Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients.

PurposeMany women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 and BRCA2. Among them, a subset has hereditary susceptibility to cancer and requires further testing. We sought to identify specific groups who remain at high risk and evaluate whether they should be offered multi-gene panel testing.MethodsWe tested 300 women on a multi-gene panel who were previously enrolled in a long-term study at UCSF. As part of their long-term care, all previously tested negative for mutations in BRCA1 and BRCA2 either by limited or comprehensive sequencing. Additionally, they met one of the following criteria: (i) personal history of bilateral breast cancer, (ii) personal history of breast cancer and a first or second degree relative with ovarian cancer, and (iii) personal history of ovarian, fallopian tube, or peritoneal carcinoma.ResultsAcross the three groups, 26 women (9%) had a total of 28 pathogenic mutations associated with hereditary cancer susceptibility, and 23 women (8%) had mutations in genes other than BRCA1 and BRCA2. Ashkenazi Jewish and Hispanic women had elevated pathogenic mutation rates. In addition, two women harbored pathogenic mutations in more than one hereditary predisposition gene.ConclusionsAmong women at high risk of breast and ovarian cancer who have previously tested negative for pathogenic BRCA1 and BRCA2 mutations, we identified three groups of women who should be considered for subsequent multi-gene panel testing. The identification of women with multiple pathogenic mutations has important implications for family testing

Preferenciasde hábitat y abundancia relativa de Tayassu pecari en un área con cacería en la región de Calakmul, Campeche, México

ResumenConocer las preferencias de hábitat y abundancia relativa de mamíferos silvestres aporta información básica para programas de conservación o manejo. El pecarí labios blancos Tayassu pecari (Link, 1795), es una especie en peligro de extinción en México. En este estudio se evaluaron las preferencias del hábitat y la abundancia relativa de esta especie en la parte sur de la Reserva de la Biosfera de Calakmul y en el ejido Nuevo Becal, ambos sitios localizados en el estado de Campeche. Se establecieron 20km de transectos en cada sitio, registrándose las especies arbóreas presentes y el número de huellas de la especie durante 4 meses de la estación de lluvias y 2 meses de la época seca. Los análisis de uso de hábitat indican que aunque el mayor número de registros es en la selva mediana, los pecaríes de labios blancos prefieren la vegetación baja inundable. Después de recorrer 240km, se obtuvo una abundancia relativa de 0.53 huellas por km caminado. Brosimum alicastrum y Manilkara zapota fueron las especies arbóreas que presentaron la mayor abundancia de frutos en los 2 sitios. El pecarí de labios blancos es una especie muy vulnerable a la deforestación y otras perturbaciones antropogénicas en su hábitat, resulta entonces importante considerar una estrategia para la conservación del hábitat del pecarí de labios blancos, tomando en cuenta no sólo las áreas protegidas, sino también áreas comunales.AbstractInvestigating the habitat preferences and relative abundance of wild mammals provides basic information for conservation or management programs. The white-lipped peccary (Tayassu pecari, PLB, for its Spanish initials) is a species classified as in danger of extinction in Mexico. This study evaluated the habitat preferences and relative abundance of this species in the southern part of the Calakmul Biosphere Reserve and the ejido Nuevo Becal, both sites are located in the state of Campeche. Twenty kilometers of transects were established at each site, in each of these sites we recorded the tree species present and the number of tracks during 4 months of the rainy season and 2 months of the dry season. The analysis of habitat use indicates that although the highest number of records occurred in the medium semi-perennial forest, the PLB preferred the low flooded forest. After surveying 240km, we obtained a relative abundance of 0.53 signs per km walked. Brosimun alicastrum and Manilkara zapota were the tree species that had the highest abundance of fruits in the 2 sites. White-lipped peccary species is very sensitive to deforestation and other anthropogenic disturbances, so it is important to develop a strategy for the conservation of the habitat of the species considering not only the protected areas, but also the communal areas

Zircon U-Pb dating of lower crustal rocks from the G.ry Sowie Massif (Central Sudetes, SW Poland): new insights on the sedimentary origin and the tectono-thermal evolution

Devonian HP‒UHP lithotectonic associations represent pivotal element of Paleozoic evolution of European Variscan belt across the continent from Portugal to Poland. The Góry Sowie Massif (GSM), located in the Central Sudetes, represents one of the best preserved outcrops of lower crustal rocks that experienced protracted Devonian tectono-metamorphic history at the easternmost extremity of the belt. The area is surrounded by Devonian ophiolite remnants (c. 400 Ma; Kryza & Pin, 2010) and by Devonian and Silurian to Carboniferous sedimentary basins in the northern and southern part, respectively. The GSM is mainly composed of paragneisses and subordinate orthogneisses, metabasites and granulite. The dominantly sedimentary association and the overall geotectonic setting contrast with other km-scale granulite complexes in the Bohemian Massif that are dominated by felsic granulites and Late Cambrian orthogneisses that experienced 340 Ma HP metamorphism. Weak Carboniferous overprint makes the GSM a key locality to better understand Devonian stages of formation of HP granulites and provenance of the whole pre-Devonian lithological association. New U‒Pb analyses were carried out on zircons from 4 migmatitic paragneisses, 3 felsic biotite-poor granulites and two biotite-rich granulites in the northern part of the GSM, in order to constrain source provenance and tectono-thermal history of the area

Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model

Aims. To study the influence of P-glycoprotein (P-glycoprotein, ABCB1, MDR1) function on placental transfer of lopinavir with ritonavir at different albumin concentrations. Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L). After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes). Fetal Transfer Rate (FTR) and Clearance Index (CLI) were compared between the 2 phases. Results. In the control phase, the clearance index of lopinavir decreased from 0.401 ± 0.058 to 0.007 ± 0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L). When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [−0.156, −0.002], P = .046) and became positive for ritonavir. Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy

The identification of a new genotype of avian paramyxoviruses type I in West-Africa provides new outcomes for phylogeny reconstruction

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Geochemistry, zircon U‒Pb and Hf isotopic compositions of lower crustal rocks from the Góry Sowie Massif (Central Sudetes, SW Poland): New insights on the sedimentary origin and tectono-thermal evolution

Devonian HP-UHP lithotectonic associations represent a pivotal element of Paleozoic evolution of the European Variscan belt across the continent from Portugal to Poland. The Góry Sowie Massif (GSM), located in the Central Sudetes, represents one of the best preserved outcrops of lower crustal rocks that experienced a protracted Devonian tectono-metamorphic history at the easternmost extremity of the belt. The area is surrounded by Devonian ophiolite remnants and Devonian to Carboniferous sedimentary basins in the northern and southern part, respectively. The GSM is mainly composed of paragneisses and subordinate orthogneisses, metabasites and granulite. The dominantly sedimentary association and the overall geotectonic setting contrast with the other km-scale granulite complexes in the Bohemian Massif that are dominated by felsic granulites and late Cambrian orthogneisses that experienced 340 Ma HP metamorphism. Weak Carboniferous overprint makes the GSM a key locality to better understand the Devonian stages of formation of HP granulites and provenance of the whole pre-Devonian lithological association. New U-Pb and Lu/Hf analyses were carried out on zircons from 4 migmatitic paragneisses, 3 felsic biotite-poor granulites and 2 biotite-rich granulites in the northern part of the GSM, and combined with geochemical analyses in order to constrain a source provenance and tectono-thermal history of the area. The paragneisses dominated by stromatic migmatite and felsic granulites occur as hundred meter-scale bodies associated with metric lenses of amphibolites, mafic and ultramafic rocks in the northern part of the massif

Time, Emotion and the Embodiment of Timing

The past few decades have seen an explosion in studies exploring the effects of emotion on time judgments. The aim of this review is to describe the results of these studies and to look at how they try to explain the time distortions produced by emotion. We begin by examining the findings on time judgments in affective disorders, which allow us to make a clear distinction between the feelings of time distortion that originate from introspection onto subjective personal experience, and the effects of emotion on the basic mechanisms involved in time perception. We then report the results of behavioral studies that have tested the effects of emotions on time perceptions and the temporal processing of different emotional stimuli (e.g. facial expressions, affective pictures or sounds). Finally, we describe our own studies of the embodiment of timing.Overall, the different results on time and emotion suggest that temporal distortions are an indicator of how our brain and body adapt to the dynamic structure of our environment