A longitudinal study of the characteristics and performances of medical students and graduates from the Arab countries

BACKGROUND: While international physician migration has been studied extensively, more focused and regional explorations are not commonplace. In many Arab countries, medical education is conducted in English and students/graduates seek postgraduate opportunities in other countries such as the United States (US). Eligibility for residency training in the US requires certification by the Educational Commission for Foreign Medical Graduates (ECFMG). This study investigates ECFMG application trends, examination performance, and US physician practice data to quantify the abilities and examine the career pathways of Arab-trained physicians. METHODS: Medical students and graduates from 15 Arab countries where English is the language of medical school instruction were studied. The performances (1(st) attempt pass rates) of individuals on the United States Medical Licensing Examination Step 1, Step 2CK (clinical knowledge), and and a combination of Step 2CS (clinical skills) and ECFMG CSA (clinical skills assessment) were tallied and contrasted by country. Based on physician practice data, the contribution of Arab-trained physicians to the US healthcare workforce was explored. Descriptive statistics (means, frequencies) were used to summarize the collected data. RESULTS: Between 1998 and 2012, there has been an increase in the number of Arab trained students/graduates seeking ECFMG certification. Examination performance varied considerably across countries, suggesting differences in the quality of medical education programs in the Eastern Mediterranean Region. Based on current US practice data, physicians from some Arab countries who seek postgraduate opportunities in the US are less likely to stay in the US following specialty training. CONCLUSION: Countries, or regions, with concerns about physician migration, physican performance, or the pedagogical quality of their training programs should conduct longitudinal research studies to help inform medical education policies

General Relativistic Gravity Gradiometry

Gravity gradiometry within the framework of the general theory of relativity involves the measurement of the elements of the relativistic tidal matrix, which is theoretically obtained via the projection of the spacetime curvature tensor upon the nonrotating orthonormal tetrad frame of a geodesic observer. The behavior of the measured components of the curvature tensor under Lorentz boosts is briefly described in connection with the existence of certain special tidal directions. Relativistic gravity gradiometry in the exterior gravitational field of a rotating mass is discussed and a gravitomagnetic beat effect along an inclined spherical geodesic orbit is elucidated.Comment: 18 pages, invited contribution to appear in "Relativistic Geodesy: Foundations and Applications", D. Puetzfeld et al. (eds.), 2018; v2: matches version published in: D. Puetzfeld and C. L\"ammerzahl (eds.) "Relativistic Geodesy" (Springer, Cham, 2019), pp. 143-15

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

An admissible level osp (1|2)-model: modulartransformations and the Verlinde formula

The modular properties of the simple vertex operator superalgebra associated with the affine Kac–Moody superalgebra osp (1|2) at level −5 4 are investigated. After classifying the relaxed highest-weight modules over this vertex operator superalgebra, the characters and supercharacters of the simple weight modules are computed and their modular transforms are determined. This leads to a complete list of the Grothendieck fusion rules by way of a continuous superalgebraic analog of the Verlinde formula. All Grothendieck fusion coefficients are observed to be non-negative integers. These results indicate that the extension to general admissible levels will follow using the same methodology once the classification of relaxed highest-weight modules is completed