799 research outputs found

    A Mixed methods study of the social support networks of female sex workers and their primary noncommercial male partners in Tijuana, Mexico

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    Female sex workers (FSWs) are at risk for multiple health harms, including HIV. This article describes a mixed methods study of the social support networks of 19 FSWs and their primary male sex partners in Tijuana, Mexico. We collected quantitative and qualitative social network data, including quantitative network measures, qualitative narratives, and network visualizations. Methodologically, we illustrate how a convergent mixed methods approach to studying personal social support networks of FSWs can yield a more holistic understanding of network composition and role. From a health-related perspective, we show how migration/deportation and stigma shape social networks and might be leveraged to support HIV prevention interventions. We believe others can benefit from a mixed methods approach to studying social network

    Defining Metrics for Short Term Success After LVAD Implant: An Analysis of the Society of Thoracic Surgeons Intermacs Registry

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    Purpose: While clinical trials evaluating left ventricular assist device (LVAD) technology typically use composite outcomes to assess efficacy, composite outcomes including patient reported outcomes (PROs) have not been utilized as benchmarks for LVAD implant center performance improvement initiatives or quality ranking. The objective of the study was to assess the feasibility of generating a patient composite outcome measure including PROs from a real world registry. Methods: Short term (ST, 180 days) adverse events (AEs) and mortality were tallied for Intermacs patients undergoing LVAD implant between 1/2012 and 12/2019. ST postoperative events included mortality on first device and frequencies of stroke, reoperation (device malfunction/other), right heart failure (RHF), prolonged respiratory failure, and/or dialysis on first device. Logistic regression was used to generate odds ratios for mortality for each AE. Separately, the EuroQOL visual analog scale (VAS) was assessed at baseline and 180 days in ST survivors. Results: Of 20,115 patients, 37% suffered at least one event, most commonly death, reoperation and stroke (Table, column A). Stroke, prolonged respiratory failure, and dialysis attributed the most to ST mortality (Table, column B). Of the 16725 patients alive at 180 days, 43% completed a VAS with 82.0% showing VAS improvement. Renal failure and RHF contributed most to failure to improve VAS (Figure). Conclusion: Assessment of a ST composite outcome metric after LVAD implant from a real world data source is feasible but limited by incomplete PRO reporting. ST adverse events display differential effects on mortality and PROs that can be used in development of global rank outcome scores. While reoperation is common, stroke, prolonged respiratory failure and renal failure conferred highest risks of ST deaths within Intermacs. Assessment of PROs should become a priority for LVAD centers to allow the field to generate a complete assessment of patient-centered outcomes

    The effect of Dnaaf5 gene dosage on primary ciliary dyskinesia phenotypes

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    DNAAF5 is a dynein motor assembly factor associated with the autosomal heterogenic recessive condition of motile cilia, primary ciliary dyskinesia (PCD). The effects of allele heterozygosity on motile cilia function are unknown. We used CRISPR-Cas9 genome editing in mice to recreate a human missense variant identified in patients with mild PCD and a second, frameshift-null deletion in Dnaaf5. Litters with Dnaaf5 heteroallelic variants showed distinct missense and null gene dosage effects. Homozygosity for the null Dnaaf5 alleles was embryonic lethal. Compound heterozygous animals with the missense and null alleles showed severe disease manifesting as hydrocephalus and early lethality. However, animals homozygous for the missense mutation had improved survival, with partially preserved cilia function and motor assembly observed by ultrastructure analysis. Notably, the same variant alleles exhibited divergent cilia function across different multiciliated tissues. Proteomic analysis of isolated airway cilia from mutant mice revealed reduction in some axonemal regulatory and structural proteins not previously reported in DNAAF5 variants. Transcriptional analysis of mouse and human mutant cells showed increased expression of genes coding for axonemal proteins. These findings suggest allele-specific and tissue-specific molecular requirements for cilia motor assembly that may affect disease phenotypes and clinical trajectory in motile ciliopathies

    IODP workshop:developing scientific drilling proposals for the Argentina Passive Volcanic Continental Margin (APVCM) – basin evolution, deep biosphere, hydrates, sediment dynamics and ocean evolution

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    The Argentine margin contains important sedimentological, paleontological and chemical records of regional and local tectonic evolution, sea level, climate evolution and ocean circulation since the opening of the South Atlantic in the Late Jurassic–Early Cretaceous as well as the present-day results of post-depositional chemical and biological alteration. Despite its important location, which underlies the exchange of southern- and northern-sourced water masses, the Argentine margin has not been investigated in detail using scientific drilling techniques, perhaps because the margin has the reputation of being erosional. However, a number of papers published since 2009 have reported new high-resolution and/or multichannel seismic surveys, often combined with multi-beam bathymetric data, which show the common occurrence of layered sediments and prominent sediment drifts on the Argentine and adjacent Uruguayan margins. There has also been significant progress in studying the climatic records in surficial and near-surface sediments recovered in sediment cores from the Argentine margin. Encouraged by these recent results, our 3.5-day IODP (International Ocean Discovery Program) workshop in Buenos Aires (8–11 September 2015) focused on opportunities for scientific drilling on the Atlantic margin of Argentina, which lies beneath a key portion of the global ocean conveyor belt of thermohaline circulation. Significant opportunities exist to study the tectonic evolution, paleoceanography and stratigraphy, sedimentology, and biosphere and geochemistry of this margin

    Elevated Expression of Squamous Cell Carcinoma Antigen (SCCA) Is Associated with Human Breast Carcinoma

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    Squamous cell carcinoma antigen (SCCA) belongs to the serine protease inhibitor (Serpin) family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC) in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360) and normal breast epithelium (n = 124). SCCA expression was scored on a tiered scale (0-3) independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%), Grade II (2.5%), and Grade III (9.4%) breast cancers (p<0.0001). Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005). No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124). SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR) double-negative tumors (p = 0.0009). Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively). This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment

    Protect global values of the Southern Ocean ecosystem

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    The Southern Ocean, which comprises ∼10% of the global ocean, is critically important to the homeostasis of the Earth system, exhibits distinctive marine biodiversity, and has tremendous scientific, diplomatic, and wilderness value. Yet, the region and its suite of global values are critically threatened by climate change, which is exacerbated by commercial fishing, an activity that provides value for relatively few industrial actors and compromises the greater values that the Southern Ocean ecosystem provides to the world. The Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), the arm of the Antarctic Treaty System responsible for managing Southern Ocean marine living resources, meets in October–November 2022 and is under pressure to strengthen fisheries management, especially toward climate change resilience. We encourage improved management practices that account for the environmental externalities arising from trade-offs between fishing and the global contribution of the Southern Ocean ecosystem, including under a changing climate.The Pew Charitable Trusts; Biodiversa ASICS. U.R.S. and the University of British Columbia–based Solving Food-Climate-Biodiversity research partnership sponsored by the Social Sciences and Humanities Research Council of Canada.http://www.sciencemag.orghj2023Plant Production and Soil Scienc

    Fish Farms at Sea: The Ground Truth from Google Earth

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    In the face of global overfishing of wild-caught seafood, ocean fish farming has augmented the supply of fresh fish to western markets and become one of the fastest growing global industries. Accurate reporting of quantities of wild-caught fish has been problematic and we questioned whether similar discrepancies in data exist in statistics for farmed fish production. In the Mediterranean Sea, ocean fish farming is prevalent and stationary cages can be seen off the coasts of 16 countries using satellite imagery available through Google Earth. Using this tool, we demonstrate here that a few trained scientists now have the capacity to ground truth farmed fish production data reported by the Mediterranean countries. With Google Earth, we could examine 91% of the Mediterranean coast and count 248 tuna cages (circular cages >40 m diameter) and 20,976 other fish cages within 10 km offshore, the majority of which were off Greece (49%) and Turkey (31%). Combining satellite imagery with assumptions about cage volume, fish density, harvest rates, and seasonal capacity, we make a conservative approximation of ocean-farmed finfish production for 16 Mediterranean countries. Our overall estimate of 225,736 t of farmed finfish (not including tuna) in the Mediterranean Sea in 2006 is only slightly more than the United Nations Food and Agriculture Organization reports. The results demonstrate the reliability of recent FAO farmed fish production statistics for the Mediterranean as well as the promise of Google Earth to collect and ground truth data

    Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Naïve Subjects in the CASTLE Study

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    CASTLE compared the efficacy of atazanavir/ritonavir with lopinavir/ritonavir, each in combination with tenofovir-emtricitabine in ARV-naïve subjects from 5 continents.Determine the baseline rate and clinical significance of TDR mutations using ultra-deep sequencing (UDS) in ARV-naïve subjects in CASTLE.A case control study was performed on baseline samples for all 53 subjects with virologic failures (VF) at Week 48 and 95 subjects with virologic successes (VS) randomly selected and matched by CD4 count and viral load. UDS was performed using 454 Life Sciences/Roche technology.Of 148 samples, 141 had successful UDS (86 subtype B, 55 non-B subtypes). Overall, 30.5% of subjects had a TDR mutation at baseline; 15.6% only had TDR(s) at <20% of the viral population. There was no difference in the rate of TDRs by B (30.2%) or non-B subtypes (30.9%). VF (51) and VS (90) had similar rates of any TDRs (25.5% vs. 33.3%), NNRTI TDRs (11.1% vs.11.8%) and NRTI TDRs (24.4% vs. 25.5%). Of 9 (6.4%) subjects with M184V/I (7 at <20% levels), 6 experienced VF. 16 (11.3%) subjects had multiple TAMs, and 7 experienced VF. 3 (2.1%) subjects had both multiple TAMs+M184V, and all experienced VF. Of 14 (9.9%) subjects with PI TDRs (11 at <20% levels): only 1 experienced virologic failure. The majority of PI TDRs were found in isolation (e.g. 46I) at <20% levels, and had low resistance algorithm scores.Among a representative sample of ARV-naïve subjects in CASTLE, TDR mutations were common (30.5%); B and non-B subtypes had similar rates of TDRs. Subjects with multiple PI TDRs were infrequent. Overall, TDRs did not affect virologic response for subjects on a boosted PI by week 48; however, a small subset of subjects with extensive NRTI backbone TDR patterns experienced virologic failure
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