Adaptive Water Resource Management for Taste and Odor Control for the Anderson Regional Joint Water System

2016 South Carolina Water Resources Conference South Carolina Water Resources at a Crossroads: Response, Readiness and Recover

Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential.

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 d and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over 1-million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA and TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective nonlethal targeting of gut microbial enzymes linked to host disease limiting systemic exposure of the inhibitor in the host

HIV risk behaviors and sociodemographic features of HIV-infected Latinos residing in a new Latino settlement area in the Southeastern United States

The Southeastern United States (US) has a rapidly growing Latino population, yet little is known about HIV-infected Latinos in the region. To help inform future prevention studies, we compared sociodemographic, clinical, and behavioral characteristics between immigrant and US-born HIV-infected Latinos using face-to-face interviews conducted at three clinics in North Carolina. Questions encompassed HIV testing, acculturation, sexual- and substance-related behaviors, and migration history. Behavioral data were compared with 451 black and white clinic patients. Differences were tested using Pearson’s and Kruskal–Wallis tests. Participants (n = 127) were primarily male (74%) and immigrants (82%). Most immigrants were Mexican (67%), had low acculturation scores (92%), and were diagnosed a median of 8 years (IQR 0–12) following immigration. Compared with US-born Latinos, immigrants had lower CD4 counts at clinic entry (median 187 vs. 371 cells/mm3) and were less likely to have graduated high school (49% vs. 78%) or have insurance (9% vs. 52%; all P 90% of participants were receiving antiretroviral therapy (ART) and most had achieved HIV RNA <50 copies/mL (62% immigrants vs. 76% US-born; P = 0.32). In conclusion, Latino immigrants were more likely to present with advanced disease, identify as heterosexual, and report different risk behaviors than US-born Latinos, yet receipt and response to ART were similar between the two groups. Prevention strategies should prioritize finding innovative methods to reach Latino immigrants for routine early testing regardless of risk stratification and include programs targeted toward the different needs of immigrant and US-born Latinos

Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome

Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03–mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9–mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches

Engaging rural Australian communities in National Science Week helps increase visibility for women researchers

During a week-long celebration of science, run under the federally-supported National Science Week umbrella, the Catch a Rising Star: women in Queensland research (CaRS) program flew scientists who identify as women to regional and remote communities in the Australian State of Queensland. The aim of the project was twofold: first, to bring science to remote and regional communities in a large, economically diverse state; and second, to determine whether media and public engagement provide career advancement opportunities for women scientists. This paper focuses on the latter goal. The data show: 1) a substantial majority (> 80%) of researchers thought the training and experience provided by the program would help develop her career as a research scientist in the future; 2) the majority (65%) thought the program would help relate her research to end users, industry partners, or stakeholders in the future; and, 3) analytics can help create a compelling narrative around engagement metrics and help to quantify influence. During the weeklong project, scientists reached 600,000 impressions on one social media platform (Twitter) using a program hashtag. The breadth and depth of the project outcomes indicate funding bodies and employers could use similar data as an informative source of metrics to support hiring and promotion decisions. Although this project focused on researchers who identify as women, the lessons learned are applicable to researchers representing a diverse range of backgrounds. Future surveys will help determine whether the CaRS program provided long-term career advantages to participating scientists and communities

Outcomes and care practices for preterm infants born at less than 33 weeks’ gestation: A quality-improvement study

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality in children younger than 5 years. We report the changes in neonatal outcomes and care practices among very preterm infants in Canada over 14 years within a national, collaborative, continuous quality-improvement program. METHODS: We retrospectively studied infants born at 23–32 weeks’ gestation who were admitted to tertiary neonatal intensive care units that participated in the Evidence-based Practice for Improving Quality program in the Canadian Neonatal Network from 2004 to 2017. The primary outcome was survival without major morbidity during the initial hospital admission. We quantified changes using process-control charts in 6-month intervals to identify special-cause variations, adjusted regression models for yearly changes, and interrupted time series analyses. RESULTS: The final study population included 50 831 infants. As a result of practice changes, survival without major morbidity increased significantly (56.6% [669/1183] to 70.9% [1424/2009]; adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06–1.10, per year) across all gestational ages. Survival of infants born at 23–25 weeks’ gestation increased (70.8% [97/137] to 74.5% [219/294]; adjusted OR 1.03, 95% CI 1.02–1.05, per year). Changes in care practices included increased use of antenatal steroids (83.6% [904/1081] to 88.1% [1747/1983]), increased rates of normothermia at admission (44.8% [520/1160] to 67.5% [1316/1951]) and reduced use of pulmonary surfactant (52.8% [625/1183] to 42.7% [857/2009]). INTERPRETATION: Network-wide quality-improvement activities that include better implementation of optimal care practices can yield sustained improvement in survival without morbidity in very preterm infants

Outcomes and resource usage of infants born at ≤ 25 weeks gestation in Canada

Objectives: To determine the outcomes and resource usage of infants born at ≤ 25 weeks gestational age (GA). Methods: Retrospective study of infants born between April 2009 and September 2011 at ≤ 25 weeks\u27 GA in all neonatal intensive care units in Canada with follow-up in the neonatal follow-up clinics. Short-term morbidities, neurodevelopmental impairment, significant neurodevelopmental impairment, and resource utilization of infants born at ≤ 24 weeks were compared with neonates born at 25 weeks. Results: Of 803 neonates discharged alive, 636 (80.4%) infants born at ≤ 25 weeks\u27 GA were assessed at 18 to 24 months. Caesarean delivery, lower birth weight, and less antenatal steroid exposure were more common in infants born ≤ 24 weeks as compared with 25 weeks. They had significantly higher incidences of ductus arteriosus ligation, severe intracranial hemorrhage, retinopathy of prematurity as well as longer length of stay, central line days, days on respiratory support, days on total parenteral nutrition, days on antibiotics, and need for postnatal steroids. Neurodevelopmental impairment rates were 68.9, 64.5, and 55.6% (P=0.01) and significant neurodevelopmental impairment rates were 39.3, 29.6, and 20.9% (P\u3c0.01) for infants ≤ 23, 24, and 25 weeks GA, respectively. Postdischarge service referrals were higher for those ≤ 23 weeks. Nonsurviving infants born at 25 weeks GA had higher resource utilization during admission than infants born less than 25 weeks. Conclusions: Adverse outcomes and resource usage were significantly higher among infants born ≤ 24 weeks GA as compared with 25 weeks GA

Addressing antimicrobial resistance through community engagement: a framework for developing contextually relevant and impactful behaviour change interventions.

BackgroundCommunity engagement (CE) interventions often explore and promote behaviour change around a specific challenge. Suggestions for behaviour change should be co-produced in partnership with the community. To facilitate this, it is essential that the intervention includes key content that unpacks the challenge of interest via multiple sources of knowledge. However, where community lived experience and academic evidence appear misaligned, tensions can appear within the co-production dynamic of CE. This is specifically so within the context of antimicrobial resistance (AMR) where ideal behaviours are often superseded by what is practical or possible in a particular community context.MethodsHere we describe a framework for the equitable development of contextually appropriate, clearly evidenced behavioural objectives for CE interventions. This framework explores different sources of knowledge on AMR, including the potentially competing views of different stakeholders.FindingsThe framework allows key content on AMR to be selected based upon academic evidence, contextual appropriateness and fit to the chosen CE approach. A case study of the framework in action exemplifies how the framework is applicable to a range of contexts, CE approaches and One Health topics beyond just AMR.ConclusionsWithin CE interventions, academic evidence is crucial to develop well-informed key content. However, this formative work should also involve community members, ensuring that their contextual knowledge is valued. The type of CE approach also needs careful consideration because methodological constraints may limit the breadth and depth of information that can be delivered within an intervention, and thus the scope of key content

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers

<p>Abstract</p> <p>Background</p> <p>To better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM_2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM_2.5and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.</p> <p>Methods</p> <p>Twenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM_2.5samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM_2.5metal exposures both with and without adjustment for total PM_2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM_2.5and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM_2.5as surrogates for the differential effects of metal exposures in models for night rMSSD.</p> <p>Results</p> <p>The median PM_2.5exposure was 650 μg/m³; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m³to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m³increase in manganese. However, even after adjusting for individual metals, increases in total PM_2.5exposures were associated with declines in night rMSSD.</p> <p>Conclusion</p> <p>These results support the cardiotoxicity of PM_2.5metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.</p

Can Historical Institutionalism be Applied to Political Regime Development in Africa?

Historical institutionalism has been used to explain the emergence of democracy and dictatorship in various regions of the world, but not applied to political development in Africa. Based on the recently refined concepts of historical institutionalism, the aim of this study is to provide a framework for the analysis of the various regime types that have been established in Africa during the last two decades: democratic, hybrid and authoritarian. Surprisingly little effort has been dedicated to a historically grounded explanation of these regime types. Against a common claim that African politics is mainly driven by informal institutions or behaviours, we argue that an institution-based examination of African politics is justified. We then provide a proposition of how to link up concepts of historical institutionalism with empirical cases in Africa, within a comparative approach. Our proposition for tracing specific development paths will not be based on the regimes as a 'whole', but on the deconstruction of a political regime into partial regimes and subsequently into selected formal and informal institutions. This will allow for an empirical analysis of the different components of a regime over long periods of time, and thus for path-dependent analyses of regime development