Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

PMCID: PMC3480949This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Gene-panel testing of breast and ovarian cancer patients identifies a recurrent RAD51C duplication

Gene-panel sequencing allows comprehensive analysis of multiple genes simultaneously and is now routinely used in clinical mutation testing of high-risk breast and ovarian cancer patients. However, only BRCA1 and BRCA2 are often analyzed also for large genomic changes. Here, we have analyzed 10 clinically relevant susceptibility genes in 95 breast or ovarian cancer patients with gene-panel sequencing including also copy number variants (CNV) analysis for genomic changes. We identified 12 different pathogenic BRCA1, BRCA2, TP53, PTEN, CHEK2, or RAD51C mutations in 18 of 95 patients (19%). BRCA1/2 mutations were observed in 8 patients (8.4%) and CHEK2 protein-truncating mutations in 7 patients (7.4%). In addition, we identified a novel duplication encompassing most of the RAD51C gene. We further genotyped the duplication in breast or ovarian cancer families (n=1149), in unselected breast (n=1729) and ovarian cancer cohorts (n=553), and in population controls (n=1273). Seven additional duplication carries were observed among cases but none among controls. The duplication associated with ovarian cancer risk (3/590 of all ovarian cancer patients, 0.5%, P=.032 compared with controls) and was found to represent a large fraction of all identified RAD51C mutations in the Finnish population. Our data emphasizes the importance of comprehensive mutation analysis including CNV detection in all the relevant genes.Peer reviewe

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Channa Reddy In Telangana Statehood Movement: Initiation, Intervention And Contribution

The present paper tries to explore some of the repeated accusations and half-truths against the Telangana leader – Dr. Marri Channa Reddy, who led the movement in 1969. It is believed that the leaders started the Telangana Statehood movement as a problem-solving movement against subregionalism. Dr. Reddy was a staunch opponent of Andhra’s internal colonization. This is not only absurd but also a parody of the truth. This is mainly due to the lack of original documents in an organized campaign for the separate state of Telangana. The print and electronic media reports speak of alarming national integration at the request of the state of Telangana. While national integration can no longer be mere integration, biased politicians and media cannot accept the exclusive right to speak on behalf of the common man. Therefore, an ordinary person needs to understand how effectively the public and leader’s participation took place in the country\u27s democratic and political process in articulating their rights and entitlements. And, thus, the initiation, intervention, and contribution of a prominent political leader of Telangana State were discussed in this paper with substantial shreds of evidence

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed

Päivähoito lastensuojelun toimintasuunnitelmissa

Tutkimuksen tarkoituksena on kuvata, kuinka päivähoito näyttäytyy kuntien laatimissa lastensuojelun toimintasuunnitelmissa. Tarkastelen päivähoitoa lastensuojelun toimintasuunnitelmissa kysymällä: Kuinka kunnat ovat kirjanneet 1) päivähoidon lapsiperheen palvelun näkökulmasta, 2) päivähoitoa lastensuojelun ehkäisevän työn kontekstina, 3) perhetyön toimijana sekä 4) moniammatillisen yhteistyön tekijänä. Tutkimuksen taustalla on viitekehys päivähoidosta yhteiskunnan taholta tarjottavana perhepalveluna, joka toimii ehkäisevän lastensuojelutyön tekijänä, ja jolta vaaditaan perhetyön ja moniammatillisen yhteistyön menetelmiä. Lastensuojelulain (2007) 12 § mukaisesti jokaisen kunnan on laadittava suunnitelma lastensuojelun järjestämisestä ja kehittämisestä. Suunnitelmaan on sisällytettävä lain vaatimat tiedot, se on hyväksyttävä kunnanvaltuustossa ja tarkistettava vähintään kerran neljässä vuodessa. Tutkimuksen aineistoksi valikoitui kymmenen Pohjois-Suomen aluehallintoviraston valvonnan piirissä olevaa internet-sivuilla julkaistua lastensuojelun toimintasuunnitelmaa. Aineiston toimintasuunnitelmista seitsemän on laadittu eri kuntien välisen yhteistyön tuloksena, kuntayhtymän tuottamana seudullisena yhteistyönä tai alueen hyvinvointistrategiaan liitettynä. Yksittäisen kunnan tai kaupungin suunnitelmaa edustavat kolme lastensuojelun toimintasuunnitelmaa. Tutkimus on teorialähtöinen, jossa aineiston analyysiin on käytetty kvalitatiivisen tutkimuksen sisällön analyysin ja dokumenttianalyysin menetelmiä. Tulosten mukaan kunnat kuvaavat päivähoitoa lapsiperheen palveluna lähinnä eri päivähoitomuotojen ja lapsen erityisen tuen tarjoajana. Päivähoito ehkäisevän lastensuojelutyön kontekstina korostuu toimintasuunnitelmissa varhaisen tuen ja vanhemmuuden tukemiseen liittyvän ammattiosaamisen haasteena. Perhetyön tekijänä päivähoito on kirjattu pääosin kuntien suunnitelmiin kehittämisen kohteena. Lasten hyvinvoinnin taustalla on koko perheen hyvinvointi, minkä vuoksi moniammatillisen yhteistyön tekijänä päivähoito näyttäytyy lastensuojelun toimintasuunnitelmissa lähinnä perheen kanssa tehtävän yhteistyön muodossa. Tähän tarvitaan kunnan eri hallintorajoja ylittävää yhteistyötä ja moniammatillisia yhteistyömenetelmiä, joihin toivotaan kehittyvän uusia toimintamalleja. Päivähoito on yksi keskeisimmistä lapsiperheiden käyttämistä yhteiskuntamme tarjoamista palveluista. Tästä huolimatta päivähoito näyttäytyy lastensuojelun toimintasuunnitelmissa yllättävän pienesti. Toimintasuunnitelmien tavoite toimia lasten ja nuorten hyvinvointityötä ohjaavina asiakirjoina on vielä tältä osin kehittymässä

Strain measurement by contour analysis

Background: The determination of yield stress curves for ductile metals from uniaxial material tests is complicated by the presence of tri-axial stress states due to necking. A need exists for a straightforward solution to this problem. Objective: This work presents a simple solution for this problem specific to axis-symmetric specimens. Equivalent uniaxial true strain and true stress, corrected for triaxiality effects, are calculated without resorting to inverse analysis methods. Methods: A computer program is presented which takes shadow images from tensile tests, obtained in a backlight configuration. A single camera is sufficient as no stereoscopic effects need to be addressed. The specimen's contours are digitally extracted, and strain is calculated from the contour change. At the same time, stress triaxiality is computed using a novel curvature fitting algorithm. Results: The method is accurate as comparison with manufactured solutions obtained from Finite Element simulations show. Application to 303 stainless steel specimens at different levels of stress triaxiality show that equivalent uniaxial true stress -- true strain relations are accurately recovered. Conclusions: The here presented computer program solves a long-standing challenge in a straightforward manner. It is expected to be a useful tool for experimental strain analysis