During the operation of supercritical CO2 (sCO2) turbomachineries, large pressure ratios, supersonic conditions and non-ideal gas fluid dynamic phenomenon may happen, which will decrease the whole cycle efficiencies. Hence non-standard designs for the turbomachineries geometry are needed. Successfully simulations in capturing non-ideal gas fluid dynamics and coupled with optimization algorithm are hard and currently not available in any commercial CFD software. Therefore, the problem of optimizing sCO2 turbomachinery is difficult to solve, which has become a major obstacle to obtain compact and high-efficiency sCO2 turbomachineries. In this study, a modularized geometry optimizer is developed to obtain the non-standard geometric designs for sCO2 turbomachineries. Multiple techniques are applied to this optimizer, include the Nelder–Mead algorithm, Mahalanobis distance and stochastic algorithm. The newly developed optimizer can successfully find the optimum satisfying the objective function under given weighting factors. The computational cost can be reduced through a stochastic algorithm. To validate the optimizer, a convergent–divergent nozzle for air with a target Mach number equal to 2.4 is optimized. Different starting points and combinations of weighting factors are used to create a Pareto front. Adjust the weighting factors for different terms of the objective function leading the optimizer to go to different directions in n-dimensional spaces. Three optimized cases, one is Mach number optimized, one is outlet flow uniformity optimized and the other is compromised case, are picked out and analyzed. The results show that the optimizer can successfully find optimized geometry than the reference case and potentially save computational cost. Due to the modularized characteristics, the components of this optimizer can be replaced with any available techniques, which mean the optimizer can be applied to solve different types of optimization problems.
Recently, there is an increased interest in supercritical CO2 and organic Rankine cycles (ORC) for their ability to achieve higher thermodynamic efficiency. However, the non-ideal gas thermodynamic in these cycles may affect the flow properties critically, necessitating the research of non-ideal compressible fluid dynamics (NICFD). Thus, simulation tools that can accurately predict fluid flows with NICFD are significant. This study presents a new approximation Riemann solver in OpenFOAM for NICFD. The new solver uses a real-gas (look-up table based) approximate Riemann flux calculator (modified from HLLC ALE flux calculator) through adding a new thermodynamic library tightly coupled with the OpenFOAM®. To validate the solver, three cases are presented, including a NASA transonic nozzle operating with air, to confirm the ability to correctly simulate the transonic flow phenomena and the shock waves; the VKI 2D cascade operated with MDM to assess the ability in simulating non-ideal gas flows typically to industrial applications; and the dense gas flow (MD4M) passing a backward ramp to illustrate the ability of the flux calculator and look-up table mechanism that can work well in the non-ideal region of fluid properties. This study can benefit future engineering applications of computational fluid mechanics of NICFD and the OpenFOAM community.
Background Long-term use of antidepressant drugs (AD), much longer than recommended by guidelines, in nursing homes (NH) is common. NH home residents may have a relatively higher risk of adverse events. Moreover, in an NH setting nursing staff and relatives are intensively involved in the decision-making process. In many countries, General Practitioners' (GPs) provide care for residents in NHs. Little is known about GPs' perspectives on discontinuation of long-term AD in NH residents. Objectives To explore GPs' views of discontinuing long-term AD in NH residents. Methods An exploratory qualitative study, with semi-structured interviews, was conducted with a purposive sample of 20 Belgian GPs. Interviews, conducted over six months in 2019, were analysed by thematic analysis. Results Twenty interviews were conducted until data saturation. The first theme, 'reluctance to rock the boat: not worth taking the risk', describes that GPs perceive discontinuation as an unpredictable risk without clear benefits. GPs' main concern was the risk of destabilising the fragile balance in an older patient. Second, 'it takes at least three to tango', captures the unspoken alliance between GPs, nursing staff and relatives and suggests that agreement of at least these three partners is required. The third, 'Opening the door: triggers to discontinue', points to severe health problems and dementia as strong facilitators for discontinuation. Conclusion Discontinuation of long-term AD in NHs is a complex process for GPs. More evidence and attention to the role nursing staff and relatives play are needed to better guide the discontinuation of AD in older NH patients.
Background: Gay, bisexual and other men who have sex with men (GBMSM) are at far greater risk of experiencing poor mental health (MH) than wider society. This disparity was exacerbated by additional 'unique to sexual minority status' COVID-19 stressors. Objective: This sequential, mixed-methods study examined remote MH help-seeking among GBMSM in the U.K. and Ireland during the first COVID-19 lockdown. Methods and Results: Quantitative survey data (n = 1368), analysed with logistic regression, suggested GBMSM experiencing moderate-to-severe anxiety and those with a past MH diagnosis were most likely to seek MH support. Thematic analysis of qualitative interview (n = 18) data identified multiple barriers and enablers to GBMSM seeking remote MH help, with the help primarily sought from GBMSM-facing organisations and generic online resources. Finally, the behaviour change wheel was used to generate theoretically informed recommendations to promote MH help-seeking among GBMSM in Scotland. Implications: We discuss how applying these recommendations in the short, medium and long term will begin to address GBMSM's MH needs, post COVID-19.
Objective: This prospective clinical study aim was to analyze the effect of the probiotic Lactobacillus reuteri Prodentis lozenges on salivary microbiome of subjects wearing fixed orthodontic appliances. Methods: Saliva samples were collected prior to consumption and 14th-day post probiotic lozenges consumption (n=40, age 18-23). Oral hygiene index-score (OHI-S) and papilla bleeding index (PBI) were recorded. The salivary microbiome was profiled by next-generation sequencing using the V3-V4 region of 16S-rRNA. Microbial composition, diversity and taxonomic biomarkers were analysed in comparison to probiotic intervention and the clinical characteristics of the cohort using standard bioinformatics tools. Results: The diversity and bacterial community structures did not change significantly in salivary microbiome of periodontally healthy subjects during short-term probiotic intervention. Probiotic consumption correlated with reduction of OHI and PBI scores (50% reduction of scores, P<0.001). The reduction of clinical indices was evident in conjunction with significantly reduced abundance of oral pathogens, such as Porphyromonas pasteri, Treponema sp., Fretibacterium fastidiosum, Kingella oralis and Propionibacterium acnes. Conclusion: Short-term probiotic intervention helped maintaining good oral health in patients undergoing fixed orthodontic therapy. Although overall oral microbiome structure remained largely unchanged, a significant alteration in the abundance of health and disease-associated species highlighted the beneficial effect of probiotic.
ABSTRACT This experimental-mixed methods investigates the impact of shifting from a traditional laboratory model to a hybrid laboratory model. The hybrid model consisted of (1) online instructions and pre-laboratory test, (2) compressed face-to-face laboratory time, and (3) post-laboratory data analysis. This study analyses whether student perceptions of a targeted intervention were correlated to a range of student performance indicators. Only a fractional improvement in student performance was observed, but evidence suggests that the use of online content led to more frequent student interaction with the learning material. The pre-laboratory tests encouraged a better preparation for the laboratory. Splitting the laboratory intervention into different phases was generally better perceived by students than the traditional style. The findings are expected to encourage course coordinators and developers to adopt concepts used in the delivery of hybrid solutions which is important due to the current emphasis on the use of online models of instruction.
The reliable and cost-efficient manufacturing of monoclonal antibodies (mAbs) is essential to fulfil their ever-growing demand. Cell death in bioreactors reduces productivity and product quality, and is largely attributed to apoptosis. In perfusion bioreactors, this leads to the necessity of a bleed stream, which negatively affects the overall process economy. To combat this limitation, death-resistant Chinese hamster ovary cell lines were developed by simultaneously knocking out the apoptosis effector proteins Bak1, Bax, and Bok with CRISPR technology. These cell lines were cultured in fed-batch and perfusion bioreactors and compared to an unmodified control cell line. In fed-batch, the death-resistant cell lines showed higher cell densities and longer culture durations, lasting nearly a month under standard culture conditions. In perfusion, the death-resistant cell lines showed slower drops in viability and displayed an arrest in cell division after which cell size increased instead. Pertinently, the death-resistant cell lines demonstrated the ability to be cultured for several weeks without bleed, and achieved similar volumetric productivities at lower cell densities than that of the control cell line. Perfusion culture reduced fragmentation of the mAb produced, and the death-resistant cell lines showed increased glycosylation in the light chain in both bioreactor modes. These data demonstrate that rationally engineered death-resistant cell lines are ideal for mAb production in perfusion culture, negating the need to bleed the bioreactor whilst maintaining product quantity and quality.
The use of animals as models of human physiology is, and has been for many years, an indispensable tool for understanding the mechanisms of human disease. In Parkinson’s disease, various mouse models form the cornerstone of these investigations. Early models were developed to reflect the traditional histological features and motor symptoms of Parkinson’s disease. However, it is important that models accurately encompass important facets of the disease to allow for comprehensive mechanistic understanding and translational significance. Circadian rhythm and sleep issues are tightly correlated to Parkinson’s disease, and often arise prior to the presentation of typical motor deficits. It is essential that models used to understand Parkinson’s disease reflect these dysfunctions in circadian rhythms and sleep, both to facilitate investigations into mechanistic interplay between sleep and disease, and to assist in the development of circadian rhythm-facing therapeutic treatments. This review describes the extent to which various genetically- and neurotoxically-induced murine models of Parkinson’s reflect the sleep and circadian abnormalities of Parkinson’s disease observed in the clinic.
The deadly SARS-CoV-2 virus has infected more than 259,502,031 confirmed cases with 5,183,003 deaths in 223 countries during the last 22 months (Dec 2019–Nov 2021), whereas approximately 7,702,859,718, vaccine doses have been administered (WHO: https://covid19.who.int/ ) as of the 24th of Nov 2021. Recent announcements of test trial completion of several new vaccines resulted in the launching of immunization for the common person around the globe highlighting a ray of hope to cope with this infection. Meanwhile, genetic variations in SARS-CoV-2 and third layer of infection spread in numerous countries emerged as a stronger prototype than the parental. New and parental SARS-CoV-2 strains appeared as a risk factor for other pre-existing diseases like cancer, diabetes, neurological disorders, kidney, liver, heart, and eye injury. This situation requires more attention and re-structuring of the currently developed vaccines and/or drugs against SARS-CoV-2 infection. Although a decline in COVID-19 infection has been reported globally, an increase in COVID-19 cases in the subcontinent and east Mediterranean area could be alarming. In this review, we have summarized the current information about the SARS-CoV-2 biology, its interaction and possible infection pathways within the host, epidemiology, risk factors, economic collapse, and possible vaccine and drug development.
Correction to: ISME Communications https://doi.org/10.1038/ s43705-021-00068-2, published online 9 December 2021 The “CH4 emissions” should be “CH4 uptake” in the sentence of “Grazing significantly decreases CH4 emissions while it increases N2O emissions basing on 14-month in situ measurement” The correct sentence should be read: Grazing significantly decreases CH4 uptake while it increases N2O emissions basing on 14-month in situ measurement.
Clinical Trial Networks in which trialists work collaboratively enable multi-site, large-scale, high-quality clinical trials to be efficiently run. Although the benefits of Clinical Trial Networks are largely known, establishing a Clinical Trial Network can be complex. There are many factors for clinicians and researchers to consider, and there is currently a paucity of information on how to form a Clinical Trial Network. This article provides a suggested roadmap on how to establish a Clinical Trial Network. The Australian Clinical Trials Alliance (ACTA) is the peak body for Clinical Trial Networks, Coordinating Centres and Registries in Australia, and has produced several resources to support the effective and efficient running of clinical trials. This guide has come about through discussions with members of the ACTA Clinical Trial Network Sector Expansion Reference Group consisting of clinical trialists, clinicians, researchers, and consumers.
The cells of origin of neurogenic heterotopic ossifications (NHOs), which develop frequently in the periarticular muscles following spinal cord injuries (SCIs) and traumatic brain injuries, remain unclear because skeletal muscle harbors two progenitor cell populations: satellite cells (SCs), which are myogenic, and fibroadipogenic progenitors (FAPs), which are mesenchymal. Lineage-tracing experiments using the Cre recombinase/LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in skeletal muscles under the control of the Pax7 or Prrx1 gene promoter, respectively. These experiments demonstrate that following muscle injury, SCI causes the upregulation of PDGFRα expression on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHOs. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury, suggesting that the cells of origin of NHOs are locally derived from the injured muscle. We validated these findings using human NHO biopsies. PDGFRα ⁺ mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice, whereas CD56 ⁺ myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to undergo uncontrolled proliferation and differentiation into osteoblasts.
The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.
Background Achieving the elimination of soil-transmitted helminth (STH) infections requires a sufficient understanding of the current epidemiological status of STH endemicity. We aimed to examine the status of STH in Myanmar – a country with the eighth highest STH prevalence in the world, 10 years after instigation of the national deworming programme. Methods In August 2016 we screened for STH infections using Kato Katz (KK) microscopy and real-time PCR (qPCR) in schoolchildren from the Bago Region township of Phyu, a STH sentinel site in Myanmar. Ten schools were randomly selected, and one stool sample each from a total of 264 students was examined. Prevalence and intensity of infection were calculated for each STH. Results High prevalence of STH was identified in the study area with 78.8% of the schoolchildren infected with at least one STH by qPCR, and 33.3% by KK. The most prevalent STH was Trichuris trichiura , diagnosed by both KK (26.1%) and qPCR (67.1%), followed by Ascaris lumbricoides (15.5% KK; 54.9% qPCR). No hookworm infections were identified by KK; however, the qPCR analysis showed a high prevalence of Ancylostoma sp. infection (29.6%) with few Necator americanus (1.1%) infections. Conclusions Despite bi-annual deworming of schoolchildren in the fourth-grade and below, STH prevalence remains stubbornly high. These results informed the expansion of the Myanmar National STH control programme to include all school-aged children by the Ministry of Health and Sports in 2017, however further expansion to the whole community should be considered along with improving sanitation and hygiene measures. This would be augmented by rigorous monitoring and evaluation, including national prevalence surveys.
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