Stopping of relativistic projectiles in two-component plasmas

Relativistic and correlation contributions to the polarizational energy losses of heavy projectiles moving in dense two-component plasmas are analyzed within the method of moments that allows one to reconstruct the Lindhard loss function from its three independently known power frequency moments. The techniques employed result in a thorough separation of the relativistic and correlation corrections to the classical asymptotic form for the polarizational losses obtained by Bethe and Larkin. The above corrections are studied numerically at different values of plasma parameters to show that the relativistic contribution enhances only slightly the corresponding value of the stopping power.This research was financially supported by the Spanish Ministerio de Educacion y Ciencia Project No. ENE2010-21116-C02-02 and by the Science Committee of the Ministry of Education and Sciences of the Republic of Kazakhstan under Grants No. 1128/GF, 1129/GF and 1099/GF. IMT acknowledges the hospitality of the al-Farabi Kazakh National University.Arkhipov, YV.; Ashikbayeva, AB.; Askaruly, A.; Davletov, AE.; Tkachenko Gorski, IM. (2013). Stopping of relativistic projectiles in two-component plasmas. EPL. 104(3):35003-p1-35003-p6. https://doi.org/10.1209/0295-5075/104/35003S35003-p135003-p6104

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Asesoramiento genético en cáncer de próstata: ¿cómo implementarlo en la práctica clínica diaria?

El cáncer de próstata tiene un protagonismo socio-sanitario innegable en nuestros días y sistemas de salud. Su impacto epidemiológico cuantitativamente está muy próximo a otros tumores como el cáncer de colon y el cáncer de mama, en los que el asesoramiento genético forma parte de su práctica clínica habitual, tanto en la evaluación inicial como en la selección de estrategias terapéuticas. Los síndromes de cáncer hereditario, mama/ovario y síndrome de Lynch, forman parte del asesoramiento genético en estos tumores y hoy día también sabemos que pueden tener relación con el cáncer de próstata. Ha llegado el momento de implementar el asesoramiento genético en cáncer de próstata desde las etapas más iniciales de su abordaje, desde la sospecha inicial hasta los tumores más avanzados.Presentamos una revisión actualizada de nuestro grupo de trabajo interdisciplinar sobre la literatura científica, guías de práctica clínica y documentos de consenso hasta la creación y redacción de un «Protocolo de asesoramiento genético en cáncer de próstata», centrado en el estudio de línea germinal, de fácil aplicabilidad en los diferentes entornos asistenciales. Dicho protocolo se encuentra actualmente implementado en nuestra práctica habitual y da respuesta a tres preguntas concretas: ¿A quién realizar asesoramiento genético en cáncer de próstata?, ¿qué panel de genes analizar?, y ¿cómo aconsejar de acuerdo con los resultados obtenidos? Otros aspectos acerca de quién debe realizar el asesoramiento genético, consideraciones éticas y normativa también son recogidos

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease