332 research outputs found
Racial discrimination and racial socialization as predictors of African American adolescents' racial identity development using latent transition analysis.
The current study examined perceptions of racial discrimination and racial socialization on racial identity development among 566 African American adolescents over three years. Latent class analyses were used to estimate identity statuses (Diffuse, Foreclosed, Moratorium and Achieved). The probabilities of transitioning from one stage to another were examined with latent transition analyses to determine the likelihood of youth progressing, regressing or remaining constant. Racial socialization and perceptions of racial discrimination were examined as covariates to assess the association with changes in racial identity status. The results indicated that perceptions of racial discrimination were not linked to any changes in racial identity. Youth who reported higher levels of racial socialization were less likely to be in Diffuse or Foreclosed compared to the Achieved group
GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.
NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments
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Duty Hour Reform and the Outcomes of Patients Treated by New Surgeons
Despite concerns that duty hour reform might adversely affect the performance of new surgeons, this national study found no impact on patient outcomes, including 30-day mortality rates, failure-to-rescue, length of stay, and use of intensive care units. These findings should allay fears that reduced work hours during residency would produce surgeons less prepared for practice than their more experienced colleagues
A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America
Rift Valley fever is a vector-borne zoonotic disease which causes high
morbidity and mortality in livestock. In the event Rift Valley fever virus is
introduced to the United States or other non-endemic areas, understanding the
potential patterns of spread and the areas at risk based on disease vectors and
hosts will be vital for developing mitigation strategies. Presented here is a
general network-based mathematical model of Rift Valley fever. Given a lack of
empirical data on disease vector species and their vector competence, this
discrete time epidemic model uses stochastic parameters following several PERT
distributions to model the dynamic interactions between hosts and likely North
American mosquito vectors in dispersed geographic areas. Spatial effects and
climate factors are also addressed in the model. The model is applied to a
large directed asymmetric network of 3,621 nodes based on actual farms to
examine a hypothetical introduction to some counties of Texas, an important
ranching area in the United States of America (U.S.A.). The nodes of the
networks represent livestock farms, livestock markets, and feedlots, and the
links represent cattle movements and mosquito diffusion between different
nodes. Cattle and mosquito (Aedes and Culex) populations are treated with
different contact networks to assess virus propagation. Rift Valley fever virus
spread is assessed under various initial infection conditions (infected
mosquito eggs, adults or cattle). A surprising trend is fewer initial
infectious organisms result in a longer delay before a larger and more
prolonged outbreak. The delay is likely caused by a lack of herd immunity while
the infections expands geographically before becoming an epidemic involving
many dispersed farms and animals almost simultaneously
Communication and Cognition in Primate Group Movement
We here review the communicative and cognitive processes underpinning collective group movement in animals. Generally, we identify 2 major axes to explain the dynamics of decision making in animal or human groups or aggregations: One describes whether the behavior is largely determined by simple rules such as keeping a specific distance from the neighbor, or whether global information is also factored in. The second axis describes whether or not the individual constituents of the group have overlapping or diverging interests. We then review the available evidence for baboons, which have been particularly well studied, but we also draw from further studies on other nonhuman primate species. Baboons and other nonhuman primates may produce specific signals in the group movement context, such as the notifying behavior of male hamadryas baboons at the departure from the sleeping site, or clear barks that are given by chacma baboons that have lost contact with the group or specific individuals. Such signals can be understood as expressions of specific motivational states of the individuals, but there is no evidence that the subjects intend to alter the knowledge state of the recipients. There is also no evidence for shared intentionality. The cognitive demands that are associated with decision making in the context of group coordination vary with the amount of information and possibly conflicting sources of information that need to be integrated. Thus, selective pressures should favor the use of signals that maintain group cohesion, while recipients should be selected to be able to make the decision that is in their own best interest in light of all the available information
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa
Somatic mutations affect key pathways in lung adenocarcinoma
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well- classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers - including NF1, APC, RB1 and ATM - and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.National Human Genome Research InstituteWe thank A. Lash, M.F. Zakowski, M.G. Kris and V. Rusch for intellectual contributions, and many members of the Baylor Human Genome Sequencing Center, the Broad Institute of Harvard and MIT, and the Genome Center at Washington University for support. This work was funded by grants from the National Human Genome Research Institute to E.S.L., R.A.G. and R.K.W.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62885/1/nature07423.pd
Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
Although genome-wide association studies have identified over 100 risk loci that explain similar to 33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa
Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium
Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a
possible role for its association with the risk of aggressive prostate cancer.
Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a
subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects
and their possible interactions.
Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22%
increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01â1.48). Genetic variants in the growth pathway gene
showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased
risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as
compared to lowest score group.
Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our
findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is
seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain âź38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio
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