Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

Puzzle-based versus traditional lecture: comparing the effects of pedagogy on academic performance in an undergraduate human anatomy and physiology II lab

BACKGROUND: A traditional lecture-based pedagogy conveys information and content while lacking sufficient development of critical thinking skills and problem solving. A puzzle-based pedagogy creates a broader contextual framework, and fosters critical thinking as well as logical reasoning skills that can then be used to improve a student’s performance on content specific assessments. This paper describes a pedagogical comparison of traditional lecture-based teaching and puzzle-based teaching in a Human Anatomy and Physiology II Lab. METHODS: Using a single subject/cross-over design half of the students from seven sections of the course were taught using one type of pedagogy for the first half of the semester, and then taught with a different pedagogy for the second half of the semester. The other half of the students were taught the same material but with the order of the pedagogies reversed. Students’ performance on quizzes and exams specific to the course, and in-class assignments specific to this study were assessed for: learning outcomes (the ability to form the correct conclusion or recall specific information), and authentic academic performance as described by (Am J Educ 104:280–312, 1996). RESULTS: Our findings suggest a significant improvement in students’ performance on standard course specific assessments using a puzzle-based pedagogy versus a traditional lecture-based teaching style. Quiz and test scores for students improved by 2.1 and 0.4 % respectively in the puzzle-based pedagogy, versus the traditional lecture-based teaching. Additionally, the assessments of authentic academic performance may only effectively measure a broader conceptual understanding in a limited set of contexts, and not in the context of a Human Anatomy and Physiology II Lab. CONCLUSION: In conclusion, a puzzle-based pedagogy, when compared to traditional lecture-based teaching, can effectively enhance the performance of students on standard course specific assessments, even when the assessments only test a limited conceptual understanding of the material

Synoptic tool for reporting of hematological and lymphoid neoplasms based on World Health Organization classification and College of American Pathologists checklist

<p>Abstract</p> <p>Background</p> <p>Synoptic reporting, either as part of the pathology report or replacing some free text component incorporates standardized data elements in the form of checklists for pathology reporting. This ensures the pathologists make note of these findings in their reports, thereby improving the quality and uniformity of information in the pathology reports.</p> <p>Methods</p> <p>The purpose of this project is to develop the entire set of elements in the synoptic templates or "worksheets" for hematologic and lymphoid neoplasms using the World Health Organization (WHO) Classification and the College of American Pathologists (CAP) Cancer Checklists. The CAP checklists' content was supplemented with the most updated classification scheme (WHO classification), specimen details, staging as well as information on various ancillary techniques such as cytochemical studies, immunophenotyping, cytogenetics including Fluorescent In-situ Hybridization (FISH) studies and genotyping. We have used a digital synoptic reporting system as part of an existing laboratory information system (LIS), CoPathPlus, from Cerner DHT, Inc. The synoptic elements are presented as discrete data points, so that a data element such as tumor type is assigned from the synoptic value dictionary under the value of tumor type, allowing the user to search for just those cases that have that value point populated.</p> <p>Results</p> <p>These synoptic worksheets are implemented for use in our LIS. The data is stored as discrete data elements appear as an accession summary within the final pathology report. In addition, the synoptic data can be exported to research databases for linking pathological details on banked tissues.</p> <p>Conclusion</p> <p>Synoptic reporting provides a structured method for entering the diagnostic as well as prognostic information for a particular pathology specimen or sample, thereby reducing transcription services and reducing specimen turnaround time. Furthermore, it provides accurate and consistent diagnostic information dictated by pathologists as a basis for appropriate therapeutic modalities. Using synoptic reports, consistent data elements with minimized typographical and transcription errors can be generated and placed in the LIS relational database, enabling quicker access to desired information and improved communication for appropriate cancer management. The templates will also eventually serve as a conduit for capturing and storing data in the virtual biorepository for translational research. Such uniformity of data lends itself to subsequent ease of data viewing and extraction, as demonstrated by rapid production of standardized, high-quality data from the hemopoietic and lymphoid neoplasm specimens.</p

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

The Vital Role of Social Workers in Community Partnerships: The Alliance for Gay, Lesbian, Bisexual, Transgender and Questioning Youth

The account of The Alliance for Gay, Lesbian, Bisexual, Transgender, and Questioning (GLBTQ) Youth formation offers a model for developing com- munity-based partnerships. Based in a major urban area, this university-community collaboration was spearheaded by social workers who were responsible for its original conceptualization, for generating community support, and for eventual staffing, administration, direct service provision, and program evaluation design. This article presents the strategic development and evolution of this community- based service partnership, highlighting the roles of schools of social work, academics, and social work students in concert with community funders, practitioners and youth, in responding to the needs of a vulnerable population

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

In search of causal variants: refining disease association signals using cross-population contrasts

<p>Abstract</p> <p>Background</p> <p>Genome-wide association (GWA) using large numbers of single nucleotide polymorphisms (SNPs) is now a powerful, state-of-the-art approach to mapping human disease genes. When a GWA study detects association between a SNP and the disease, this signal usually represents association with a set of several highly correlated SNPs in strong linkage disequilibrium. The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up.</p> <p>Results</p> <p>We implemented a systematic method for testing association across diverse population samples having differing histories and LD patterns, using a logistic regression framework. The hypothesis is that important underlying biological mechanisms are shared across human populations, and we can filter correlated variants by testing for heterogeneity of genetic effects in different population samples. This approach formalizes the descriptive comparison of p-values that has typified similar cross-population fine-mapping studies to date. We applied this method to correlated SNPs in the cholinergic nicotinic receptor gene cluster <it>CHRNA5-CHRNA3-CHRNB4</it>, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-American samples. Of the 10 SNPs genotyped in the r²≥ 0.8 bin for <it>rs16969968</it>, three demonstrated significant cross-population heterogeneity and are filtered from priority follow-up; the remaining SNPs include <it>rs16969968 </it>(heterogeneity p = 0.75). Though the power to filter out rs16969968 is reduced due to the difference in allele frequency in the two groups, the results nevertheless focus attention on a smaller group of SNPs that includes the non-synonymous SNP rs16969968, which retains a similar effect size (odds ratio) across both population samples.</p> <p>Conclusion</p> <p>Filtering out SNPs that demonstrate cross-population heterogeneity enriches for variants more likely to be important and causative. Our approach provides an important and effective tool to help interpret results from the many GWA studies now underway.</p

The prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review

BACKGROUND: Anaphylactoid reactions to iodinated contrast media are relatively common and potentially life threatening. Opinion is divided as to the utility of medications for preventing these reactions. We performed a systematic review to assess regimes for the prevention of anaphylactoid reactions to iodinated contrast media. METHODS: Searches for studies were conducted in the Medline, EMBASE, CINAHL and CENTRAL databases. Bibliographies of included studies and review articles were examined and experts were contacted. Randomised clinical trials that examined agents given prior to iodinated contrast material for the prevention of anaphylactoid reactions were included in the review. The validity of the included studies was examined using a component approach. RESULTS: Six studies met the inclusion criteria, but only one of these fulfilled all of the validity criteria. There were four studies that examined the use of H1 antihistamines, each was used to prevent anaphylactoid reactions to ionic contrast. The random effects pooled relative risk demonstrated a significant reduction in the overall rate of anaphylactoid reactions (RR = 0.4, 95% CI 0.18-0.9, p = 0.027). There were insufficient studies to produce a pooled statistic for the use of corticosteroids, however regimes of steroids (methylprednisolone 32 mg) given at least six hours and again two hours prior to the administration of contrast suggested a reduction in the incidence of anaphylactoid reactions. CONCLUSION: In conclusion, there are few high quality randomised clinical trials that have addressed the question of the optimal methods to prevent allergic type reactions to iodinated radiological contrast media. Allowing for these limitations, the results suggest that H1 antihistamines given immediately prior to the administration of ionic contrast may be useful in preventing reactions to ionic contrast and are suggestive of a protective effect of corticosteroids when given in two doses at least six hours prior and again two hours prior to the administration of contrast, both ionic and non-ionic. These agents should be considered for use in patients who are at high risk of an anaphylactoid reaction to contrast media and for who prophylactic therapy is considered necessary. Further research is needed before definitive recommendations can be made

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits