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In this work, three variants of the Brayton cycle incorporating concentrated solar technologies and dual regenerative systems are modeled. The first variant employs reheat, intercooling, and regeneration, the second applies intercooling and regeneration while the third case involves regeneration only. With the application of the entropy generation method and particle swarm algorithm (PSA), processes with the largest irreversibilities are noted, minimized and the geometric parameters of participating components are optimized.Results show that irreversibilities occurring in the systems were largely due to finite temperature differences within components. In all cases, the solar receiver and intercooler are the dominant and modest sources of entropy generation respectively. The regenerative system entropy generation is highest in the first case while decreasing in the second and third cases respectively. An improvement in the exergy/availability was observed in the first case, as the first and second law efficiency peaks at 44.9% and 59.68% respectively. Though, with a lower second law efficiency than the former, its percentage network output is equal to the first case at 43%. The aspect ratio, hydraulic diameter, and length of the receiver were observed to vary to enhance greater heat capture and increase the turbine inlet temperature (TIT). The high temperature (HT) regenerator had its geometric properties of a higher magnitude than the low temperature (LT) system as the waste heat recovery is aided by an enhanced heat transfer surface area. In comparison with the single regeneration system, the network output of the dual model was about 33.5% with a significant reduction in the entropy generated, creating a trade-off between operating the system for more power or less generation of irreversibilities.

The receiver and heat exchangers in a Solar Thermal Brayton Cycle (STBC) have been the main sources of exergy loss. Duct profiles used in the heat exchange process have been observed to possess varying degrees of heat transfer effectiveness. To this end, the effects of the elliptical, circular and rectangular absorber tubes are investigated on three variants of the dual serial-regenerative STBC models employing reheater, intercooler, or in a combined arrangement. Also, the impact of the parallel plate heat exchanger (PPHE) and spiral plate heat exchangers (SPHE) on irreversibility is investigated. The particle swarm algorithm (PSA), a stochastic optimization tool is used for the minimization of irreversibilities within the cycle and optimization of the geometric parameters of the STBC components. The largest irreversibility loss on a component-basis is observed on the receiver. The rectangular absorber system for the receiver has the least irreversibility loss compared to other profiles studied, though, a higher internal to external irreversibility ratio was noticed. Improved exergy use via the dual regenerative system was observed on all models with reductions of 22% and 15% in irreversibility obtained from the receiver and recuperator respectively. In addition, the SPHE produced less irreversibilities compared to the PPHE system and this could be attributed to its large surface area available for heat transfer. An optimal second law efficiency of 62% and 74% on the PPHE and SPHE STBC systems, respectively is achieved at around a pressure ratio of 2.2. The dual serial-regenerative system without reheats and intercooling has the advantage of optimal energy available and efficient exergy use followed by the combined system.

Background: Increasing evidence suggests that exposure to residential greenness is associated with positive health outcomes among urban populations. However, few studies have considered effects on adiposity development in a longitudinal setting. Objectives: This study aimed to explore the association between long-term exposure to urban residential greenness and markers of adiposity. Methods: A cohort of 5126 adults from five municipalities in Stockholm County was examined clinically at baseline (1992–1998) and follow-up (2002–2006) after on average nine years. Time-weighted average exposure to urban greenness was estimated by Normalized Difference Vegetation Index (NDVI) within 100 m, 250 m, and 500 m buffers around the residential addresses of each participant. Multiple linear and Poisson regression models were used to estimate associations between greenness and change in weight and waist circumference as well as risk of overweight, obesity and central obesity. Co-exposures to air pollution, traffic noise and distance to water were also examined. Results: In women, higher levels of residential greenness were associated with a reduced increase in waist circumference during follow-up (β = −0.11 cm/year, 95% CI −0.14; −0.08 per one interquartile range increase in NDVI) and decreased risk for central obesity (IRR = 0.88: 95% CI 0.79; 0.99) in the 500 m buffer. No associations were observed for men or with regard to weight development or the risk of developing overweight or obesity. Exposure to low NDVI levels in combination with high NOx from road traffic and transportation noise as well as long distance to water rendered statistically significant increases in waist circumference in both sexes. Conclusion: Higher long-term exposure to greenness was associated with a reduced increase in waist circumference and lower risk of central adiposity in women but not in men. In both sexes, low NDVI exposure in combination with other environmental risk factors appeared particularly harmful. Keywords: Residential greenness, NDVI, Adiposity, BMI, Waist circumference, Weight

Summary: Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. Findings: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). Interpretation: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. Funding: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Summary: Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota’s therapeutic potential in countering DAL’s impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.

We report the repair of a double aortic arch, coarctation of the aorta, and left subclavian artery (LSCA) aneurysm using a hybrid procedure in a 47-year-old woman. The patient underwent repair through a median sternotomy incision to bypass the left common carotid artery and LSCA. An endovascular approach was used to repair the coarctation of the aorta and to occlude the right aortic arch. Repair of this anomaly was advised because of worsening clinical symptoms and potential for fatal rupture or dissection of the LSCA aneurysm. Hybrid repair simplified what would have required a multistage open repair. Keywords: Double aortic arch, Hybrid repair, Vascular ring, Coarctation, Aneurysm, Pseudoaneurysm

Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny.

TET proteins have been found to play an important role in active demethylation at CpG sites in mammals. There are some reports implicating their functions in removal of DNA methylation imprint at the imprinted regions in the germline. However, it is not well established whether TET proteins can also be involved in demethylation of DNA methylation imprint in embryonic stem (ES) cells. Here we report that loss of TET proteins caused a significant increase in DNA methylation at the Igf2–H19 imprinted region in ES cells. We also observed a variable increase in DNA methylation at the Peg1 imprinted region in the ES clones devoid of TET proteins, in particular in the differentiated ES cells. By contrast, we did not observe a significant increase of DNA methylation imprint at the Peg3, Snrpn and Dlk1–Dio3 imprinted regions in ES cells lacking TET proteins. Interestingly, loss of TET proteins did not result in a significant increase of DNA methylation imprint at the Igf2–H19 and Peg1 imprinted regions in the embryoid bodies (EB). Therefore, TET proteins seem to be differentially involved in maintaining DNA methylation imprint at a subset of imprinted regions in ES cells and EBs.

Rat and human very low density lipoproteins (VLDL) were fractionated by zonal ultracentrifugation, yielding sharply defined fractions with narrow sedimentation limits. Sedimentation coefficients for the individual fractions were determined at two densities with the analytical ultracentrifuge, and the results were analyzed to yield buoyant densities and molecular weights for the particles in each fraction. For the rat lipoproteins, the weight concentrations of triglycerides, cholesterol, phospholipid, and protein were determined for each fraction, and their molar concentrations of apolipoprotein B were measured with a radioimmunoassay. For the human lipoproteins the corresponding values were taken from Patsch et al. (Patsch, W., J. R. Patsch, G. M. Kostner, S. Sailer, and H. Braunsteiner. 1978. Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation. J. Biol. Chem. 253:4911-4915). From these data, a ratio of the number of apoB peptides to the number of lipoprotein particles was calculated for each fraction. This ratio was close to 1 for all VLDL fractions, ranging in particle diameter from about 40 to 80 mm and 30 to 50 mm, respectively, for rat and human VLDL. The majority rat VLDL contain B-48 rather than B-100 as their (single) apoB peptide. Based on these data, we proposed that only a single copy of B-48 is required for VLDL assembly in rat liver, unless nascent hepatic VLDL contain additional apoB peptides which are uniformly lost from the plasma VLDL particles when they are analyzed.

Ocean acidification and deoxygenation co-occur in marine environments, causing deterioration of marine ecosystems. However, effects of compound stresses on marine organisms and their physiological coping mechanisms are largely unknown. Here, we show how high pCO 2 and low dissolved oxygen (DO) cause transcriptomic changes in eggs of a demersal fish (Sillago japonica), which are fully exposed to such stresses in natural environment. Overall gene expression was affected more strongly by low DO than by high pCO 2 . Enrichment analysis detected significant stress responses such as glycolytic processes in response to low DO. Increased expression of a group of glycolytic genes under low DO conditions is presumably because oxygen depletion disables the electron transfer pathway, complementing ATP production in the glycolytic pathway. Contrary to expectations, apparent mitigation of gene expression changes was dominant under combined stress conditions, and may represent an innate fish adaptive trait for severe environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Health-based exposure limits (HBELs) are derived for leachables from polymeric components that interact with the drug substance which exceed a safety concern threshold (SCT). However, given the nature of leachables, there is not always chemical-specific toxicology data. Read-across methodology specific to extractables and leachables (E&Ls) was developed based on survey data collected from 11 pharmaceutical companies and methodology used in other industries. One additional challenge for E&L read-across is most toxicology data is from the oral route of administration, whereas the parenteral route is very common for the leachable HBEL derivation. A conservative framework was developed to estimate oral bioavailability and the corresponding oral to parenteral extrapolation factor using physical chemical data. When this conservative framework was tested against 73 compounds with oral bioavailability data, it was found that the predicted bioavailability based on physico-chemical properties was conservatively greater than or equal to the experimental bioavailability 79% of the time. In conclusion, an E&L read-across methodology has been developed to provide a consistent, health protective framework for deriving HBELs when toxicology data is limited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Acute and chronic Δ 9 -THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ 9 -THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ 9 -THC's effects on CB1R and MOR levels and locomotor activity., Main Methods: Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ 9 -THC [0.75mg/kg (low dose or LD) or 2.0 mg/kg (high dose or HD)] or vehicle for 24 days, and locomotion in the open field was tested after the first and fourth weeks of chronic Δ 9 -THC exposure. Brains were harvested at the end of treatment. [ 3 H] SR141716A and [ 3 H] DAMGO autoradiography assessed CB1R and MOR levels, respectively., Key Findings: Relative to each other, chronic HD rats showed reduced vertical plane (VP) entries and time, while LD rats had increased VP entries and time for locomotion, as assessed by open-field testing; no effects were found relative to the control. Autoradiography analyses showed that HD Δ 9 -THC significantly decreased CB1R binding relative to LD Δ 9 -THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ 9 -THC rats displayed elevated binding in the primary motor (33% increase) and hypothalamic (33% increase) regions compared with controls. No significant differences were observed in MOR binding for the LD or HD compared to the control., Significance: These results demonstrate that chronic Δ 9 -THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The zero-price conundrum occurs when a clinically effective drug can justify no greater than a price of zero based on cost-effectiveness criteria from a health system perspective. This is relevant for health systems that require evidence of cost-effectiveness, in addition to safety and efficacy for drug approval and other analyses that may shape drug coverage policies, such as budget impact and comparative effectiveness. This study aimed to clarify and explore the zero-price conundrum to provide a resource in the development of practical and methodological solutions., Methods: We specified equations representing previously identified zero-price scenarios and used them to elucidate factors contributing to the zero-price conundrum and explore relationships between them. We present real-world considerations and discuss solutions from the literature., Results: The analyses demonstrated that a primary cause of the zero-price problem for a new drug that increases quality-adjusted survival pertains to healthcare costs beyond the influence of the new drug, specifically, disease background costs, costs of existing drugs used in a combination regimen, and costs of future health interventions patients may become eligible to receive. Pragmatic solutions have been to exclude such costs from cost-effectiveness analyses. Proposed modifications to cost-effectiveness analysis include assessing each drug in a combination regimen based on its relative contribution to improved health., Conclusions: The zero-price dilemma may arise more frequently as the number of drugs in high-cost disease areas continues to grow. As cost-effectiveness methods evolve, there is the opportunity to develop robust solutions that can be applied consistently., (Copyright © 2023. Published by Elsevier Inc.)

The presence of SARS-CoV-2 in untreated sewage has been confirmed in many countries but its incidence and infection risk in contaminated waters is poorly understood. The River Thames in the UK receives untreated sewage from 57 Combined Sewer Overflows (CSOs), with many discharging dozens of times per year. This study investigated if such discharges provide a pathway for environmental transmission of SARS-CoV-2. Samples of wastewater, surface water, and sediment collected close to six CSOs on the River Thames were assayed over eight months for SARS-CoV-2 RNA and infectious virus. Bivalves were also sampled as an indicator species of viral bioaccumulation. Sediment and water samples from the Danube and Sava rivers in Serbia, where raw sewage is also discharged in high volumes, were assayed as a positive control. No evidence of SARS-CoV-2 RNA or infectious virus was found in UK samples, in contrast to RNA positive samples from Serbia. Furthermore, this study shows that infectious SARS-CoV-2 inoculum is stable in Thames water and sediment for <3 days, while SARS-CoV-2 RNA is detectable for at least seven days. This indicates that dilution of wastewater likely limits environmental transmission, and that detection of viral RNA alone is not an indication of pathogen spillover., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Persistent post-concussive symptoms (PPCS) are debilitating and endure beyond the usual recovery period after mild traumatic brain injury (mTBI). Altered neurotransmission, impaired energy metabolism and oxidative stress have been examined acutely post-injury but have not been explored extensively in those with persistent symptoms. Specifically, the antioxidant glutathione (GSH) and the excitatory and inhibitory metabolites, glutamate (Glu) and γ-aminobutyric acid (GABA), are seldom studied together in the clinical mTBI literature. While Glu can be measured using conventional magnetic resonance spectroscopy (MRS) methods at 3 Tesla, GABA and GSH require the use of advanced MRS methods. Here, we used the recently established Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) to simultaneously measure GSH and GABA and short-echo time point resolved spectroscopy (PRESS) to measure Glu to gain new insight into the pathophysiology of PPCS. Twenty-nine adults with PPCS (mean age: 45.69 years, s.d.: 10.73, 22 females, 7 males) and 29 age- and sex-matched controls (mean age: 43.69 years, s.d.: 11.00) completed magnetic resonance spectroscopy scans with voxels placed in the anterior cingulate and right sensorimotor cortex. Relative to controls, anterior cingulate Glu was significantly reduced in PPCS. Higher anterior cingulate GABA was significantly associated with a higher number of lifetime mTBIs, suggesting GABA may be upregulated with repeated incidence of mTBI. Furthermore, GSH in both regions of interest was positively associated with symptoms of sleepiness and headache burden. Collectively, our findings suggest that the antioxidant defense system is active in participants with PPCS, however this may be at the expense of other glutamatergic functions such as cortical excitation and energy metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Interventions that target anxiety/depressive symptoms in the context of smoking treatment have shown promise irrespective of psychiatric diagnosis. Yet, these tailored treatments are largely absent for persons who smoke and are living with HIV (SLWH)., Objective: To evaluate a novel, smoking cessation intervention that addresses anxiety/depression and HIV-related health (QUIT) against a time-matched control (TMC) and a standard of care (SOC) condition., Methods: SLWH (N = 180) will be recruited and enrolled from 3 medical clinics in Boston, MA, and Houston, TX. The trial will consist of a baseline assessment, a 10-week intervention/assessment period, and follow-up assessments, accounting for a total study duration of approximately 8 months. All participants will complete a baseline visit and a pre-randomization standardized psychoeducation visit, and will then be randomized to one of three conditions: QUIT, TMC, or SOC. QUIT and TMC will consist of nine 60-min, cognitive behavioral therapy-based, individual weekly counseling sessions using standard smoking cessation counseling; additionally, QUIT will target anxiety and depressive symptoms by addressing underlying mechanisms related to mood and quit difficulty. SOC participants will complete weekly self-report surveys for nine weeks. All participants will be encouraged to quit at Session 7 and will be offered nicotine replacement therapy to help., Conclusions: QUIT is designed to improve smoking cessation in SLWH by addressing anxiety and depression and HIV-related health issues. If successful, the QUIT intervention would be ready for implementation and dissemination into "real-world" behavioral health and social service settings consistent with the four objectives outlined in NIDA's Strategic Plan., (Copyright © 2021. Published by Elsevier Inc.)

Escherichia coli O157:H7 risk associated with the consumption of fresh cut-cos lettuce during Australian industrial practices was assessed. A probabilistic risk assessment model was developed and implemented in the @Risk software by using the Monte Carlo simulation technique with 1,000,000 iterations. Australian preharvest practices yielded predicted annual mean E. coli O157:H7 levels from 0.2 to -3.4 log CFU/g and prevalence values ranged from 2 to 6.4%. While exclusion of solar radiation from the baseline model yielded a significant increase in concentration of E. coli O157:H7 (-5.2 -log fold), drip irrigation usage, exclusion of manure amended soil and rainfall reduced E. coli O157:H7 levels by 7.4, 6.5, and 4.3-log fold, respectively. The microbial quality of irrigation water and irrigation type both had a significant effect on E. coli O157:H7 concentrations at harvest (p < 0.05). The probability of illness due to consumption of E. coli O157:H7 contaminated fresh cut-cos lettuce when water washing interventions were introduced into the processing module, was reduced by 1.4-2.7-log fold (p < 0.05). This study provides a robust basis for assessment of risk associated with E. coli O157:H7 contamination on fresh cut-cos lettuce for industrial practices and will assist the leafy green industry and food safety authorities in Australia to identify potential risk management strategies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To describe gender differences in health-related quality of life and characterise discharged patients' perceptions of follow-up needs after extracorporeal membrane oxygenation., Research Methodology/design: A descriptive, comparative cross-sectional pilot design was used. Adult patients receiving extracorporeal membrane oxygenation discharged between January 1, 2016 and March 31, 2018 participated in telephone interviews., Setting: A 580-bed community teaching hospital in south central Pennsylvania., Main Outcome Measures: Health-related quality of life was measured with the Rand 36-item Short Form Health Survey. Open-ended questions identified post-discharge healthcare services and perceived follow-up needs., Results: Of 30 eligible patients, 24 completed a telephone interview. All health-related quality of life dimensions, except for role-emotional and mental health, were lower in post- extracorporeal membrane oxygenation patients at follow-up compared to national norms. Women scored lower than men in all health-related quality of life dimensions. The most frequent post-discharge services used were physical therapy (66.7%), rehabilitation (62.5%) and occupational therapy (54.2%). The need for coordination of care post-discharge was identified., Conclusions: Given long-term sequelae of extracorporeal membrane oxygenation on health-related quality of life and gender differences in health-related quality of life outcomes, ongoing interdisciplinary follow-up is imperative to ensure comprehensive patient management across the continuum of care., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The efficacy of thin layer in situ soil amendments was tested as a potential tool for methylmercury (MeHg) risk mitigation in Penobscot River, ME, salt marsh. Salt marshes are sites of high MeHg accumulation within the Penobscot, and key targets for remediation. The study was a fully-crossed small plot study, with four treatments (activated carbon (AC), biochar, FeCl 2 , and lime) and unamended controls at two sites. Plots were monitored for two years. Porewater MeHg concentrations were the main endpoint, with impacts on sediment biogeochemistry as a secondary study goal. AC-based SediMite™ was effective in reducing MeHg, and to a less extent total Hg, in surficial pore waters. AC reduced MeHg concentrations by >90% at the one month time point, and continued to significantly reduce pore water MeHg through about a year. AC was less effective in reducing total Hg in pore water, yielding about 70% reduction at one month, and 50-65% reduction at 8months. Biochar provided lower, and more variable reduction in porewater MeHg, but was not effective in reducing total Hg. Biochar amendment also increased soil MeHg. Neither FeCl 2 nor lime amendments reduced pore water Hg or MeHg levels. About 50% of AC treatment applied as SediMite™ pellets was retained in marsh soils after one year. This study is one of the first field trials of in situ amendment for MeHg remediation. Our results show that thin-layer AC placement is a potential remediation tool for Hg risk to biota, especially in marshes where net MeHg accumulation is often strong., (Published by Elsevier B.V.)