257 research outputs found
Social Networking Technology, Social Network Composition, and Reductions in Substance Use Among Homeless Adolescents
Peer-based prevention programs for homeless youth are complicated by the potential for reinforcing high-risk behaviors among participants. The goal of this study is to understand how homeless youth could be linked to positive peers in prevention programming by understanding where in social and physical space positive peers for homeless youth are located, how these ties are associated with substance use, and the role of social networking technologies (e.g., internet and cell phones) in this process. Personal social network data were collected from 136 homeless adolescents in Los Angeles, CA. Respondents reported on composition of their social networks with respect to: home-based peers and parents (accessed via social networking technology; e.g., the internet, cell phone, texting), homeless peers and agency staff (accessed face-to-face) and whether or not network members were substance-using or non-substance-using. Associations between respondent’s lifetime cocaine, heroin, and methamphetamine use and recent (previous 30 days) alcohol and marijuana use were assessed by the number of non-substance-using versus substance-using ties in multivariate linear regression models. 43% of adolescents reported a non-substance-using home-based tie. More of these ties were associated with less recent alcohol use. 62% of adolescents reported a substance-using homeless tie. More of these ties were associated with more recent marijuana use as well as more lifetime heroin and methamphetamine use. For homeless youth, who are physically disconnected from positive peers, social networking technologies can be used to facilitate the sorts of positive social ties that effective peer-based prevention programs require
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.
Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition
Estimating Incidence Curves of Several Infections Using Symptom Surveillance Data
We introduce a method for estimating incidence curves of several co-circulating infectious pathogens, where each infection has its own probabilities of particular symptom profiles. Our deconvolution method utilizes weekly surveillance data on symptoms from a defined population as well as additional data on symptoms from a sample of virologically confirmed infectious episodes. We illustrate this method by numerical simulations and by using data from a survey conducted on the University of Michigan campus. Last, we describe the data needs to make such estimates accurate
Isolates of Liao Ning Virus from Wild-Caught Mosquitoes in the Xinjiang Province of China in 2005
Liao ning virus (LNV) is related to Banna virus, a known human-pathogen present in south-east Asia. Both viruses belong to the genus Seadornavirus, family Reoviridae. LNV causes lethal haemorrhage in experimentally infected mice. Twenty seven isolates of LNV were made from mosquitoes collected in different locations within the Xinjiang province of north-western China during 2005. These mosquitoes were caught in the accommodation of human patients with febrile manifestations, or in animal barns where sheep represent the main livestock species. The regions where LNV was isolated are affected by seasonal encephalitis, but are free of Japanese encephalitis (JE). Genome segment 10 (Seg-10) (encoding cell-attachment and serotype-determining protein VP10) and Seg-12 (encoding non-structural protein VP12) were sequenced for multiple LNV isolates. Phylogenetic analyses showed a less homogenous Seg-10 gene pool, as compared to segment 12. However, all of these isolates appear to belong to LNV type-1. These data suggest a relatively recent introduction of LNV into Xinjiang province, with substitution rates for LNV Seg-10 and Seg-12, respectively, of 2.29×10−4 and 1.57×10−4 substitutions/nt/year. These substitution rates are similar to those estimated for other dsRNA viruses. Our data indicate that the history of LNV is characterized by a lack of demographic fluctuations. However, a decline in the LNV population in the late 1980s - early 1990s, was indicated by data for both Seg-10 and Seg-12. Data also suggest a beginning of an expansion in the late 1990s as inferred from Seg-12 skyline plot
Germline MC1R status influences somatic mutation burden in melanoma
The major genetic determinants of cutaneous melanoma risk in the general population are disruptive variants (R alleles) in the melanocortin 1 receptor (MC1R) gene. These alleles are also linked to red hair, freckling, and sun sensitivity, all of which are known melanoma phenotypic risk factors. Here we report that in melanomas and for somatic C>T mutations, a signature linked to sun exposure, the expected single-nucleotide variant count associated with the presence of an R allele is estimated to be 42% (95% CI, 15-76%) higher than that among persons without an R allele. This figure is comparable to the expected mutational burden associated with an additional 21 years of age. We also find significant and similar enrichment of non-C>T mutation classes supporting a role for additional mutagenic processes in melanoma development in individuals carrying R alleles
The Functioning of the Drosophila CPEB Protein Orb Is Regulated by Phosphorylation and Requires Casein Kinase 2 Activity
The Orb CPEB protein regulates translation of localized mRNAs in Drosophila ovaries. While there are multiple hypo- and hyperphosphorylated Orb isoforms in wild type ovaries, most are missing in orbF303, which has an amino acid substitution in a buried region of the second RRM domain. Using a proteomics approach we identified a candidate Orb kinase, Casein Kinase 2 (CK2). In addition to being associated with Orb in vivo, we show that ck2 is required for orb functioning in gurken signaling and in the autoregulation of orb mRNA localization and translation. Supporting a role for ck2 in Orb phosphorylation, we find that the phosphorylation pattern is altered when ck2 activity is partially compromised. Finally, we show that the Orb hypophosphorylated isoforms are in slowly sedimenting complexes that contain the translational repressor Bruno, while the hyperphosphorylated isoforms assemble into large complexes that co-sediment with polysomes and contain the Wisp poly(A) polymerase
A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study
There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development
Reducing length of stay for acute diabetic foot episodes: employing an extended scope of practice podiatric high-risk foot coordinator in an acute foundation trust hospital
BACKGROUND: To enhance the acute management of people with diabetic foot disease requiring admission, an extended scope of practice, podiatric high-risk foot coordinator position, was established at the Great Western Hospital, Swindon in 2010. The focus of this new role was to facilitate more efficient and timely management of people with complex diabetic foot disease. The aim of this project was to investigate the impact of the podiatric high-risk foot coordinator role on length of stay, rate of re-admission and bed cost. METHOD: This study evaluated the difference in length of stay and rate of re-admission between an 11- month pre-pilot period (November 2008 to October 2009) and a 10-month pilot period (August 2010 to June 2011). The estimated difference in bed cost between the pre-pilot and pilot audits was also calculated. Inclusion criteria were restricted to inpatients admitted with a diabetic foot ulcer, gangrene, cellulitis or infection as the primary cause for admission. Eligible records were retrieved using ICD-10 (V9) coding via the hospital clinical audit department for the pre-pilot period and a unique database was used to source records for the pilot phase. RESULTS: Following the introduction of the podiatric high-risk foot coordinator, the average length of stay reduced from 33.7 days to 23.3 days (mean difference 10.4 days, 95% CI 0.0 to 20.8, p = 0.050). There was no statistically significant difference in re-admission rate between the two study periods, 17.2% (95% CI 12.2% to 23.9%) in the pre-pilot phase and 15.4% (95% CI 12.0% to 19.5%) in the pilot phase (p = 0.820). The extrapolated annual cost saving following the implementation of the new coordinator role was calculated to be £234,000 for the 2010/2011 year. CONCLUSIONS: This audit found that the extended scope of practice coordinator role may have a positive impact on reducing length of stay for diabetic foot admissions. This paper advocates the role of a podiatric high-risk foot coordinator utilising an extended scope of practice model, although further research is needed
The Contribution of Occult Precipitation to Nutrient Deposition on the West Coast of South Africa
The Strandveld mediterranean-ecosystem of the west coast of South Africa supports floristically
diverse vegetation growing on mostly nutrient-poor aeolian sands and extending from
the Atlantic Ocean tens of kilometers inland. The cold Benguela current upwelling interacts
with warm onshore southerly winds in summer causing coastal fogs in this region. We hypothesized
that fog and other forms of occult precipitation contribute moisture and nutrients
to the vegetation. We measured occult precipitation over one year along a transect running
inland in the direction of the prevailing wind and compared the nutrient concentrations with
those in rainwater. Occult deposition rates of P, N, K, Mg, Ca, Na, Al and Fe all decreased
with distance from the ocean. Furthermore, ratios of cations to Na were similar to those of
seawater, suggesting a marine origin for these. In contrast, N and P ratios in occult precipitation
were higher than in seawater. We speculate that this is due to marine foam contributing
to occult precipitation. Nutrient loss in leaf litter from dominant shrub species was
measured to indicate nutrient demand. We estimated that occult precipitation could meet
the demand of the dominant shrubby species for annual N, P, K and Ca. Of these species,
those with small leaves intercepted more moisture and nutrients than those with larger
leaves and could take up foliar deposits of glycine, NO3-, NH4
+ and Li (as tracer for K)
through leaf surfaces. We conclude that occult deposition together with rainfall deposition
are potentially important nutrient and moisture sources for the Strandveld vegetation that
contribute to this vegetation being floristically distinct from neighbouring nutrient-poor Fynbos
vegetation
Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination
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