A probabilistic generative model for GO enrichment analysis

The Gene Ontology (GO) is extensively used to analyze all types of high-throughput experiments. However, researchers still face several challenges when using GO and other functional annotation databases. One problem is the large number of multiple hypotheses that are being tested for each study. In addition, categories often overlap with both direct parents/descendents and other distant categories in the hierarchical structure. This makes it hard to determine if the identified significant categories represent different functional outcomes or rather a redundant view of the same biological processes. To overcome these problems we developed a generative probabilistic model which identifies a (small) subset of categories that, together, explain the selected gene set. Our model accommodates noise and errors in the selected gene set and GO. Using controlled GO data our method correctly recovered most of the selected categories, leading to dramatic improvements over current methods for GO analysis. When used with microarray expression data and ChIP-chip data from yeast and human our method was able to correctly identify both general and specific enriched categories which were overlooked by other methods

Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease

We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus <0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.Peer reviewe

Ethics in Supervision

We aim to achieve a short analysis of the ethics in supervision of social work, because this may influence the decisions took in case work. Both supervisees and supervisors make decisions to work with one another in a variety of ways, and to handle the cases. So we bring to the reader’s attention the supervision standards, the supervision contract where we are interested to see what is specify about ethics. Also we would like to see how the ethical decisions took can influence the life of the beneficiary.ethics, supervision, standards, practice, ethical decision

Unifying the Hepatopancreatobiliary Surgery Fellowship curriculum via Delphi consensus

BACKGROUND: Hepatopancreatobiliary (HPB) Fellowship training in the Americas consists of 3 distinctive routes with variable curricula: Surgical Oncology Fellowship via the Society of Surgical Oncology (SSO), Abdominal Transplant Surgery Fellowship via the American Society of Transplant Surgeons (ASTS), and HPB Fellowship via the Americas Hepato-PancreatoBiliary Association (AHPBA). Our objective was to establish a pan-American consensus among HPB surgeons, surgical oncologists, abdominal transplant surgeons, and general surgery residency program directors (GSPDs) on a core knowledge curriculum for HPB fellowship, and to identify topics appropriate for general surgery residency and subspecialty beyond HPB fellowship. STUDY DESIGN: A 3-round modified Delphi process was used. Baseline statements were developed by the Education and Training Committee of the AHPBA, in collaboration with representatives of the SSO, ASTS, and GSPDs. The expert panel, consisting of members of the 3 societies together with GSPDs, rated the statements on a 5-point Likert scale and suggested editing or adding new statements. A statement was included in the final curriculum when Cronbach's alpha value was >= 0.8 and >= 80% of the panel agreed on inclusion. RESULTS: The response rate was 100% for the first round, and 98% for the second and third rounds. Eighty-nine of 138 proposed statements were included in the final HPB fellowship curriculum. Curricula for general surgery residency and subspecialty beyond HPB fellowship included 50 and 29 statements, respectively. CONCLUSIONS: A multinational consensus on core knowledge for an HPB fellowship curriculum was achieved via the modified Delphi method. This core curriculum may be used to standardize HPB fellowship training across different pathways in the Americas

Reliability of the Expanded Cutting Alignment Scoring Tool (E-CAST) to Assess Trunk and Limb Alignment During a 45-Degree Side-Step Cut

Current clinical screening tools assessing risky movements during cutting maneuvers do not adequately address sagittal plane foot and ankle evaluations. The Cutting Alignment Scoring Tool (CAST) is reliable in evaluating frontal plane trunk and lower extremity alignment during a 45-degree side-step cut. The Expanded Cutting Alignment Scoring Tool (E-CAST) includes two new sagittal plane variables, knee flexion and ankle plantarflexion angle. To assess the inter-and intra-rater reliability of the E-CAST to evaluate trunk and lower extremity alignment during a 45-degree side-step cut. Repeated Measures. Participants included 25 healthy females (13.8 ± 1.4 years) regularly participating in cutting or pivoting sports. Participants were recorded performing a side-step cut in frontal and sagittal planes. One trial was randomly selected for analysis. Two physical therapists independently scored each video using the E-CAST on two separate occasions, with randomization and a two-week wash-out between rounds. Observed movement variables were awarded a score of "1", with higher scores representing poorer technique. Intraclass correlation coefficients (ICC) and 95% confident intervals (95% CI) were calculated for the total score, and a kappa coefficient (k) was calculated for each variable. The cumulative intra-rater reliability was good (ICC=0.78, 95% CI 0.59-0.96) and the cumulative inter-rater reliability was moderate (ICC=0.71, 95% CI 0.50-0.91). Intra-rater kappa coefficients ranged from moderate to excellent for all variables (k= 0.50-0.84) and inter-rater kappa coefficients ranged from slight to excellent for all variables (k=0.20-0.90). The addition of two sagittal plane variables resulted in lower inter-rater ICC compared to the CAST (ICC= 0.81, 95% CI 0.64-0.91). The E-CAST is a reliable tool to evaluate trunk and LE alignment during a 45-degree side-step cut, with good intra-rater and moderate inter-rater reliability. Level 2, Diagnosis