Evidence of Balanced Diversity at the Chicken Interleukin 4 Receptor Alpha Chain Locus

Background: The comparative analysis of genome sequences emerging for several avian species with thefully sequenced chicken genome enables the genome-wide investigation of selective processes infunctionally important chicken genes. In particular, because of pathogenic challenges it is expected thatgenes involved in the chicken immune system are subject to particularly strong adaptive pressure.Signatures of selection detected by inter-species comparison may then be investigated at the populationlevel in global chicken populations to highlight potentially relevant functional polymorphisms.Results: Comparative evolutionary analysis of chicken (Gallus gallus) and zebra finch (Taeniopygia guttata)genes identified interleukin 4 receptor alpha-chain (IL-4Rα), a key cytokine receptor as a candidate with asignificant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencingand detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa,commercial broilers, and in outgroup species red jungle fowl (JF), grey JF, Ceylon JF, green JF, grey francolinand bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, actingto preserve different high-frequency alleles at two nonsynonymous sites.Conclusion: Haplotype networks indicate that red JF is the primary contributor of diversity at chickenIL-4Rα: the signature of variation observed here may be due to the effects of domestication, admixtureand introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor inthe immune system, so balancing selection related to the host response to pathogens cannot be excluded

Evidence of balanced diversity at the chicken interleukin 4 receptor alpha chain locus

<p>Abstract</p> <p>Background</p> <p>The comparative analysis of genome sequences emerging for several avian species with the fully sequenced chicken genome enables the genome-wide investigation of selective processes in functionally important chicken genes. In particular, because of pathogenic challenges it is expected that genes involved in the chicken immune system are subject to particularly strong adaptive pressure. Signatures of selection detected by inter-species comparison may then be investigated at the population level in global chicken populations to highlight potentially relevant functional polymorphisms.</p> <p>Results</p> <p>Comparative evolutionary analysis of chicken (<it>Gallus gallus</it>) and zebra finch (<it>Taeniopygia guttata</it>) genes identified interleukin 4 receptor alpha-chain (IL-4Rα), a key cytokine receptor as a candidate with a significant excess of substitutions at nonsynonymous sites, suggestive of adaptive evolution. Resequencing and detailed population genetic analysis of this gene in diverse village chickens from Asia and Africa, commercial broilers, and in outgroup species red jungle fowl (JF), grey JF, Ceylon JF, green JF, grey francolin and bamboo partridge, suggested elevated and balanced diversity across all populations at this gene, acting to preserve different high-frequency alleles at two nonsynonymous sites.</p> <p>Conclusion</p> <p>Haplotype networks indicate that red JF is the primary contributor of diversity at chicken IL-4Rα: the signature of variation observed here may be due to the effects of domestication, admixture and introgression, which produce high diversity. However, this gene is a key cytokine-binding receptor in the immune system, so balancing selection related to the host response to pathogens cannot be excluded.</p

Eating Paradise: Food as Coloniality and Leisure

Sandals Resorts’ Gourmet Discovery Dining programme continues the company’s practice of marketing difference by combining tourism with the commodification of food from non-Western cultures (Dodman and Rhiney 2008). The article draws on bell hooks’ (1992) concept of ‘eating the other’ and the analysis undertakes an interdisciplinary approach that combines visual analysis with Anibal Quijano’s (2007) concept of modernity/coloniality. The discussion explores the trends of global multiculturalism that have been adopted by Sandals in a hybridized cut and mix approach to selling a packaged ideal of the Caribbean. The visual techniques devised to create a culinary holiday package are overlaid onto a manufactured and homogenised or McDonaldized (Ritzer and Liska 1997) Caribbean that provides insight into the way in which global neoliberal multiculturalism is framed by ongoing colonial relations after formal colonial rule has ended in the Caribbean region

Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda

Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda.We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (> or =15 years old, n = 528). We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST), and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response.Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Low-intensity cognitive-behaviour therapy interventions for obsessive-compulsive disorder compared to waiting list for therapist-led cognitive-behaviour therapy: 3-arm randomised controlled trial of clinical effectiveness

Background Obsessive-compulsive disorder (OCD) is prevalent and without adequate treatment usually follows a chronic course. “High-intensity” cognitive-behaviour therapy (CBT) from a specialist therapist is current “best practice.” However, access is difficult because of limited numbers of therapists and because of the disabling effects of OCD symptoms. There is a potential role for “low-intensity” interventions as part of a stepped care model. Low-intensity interventions (written or web-based materials with limited therapist support) can be provided remotely, which has the potential to increase access. However, current evidence concerning low-intensity interventions is insufficient. We aimed to determine the clinical effectiveness of 2 forms of low-intensity CBT prior to high-intensity CBT, in adults meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for OCD. Methods and findings This study was approved by the National Research Ethics Service Committee North West–Lancaster (reference number 11/NW/0276). All participants provided informed consent to take part in the trial. We conducted a 3-arm, multicentre randomised controlled trial in primary- and secondary-care United Kingdom mental health services. All patients were on a waiting list for therapist-led CBT (treatment as usual). Four hundred and seventy-three eligible patients were recruited and randomised. Patients had a median age of 33 years, and 60% were female. The majority were experiencing severe OCD. Patients received 1 of 2 low-intensity interventions: computerised CBT (cCBT; web-based CBT materials and limited telephone support) through “OCFighter” or guided self-help (written CBT materials with limited telephone or face-to-face support). Primary comparisons concerned OCD symptoms, measured using the Yale-Brown Obsessive Compulsive Scale–Observer-Rated (Y-BOCS-OR) at 3, 6, and 12 months. Secondary outcomes included health-related quality of life, depression, anxiety, and functioning. At 3 months, guided self-help demonstrated modest benefits over the waiting list in reducing OCD symptoms (adjusted mean difference = −1.91, 95% CI −3.27 to −0.55). These effects did not reach a prespecified level of “clinically significant benefit.” cCBT did not demonstrate significant benefit (adjusted mean difference = −0.71, 95% CI −2.12 to 0.70). At 12 months, neither guided self-help nor cCBT led to differences in OCD symptoms. Early access to low-intensity interventions led to significant reductions in uptake of high-intensity CBT over 12 months; 86% of the patients allocated to the waiting list for high-intensity CBT started treatment by the end of the trial, compared to 62% in supported cCBT and 57% in guided self-help. These reductions did not compromise longer-term patient outcomes. Data suggested small differences in satisfaction at 3 months, with patients more satisfied with guided self-help than supported cCBT. A significant issue in the interpretation of the results concerns the level of access to high-intensity CBT before the primary outcome assessment. Conclusions We have demonstrated that providing low-intensity interventions does not lead to clinically significant benefits but may reduce uptake of therapist-led CBT

Digital IAPT: the effectiveness & cost-effectiveness of internet-delivered interventions for depression and anxiety disorders in the Improving Access to Psychological Therapies programme: study protocol for a randomised control trial

BACKGROUND: Depression and anxiety are common mental health disorders worldwide. The UK's Improving Access to Psychological Therapies (IAPT) programme is part of the National Health Service (NHS) designed to provide a stepped care approach to treating people with anxiety and depressive disorders. Cognitive Behavioural Therapy (CBT) is widely used, with computerised and internet-delivered cognitive behavioural therapy (cCBT and iCBT, respectively) being a suitable IAPT approved treatment alternative for step 2, low- intensity treatment. iCBT has accumulated a large empirical base for treating depression and anxiety disorders. However, the cost-effectiveness and impact of these interventions in the longer-term is not routinely assessed by IAPT services. The current study aims to evaluate the clinical and cost-effectiveness of internet-delivered interventions for symptoms of depression and anxiety disorders in IAPT. METHODS: The study is a parallel-groups, randomised controlled trial examining the effectiveness and cost-effectiveness of iCBT interventions for depression and anxiety disorders, against a waitlist control group. The iCBT treatments are of 8 weeks duration and will be supported by regular post-session feedback by Psychological Wellbeing Practitioners. Assessments will be conducted at baseline, during, and at the end of the 8-week treatment and at 3, 6, 9, and 12-month follow-up. A diagnostic interview will be employed at baseline and 3-month follow-up. Participants in the waitlist control group will complete measures at baseline and week 8, at which point they will receive access to the treatment. All adult users of the Berkshire NHS Trust IAPT Talking Therapies Step 2 services will be approached to participate and measured against set eligibility criteria. Primary outcome measures will assess anxiety and depressive symptoms using the GAD-7 and PHQ-9, respectively. Secondary outcome measures will allow for the evaluation of long-term outcomes, mediators and moderators of outcome, and cost-effectiveness of treatment. Analysis will be conducted on a per protocol and intention-to-treat basis. DISCUSSION: This study seeks to evaluate the immediate and longer-term impact, as well as the cost effectiveness of internet-delivered interventions for depression and anxiety. This study will contribute to the already established literature on internet-delivered interventions worldwide. The study has the potential to show how iCBT can enhance service provision, and the findings will likely be generalisable to other health services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN ISRCTN91967124. DOI: https://doi.org/10.1186/ISRCTN91967124 . Web: http://www.isrctn.com/ISRCTN91967124 . Clinicaltrials.gov : NCT03188575. Trial registration date: June 8, 2017 (prospectively registered)

Migration as a form of workforce attrition: a nine-country study of pharmacists

Background There is a lack of evidence to inform policy development on the reasons why health professionals migrate. Few studies have sought to empirically determine factors influencing the intention to migrate and none have explored the relationship between factors. This paper reports on the first international attempt to investigate the migration intentions of pharmacy students and identify migration factors and their relationships. Methods Responses were gathered from 791 final-year pharmacy students from nine countries: Australia, Bangladesh, Croatia, Egypt, Portugal, Nepal, Singapore, Slovenia and Zimbabwe. Data were analysed by means of Principal Components Analysis (PCA) and two-step cluster analysis to determine the relationships between factors influencing migration and the characteristics of subpopulations most likely and least likely to migrate. Results Results showed a significant difference in attitudes towards the professional and sociopolitical environment of the home country and perceptions of opportunities abroad between those who have no intention of migrating and those who intend to migrate on a long-term basis. Attitudes of students planning short-term migration were not significantly different from those of students who did not intend to migrate. These attitudes, together with gender, knowledge of other migrant pharmacists and past experiences abroad, are associated with an increased propensity for migration. Conclusion Given the influence of the country context and environment on migration intentions, research and policy should frame the issue of migration in the context of the wider human resource agenda, thus viewing migration as one form of attrition and a symptom of other root causes. Remuneration is not an independent stand-alone factor influencing migration intentions and cannot be decoupled from professional development factors. Comprehensive human resource policy development that takes into account the issues of both remuneration and professional development are necessary to encourage retention