John W.

Abstract In the 465,000 km Canadian Prairies ecozone, robust hydrological input data for hydraulic model applications are uncommon because

Background: Acute pancreatitis (AP) can be life-threatening with unpredictable severity. Despite advances in management, its pathogenesis remains unclear. This study investigated metabolites and lipoprotein profiles in AP patients of African descent to understand the underlying pathophysiological conditions so as to inform prognosis and management. Methods: Serum samples were collected from 9 healthy controls (HCs) and 30 AP patients (8 with mild AP, 14 with moderately severe AP, and 8 with severe AP) on days 1, 3, 5, and 7 post epigastric pain and subjected to nuclear magnetic resonance (NMR) spectroscopy. Wilcoxon and Kruskal–Wallis rank-sum tests compared numerical covariates. Lipoprotein characterization was performed using the Liposcale test, and Spearman’s rank test assessed data correlations. The p-values < 0.05 indicated significance. Results: Thirty-eight metabolic signals and information on lipoprotein subclasses were identified from the NMR spectra. The severity of AP correlated with increased levels of 3-hydroxybutyrate and acetoacetate and decreased levels of ascorbate. Distinct metabolic phenotypes were identified and characterized by unique inflammatory and lipoprotein profiles. High-density lipoprotein cholesterol (HDL-C) decreased across all the metabolic phenotypes of AP when compared with the HC, while elevated immediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels were observed. Time-dependent changes in metabolites were indicative of responsiveness to therapy. Conclusions: Our findings indicate that dysregulated metabolites and lipoproteins can be used to differentiate AP disease state and severity. Furthermore, integrating clinical parameters with data on metabolic and lipoprotein perturbations can contribute to a better understanding of the complex pathophysiology of AP.

Neuromyelitis optica spectrum disorders (NMOSD) comprise autoimmune diseases imposing substantial disability. We compared an NMOSD-targeted disability assessment of mobility, vision, and self-care domains (individually and composite) with the multiple sclerosis-targeted Expanded Disability Status Scale (EDSS) to assess NMOSD disease burden. An overall cohort (n = 505) and a subset of these patients with an enriched dataset (n = 198) were analyzed from the CIRCLES longitudinal, observational database of patients with AQP4-IgG–seropositive or –seronegative NMOSD in North America. Multinomial modeling was used to identify temporal correlates of disability improvement, stability, and worsening. Prior on-study relapse correlated with worsening mobility (OR, 3.08; 95% CI: 1.61–5.90), vision (OR, 3.99; 95% CI: 2.03–7.86), self-care disability (OR, 1.90; 95% CI: 1.07–3.38), and mean composite index disability (OR, 4.20; 95% CI: 1.71–10.34). Higher vision disability was associated with Black race, shorter time on-study, and AQP4-IgG–seropositive status in patients ≥ 18 years (p < 0.05). Disease onset phenotype and sex correlated with pain interference (p < 0.05). These correlates of NMOSD disability were undetected by EDSS. The CIRCLES real-world experience supports the need for NMOSD-specific disability assessment to improve recognition of disease burden, facilitate proactive clinical management, offer insights into resilience, and inform clinical trial design.

Climate change, through more frequent extreme weather events, and urban sprawl, by increasing runoff, are two critical threats to drainage networks, impacting both public health and property. Augmenting drainage networks to withstand additional stress by enlarging conduits or constructing new detention facilities requires a significant financial investment. The goal of this study is to enhance urban resilience by optimizing real-time control (RTC) systems for drainage networks that optimize the flow control devices (FCDs), which could mitigate the need to invest in major construction costs. RTC is an approach that can help mitigate flooding in urban areas. This study is the first to optimize feedback controllers in SWMM, as well as the first to simultaneously optimize the number, location, and proportional–integral–derivative (PID) controllers for FCDs through two nested genetic algorithms (GAs), and especially within a unified environment (i.e., Python), which led to more efficient management of the process, thereby enhancing the efficiency of urban drainage network optimization. This study examined the impact of optimized RTC on the urban drainage network (UDN) in a part of New Orleans, LA, USA, under 1-, 2-, 5-, and 10-year storm events. The optimized RTC resulted in an improvement of up to 50% in network performance during a design storm. The results demonstrate the applicability in an urban environment where storms, flooding, and financial investments are critical to the management of stormwater drainage.

Open Access Article by Paul F. Gillespie Paul F. Gillespie SciProfiles Scilit Preprints.org

The aim of fungal treatment of organic matter for ruminants is the improvement of its degradability. So far, such treatment appears to be time-consuming and improvement has been modest. In previous work, we observed within three white rot species that there is modest (Ceriporiopsis subvermispora) or low (Lentinula edodes and Pleurotus eryngii) variation in fiber degradation in wheat straw during seven weeks of incubation. By extending and re-examining the data from all three species, we see that strains of C. subvermispora show the largest variation and improvement in the degradability of treated wheat straw. In addition, C. subvermispora also generated the highest absolute amount of degradable organic matter, a parameter not calculated before, but is very relevant for the economic feasibility of fungal treatment. In estimating fungal growth, we found no good correlation between an increase in ergosterol and a decrease in plant biomass, indicating a variation within fungal species of the ergosterol/fungal biomass ratio and/or a variation in carbon use efficiency, which has also not been analyzed before. This work contributes to the knowledge of how fungi degrade lignocellulose and further specifies what can be targeted for breeding to make fungal pretreatment economically feasible for upgrading organic waste streams into ruminal feed.

Department of Urology, Royal Brisbane and Women's Hospital, Butterfield St., Brisbane 4029, Australia

The bioenergetic deficits observed in Amyotrophic Lateral Sclerosis result from the disruption of mitochondria-associated ER membranes. Here, the authors show that this disruption impairs the use of glucose-derived pyruvate, which over time hinders mitochondrial electron flow.

Background In moderate-to-high malaria transmission regions, the World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) alongside insecticide-treated bed nets to reduce the adverse consequences of pregnancy-associated malaria. Due to high-grade Plasmodium falciparum resistance to SP, novel treatment regimens need to be evaluated for IPTp, but these increase pill burden and treatment days. The present qualitative study assessed the acceptability of IPTp-SP plus dihydroartemisinin-piperaquine (DP) in Papua New Guinea, where IPTp-SP was implemented in 2009. Methods Individual in-depth interviews (IDIs) and focus group discussions were conducted at health facilities where a clinical trial evaluated IPTp-SP plus DP (three-day regimen) versus IPTp-SP plus DP-placebo. IDIs were conducted with: (1) trial participants at different stages of engagement with ANC and IPTp, e.g. first antenatal clinic visit, subsequent antenatal clinic visits and postpartum; (2) local health workers (nurses, community health workers, midwives, health extension officers, doctors); and (3) representatives of district, provincial and national health authorities involved in programming ANC and IPTp. Focus group discussions comprised pregnant women only, including those engaged in the clinical trial and those receiving routine ANC outside of the trial. All interviews were audio recorded and transcribed. Transcripts were analysed using inductive and deductive thematic analysis applying a framework assessing: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy. Results Women expressed positive feelings and attitudes towards SP plus DP/DP-placebo; reported limited side effects; and found the size, number, colour, and taste of study medicines acceptable. Health workers and policymakers were concerned that, compared to SP alone, additional tablets, frequency (three-day regimen), and tablet size might be barriers to acceptability for users outside a non-trial setting. There was a high perceived effectiveness of SP plus DP; most women reported that they did not get malaria or felt sick during pregnancy. Broader healthcare benefits received through trial participation and the involvement of health workers, relatives and community members in the clinical trial enabled antenatal clinic attendance and perceived acceptability of this IPTp regimen. Conclusions In the trial context, IPTp-SP plus DP was acceptable to both users and providers. Healthcare providers were concerned about the realities of acceptability and adherence to SP plus DP outside a clinical trial setting.

Abstract Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene.