20 research outputs found
Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia
Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 Ă 10-20), ER-negative BC (P=1.1 Ă 10-13), BRCA1-associated BC (P=7.7 Ă 10-16) and triple negative BC (P-diff=2 Ă 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 Ă 10-3) and ABHD8 (P<2 Ă 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3âČ-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk
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 = 2.7Ă10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4Ă10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4Ă10-8, 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
Fitorremediação de solos contaminados com arsĂȘnio (As) utilizando braquiĂĄria Phytoremediation of arsenic-contaminated soils using Brachiaria grass
Conduziu-se este trabalho, com o objetivo de avaliar o potencial fitoextrator de arsĂȘnio (As) da Brachiaria decumbens Stapf., cultivada em casa de vegetação, utilizando-se seis solos: Latossolo Amarelo DistrĂłfico (LAd), Latossolo Vermelho DistrĂłfico (LVd), Neossolo FlĂșvico (RU), Neossolo QuartzarĂȘnico (RQ), Gleissolo HĂĄplico (GX) e Gleissolo MelĂąnico (GM). O As foi adicionado aos solos na forma de arsenato de sĂłdio heptahidratado nas doses 0, 25, 50, 200 e 800 mg kg-1. As plantas foram coletadas 55 dias apĂłs a semeadura, separadas em parte aĂ©rea e raiz e, apĂłs secagem do material em estufa, o mesmo foi digerido segundo o mĂ©todo 3051 da USEPA, sendo o teor de As determinado por espectrofotometria de absorção atĂŽmica (EEA) com forno de grafite. Observou-se redução no desenvolvimento da braquiĂĄria de forma diferenciada nas seis classes de solo. Houve baixa translocação do As, da raiz para a parte aĂ©rea, sendo essa espĂ©cie considerada tolerante ao elemento e nĂŁo hiperacumuladora, podendo ser utilizada em programas de revegetação de ĂĄreas contaminadas pelo elemento.<br>This work evaluated the phytoextraction potential of arsenic (As) by Brachiaria decumbens growing under greenhouse conditions in six soils: a Dystrophic Yellow Latosol (LAd), a Dystrophic Red Latosol (LVd), a Fluvic Neosol (RU), a Quartzenic Neosol (RQ), a Haplic Gleysol (GX), and a Melanic Gleysol (GM). Arsenic was added to the soils as sodium arsenate heptahydrate (Na2HAsO4.7H2O) at the following doses: 0, 25, 50, 200, and 800 mg kg-1. The plants were collected 55 days after planting for determination of shoot and root dry matter production. Arsenic shoot and root contents were evaluated after digestion according to the USEPA 3051A method, following analysis by graphite furnace atomic absorption spectroscopy. Plant development was differently affected by As in the six different soil classes. There was low translocation of As and consequently most of the As was detected in the roots of Brachiaria decumbens. Therefore, this species could be considered tolerant but not an accumulator of arsenic, thus being indicated for revegetation programs in As-polluted soils and sediments
VÀlttelevÀn kiintymyssuhteen merkitys lapsen hyvinvoinnille
Tarkoituksena tÀssÀ opinnÀytetyössÀ on koota tutkimustietoa vÀlttelevÀstÀ kiintymyssuhteesta ja sen merkityksestÀ lapsen hyvinvoinnille. Tavoitteena oli kehittÀÀ ammatillista osaamista teoriapohjan osalta ja kÀsitellÀ tutkittavaa aihetta psykiatrisen hoitotyön nÀkökulmasta, mikÀ on suuntautumiseni.
Tutkimuskysymys on jaettu kahteen osaan: vanhempien ja lapsen vÀlinen kiintymyssuhde ja lapsen kehitys ja hyvinvointi. NÀiden osien ulottuvilta on haettu tutkimusartikkeleita, tutkimusraportteja ja asiantuntijakirjoituksia, joista on koottu tiivistelmiÀ kirjallisuuskatsauksen tapaan. Pohdinnassa on eritelty aineistoa tarkemmin tutkimuskysymyksen osalta.
Kiintymyssuhde kehittyy lapsella varhaisen vuorovaikutuksen kautta 0â2-vuotiaana. Jos vanhemmat laiminlyövĂ€t kommunikoinnin lapsen kanssa, emotionaalinen kehitys jÀÀ vajaaksi eikĂ€ lapsi opi ilmaisemaan omia tarpeitaan ja tunteitaan. VĂ€lttelevĂ€n kiintymyssuhteen seuraukset voivat olla laajat epĂ€sosiaalisuudesta kognitiivisiin hĂ€iriöihin. EpĂ€sosiaalisuuteen kytkeytyviin hĂ€iriöihin kuuluu puhumattomuus, eristĂ€ytyminen ja laajemmin kroonistunut masennus, mihin taas liittyy vahva itsetuhoisuuden riski