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Electrocardiographically occult occlusive myocardial infarction (OOMI), defined as coronary artery occlusion requiring revascularization without ST-segment elevation on electrocardiogram (ECG), is associated with delayed diagnosis resulting in higher morbidity. Left ventricular (LV) wall motion abnormalities (WMA) appreciated on echocardiography can expedite OOMI diagnosis. We sought to determine whether point-of-care ultrasound (PoCUS) demonstrating WMA expedites revascularization time when performed on emergency department patients being evaluated for OOMI.This was a single-site retrospective cohort study over a 38-month period. All admitted adult ED patients ≥35 years of age evaluated by the emergency physician with PoCUS for LV function, an ECG, and a standard troponin I biomarker assay were included. Patients with ST-segment elevation myocardial infarction (STEMI), prior LV dysfunction, fever ≥100.4 °F, or hypotension were excluded. A structured chart abstraction was performed for relevant demographic and clinical characteristics.We screened 1561 ED patients who underwent cardiac PoCUS for eligibility: 874 met exclusion criteria, 453 were discharged, and 234 were included in the analysis. Twenty-three patients had coronary interventions, of which 14 had WMA. PoCUS was performed 36 min (IQR -9-68) before troponin resulted (n = 234) and 39 min (IQR -23-96) before the first troponin elevation (n = 85). Twenty of the 23 patients diagnosed with OOMI had elevated troponins prior to catheterization with time from PoCUS to first troponin elevation of 43 min (IQR 9-263). Of these patients, 11 had WMA identified on PoCUS, and the WMA was appreciated 47 min (IQR 26-255) prior to troponin elevation. The time from ED arrival to revascularization was 673 min (IQR 251-2158); 432 min (IQR 209-1300) among patients with WMA (n = 14) compared with 2158 min (IQR 552-3390) for those without WMA (n = 9).Cardiac PoCUS may identify OOMI earlier than standard evaluation and may expedite definitive management.

BackgroundCalcium channel blockers (CCBs) are common antihypertensive medications. Pharmacogenetic variants affect CCB clinical outcomes, although effect sizes are modest in community samples. Variation in patient characteristics may also predict CCB outcomes, and variation attributable to relevant polygenic scores is less prone to confounding. We aimed to test associations between genetically predicted patient characteristics plus pharmacogenetic variants with CCB outcomes in a large community cohort.MethodsWe extended our analysis of 32,000 UK Biobank dihydropiridine CCBs treated participants (mean duration 5.9 years) testing 23 variants, whereNUMA1rs10898815 andRYR3rs877087 showed the most robust associations (for discontinuation and heart failure, respectively). We calculated polygenic scores for systolic and diastolic blood pressures (SBP and DBP), body fat mass, waist hip ratio, lean mass, serum calcium, eGFR, lipoprotein A, urinary sodium, and liver fibrosis. Outcomes were CCB discontinuation, heart failure, coronary heart disease and chronic kidney disease.ResultsFor heart failure, the highest risk 20% of polygenic scores for fat mass, lean mass and lipoprotein A were associated with increased risks (Hazard-Ratio (HR)Fat-mass 1.46, 95% CI 1.25-1.70, p=1*10-6; HRLean-mass 1.20, 95%CI 1.04-1.38, p=0.01; HRLipoproteinA 1.29, 95% CI 1.12 to 1.48, p= 4*10-4), versus the lowest risk 20% of each score respectively. Across the cohort,RYR3T-allele modestly increased heart failure risks (HR 1.13: 1.02-1.25) versus non-carriers, but in subsets with high fat mass, lean mass, and lipoprotein A scores, estimates were substantially larger, e.g., in females aged 65-70 the heart failure Relative Risk was 4.4 (95% CI 1.54-12.4) versus no T-alleles and low scores.For CCB discontinuation, high polygenic scores for fat mass and lean mass increased risks versus the lowest 20%, whereas high SBP and DBP scores decreased discontinuation risks. Hazard ratios for discontinuation with the pharmacogenetic NUMA1 rs10898815 A-allele (overall HR 1.07: 1.02-1.12) were higher (HR 1.17: 1.05-1.29) in those with high polygenic scores for fat mass and lean mass.ConclusionPolygenic scores affecting adiposity and lipoprotein A levels add to known pharmacogenetic variants in predicting key clinical outcomes in CCB treatment. Combining pharmacogenetic variants and relevant individual characteristic polygenic scores may help for personalizing prescribing.What is needed, what do we add?We previously showed that pharmacogenetic variants inRYR3andNUMA1were associated with key clinical outcomes in community CCB patients, although effect sizes were modest. Various patient characteristics reportedly affect CCB outcomes. We therefore tested effects of relevant patient characteristics using polygenic scores. They minimize the effect of unmeasured confounders as genotypes are invariant since conception and reflect lifetime exposure to the risk factor. We showed that combining associated scores with the pharmacogenetic variants improved outcome prediction.

The other-race effect (ORE) is a well-known phenomenon in which people discriminate and recognize faces from their ethnic group more accurately than faces from other ethnic groups. Holistic processing, or the mandatory tendency to process all parts of an object together, has been proposed as an explanation for the ORE. According to the holistic perspective of the ORE, other-race faces might be subject to weaker holistic processing than own-race faces. However, evidence for this hypothesis is inconsistent. Although it is generally assumed that holistic processing helps the individuation of objects, holistic processing may also come at a cost. Specifically, holistic processing may reduce the capacity to localize changes in the constituent parts of an object, but not in detecting changes to an object as a whole. In the present study, we examined change detection and change localization accuracy for Caucasian and African faces, and houses. Performance was better for change detection than change localization for Caucasian faces. While clear costs of holistic processing for Caucasian faces were thus found, the difference between change localization and change detection was not obvious for African faces. However, childhood exposure to other-race people correlated with change detection for African faces, but not with change localization for African faces. Our results thus show that holistic processing of other-race faces may depend on early contact with other-race people.

Early maladaptive schemas (EMS), as lifelong psychological structures, tend to be associated with psychopathological symptomatology. Previous research has suggested that schemas act as psychological vulnerabilities to stressful life situations, such as the present worldwide COVID-19 pandemic. In this context, anxiety and psychological distress have been documented as two of the main psychological symptoms associated with the COVID-19 pandemic. However, the associations between specific EMS and COVID-19 anxiety remain unexplored. Therefore, this study aims to explore the relationships between EMS, COVID-19 anxiety as well as other mental health variables such as psychological well-being, distress and life satisfaction.In a cross-sectional design, 249 individuals (M = 34.2, SD = 12.0) completed several self-report measures.EMS from different schematic domains were positively associated with COVID-19 anxiety and psychological distress and negatively associated with psychological well-being and life satisfaction. An EMS hierarchical regression model predicted COVID-19 anxiety. Mistrustfulness and vulnerability to harm and illness mediated the relationships between COVID-19 anxiety, psychological distress and life satisfaction.According to these results, mistrustfulness and vulnerability to harm and illness can act as underlying variables for the decrease in mental health associated with the COVID-19 pandemic.

The ceramic industry is one of the pillars of the Brazilian economy, characterized by making low-cost products and an obsolete manufacturing process from a technological point of view. Among the various stages of production of ceramic materials, drying is one of the most energy-consuming and, in general, causes structural damage to the product, compromising its mechanical performance and final quality. Despite the relevance, studies on the drying of ceramic materials are mostly conducted at the experimental level and limited to some specific operational conditions. In this scenario, this research aims to theoretically study the heat and mass transfers in industrial ceramic blocks during drying. Based on the lumped analysis method, and considering the dimensional variations of the material, new phenomenological mathematical models and their respective analytical solutions are proposed to describe the kinetics of mass loss and heating of the material. The predicted results referring to the thermal and gravimetric behavior of the block during the oven drying process under different conditions are compared with the experimental data, obtaining excellent agreement between the results. Furthermore, the transport coefficients were estimated, proving the dependence of these parameters on the drying air conditions. The convective mass transfer coefficient ranged from 6.69 × 10–7 to 15.97 × 10–7 m/s on the outer surface of the block and from 0.70 × 10–7 to 1.03 × 10–7 m/s on the inner surface of the material when the drying air temperature ranged from 50 to 100 °C. The convective heat transfer coefficient ranged from 4.79 to 2.04 W/(m2.°C) on the outer surface of the block and from 1.00 to 0.94 W/(m2.°C) on the inner surface of the material when air temperature ranged from 50 to 100 °C.

Pharmacogenetic variants impact dihydropyridine calcium-channel blockers (dCCBs; e.g., amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in pharmacogenomics knowledge base PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB.We analysed up to 32 360 UK Biobank participants prescribed dCCB in primary care (from UK general practices, 1990-2017). We investigated 23 genetic variants. Outcomes were incident diagnosis of coronary heart disease, heart failure (HF), chronic kidney disease, oedema and switching antihypertensive medication.Participants were aged 40-79 years at first dCCB prescription. Carriers of rs877087 T allele in RYR3 had increased risk of hazard ratio (HF 1.13: 95% confidence interval 1.02 to 1.25, P = .02). Although nonsignificant after multiple testing correction, the association is consistent with prior evidence. We estimated that if rs877087 T allele could experience the same treatment effect as noncarriers, the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95% confidence interval 3.1 to 15.4). In patients with a history of heart disease prior to dCCB (n = 2296), rs877087 homozygotes had increased risk of new coronary heart disease or HF compared to CC variant. rs10898815 in NUMA1 and rs776746 in CYP3A5 increased likelihood of switching to an alternative antihypertensive. The remaining variants were not strongly or consistently associated with studied outcomes.Patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of pharmacogenetics variants supported by clinical evidence of association with adverse events.

According to the experiential avoidance and psychological inflexibility model proposed by Acceptance and Commitment Therapy, cognitive fusion is a core component of psychological disorders and mental health. Also, previous theorizations proposed that cognitive fusion may be independent of diagnosis, which means that it may also be present in the non-clinical population. However, evidence for this assumption is still sparse. Therefore, this study aimed to explore the relationships between cognitive fusion, symptomatology and psychological well-being in a non-clinical sample. The total sample consisted of 224 subjects (Mage = 30.6, SD = 11.5). Participants completed self-report questionnaires in a cross-sectional design. Results show medium to strong positive correlations between cognitive fusion and symptomatology and negative correlations between cognitive fusion and well-being. Furthermore, cognitive fusion was a significant mediator of the relationship between psychological well-being and symptomatology. Our results support the assumption that cognitive fusion, as a component of psychological inflexibility, may be a core transdiagnostic variable in mental health.

We investigated the relationship between holistic processing and face processing using a latent variables approach. Three versions of the composite paradigm were used to measure holistic processing: Vanderbilt Holistic Face Processing Test, a sequential composite matching task, and a simultaneous composite matching task. Three tasks were used to measure face perception and face memory abilities respectively. We had three pairs of tasks such that within each pair (of memory and perception task), the stimuli involved, the requirement for matching across viewpoints, etc., are the same, such that the only difference is whether perception or memory is taxed. There were no significant correlations between the different versions of the composite task. We discovered no evidence to support a distinction between face perception and face memory, suggesting the existence of a general face processing factor. Finally, there was no evidence that holistic processing (as captured by either of the three composite tasks) is predictive of better face processing per se, casting doubts on the role of holistic processing in differentiating different levels of efficiency in face processing.

Stroke events increase the risk of developing dementia, 10% for a first-ever stroke and 30% for recurrent strokes. However, the effects of stroke on global cognition, leading up to dementia, remain poorly understood. We investigated: (i) post-stroke trajectories of cognitive change, (ii) trajectories of cognitive decline in those who develop dementia over periods of follow-up length and (iii) risk factors precipitating the onset of dementia. Prospective cohort of hospital-based stroke survivors in North-East England was followed for up to 12 years. In this study, we included 355 stroke survivors of ≥75 years of age, not demented 3 months post-stroke, who had had annual assessments during follow-up. Global cognition was measured annually and characterized using standardized tests: Cambridge Cognition Examination—Revised and Mini-Mental State Examination. Demographic data and risk factors were recorded at baseline. Mixed-effects models were used to study trajectories in global cognition, and logistic models to test associations between the onset of dementia and key risk factors, adjusted for age and sex. Of the 355 participants, 91 (25.6%) developed dementia during follow-up. The dementia group had a sharper decline in Cambridge Cognition Examination—Revised (coeff. = −1.91, 95% confidence interval = −2.23 to −1.59, P

Introduction During the COVID-19 pandemic, pre-existing dementia was associated with a 3x increase in risk of hospitalisation and (25.6%) of COVID-19 related deaths had dementia. However, it is unclear whether people living with dementia are at higher risk of COVID-19 due to dementia or whether there may be a biologically plausible link between dementia and COVID-19. The ApoE e4 allele is highly associated with dementia. We aimed to test the COVID-19 risk associated with dementia and the association between ApoE e4e4 allele and COVID-19 with the aim of clarifying biological vulnerability. Methods UK Biobank (England) participants baseline (2006 to 2010), plus secondary care data to 2017. Separate analysis tested dementia and ApoE genotype association with COVID-19 status (16th March-31st May 2020) or mortality (to March 31, 2020, plus incomplete deaths from April, 2020) in logistic models, adjusted for demographics and technical covariates. Results In 269,070 participants aged 65+, including 507(0.2%) hospitalized COVID-19 patients, those with pre-existing dementia were at increased risk of being hospitalized for COVID-19 (OR = 3.50 95% CI 1.93 to 6.34) and also for COVID-19 and death (OR = 7.30 95% CI 3.28–16.21). In 375,689 European-ancestry UKB participants, ApoE e4e4 homozygotes were more likely to be COVID-19 test positives (reaching genome-wide significance: OR = 2.24, 95% CI:1.72–2.93, p = 3.24 × 10–9) and of mortality with test-confirmed COVID-19 (OR = 4.29, 95% CI: 2.38–7.72, p = 1.22 × 10–6), compared to e3e3s homozygotes. The associations were little changed in subsets of participants who were free of diseases associated with ApoE e4 and COVID-19 severity. Conclusion Dementia was found to be disproportionally common in older adults who develop severe COVID-19. We have shown a plausible genetic pathway of increased COVID-19 risk with dementia, therefore suggesting that the positive association between dementia and COVID-19 is not just the result of high cases of COVID-19 in care homes.

Resumo Descreve-se uma atividade pedagógica com estudantes do Mestrado e Pós-Licenciatura em Enfermagem de Saúde Materna e Obstetrícia, aplicando princípios da prática simulada na realização da sutura perineal após o parto. Este procedimento causa muita insegurança e gera grande ansiedade nos estudantes, quando iniciam estágio em bloco de partos. Os objetivos deste artigo são desenvolver competências psicomotoras nos estudantes para a reconstituição cirúrgica perineal; aumentar a autoconfiança dos estudantes para o procedimento. Metodologia qualitativa, com 2 momentos de recolha de dados aplicados a dois cursos. Questionário com perguntas abertas, sessão de “focus group” e filmagem. Análise de conteúdo das respostas às perguntas abertas e verbatim do “focus group”. Como Resultados destaca-se uma estreita relação entre a simulação e o desenvolvimento de competências. Os estudantes salientaram a importância da atividade pedagógica na aquisição de competências de sutura, reforço da autoconfiança e na diminuição da ansiedade inicial. O uso da investigação qualitativa permitiu identificar o impacto da prática simulada no desenvolvimento de competências dos estudantes, identificar aspetos a aperfeiçoar na metodologia, contribuindo para a melhoria das práticas pedagógicas. Abstract A pedagogical activity with Master’s Degree and Postgraduate students in Maternal Health and Obstetrics Nursing is described, applying principles of simulated practice in perineal suturing after delivery. This procedure causes a lot of insecurity and generates great anxiety in the students, when they start the internship in a delivery room. Objectives: to develop the psychomotor skills in students for perineal surgical reconstruction; increase students’ self-confidence to perform the procedure. Methodology: qualitative, with 2 moments of data collection applied to two courses. Questionnaire with open questions, focus group session and filming. Content analysis of the answers to the questions and verbatim of the focus group. Results: a close relationship was observed between simulation and skills development. Conclusion: the students emphasized the importance of the pedagogical activity in the acquisition of suturing skills, improving their self-confidence and reducing the initial anxiety. The use of the qualitative research allowed identifying the impact of the simulated practice on the development of the students’ skills and to identify aspects to be improved, contributing to the progress of pedagogical practices.

The bouba-kiki effect, or the symbolic association between certain speech sounds and rounded or angular shapes, is widely thought to be universal. However, two studies have failed to replicate this effect with neurotypical participants in the classical paradigm, one conducted in Papua New Guinea (Ross & Rogers, 1975), and the other conducted in Nepal (Styles & Gawne, 2017). As both experiments employed auditory stimuli inconsistent with the sound structure of the respective native language, Styles and Gawne (2017) proposed that pseudoword legality is a prerequisite for sound-symbolic associations to form. In this study, we conducted the first experimental test of this hypothesis, by assessing participants’ performance on the bouba-kiki task as a function of pseudoword phonotactic legality. Our results indicate that phonotactic violations may disrupt the bouba-kiki effect, albeit only when they cause the speech stimuli to be perceived as significantly strange (not “word-like”). We thus conclude that sound symbolism fails whenever phonotactic violations prevent the assemblance of the phonological representations of the target pseudowords.

BackgroundDihydropiridine calcium channel blockers (dCCB) (e.g. amlodipine) are widely used for treating hypertension. Pharmacogenetic variants impact treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB, including in high-risk subgroups.MethodsWe analysed up to 32,360 UK Biobank European-ancestry participants prescribed dCCB in primary care electronic health records (from UK General Practices, 1990 to 2017). We investigated 23 genetic variants in 16 genes reported in PharmGKB, including CYP3A5 and RYR3. Outcomes were incident diagnosis of coronary heart disease (CHD), heart failure (HF), chronic kidney disease (CKD), edema, and switching antihypertensive medication. Secondary analysis in patients with history of heart disease was also performed.ResultsParticipants were aged 40 to 79 years at first dihydropyridine prescription (treatment duration 1 month to 40 years, mean 5.9 years). Carriers of rs877087 T allele in the ryanodine receptor 3 (RYR3) had increased risk of HF (Hazard Ratio 1.13: 95% Confidence Intervals 1.02 to 1.25, p=0.02). We estimated that if rs877087 T allele carriers were prescribed an alternative treatment the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95%CI 3.1 to 15.4). In patients with a history of heart disease when first prescribed dCCB (N=2,296), RYR3 rs877087 homozygotes had increased risk of new CHD or HF compared to CC variant (HR 1.25, 95%CI 1.09 to 1.44, p=0.002). Two variants increased likelihood of switching to an alternate antihypertensive medication (rs10898815 in gene NUMA1 HR 1.16: 95%CI 1.07 to 1,27, p=0.0009; rs776746 in CYP3A5 HR 1.59: 95%CI 1.09 to 2.32, p=0.02). rs776746 in CYP3A5 also increased CKD risk (HR 2.12, p=0.002). The remaining previously reported variants were not strongly or consistently associated with the studied clinical outcomes.ConclusionsIn this large primary care cohort, patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of such pharmacogenetics variants supported by clinical evidence of association with adverse events.

OBJECTIVES: Delirium is common in older adults, especially following hospitalization. As low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship. DESIGN: Prospective cohort analysis. SETTING: Community-based cohort study of adults from 22 cities across the United Kingdom (the UK Biobank). PARTICIPANTS: Adults aged 60 years or greater by the end of follow-up in the linked hospital inpatient admissions data, up to 14 years after baseline (n=351,320). MEASUREMENTS: At baseline, serum vitamin D (25-OH-D) levels were measured. We used time-to-event models to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CIs) for the association between vitamin D deficiency and incident hospital-diagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk. RESULTS: 3,634 (1.03%) participants had at least one incident hospital-diagnosed delirium episode. Vitamin D deficiency (50 nmol/L). Increased risk was not limited to the deficient group: insufficient levels (25–50 nmol/L) were also at increased risk (HR 1.38: 1.28 to 1.49, p=4*10(−18)). The association was independent of calcium levels, hospital-diagnosed fractures, dementia, and other relevant co-factors. In genetic analysis, participants carrying more vitamin D-increasing variants had reduced likelihood of incident delirium diagnosis (HR 0.80 per standard deviation increase in genetically instrumented vitamin D: 0.73 to 0.87; p=2*10(−7)). CONCLUSION: Progressively lower vitamin D levels predicted increased risks of incident hospital-diagnosed delirium, and genetic evidence supports a shared causal pathway. As low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.

Importance risk factors for delirium in hospital inpatients are well established, but less is known about whether delirium occurring in the community or during an emergency admission to hospital care might be predicted from routine primary-care records. Objectives identify risk factors in primary-care electronic health records (PC-EHR) predictive of delirium occurring in the community or recorded in the initial episode in emergency hospitalisation. Test predictive performance against the cumulative frailty index. Design Stage 1: case-control; Stages 2 and 3: retrospective cohort. Setting clinical practice research datalink: PC-EHR linked to hospital discharge data from England. Subjects Stage 1: 17,286 patients with delirium aged ≥60 years plus 85,607 controls. Stages 2 and 3: patients ≥ 60 years (n = 429,548 in 2015), split into calibration and validation groups. Methods Stage 1: logistic regression to identify associations of 110 candidate risk measures with delirium. Stage 2: calibrating risk factor weights. Stage 3: validation in independent sample using area under the curve (AUC) receiver operating characteristic. Results fifty-five risk factors were predictive, in domains including: cognitive impairment or mental illness, psychoactive drugs, frailty, infection, hyponatraemia and anticholinergic drugs. The derived model predicted 1-year incident delirium (AUC = 0.867, 0.852:0.881) and mortality (AUC = 0.846, 0.842:0.853), outperforming the frailty index (AUC = 0.761, 0.740:0.782). Individuals with the highest 10% of predicted delirium risk accounted for 55% of incident delirium over 1 year. Conclusions a risk factor model for delirium using data in PC-EHR performed well, identifying individuals at risk of new onsets of delirium. This model has potential for supporting preventive interventions.

Objective: The Coronavirus disease 2019 (COVID-19) pandemic was previously associated with psychopathological symptoms. However, the psychological mechanisms underlying these associations are largely unexplored. Previous studies suggested associations between metacognitive abilities (e.g., mastery) and symptomatology, which may have impacts on COVID-19 perceptions. This study aims to explore, using path analysis, the mediational role of Critical Distance (differentiation and decentration abilities) and Mastery on the relationships between COVID-19 perceptions and psychological well-being and distress. Methods: In a cross-sectional design, 227 participants (M = 34.21, SD = 10.9) filled self-report questionnaires. Results: Metacognitive abilities were negatively correlated with psychopathological symptoms. Both Critical Distance and Mastery mediated the path from COVID-19 perceived severity and anxiety to psychological distress and well-being. Critical Distance seems to augment Mastery which tends to increase psychological well-being and limited psychological distress. Conclusions: Metacognition seems to play a mediational role on the relationship between COVID-19 perceptions and mental health. Clinical psychologists and psychotherapists may enhance psychological interventions regarding COVID-19 psychopathological symptomatology by working on metacognitive Critical Distance and Mastery abilities. info:eu-repo/semantics/acceptedVersion

The need to decarbonise our energy system push us toward the use of different clean renewable energy sources, such as solar, wind and hydroelectric energy. It is well known that some of these renewable energy sources suffer of intermittence, which requires the conventional dispatchable power plants to become more flexible to respond to any power change to ensure a stable electrical grid. For this specific purpose, the European project XFLEX HYDRO is focusing on the hydropower sector, with seven demonstrators in three different countries to demonstrate the possibility to enhance the flexibility, one option being to use the variable-speed technology combined with smart digital control. Among these seven demonstrators, one is the Alto Lindoso hydropower plant owned by EDP and located in North-West of Portugal. It consists of two fixed-speed vertical Francis turbines with a high head of approximately 275 m and a rated power of 317 MW. The objective of this demonstrator is to assess the potential of a variable speed using the Doubly Fed Induction Machine (DFIM) technology to increase the flexibility of the power and the lifetime of the turbine. Therefore, this paper explores numerically the hydraulic behaviour of the model runner when operated at a selected part load conditions (60% BEP) with the rotational speed changed by ±10%. Second, a FEM analysis is carried out to evaluate the runner blades damage rate. This preliminary study showed that in term of wear and tear, the variable speed technology would bring in an advantage.

The primary goal of our work is to address the issues concerning the application of sustainability concepts in the Higher Education Campus of the Faculty of Architecture at Universidade de Lisboa. Sustainable actions and attitudes are part of the sustainable principles of the Sustainable Development Goals adopted in the 2030 Agenda by all member states of the United Nations. This exploratory research is based on a review of the international literature specialized in sustainability assessment in Higher Education Institutions. A qualitative research approach was applied, using a questionnaire adapted from the European University Association in 2021, as a research instrument, with the objective of knowing the perception and opinion of the Faculty of Architecture (FA) academic community on some of the collective actions of greening. Based on a survey carried out on a non-probabilistic sample selected from Campus users, a qualitative interpretation and discussion of the data obtained were performed. With this investigation, we intend to know the challenges and initiatives practiced in this Campus in defense of sustainability and contribute towards a changeover the environmental, social, and economic awareness of the campus community.

Background Seamounts are underwater mountains which typically rise rather steeply at least several hundred meters above the deep-sea floor. These geological features interrupt water flow and hence may induce changes in the circulation of different water masses, in turn causing different physical and biological effects. For this reason, seamounts are biodiversity hotspots, housing a wide number of species, as is with the case of the Seine and Unicorn seamounts, which are a part of the Madeira-Tore seamount chain located between Portugal mainland, southwestern Europe and Madeira archipelago (NE Atlantic). Methods Fisheries independent surveys allowed the collection of Chondrichthyes specimens from the Seine and Unicorn seamounts. Individuals were caught over the course of two research cruises, first in 2004 and later in 2017, with species distribution ranging from the summit down to 2500 m of depth. Results Fifteen species belonging to 7 different taxonomical families were collected in the two surveyed areas. Two species were recorded for the first time and added to the checklist of the Seine seamount (Centrophorus granulosus and Somniosus rostratus), and three species for the Unicorn seamount (C. granulosus, Centroscymnus coelolepis and Centroselachus crepidater). Distribution and frequency of occurrence for the collected species were evaluated in relation to depth. Conclusions This work is a valuable contribution to the knowledge of seamount-associated fish fauna. Moreover, the checklist of sharks, rays and chimaeras was updated for the Seine and Unicorn seamounts, summing up 20 species.

The COVID-19 pandemic imposed a set of drastic worldwide changes to and restrictions on daily life. Despite predictions of the harmful impacts of the pandemic on mental health, empirical data are lacking. This study sought to examine the relationship between individuals' perceptions about COVID-19 and scores on mental health indexes.In this cross-sectional study, 183 individuals answered self-report questionnaires. A new inventory based on the health belief model (HBM) developed in Portugal was explored with a factor analysis, which revealed two significant factors: COVID-19 anxiety and perceived severity of the disease.Results showed that anxiety about COVID-19 was positively correlated with psychological distress, somatization, and paranoid ideation and was negatively correlated with psychological well-being. COVID-19 anxiety mediated the relationship between symptomatology and mental health.Perceptions about COVID-19 seem to play pivotal roles in mental health. These results may inform interventions focused on reducing psychological distress and symptomatology and on increasing psychological well-being.

High blood pressure (BP) affects 75% of people aged over 70. Ageing alters BP homeostasis, resulting in postural hypotension and increased BP variability. Co-morbidity and frailty add complexity to understanding BP changes in later life. Longitudinal BP declines are likely driven by accumulating co-morbidity and are accelerated in both frailty and dementia. This narrative review summarises what is known about the association between BP and frailty, the clinical management of BP in frailty and the association between BP, cognitive decline and dementia.

BackgroundHigher continuity of GP care (CGPC), that is, consulting the same doctor consistently, can improve doctor–patient relationships and increase quality of care; however, its effects on patients with dementia are mostly unknown.AimTo estimate the associations between CGPC and potentially inappropriate prescribing (PIP), and with the incidence of adverse health outcomes (AHOs) in patients with dementia.Design and settingA retrospective cohort study with 1 year of follow-up anonymised medical records from 9324 patients with dementia, aged ≥65 years living in England in 2016.MethodCGPC measures include the Usual Provider of Care (UPC), Bice–Boxerman Continuity of Care (BB), and Sequential Continuity (SECON) indices. Regression models estimated associations with PIPs and survival analysis with incidence of AHOs during the follow-up adjusted for age, sex, deprivation level, 14 comorbidities, and frailty.ResultsThe highest quartile (HQ) of UPC (highest continuity) had 34.8% less risk of delirium (odds ratio [OR] 0.65, 95% confidence interval [CI] = 0.51 to 0.84), 57.9% less risk of incontinence (OR 0.42, 95% CI = 0.31 to 0.58), and 9.7% less risk of emergency admissions to hospital (OR 0.90, 95% CI = 0.82 to 0.99) compared with the lowest quartile. Polypharmacy and PIP were identified in 81.6% (n = 7612) and 75.4% (n = 7027) of patients, respectively. The HQ had fewer prescribed medications (HQ: mean 8.5, lowest quartile (LQ): mean 9.7, PPConclusionHigher CGPC for patients with dementia was associated with safer prescribing and lower rates of major adverse events. Increasing continuity of care for patients with dementia may help improve treatment and outcomes.

Background While Alzheimer disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association are unclear. We tested whether dysregulation of cholesterol catabolism, through its conversion to primary bile acids (BAs), was associated with dementia pathogenesis. Methods and findings We used a 3-step study design to examine the role of the primary BAs, cholic acid (CA), and chenodeoxycholic acid (CDCA) as well as their principal biosynthetic precursor, 7α-hydroxycholesterol (7α-OHC), in dementia. In Step 1, we tested whether serum markers of cholesterol catabolism were associated with brain amyloid accumulation, white matter lesions (WMLs), and brain atrophy. In Step 2, we tested whether exposure to bile acid sequestrants (BAS) was associated with risk of dementia. In Step 3, we examined plausible mechanisms underlying these findings by testing whether brain levels of primary BAs and gene expression of their principal receptors are altered in AD. Step 1: We assayed serum concentrations CA, CDCA, and 7α-OHC and used linear regression and mixed effects models to test their associations with brain amyloid accumulation (N = 141), WMLs, and brain atrophy (N = 134) in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing, community-based cohort study that began in 1958. Participants in the BLSA neuroimaging sample were approximately 46% male with a mean age of 76 years; longitudinal analyses included an average of 2.5 follow-up magnetic resonance imaging (MRI) visits. We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (N = 1,666) to validate longitudinal neuroimaging results in BLSA. ADNI is an ongoing, community-based cohort study that began in 2003. Participants were approximately 55% male with a mean age of 74 years; longitudinal analyses included an average of 5.2 follow-up MRI visits. Lower serum concentrations of 7α-OHC, CA, and CDCA were associated with higher brain amyloid deposition (p = 0.041), faster WML accumulation (p = 0.050), and faster brain atrophy mainly (false discovery rate [FDR] p = 4 million registrants from general practice clinics in the United Kingdom, we tested whether patients using BAS (BAS users; 3,208 with ≥2 prescriptions), which reduce circulating BAs and increase cholesterol catabolism, had altered dementia risk compared to those on non-statin lipid-modifying therapies (LMT users; 23,483 with ≥2 prescriptions). Patients in the study (BAS/LMT) were approximately 34%/38% male and with a mean age of 65/68 years; follow-up time was 4.7/5.7 years. We found that BAS use was not significantly associated with risk of all-cause dementia (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.72–1.46, p = 0.88) or its subtypes. We found a significant difference between the risk of VaD in males compared to females (p = 0.040) and a significant dose–response relationship between BAS use and risk of VaD (p-trend = 0.045) in males. Step 3: We assayed brain tissue concentrations of CA and CDCA comparing AD and control (CON) samples in the BLSA autopsy cohort (N = 29). Participants in the BLSA autopsy cohort (AD/CON) were approximately 50%/77% male with a mean age of 87/82 years. We analyzed single-cell RNA sequencing (scRNA-Seq) data to compare brain BA receptor gene expression between AD and CON samples from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 46). ROSMAP is an ongoing, community-based cohort study that began in 1994. Participants (AD/CON) were approximately 56%/36% male with a mean age of 85/85 years. In BLSA, we found that CA and CDCA were detectable in postmortem brain tissue samples and were marginally higher in AD samples compared to CON. In ROSMAP, we found sex-specific differences in altered neuronal gene expression of BA receptors in AD. Study limitations include the small sample sizes in the BLSA cohort and likely inaccuracies in the clinical diagnosis of dementia subtypes in primary care settings. Conclusions We combined targeted metabolomics in serum and amyloid positron emission tomography (PET) and MRI of the brain with pharmacoepidemiologic analysis to implicate dysregulation of cholesterol catabolism in dementia pathogenesis. We observed that lower serum BA concentration mainly in males is associated with neuroimaging markers of dementia, and pharmacological lowering of BA levels may be associated with higher risk of VaD in males. We hypothesize that dysregulation of BA signaling pathways in the brain may represent a plausible biologic mechanism underlying these results. Together, our observations suggest a novel mechanism relating abnormalities in cholesterol catabolism to risk of dementia., Vijay Varma and co-workers study cholesterol and bile acid metabolism in dementia., Author summary Why was this study done? Hypercholesterolemia is associated with increased risk of Alzheimer disease (AD) and vascular dementia (VaD). However, cholesterol is impermeable to the blood–brain barrier (BBB), and it is unclear how peripheral cholesterol mediates risk of dementia. While prior research has examined the relationship between de novo cholesterol biosynthesis and dementia, few studies have assessed the role of cholesterol catabolism and its principal breakdown products, oxysterols, and primary bile acids (BAs) in dementia. What did the researchers do and find? We examined the role of cholesterol catabolism in dementia pathogenesis by first testing the association between serum oxysterols and BAs and neuroimaging markers of dementia. We also tested whether exposure to bile acid sequestrants (BAS) was associated with risk of dementia in a large, real-world clinical dataset. Finally, we tested plausible mechanisms underlying these associations by examining whether primary BAs and mRNA of their receptors were altered in the brain in dementia. We found that lower serum levels of 7α-hydroxycholesterol (7α-OHC) and primary BAs were associated with higher brain amyloid deposition, faster WML accumulation, and faster brain atrophy mainly in males. Consistent with this finding, we observed a sex difference in the association between use of BAS and risk of VaD. We found that primary BAs were detectable in the brain, and levels of gene expression of BA receptors were altered in AD mainly in males. What do these findings mean? Our findings suggest that cholesterol catabolism and BA synthesis may impact dementia progression through sex-specific effects on signaling pathways in the brain. These results set the stage for experimental studies to test whether BA signaling in the brain may be a novel therapeutic target in dementia.

Pumps running as turbines are suitable hydraulic machines for micro hydropower applications. The selection of the proper pumps to install in a given site still remains a major challenge, as pump manufacturers do not provide the characteristic curves data in the turbine mode. Also, the accurate prediction and modelling of the pumps running as turbines characteristic curves still remain a major difficulty as existing methodologies still lack accuracy, especially in the part load and full load operating regions. This paper proposes a new two-step methodology based on the Hermite polynomial chaos expansion for predicting the characteristic curves of pumps running as turbines and modelling their variable speed operation, aiming at improving the prediction accuracy. Firstly, bivariate continuous surrogate functions are established for predicting the turbine mode and the extended operation mode characteristic curves inside a closed interval of unit specific speed values. These surrogate functions are developed by calibrating empirical coefficients based on collected experimental data. Secondly, a hill chart model is determined for describing the variable speed operation of a given pump running as a turbine. This hill chart model allows identifying the discharge and the rotational speed set points for maximising efficiency for a given operating condition. The proposed prediction surrogate functions and the variable speed hill chart model are useful engineering tools for improving the design of pump as turbine hydropower plants and for optimising the pump running as turbine control settings to maximise the produced energy.

Background Age and disease prevalence are the 2 biggest risk factors for Coronavirus disease 2019 (COVID-19) symptom severity and death. We therefore hypothesized that increased biological age, beyond chronological age, may be driving disease-related trends in COVID-19 severity. Methods Using the UK Biobank England data, we tested whether a biological age estimate (PhenoAge) measured more than a decade prior to the COVID-19 pandemic was predictive of 2 COVID-19 severity outcomes (inpatient test positivity and COVID-19-related mortality with inpatient test-confirmed COVID-19). Logistic regression models were used with adjustment for age at the pandemic, sex, ethnicity, baseline assessment centers, and preexisting diseases/conditions. Results Six hundred and thirteen participants tested positive at inpatient settings between March 16 and April 27, 2020, 154 of whom succumbed to COVID-19. PhenoAge was associated with increased risks of inpatient test positivity and COVID-19-related mortality (ORMortality = 1.63 per 5 years, 95% CI: 1.43–1.86, p = 4.7 × 10−13) adjusting for demographics including age at the pandemic. Further adjustment for preexisting diseases/conditions at baseline (ORM = 1.50, 95% CI: 1.30–1.73 per 5 years, p = 3.1 × 10−8) and at the early pandemic (ORM = 1.21, 95% CI: 1.04–1.40 per 5 years, p = .011) decreased the association. Conclusions PhenoAge measured in 2006–2010 was associated with COVID-19 severity outcomes more than 10 years later. These associations were partly accounted for by prevalent chronic diseases proximate to COVID-19 infection. Overall, our results suggest that aging biomarkers, like PhenoAge may capture long-term vulnerability to diseases like COVID-19, even before the accumulation of age-related comorbid conditions.

Environmental flow assessments (e-flows) are relatively new practices, especially in developing countries such as Nepal. This study presents a comprehensive analysis of the influence of hydrologically based e-flow methods in the natural flow regime. The study used different hydrological-based methods, namely, the Global Environmental Flow Calculator, the Tennant method, the flow duration curve method, the dynamic method, the mean annual flow method, and the annual distribution method to allocate e-flows in the Kaligandaki River. The most common practice for setting e-flows consists of allocating a specific percentage of mean annual flow or portion of flow derived from specific percentiles of the flow duration curve. However, e-flow releases should mimic the river’s intra-annual variability to meet the specific ecological function at different river trophic levels and in different periods over a year covering biotas life stages. The suitability of the methods was analyzed using the Indicators of Hydrological Alterations and e-flows components. The annual distribution method and the 30%Q-D (30% of daily discharge) methods showed a low alteration at the five global indexes for each group of Indicators of Hydrological Alterations and e-flows components, which allowed us to conclude that these methods are superior to the other methods. Hence, the study results concluded that 30%Q-D and annual distribution methods are more suitable for the e-flows implementation to meet the riverine ecosystem’s annual dynamic demand to maintain the river’s health. This case study can be used as a guideline to allocate e-flows in the Kaligandaki River, particularly for small hydropower plants.

Loneliness may be a consequence of social distancing, a measure imposed by several governments to try to reduce the contagion of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Despite being necessary, this measure may have thus caused a rise in mental health issues, leading to higher psychological distress and symptomatology. Thus, it is also important to explore how loneliness relates to the regulation of psychological needs. This study aims to explore the relationships between loneliness, symptomatology, and the regulation of psychological needs. 142 individuals (M age=32.7, SD=10.9), answered self-report questionnaires in a cross-sectional design. Results show that loneliness is positively correlated with symptomatology and difficulties in the regulation of psychological needs, with these relationships being mediated by psychological distress and psychological well-being. We discuss our results with a focus on loneliness and related psychopathological symptomatology, as they seem to be core factors in the regulation of psychological needs.

BackgroundHospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes, or coronary heart disease, but whether these comorbidities are true risk factors (ie, more common than in the general older population) is unclear. We estimated associations between preexisting diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort.MethodsUK Biobank (England) participants with baseline assessment 2006–2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and preexisting common diagnoses association tested with hospitalized laboratory-confirmed COVID-19 (March 16 to April 26, 2020), alone or with mortality, in logistic models.ResultsOf 269 070 participants aged older than 65, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common comorbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (21.5%), type 2 diabetes (type 2, 19. 9%), and asthma (17.6%). However, in models adjusted for comorbidities, age group, sex, ethnicity, and education, preexisting diagnoses of dementia, type 2 diabetes, chronic obstructive pulmonary disease, pneumonia, depression, atrial fibrillation, and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first 5 remaining statistically significant for related mortality. Chronic kidney disease and asthma were risk factors for COVID-19 hospitalization in women but not men.ConclusionsThere are specific high-risk preexisting comorbidities for COVID-19 hospitalization and related deaths in community-based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.

With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults, who account for the majority of severe illness and deaths. The age-related susceptibility is partly explained by increased comorbidities including dementia and type II diabetes [1]. While it is unclear why these diseases predispose risk, we hypothesize that increased biological age, rather than chronological age, may be driving disease-related trends in COVID-19 severity with age. To test this hypothesis, we applied our previously validated biological age measure (PhenoAge) [2] composed of chronological age and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020) [3]. Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2×10−6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age and pre-existing diseases or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.

We previously reported that the ApoE e4e4 genotype was associated with COVID-19 test positivity (OR=2.31, 95% CI: 1.65 to 3.24, p=1.19×10-6) in the UK Biobank (UKB) cohort, during the epidemic peak in England, from March 16 to April 26, 2020. With more COVID-19 test results (March 16 to May 31, 2020) and mortality data (to April 26, 2020) linked to UKB, we re-evaluated the ApoE e4 allele association with COVID-19 test positivity, and with all-cause mortality following test-confirmed COVID-19. Logistic regression models compared ApoE e4e4 participants (or e3e4s) to e3e3s with adjustment for sex; age on April 26th or age at death; baseline UKB assessment center in England (accounting for geographical differences in viral exposures); genotyping array type; and the top five genetic principal components (accounting for possible population admixture). ApoE e4e4 genotype was associated with increased risks of test positivity (OR=2.24, 95% CI: 1.72 to 2.93, p=3.24×10-9) and of mortality with test-confirmed COVID-19 (OR=4.29, 95% CI: 2.38 to 7.72, p=1.22×10-6), compared to e3e3s. Independent replications are needed to confirm our findings and mechanistic work is needed to understand how ApoE e4e4 results in the marked increase in vulnerability, especially for COVID-19 mortality. These findings also demonstrate that risks for COVID-19 mortality are not simply related to advanced chronological age or the comorbidities commonly seen in aging.

Holistic processing of visual words (i.e., obligatory encoding of/attending to all letters of a word) could be a marker of expert word recognition. In the present study, we thus examined for the first time whether there is a direct relation between the word-composite effect (i.e., all parts of a visual word are fully processed when observers perform a task on a word part) and fast access to the orthographic lexicon by visual word experts (i.e., fluent adult readers). We adopted an individual differences approach and used the word-frequency effect (i.e., faster recognition of high- than low-frequency words) in an independent lexical decision task as a proxy of fast access to lexical orthographic representations. Fluent readers with larger word-composite effect showed smaller word-frequency effect. This correlation was mainly driven by an association between a larger composite effect and faster lexical decision on low-frequency words, probably because these lexical representations are less stable and integrated/unitized, hence allowing differentiating among fluent readers. We thus showed that holistic processing of visual words is indeed related to higher efficiency in visual word recognition by skilled readers.