Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

La simulación clínica como factor de reducción de estrés en los estudiantes de enfermería

Introducción: El miedo al fracaso es una realidad presente en todas las profesiones. En algunas, como las asentadas en las ciencias de la salud, entraña además el riesgo añadido de tratar con vidas humanas. Con el tiempo, el profesional adquiere una experiencia que afianza su seguridad en su día a día. Sin embargo, los estudiantes en prácticas no disponen de este recurso al enfrentarse por primera vez al paciente. Material y método: Se ha realizado una consulta bibliográfica uniendo los descriptores “estrés psicológico” y “prácticas clínicas” en el contexto del estudiante de enfermería. Se seleccionan los artículos que recoja experiencias negativas de estudiantes en sus prácticas clínicas. Posteriormente, se analizan los datos recogida en ellos. En paralelo, se busca la información disponible de diversos centros de simulación clínica, así como catálogos de distribuidores, y se realiza otra consulta bibliográfica con el descriptor “simulación de paciente”; también en el contexto del estudiante de enfermería. Se seleccionan los artículos que propongan experiencias con grupos de estudiantes y muestren resultados. Resultados: El nivel de estrés de los estudiantes de enfermería es elevado e inversamente proporcional a la edad. Determinados rasgos personales como una baja autoestima pueden actuar como factor de riesgo en tendencias autolíticas. Añadido a esto se incluye la alta tasa de accidentes biológicos, ya que más de la mitad de los estudiantes de enfermería han sufrido o sufrirán uno. La simulación clínica permite realizar estas tareas y técnicas con anterioridad en un entorno controlado, dejando que el estudiante se habitúe al ámbito clínico de forma más progresiva. Conclusiones: La simulación es un aspecto clave de la formación de los estudiantes de enfermería, ya que puede reducir los accidentes biológicos y dotar a los futuros profesionales de confianza y experiencia previa a la práctica clínica

Near-Simultaneous Polar and DMSP Measurements of Topside Ionosphere Field - Aligned Flows at High Latitudes

Near-simultaneous observations of topside 0' parallel flows are presented for four periods of measurement by POLAR and DMSP satellites during April 1996. The POLAR measurements are from Southern perigee measurements near 5000 km altitude, while the DMSP measurements were from 840 km altitude. These observations provide a view of wide-spread upward/downward ionospheric O(+) flows over the broad polar region along extended and multiple distinct satellite tracks. In general, the velocities are upward toward expected cleft and auroral latitudes, typically about a 2-10 km/s at 5000 km altitude, and 0-2 km/s at 840 km altitudes. At the highest, polar cap latitudes, downward velocities are more frequent at both altitudes, but especially at the lower 840 km altitude. The downward velocities were typically a few hundred d s at 840 altitude, and 0-1 km/s at 5000 km altitude. In some instances, apparently downward velocities were observed at 840 km altitudes while upward 0' flows were observed at 5000 km altitude on the same flux tube. The O+ density were characteristically 1-10 O(+)/cu cm at 5000 km altitude and 10(exp 3) - 10(exp 40 O(+)/cu cm at 840 km altitude, while the O(+) flux were characteristically 1 10(exp 5) - 10(exp 7) O(+)+/sq cm -sec at 5000 km altitudes and characteristically 10(exp 7) - 10(exp 9) O(+)/sq cm -sec at 840 km altitude. We have also examined the dual altitude parameter measurements for a polar cap field line, the POLAR and DMSP measurements approximately 30 minutes apart, and compared them with results from a transport simulation in which a flux tube was subjected to a brief pulse of soft electron precipitation and topside transverse ion heating. The simulated density and velocity altitude profiles for 5 minutes later generally matched the observations, except that the observed downward velocities (500 - 600 m/s) at 840 km altitude were much larger than those simulated