multiRegionFoam -- A Unified Multiphysics Framework for Multi-Region Coupled Continuum-Physical Problems

This paper presents a unified framework, called multiRegionFoam, for solving multiphysics problems of the multi-region coupling type within OpenFOAM (FOAM-extend). This framework is intended to supersede the existing solver with the same name. The design of the new framework is modular, allowing users to assemble a multiphysics problem region-by-region and coupling conditions interface-by-interface. The present approach allows users to choose between deploying either monolithic or partitioned interface coupling for each individual transport equation. The formulation of boundary conditions is generalised in the sense that their implementation is based on the mathematical jump/transmission conditions in the most general form for tensors of any rank. The present contribution focuses on the underlying mathematical model for these types of multiphysics problems, as well as on the software design and resulting code structure that enable a flexible and modular approach. Finally, deployment for different multi-region coupling cases is demonstrated, including conjugate heat, multiphase flows and fuel-cells

Psychoative herbs commercialized in streets of Diadema (SP, Brazil): risk in its consumption

O comércio popular de drogas vegetais sem a garantia da qualidade implica em risco sanitário. O presente estudo fez uma análise interdisciplinar da rede de comércio de drogas vegetais (DVs) com foco nas drogas vegetais psicoativas (DVPs), disponíveis no comércio popular da Cidade de Diadema, e os riscos associados ao seu consumo. Métodos da etnofarmacologia, tais como: entrevistas informais, semi-estruturadas e observação participante foram utilizados para a realização do trabalho de campo; durante o qual, selecionaram-se quatro comerciantes, a fim de registrar a obtenção, manipulação, acondicionamento e tipos de DVs comercializadas. Foram registradas 63 DVs que remetiam a atividade psicoativa (DVPs) e, categorizadas em estimulantes (67%), depressoras (27%), depressoras e estimulantes (1%) e finalmente algumas não puderam ser definidas (5%). Essas DVPs tiveram seus nomes populares, forma de preparo e uso, partes utilizadas, contraindicações e doses registradas. Dezoito das 63 DVPs foram selecionadas segundo critérios do estudo, e seus lotes foram adquiridos dos entrevistados, a fim de serem analisados pela microbiologia (61 lotes) e farmacognosia (somente 22 daqueles, referentes a apenas 8 DVPs). Os resultados obtidos por essas áreas, somados a consultas em literaturas científicas, acerca de descrições de reações adversas, serviram de subsídio para a análise final dessas DVPs no contexto da farmacovigilância. Observaram-se deficiências principalmente na manipulação e acondicionamento das DVs por parte dos comerciantes, favorecendo sua contaminação e degradação. Os resultados das análises microbiológicas detectaram que 16% das DVPs analisadas apresentaram populações de bactérias (aeróbias e enterobactérias) superiores a 105 UFC/g e 31%, populações de fungos (bolores e leveduras) superiores a 103 UFC/g e a presença de espécies microbianas indicadoras de risco em 17 DVPs, especificamente em 74% dos 61 lotes, além de fungos produtores de aflatoxinas B1 e/ou B2 em quatro deles. Os resultados da farmacognosia demonstraram que 73% dos lotes foram reprovados ao menos em um dos demais parâmetros analisados (presença de contaminantes, caracterização e perfil cromatográfico). Sendo que, 50% dos 22 lotes analisados não coincidem com as especificações da farmacopéia e 36% apresentaram contaminação por outros órgãos vegetais, superior ao permitido nas monografias e um lote apresentou contaminação por insetos. Todos os 22 lotes foram reprovados na avaliação do rótulo (nomenclatura e validade) e praticamente todas as embalagens foram consideradas inadequadas. Além dos dados obtidos nessas análises, descrições de contra-indicações, efeitos adversos e interações medicamentosas foram encontradas na literatura científica para as 3 DVPs que tiveram sua identidade confirmada pela farmacognosia (camomila, ginkgo biloba e guaraná). Os resultados obtidos nesse estudo possibilitam observar as prioridades de adequação sanitária do comércio popular de DVs, bem como, traçar um perfil da qualidade das DVPs comercializadas segundo os parâmetros analisados. Conclui-se que essas DVPs reúnem importantes fatores capazes de causar danos à saúde dos consumidores, especialmente para alguns grupos como gestantes e indivíduos imunossuprimidos.The popular trade of herbal drugs without quality assurance implies a health risk. This study was an interdisciplinary analysis of the herbal drugs (DVs) trade network with focus on psychoactive drug plant (DVPs) available on the Brazilian city of Diadema, and risks associated with its consumption. Methods of ethnopharmacology, such as informal interviews, semi-structured interviews and participant observation were used for the completion of the fieldwork, during which four tradesmen were selected to register the collection, handling, packaging and types of DVs marketed. We registered 63 DVs that referred to psychoactive activity (DVPs) and categorized as stimulants (67%), depressants (27%), depressants and stimulants (1%) and finally some could not be set (5%). These DVPs had their popular names, preparations and uses, used parts, contraindications, and doses recorded. Eighteen of the 63 DVPs were selected according to the study criteria, and their lots were purchased by the selected tradesmen to be examined by microbiology (61 lots) and Pharmacognosy (only 22 of those lots, related to only 8 DVPs). The results for these areas, together with query in the scientific literature concerning descriptions of adverse reactions, provided the grant for the final analysis of these DVPs in the context of pharmacovigilance. Deficiencies were observed mainly in the handling and packaging of DVs by the traders, favoring its contamination and degradation. The microbiological analysis found that 16% of DVPs analyzed showed populations of bacteria (aerobic and Enterobacteriaceae) exceeding 105 CFU/g and 31%, populations of fungi (molds and yeasts) exceeding 103 CFU/g and the presence of risk indicator microbial species in 17 DVPs, specifically in 74% of the 61 lots, in addition to aflatoxin B1 or B2 producing fungi in four of them. The results of pharmacognosy showed that 73% had failed at least one of the parameters (contaminants, characterization and chromatographic profile), 50% of the 22 lots analyzed did not match the specifications of the pharmacopoeia, 36% were contaminated by other plant organs than those permitted in the monographs and a lot contamination by insects was found. All 22 lots have been disapproved in the evaluation of the label (classification and validity) and virtually all packages were considered inadequate. In addition to data obtained from such analysis, descriptions of contraindications, adverse effects and drug interactions were found in the literature for 3 DVPs who had their identity confirmed by the Pharmacognosy (chamomile, ginkgo biloba and guarana). The results obtained here allow us to observe the priorities of sanitary adequacy of the DVs popular trade, as well as establishing a profile of quality of DVPs marketed according to the analyzed parameters. We conclude that these DVPs gather important factors that could cause damage to the consumers health, especially for some groups such as pregnant women and immunosuppressed individuals.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)TEDEBV UNIFESP: Teses e dissertaçõe

Widening access to medicine may improve general practitioner recruitment in deprived and rural communities:survey of GP origins and current place of work

BACKGROUND: Widening access to medicine in the UK is a recalcitrant problem of increasing political importance, with associated strong social justice arguments but without clear evidence of impact on service delivery. Evidence from the United States suggests that widening access may enhance care to underserved communities. Additionally, rural origin has been demonstrated to be the factor most strongly associated with rural practice. However the evidence regarding socio-economic and rural background and subsequent practice locations in the UK has not been explored. The aim of this study was to investigate the association between general practitioners’ (GPs) socio-economic and rural background at application to medical school and demographic characteristics of their current practice. METHOD: The study design was a cross-sectional email survey of general practitioners practising in Scotland. Socio-economic status of GPs at application to medical school was assessed using the self-coded National Statistics Socio-Economic Classification. UK postcode at application was used to define urban–rural location. Current practice deprivation and remoteness was measured using NHS Scotland defined measures based on registered patients’ postcodes. RESULTS: A survey was sent to 2050 Scottish GPs with a valid accessible email address, with 801 (41.5 %) responding. GPs whose parents had semi-routine or routine occupations had 4.3 times the odds of working in a deprived practice compared to those with parents from managerial and professional occupations (95 % CI 1.8–10.2, p = 0.001). GPs from remote and rural Scottish backgrounds were more likely to work in remote Scottish practices, as were GPs originating from other UK countries. CONCLUSION: This study showed that childhood background is associated with the population GPs subsequently serve, implying that widening access may positively affect service delivery in addition to any social justice rationale. Longitudinal research is needed to explore this association and the impact of widening access on service delivery more broadly

Interactivity and Reward-Related Neural Activation during a Serious Videogame

This study sought to determine whether playing a “serious” interactive digital game (IDG) – the Re-Mission videogame for cancer patients – activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society