Validation of a high resolution NGS method for detecting spinal muscular atrophy carriers among phase 3 participants in the 1000 Genomes Project

BACKGROUND: Spinal muscular atrophy (SMA) is the most common pan-ethnic cause of early childhood death due to mutations in a single gene, SMN1. Most chromosome 5 homologs have a functional gene and dysfunctional copy, SMN2, with a single synonymous base substitution that results in faulty RNA splicing. However, the copy number of SMN1 and SMN2 is highly variable, and one in 60 adults worldwide are SMA carriers. Although population-wide screening is recommended, current SMA carrier tests have not been incorporated into targeted gene panels. METHODS: Here we describe a novel computational protocol for determining SMA carrier status based solely on individual exome data. Our method utilizes a Bayesian hierarchical model to quantify an individual’s carrier probability given only his or her SMN1 and SMN2 reads at six loci of interest. RESULTS: We find complete concordance with results obtained with the current qPCR-based testing standard in known SMA carriers and affecteds. We applied our protocol to the phase 3 cohort of the 1,000 Genomes Project and found carrier frequencies in multiple populations consistent with the present literature. CONCLUSION: Our process is a convenient, robust alternative to qPCR, which can easily be integrated into the analysis of large multi-gene NGS carrier screens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12881-015-0246-2) contains supplementary material, which is available to authorized users

NEO link and FTI Database

Raw data includes 100,000 observations on the Fisher Temperament Instrument. Fisher, H. E., Island, H. D., Rich, J., Marchalik, D. & Brown, L. L. Four broad temperament dimensions: description, convergent validation correlations, and comparison with the Big Five. Front. Psychol. 6, 153 (2015)

Personality proposal documents

We propose and provide evidence for a novel conceptualization of human personality framed on the proposition that human minds operate unknowingly as self-contained, self-centered personal instruments for measuring their own personalities. We appreciate all comments and constructive critiques

Carrier Screening is a Deficient Strategy for Determining Sperm Donor Eligibility and Reducing Risk of Disease in Recipient Children

Aims: DNA-based carrier screening is a standard component of donor eligibility protocols practiced by U.S. sperm banks. Applicants who test positive for carrying a recessive disease mutation are typically disqualified. The aim of our study was to examine the utility of a range of screening panels adopted by the industry and the effectiveness of the screening paradigm in reducing a future child's risk of inheriting disease. Methods: A cohort of 27 donor applicants, who tested negative on an initial cystic fibrosis carrier test, was further screened with three expanded commercial carrier testing panels. These results were then compared to a systematic analysis of the applicants' DNA using next-generation sequencing (NGS) data. Results: The carrier panels detected serious pediatric disease mutations in one, four, or six donor applicants. Because each panel screens distinct regions of the genome, no single donor was uniformly identified as carrier positive by all three panels. In contrast, systematic NGS analysis identified all donors as carriers of one or more mutations associated with severe monogenic pediatric disease. These included 30 variants classified as “pathogenic” based on clinical observation and 66 with a high likelihood of causing gene dysfunction. Conclusion: Despite tremendous advances in variant identification, understanding, and analysis, the vast majority of disease-causing mutation combinations remain undetected by commercial carrier screening panels, which cover a narrow, and often distinct, subset of genes and mutations. The biological reality is that all donors and recipients carry serious recessive disease mutations. This challenges the utility of any screening protocol that anchors donor eligibility to carrier status. A more effective approach to reducing recessive disease risk would consider joint comprehensive analysis of both donor and recipient disease mutations. This type of high-resolution recessive disease risk analysis is now available and affordable, but industry practice must be modified to incorporate its use

Erosion in Medical Students' Attitudes About Telling Patients They Are Students

OBJECTIVE: To study the attitudes of preclinical and clinical medical students toward the importance of telling patients they are students, and to compare their attitudes with those of patients. METHODS: We conducted a cross-sectional survey of medical students from five Philadelphia medical schools, and a longitudinal follow-up in one medical school, to assess the importance students place on telling patients they are medical students before interacting with them. We asked similar questions of 100 general medical outpatients from two academically affiliated hospitals. MAIN RESULTS: In total, 2,603 students (58%) responded to the cross-sectional survey, 74 (50%) responded to the longitudinal survey, and 100 patients responded to our interview survey (94% response rate). In the cross-sectional survey, there were negligible differences in the importance that patients and medical students placed on informing alert patients that they are interacting with students in nonsurgical settings. In surgical settings involving anesthetized patients, patients placed significantly more importance on being informed of students' roles in their surgery than did students, and preclinical students placed more importance on this than did clinical students. Results from the cross-sectional survey were supported by the longitudinal survey, in which fourth-year medical students placed significantly less importance on informing patients of their student status than the same cohort had done 2 years previously. CONCLUSIONS: Medical students place less importance on informing patients about their student status than patients desire, especially in surgical settings in which the patient is to be anesthetized. Medical students already having completed a clinical rotation stray further from patient ideals than preclinical medical students. These findings suggest that, as medical students advance in their training, they suffer an erosion in their attitudes about telling patients they are students

The impact of an ECG computer analysis program on the cardiologist\u27s interpretation. A cooperative study

Nine experienced electrocardiographers and the ECG computer program developed in the Veterans Administration (AVA 4.0) were evaluated against ECG-independent evidence of 180 patients\u27 true diagnoses. A cross section of cardiac abnormalities was included. Each reader was given the 12-lead and orthogonal 3-lead ECG. The impact of ECG computer reports on the interpretations by the nine readers was evaluated by comparing their interpretations before and after the addition of a computer report. Using only high probability statements, the average accuracy of ECG diagnosis by the nine readers was 54%. It increased to 62% when the computer report was added. Computer interpretation was correct in 76%. It was shown that the Bayesian classification method together with multivariate analysis, used in the VA program, are mainly responsible for the improvement in diagnostic accuracy. © 1983 Research in Electrocardiology, Inc

Informatics and Computational Thinking: A Teacher Professional Development Proposal Based on Social-Constructivism

Teaching informatics with a socio-constructivist approach is the theme of the Professional Development (PD) proposal for teachers we present in this paper. This proposal is built upon the expertise we developed in the last few years by designing and delivering enrichment activities to school students, where constructivist strategies are used to let students discover informatics as a scientific discipline, and to promote computational thinking skills and problem solving competences. Starting from the analysis of teachers\u2019 training needs, we structured the proposal into different units. We highlight their goals and contents, and illustrate some of the proposed activities. We held some training sessions to test our proposal; we report our findings and the feedback from the participants who amount to a total of ninety-five in-service and prospective teachers