350 research outputs found

    Public Health Outcomes as a Measure of Efficacy of Syringe Exchange Programs

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    Introduction. A syringe exchange is a public health intervention that offers nonjudgmental services to intravenous drug users (IVDU), providing clean syringes in exchange for used syringes. While prior studies demonstrated that syringe exchanges can reduce transmission of HIV, hepatitis C, and other blood-borne pathogens, other measures of health improvements have been less studied. Methods. 91 members of Vermont CARES syringe exchange program were surveyed on their healthcare practices. New members were defined asprogram. Results. Long-term members tended to have a primary care provider (PCP). Lack of insurance and fear of judgment were commonly cited reasons for not having a PCP. Long-term members were significantly less likely (p=0.04) to use costly emergency department (ED) services and less likely to reuse their own or another person\u27s needles. Long-term members were more likely to be in addiction treatment and reported a greater desire to abstain from drug use. New members were more likely to obtain hepatitis C and HIV testing in the past year. Discussion. Subjects responded positively to the possibility of accessing PCP services through VT CARES, offering a continuation of the nonjudgmental healthcare environment. Decreased ED visits significantly correlated with longer membership, reflecting the positive impact of the syringe exchange education services on reducing healthcare costs. Decreased testing among long-term members may reflect prior knowledge of their status. Long-term members were less likely to reuse their own needles or ones used by another person, suggesting the distribution of clean syringes encourages safer injection practices.https://scholarworks.uvm.edu/comphp_gallery/1247/thumbnail.jp

    Kaluza-Klein bundles and manifolds of exceptional holonomy

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    We show how in the presence of RR two-form field strength the conditions for preserving supersymmetry on six- and seven-dimensional manifolds lead to certain generalizations of monopole equations. For six dimensions the string frame metric is Kaehler with the complex structure that descends from the octonions if in addition we assume F^{(1,1)}=0. The susy generator is a gauge covariantly constant spinor. For seven dimensions the string frame metric is conformal to a G_2 metric if in addition we assume the field strength to obey a selfduality constraint. Solutions to these equations lift to geometries of G_2 and Spin(7) holonomy respectively.Comment: LaTeX, 13 page

    Rank two quadratic pairs and surface group representations

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    Let XX be a compact Riemann surface. A quadratic pair on XX consists of a holomorphic vector bundle with a quadratic form which takes values in fixed line bundle. We show that the moduli spaces of quadratic pairs of rank 2 are connected under some constraints on their topological invariants. As an application of our results we determine the connected components of the SO0(2,3)\mathrm{SO}_0(2,3)-character variety of XX.Comment: 37 pages, 1 figur

    Arf family GTP loading is activated by, and generates, positive membrane curvature

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    Small G-proteins belonging to the Arf (ADP-ribosylation factor) family serve as regulatory proteins for numerous cellular processes through GTP-dependent recruitment of effector molecules. In the present study we demonstrate that proteins in this family regulate, and are regulated by, membrane curvature. Arf1 and Arf6 were shown to load GTP in a membrane-curvature-dependent manner and stabilize, or further facilitate, changes in membrane curvature through the insertion of an amphipathic helix

    Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis

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    BACKGROUND: Drug resistance is a major problem in ovarian cancer. Triggering apoptosis using death ligands such as tumour necrosis factor-related apoptosis inducing ligand (TRAIL) might overcome chemoresistance. METHODS: We investigated whether acquired cisplatin resistance affects sensitivity to recombinant human (rh) TRAIL alone or in combination with cisplatin in an ovarian cancer cell line model consisting of A2780 and its cisplatin-resistant subline CP70. RESULTS: Combining cisplatin and rhTRAIL strongly enhanced apoptosis in both cell lines. CP70 expressed less caspase 8 protein, whereas mRNA levels were similar compared with A2780. Pre-exposure of particularly CP70 to cisplatin resulted in strongly elevated caspase 8 protein and mRNA levels. Caspase 8 mRNA turnover and protein stability in the presence or absence of cisplatin did not differ between both cell lines. Cisplatin-induced caspase 8 protein levels were essential for the rhTRAIL-sensitising effect as demonstrated using caspase 8 small-interfering RNA (siRNA) and caspase-8 overexpressing constructs. Cellular FLICE-inhibitory protein (c-FLIP) and p53 siRNA experiments showed that neither an altered caspase 8/c-FLIP ratio nor a p53-dependent increase in DR5 membrane expression following cisplatin were involved in rhTRAIL sensitisation. CONCLUSION: Cisplatin enhances rhTRAIL-induced apoptosis in cisplatin-resistant ovarian cancer cells, and induction of caspase 8 protein expression is the key factor of rhTRAIL sensitisation. British Journal of Cancer (2011) 104, 1278-1287. doi:10.1038/bjc.2011.84 www.bjcancer.com (C) 2011 Cancer Research U

    Australian vegetated coastal ecosystems as global hotspots for climate change mitigation

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    Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO2 emission benefits of VCE conservation and restoration. Australia contributes 5–11% of the C stored in VCE globally (70–185 Tg C in aboveground biomass, and 1,055–1,540 Tg C in the upper 1 m of soils). Potential CO2 emissions from current VCE losses are estimated at 2.1–3.1 Tg CO2-e yr-1, increasing annual CO2 emissions from land use change in Australia by 12–21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions

    Do list size and remuneration affect GPs' decisions about how they provide consultations?

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    Background: Doctors' professional behaviour is influenced by the way they are paid. When GPs are paid per item, i.e., on a fee-for-service basis (FFS), there is a clear relationship between workload and income: more work means more money. In the case of capitation based payment, workload is not directly linked to income since the fees per patient are fixed. In this study list size was considered as an indicator for workload and we investigated how list size and remuneration affect GP decisions about how they provide consultations. The main objectives of this study were to investigate a) how list size is related to consultation length, waiting time to get an appointment, and the likelihood that GPs conduct home visits and b) to what extent the relationships between list size and these three variables are affected by remuneration. Methods: List size was used because this is an important determinant of objective workload. List size was corrected for number of older patients and patients who lived in deprived areas. We focussed on three dependent variables that we expected to be related to remuneration and list size: consultation length; waiting time to get an appointment; and home visits. Data were derived from the second Dutch National Survey of General Practice (DNSGP-2), carried out between 2000 and 2002. The data were collected using electronic medical records, videotaped consultations and postal surveys. Multilevel regression analyses were performed to assess the hypothesized relationships. Results: Our results indicate that list size is negatively related to consultation length, especially among GPs with relatively large lists. A correlation between list size and waiting time to get an appointment, and a correlation between list size and the likelihood of a home visit were only found for GPs with small practices. These correlations are modified by the proportion of patients for whom GPs receive capitation fees. Waiting times to get an appointment tend to become shorter with increasing patient lists when there is a larger capitation percentage. The likelihood that GPs will conduct home visit rises with increasing patient lists when the capitation percentage is small. Conclusion: Remuneration appears to affect GPs' decisions about how they provide consultations, especially among GPs with relatively small patient lists. This role is, however, small compared to other factors such as patient characteristics.

    Predictive Power Estimation Algorithm (PPEA) - A New Algorithm to Reduce Overfitting for Genomic Biomarker Discovery

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    Toxicogenomics promises to aid in predicting adverse effects, understanding the mechanisms of drug action or toxicity, and uncovering unexpected or secondary pharmacology. However, modeling adverse effects using high dimensional and high noise genomic data is prone to over-fitting. Models constructed from such data sets often consist of a large number of genes with no obvious functional relevance to the biological effect the model intends to predict that can make it challenging to interpret the modeling results. To address these issues, we developed a novel algorithm, Predictive Power Estimation Algorithm (PPEA), which estimates the predictive power of each individual transcript through an iterative two-way bootstrapping procedure. By repeatedly enforcing that the sample number is larger than the transcript number, in each iteration of modeling and testing, PPEA reduces the potential risk of overfitting. We show with three different cases studies that: (1) PPEA can quickly derive a reliable rank order of predictive power of individual transcripts in a relatively small number of iterations, (2) the top ranked transcripts tend to be functionally related to the phenotype they are intended to predict, (3) using only the most predictive top ranked transcripts greatly facilitates development of multiplex assay such as qRT-PCR as a biomarker, and (4) more importantly, we were able to demonstrate that a small number of genes identified from the top-ranked transcripts are highly predictive of phenotype as their expression changes distinguished adverse from nonadverse effects of compounds in completely independent tests. Thus, we believe that the PPEA model effectively addresses the over-fitting problem and can be used to facilitate genomic biomarker discovery for predictive toxicology and drug responses
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