graduates being able to provide culturally safe practice. This article highlights the emergence of culturally safe practices in the Australian and Aotearoa New Zealand optometry curricula over the last five years incorporating Indigenous ways of knowing, being and doing into the curricula, understanding the local Indigenous histories and contexts, the adoption of online cultural education modules, and clinical placement partnerships with local Indigenous communities. Whilst there is still much work to do to achieve the goal of graduating culturally safe optometrists, this paper focuses on features that enable or impede progress in the development of culturally safe practices within the optometry programmes to improve eye health equity for Indigenous recognise the diversity of Indigenous cultures across Australia and NZ

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD

Investor heterogeneity and the cross-section of U.K. investment trust performance

We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance

Ultrasound, CT, MRI, or PET-CT for staging and re-staging of adults with cutaneous melanoma.

BACKGROUND: Melanoma is one of the most aggressive forms of skin cancer, with the potential to metastasise to other parts of the body via the lymphatic system and the bloodstream. Melanoma accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Various imaging tests can be used with the aim of detecting metastatic spread of disease following a primary diagnosis of melanoma (primary staging) or on clinical suspicion of disease recurrence (re-staging). Accurate staging is crucial to ensuring that patients are directed to the most appropriate and effective treatment at different points on the clinical pathway. Establishing the comparative accuracy of ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT imaging for detection of nodal or distant metastases, or both, is critical to understanding if, how, and where on the pathway these tests might be used. OBJECTIVES: Primary objectivesWe estimated accuracy separately according to the point in the clinical pathway at which imaging tests were used. Our objectives were:• to determine the diagnostic accuracy of ultrasound or PET-CT for detection of nodal metastases before sentinel lymph node biopsy in adults with confirmed cutaneous invasive melanoma; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging in adults with cutaneous invasive melanoma:○ for detection of any metastasis in adults with a primary diagnosis of melanoma (i.e. primary staging at presentation); and○ for detection of any metastasis in adults undergoing staging of recurrence of melanoma (i.e. re-staging prompted by findings on routine follow-up).We undertook separate analyses according to whether accuracy data were reported per patient or per lesion.Secondary objectivesWe sought to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for whole body imaging (detection of any metastasis) in mixed or not clearly described populations of adults with cutaneous invasive melanoma.For study participants undergoing primary staging or re-staging (for possible recurrence), and for mixed or unclear populations, our objectives were:• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of nodal metastases;• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases; and• to determine the diagnostic accuracy of ultrasound, CT, MRI, or PET-CT for detection of distant metastases according to metastatic site. SEARCH METHODS: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists as well as published systematic review articles. SELECTION CRITERIA: We included studies of any design that evaluated ultrasound (with or without the use of fine needle aspiration cytology (FNAC)), CT, MRI, or PET-CT for staging of cutaneous melanoma in adults, compared with a reference standard of histological confirmation or imaging with clinical follow-up of at least three months' duration. We excluded studies reporting multiple applications of the same test in more than 10% of study participants. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2)). We estimated accuracy using the bivariate hierarchical method to produce summary sensitivities and specificities with 95% confidence and prediction regions. We undertook analysis of studies allowing direct and indirect comparison between tests. We examined heterogeneity between studies by visually inspecting the forest plots of sensitivity and specificity and summary receiver operating characteristic (ROC) plots. Numbers of identified studies were insufficient to allow formal investigation of potential sources of heterogeneity. MAIN RESULTS: We included a total of 39 publications reporting on 5204 study participants; 34 studies reporting data per patient included 4980 study participants with 1265 cases of metastatic disease, and seven studies reporting data per lesion included 417 study participants with 1846 potentially metastatic lesions, 1061 of which were confirmed metastases. The risk of bias was low or unclear for all domains apart from participant flow. Concerns regarding applicability of the evidence were high or unclear for almost all domains. Participant selection from mixed or not clearly defined populations and poorly described application and interpretation of index tests were particularly problematic.The accuracy of imaging for detection of regional nodal metastases before sentinel lymph node biopsy (SLNB) was evaluated in 18 studies. In 11 studies (2614 participants; 542 cases), the summary sensitivity of ultrasound alone was 35.4% (95% confidence interval (CI) 17.0% to 59.4%) and specificity was 93.9% (95% CI 86.1% to 97.5%). Combining pre-SLNB ultrasound with FNAC revealed summary sensitivity of 18.0% (95% CI 3.58% to 56.5%) and specificity of 99.8% (95% CI 99.1% to 99.9%) (1164 participants; 259 cases). Four studies demonstrated lower sensitivity (10.2%, 95% CI 4.31% to 22.3%) and specificity (96.5%,95% CI 87.1% to 99.1%) for PET-CT before SLNB (170 participants, 49 cases). When these data are translated to a hypothetical cohort of 1000 people eligible for SLNB, 237 of whom have nodal metastases (median prevalence), the combination of ultrasound with FNAC potentially allows 43 people with nodal metastases to be triaged directly to adjuvant therapy rather than having SLNB first, at a cost of two people with false positive results (who are incorrectly managed). Those with a false negative ultrasound will be identified on subsequent SLNB.Limited test accuracy data were available for whole body imaging via PET-CT for primary staging or re-staging for disease recurrence, and none evaluated MRI. Twenty-four studies evaluated whole body imaging. Six of these studies explored primary staging following a confirmed diagnosis of melanoma (492 participants), three evaluated re-staging of disease following some clinical indication of recurrence (589 participants), and 15 included mixed or not clearly described population groups comprising participants at a number of different points on the clinical pathway and at varying stages of disease (1265 participants). Results for whole body imaging could not be translated to a hypothetical cohort of people due to paucity of data.Most of the studies (6/9) of primary disease or re-staging of disease considered PET-CT, two in comparison to CT alone, and three studies examined the use of ultrasound. No eligible evaluations of MRI in these groups were identified. All studies used histological reference standards combined with follow-up, and two included FNAC for some participants. Observed accuracy for detection of any metastases for PET-CT was higher for re-staging of disease (summary sensitivity from two studies: 92.6%, 95% CI 85.3% to 96.4%; specificity: 89.7%, 95% CI 78.8% to 95.3%; 153 participants; 95 cases) compared to primary staging (sensitivities from individual studies ranged from 30% to 47% and specificities from 73% to 88%), and was more sensitive than CT alone in both population groups, but participant numbers were very small.No conclusions can be drawn regarding routine imaging of the brain via MRI or CT. AUTHORS' CONCLUSIONS: Review authors found a disappointing lack of evidence on the accuracy of imaging in people with a diagnosis of melanoma at different points on the clinical pathway. Studies were small and often reported data according to the number of lesions rather than the number of study participants. Imaging with ultrasound combined with FNAC before SLNB may identify around one-fifth of those with nodal disease, but confidence intervals are wide and further work is needed to establish cost-effectiveness. Much of the evidence for whole body imaging for primary staging or re-staging of disease is focused on PET-CT, and comparative data with CT or MRI are lacking. Future studies should go beyond diagnostic accuracy and consider the effects of different imaging tests on disease management. The increasing availability of adjuvant therapies for people with melanoma at high risk of disease spread at presentation will have a considerable impact on imaging services, yet evidence for the relative diagnostic accuracy of available tests is limited

Evidence and ideology as a rationale for light-therapy in Russia: from the Soviet Union to the present day.

Light therapy is still used to treat a number of common diseases in Russia. The practice is firmly anchored in history: Soviet clinical practice was divorced from the emerging field of evidence-based medicine. Medical researchers were cut off from international medical research and scientific literature, with much Soviet scientific activity based on a particular socialist ideology. In this study, the use of light therapy serves as a case study to explore tensions between international evidence-based medicine and practices developed in isolation under the Soviet Union, the legacy of which is to the detriment of many patients today. We used four different search methods to uncover scientific and grey literature, both historical and contemporary. We assessed the changing frequency of publications over time and contrasted the volume of literature on light therapy with more orthodox treatments such as statins and painkillers. Our search found an increasing number and comparatively large body of scientific publications on light therapy in the Russian language, and many publications emanating from prestigious Russian institutions. Combined with our analysis of the historical literature and our appraisal of 22 full text articles, this leads us to suggest that light therapy entered mainstream Soviet medical practice before the Stalinist period and still occupies an important position in contemporary Russian clinical practice. We propose that this outdated treatment survives in Russia in part due to the political, economic and social forces that helped to popularize it during Soviet times, and by the seeming justification offered by poorly executed studies

Combining a leadership course and multi-source feedback has no effect on leadership skills of leaders in postgraduate medical education. An intervention study with a control group

<p>Abstract</p> <p>Background</p> <p>Leadership courses and multi-source feedback are widely used developmental tools for leaders in health care. On this background we aimed to study the additional effect of a leadership course following a multi-source feedback procedure compared to multi-source feedback alone especially regarding development of leadership skills over time.</p> <p>Methods</p> <p>Study participants were consultants responsible for postgraduate medical education at clinical departments. Study design: pre-post measures with an intervention and control group. The intervention was participation in a seven-day leadership course. Scores of multi-source feedback from the consultants responsible for education and respondents (heads of department, consultants and doctors in specialist training) were collected before and one year after the intervention and analysed using Mann-Whitney's U-test and Multivariate analysis of variances.</p> <p>Results</p> <p>There were no differences in multi-source feedback scores at one year follow up compared to baseline measurements, either in the intervention or in the control group (p = 0.149).</p> <p>Conclusion</p> <p>The study indicates that a leadership course following a MSF procedure compared to MSF alone does not improve leadership skills of consultants responsible for education in clinical departments. Developing leadership skills takes time and the time frame of one year might have been too short to show improvement in leadership skills of consultants responsible for education. Further studies are needed to investigate if other combination of initiatives to develop leadership might have more impact in the clinical setting.</p

The Protection of Animals through Human Rights. The Case-Law of the European Court of Human Rights

The chapter discusses the potential of a human rights framework to contribute to the growth and development of global animal law. It takes as example the jurisprudence of the European Court of Human Rights, and examine the major trends in the Court’s judgments and admissibility decisions that directly or indirectly concern the rights or welfare of animals. It is concluded that the Court is not indifferent to the welfare of animals, but that animal welfare is instrumentalised: it is understood not as a good in itself, but is instead valued for its implications for human welfare and rights. The chapter then considers the obstacles that the anthropocentrism of the human rights idea and the instrumentalisation of animal concerns present to the use of human rights frameworks to further the development of global animal law, as well as the opportunities that exist in the meeting of these paradigms. It concludes that although the telos of human rights law is different from that of animal law, nevertheless there exist many overlapping concerns within which mutually beneficial interactions are possible