ABSTRACT
Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10-5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.
Subject(s)
Cardiovascular Diseases , Heart Failure , Hypertension , Humans , Calcium Channel Blockers/therapeutic use , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , Pharmacogenomic Variants , Cardiovascular Diseases/chemically induced , Risk Factors , Heart Failure/drug therapy , Heart Disease Risk Factors , Lipoprotein(a)/therapeutic useABSTRACT
BACKGROUND: Despite similar diagnostic effectiveness for renal colic, computed tomography (CT) is more resource intensive than point-of-care ultrasound (PoCUS). We sought to compare Emergency Department (ED) length of stay (LOS) among patients with renal colic according to imaging modality utilized. We secondarily compared rates of infection, return ED visits, missed significant pathology, and urologic intervention. METHODS: This was a 12-month (1/1/22-12/31/22) multi-site retrospective cohort study of all patients diagnosed with renal colic who presented to the ED on days when at least one patient had a billable renal PoCUS examination performed. Patients with a history of genitourinary malignancy, pregnancy, renal transplant, hemodialysis, single kidney, prior visit for renal colic in the previous 30 days, or an incomplete workup were excluded. Median ED LOS was compared using a Wilcoxon rank sum test, and the 95% confidence limits for the difference between medians was calculated. Secondary outcomes were compared using a Fisher's Exact test. RESULTS: Of 415 patients screened, 325 were included for analysis: 150 had CT alone, 80 had PoCUS alone, 54 had PoCUS plus CT, and 41 had neither. Median LOS for PoCUS alone was 75.0 (95% CI 39.3-110.7) minutes shorter than CT alone (231.5 vs. 307.0 min, p < 0.0001). Similar rates of infection, return visits, and missed pathology occurred across all groups (p > 0.10). Urologic interventions were higher in the PoCUS plus CT (25.9%) group compared to CT alone (7.3%), PoCUS alone (2.5%), and neither (7.3%), p < 0.0001. CONCLUSION: Among patients with renal colic, PoCUS was associated with shorter ED LOS compared to CT, without differences in infection rates, return visits, or missed pathology. Patients with PoCUS plus CT had a higher rate of urologic interventions, suggesting PoCUS may have a role in identifying patients who would most benefit from CT.
Subject(s)
Renal Colic , Humans , Length of Stay , Renal Colic/diagnostic imaging , Point-of-Care Systems , Retrospective Studies , Ultrasonography/methods , Tomography, X-Ray Computed , Emergency Service, HospitalABSTRACT
Holistic processing aids in the discrimination of visually similar objects, but it may also come with a cost. Indeed holistic processing may improve the ability to detect changes to a face while impairing the ability to locate where the changes occur. We investigated the capacity to detect the occurrence of a change versus the capacity to detect the localization of a change for faces, houses, and words. Change detection was better than change localization for faces. Change localization outperformed change detection for houses. For words, there was no difference between detection and localization. We know from previous studies that words are processed holistically. However, being an object of visual expertise processed holistically, visual words are also a linguistic entity. Previously, the word composite effect was found for phonologically consistent words but not for phonologically inconsistent words. Being an object of visual expertise for which linguistic information is important, letter position information, is also crucial. Thus, the importance of localization of letters and features may augment the capacity to localize a change in words making the detection of a change and the detection of localization of a change equivalent.
Subject(s)
Linguistics , Pattern Recognition, Visual , HumansABSTRACT
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Coronary Disease , Heart Failure , Hypertension , Humans , Calcium Channel Blockers/adverse effects , Antihypertensive Agents/adverse effects , Hypertension/drug therapy , Pharmacogenetics , Calcium , Cytochrome P-450 CYP3A/genetics , Pharmacogenomic Variants , Ryanodine Receptor Calcium Release Channel/genetics , Heart Failure/drug therapy , Heart Failure/epidemiology , Heart Failure/genetics , Coronary Disease/complications , Treatment OutcomeABSTRACT
Shape memory alloy (SMA) micro cables have a wide potential for attenuation of vibrations and structural health monitoring due to energy dissipation. This work evaluates the effect of SMA thermomechanical coupling during dynamic cycling and the fatigue life of NiTi SMA micro cables submitted to tensile loadings at frequencies from 0.25 Hz to 10 Hz. The thermomechanical coupling was characterized using a previously developed methodology that identifies the self-heating frequency. When dynamically loaded above this frequency, the micro cable response is dominated by the self-heating, stiffening significantly during cycling. Once above the self-heating frequency, structural and functional fatigues of the micro cable were evaluated as a function of the loading frequency for the failure of each individual wire. All tests were performed on a single wire with equal cross-section area for comparison purposes. We observed that the micro cable's functional properties regarding energy dissipation capacity decreased throughout the cycles with increasing frequency. Due to the additional friction between the filaments of the micro cable, this dissipation capacity is superior to that of the single wire. Although its fatigue life is shorter, its delayed failure compared to a single wire makes it a more reliable sensor for structural health monitoring.
Subject(s)
Shape Memory Alloys , Titanium , Humans , Materials Testing , Stress, Mechanical , Titanium/chemistry , FatigueABSTRACT
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.
Subject(s)
Facial Recognition , Humans , Latent Class AnalysisABSTRACT
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 < 0.01) and Mini-Mental State Examination (coeff. = -0.46, 95% confidence interval = -0.58 to -0.34, P < 0.01) scores during follow-up. Stroke survivors who developed dementia within 3 years after stroke showed a steep decline in global cognition. However, a period of cognitive stability after stroke lasting 3 years was identified for individuals diagnosed with dementia in 4-6 years (coeff. = 0.28, 95% confidence interval = -3.28 to 3.8, P = 0.88) of 4 years when diagnosed at 7-9 years (coeff. = -3.00, 95% confidence interval = -6.45 to 0.45, P = 0.09); and of 6 years when diagnosed at 10-12 years (coeff. = -6.50, 95% confidence interval = -13.27 to 0.27, P = 0.06). These groups then showed a steep decline in Cambridge Cognition Examination-Revised in the 3 years prior to diagnosis of dementia. Risk factors for dementia within 3 years include recurrent stroke (odds ratio = 3.99, 95% confidence interval = 1.30-12.25, P = 0.016) and previous disabling stroke, total number of risk factors for dementia (odds ratio = 2.02, 95% confidence interval = 1.26-3.25, P = 0.004) and a Cambridge Cognition Examination-Revised score below 80 at baseline (odds ratio = 3.50, 95% confidence interval = 1.29-9.49, P = 0.014). Our unique longitudinal study showed cognitive decline following stroke occurs in two stages, a period of cognitive stability followed by rapid decline before a diagnosis of dementia. This pattern suggests stroke may predispose survivors for dementia by diminishing cognitive reserve but with a smaller impact on cognitive function, where cognitive decline may be precipitated by subsequent events, e.g. another cerebrovascular event. This supports the assertion that the development of vascular dementia can be stepwise even when patients have small stroke lesions.
ABSTRACT
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Cardiac PoCUS may identify OOMI earlier than standard evaluation and may expedite definitive management.
Subject(s)
Myocardial Infarction , ST Elevation Myocardial Infarction , Adult , Electrocardiography/methods , Humans , Myocardial Infarction/diagnostic imaging , Point-of-Care Systems , Retrospective Studies , ST Elevation Myocardial Infarction/diagnosis , Troponin IABSTRACT
Recently, paradigms in the face recognition literature have been adopted to reveal holistic processing in word recognition. It is unknown, however, whether different measures of holistic word processing share similar underlying mechanisms, and whether fluent word reading relies on holistic word processing. We measured holistic processing effects in three paradigms (composite, configural sensitivity, part-whole) as well as in reading fluency (3DM task: reading aloud high- and low-frequency words and pseudowords). Bin scores were used to combine accuracy and response time variables in the quest for a more comprehensive, reliable, and valid measure of holistic processing. Weak correlations were found between the different holistic processing measures, with only a significant correlation between the configural sensitivity effect and part-whole effect (r = .32) and a trend of a positive correlation between the word composite effect and configural sensitivity effect (r = .21). Of the three holistic processing measures, only one (part-whole effect) correlated with a lexical access measure of 3DM (r = .23). We also performed a principal component analysis (PCA) of performance in the three lists of 3DM, with the second most probably reflecting lexical access processes. There was a tendency for a positive correlation between part-whole bin measure and Component 2 of PCA. We also found a positive correlation between composite aligned in accuracy and Component 2 of PCA.Our results show that different measures of holistic word processing reflect predominantly different mechanisms, and that differences among normal readers in word reading do not seem to depend highly on holistic processing.
Subject(s)
Facial Recognition , Reading , Humans , Reaction Time , Word ProcessingABSTRACT
Despite technological advances in the production processes of the materials for ceramic façade coatings, the problems of detachments are still frequent. Therefore, this work aims to investigate, through a literature review, the existing gaps related to the adhesion ability of adhesive mortars, identifying new research needs that can better explain the behavior of the material. In addition, an experimental procedure was developed to evaluate the mechanical capacity of adhesive mortars when subjected to cyclic stresses. Dynamic stress measurements are presented for several blocks of mortar and on similar blocks but with a slot drilled prior to measurements (intended to represent failure). From these data we calculated values of stress energy, elastic energy, and dissipated energy. The experimental results showed that the energy involved in the test process accompanied the load values and current stress values. The mortar samples with the previous failure absorbed and dissipated less energy than mortars without failure, showing that materials that have less energy to dissipate, are materials that have developed less capacity to adhere, that is, to keep their parts together.
ABSTRACT
In this work, recycled poly(ethylene terephthalate) (PETR) was blended with virgin high-density polyethylene (HDPE) in an internal mixer in an attempt to obtain a material with improved properties. A compatibilizer (PE-g-MA) and a chain extender (Joncryl) were added to the PETR/HDPE blend and the rheological and thermal properties of the modified and unmodified blends as well as those of virgin PET with virgin HDPE (PETV/HDPE). All the blends were characterized by torque rheometry, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The data obtained indicate that the incorporation of either the chain extender or the compatibilizer agent led to increases in torque (and hence in viscosity) of the blend compared to that of the neat polymers. The joint incorporation of the chain extender and compatibilizer further increased the viscosity of the systems. Their effect on the crystallinity parameters of HDPE was minimal, but they reduced the crystallinity and crystallization temperature of virgin and recycled PET in the blends. The thermal stability of the PETR/HDPE blend was similar to that of the PETV/HDPE blend, and it was not affected by the incorporation of the chain extender and/or compatibilizer.
ABSTRACT
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.
Subject(s)
COVID-19 , Metacognition , Humans , Mental Health , Cross-Sectional Studies , Anxiety Disorders/psychology , Anxiety/psychologyABSTRACT
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.
Subject(s)
Face , Recognition, Psychology , Child , Ethnicity , Humans , Individuation , White PeopleABSTRACT
BACKGROUND: 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. METHODS: In a cross-sectional design, 249 individuals (M = 34.2, SD = 12.0) completed several self-report measures. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
COVID-19 , Adaptation, Psychological , Anxiety/complications , Cross-Sectional Studies , Depression , Humans , Pandemics , Surveys and QuestionnairesABSTRACT
BACKGROUND: Higher 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. AIM: To 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 SETTING: A 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. METHOD: CGPC 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. RESULTS: The 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, P<0.01) and had fewer PIPs (HQ: mean 2.1, LQ: mean 2.5, P<0.01), including fewer loop diuretics in patients with incontinence, drugs that can cause constipation, and benzodiazepines with high fall risk. The BB and SECON measures produced similar findings. CONCLUSION: Higher 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.
Subject(s)
Dementia , Aged , Continuity of Patient Care , Dementia/drug therapy , Dementia/epidemiology , Hospitalization , Humans , Inappropriate Prescribing , Polypharmacy , Retrospective StudiesABSTRACT
OBJECTIVE: To determine whether CYP2C19 loss-of-function (LoF) alleles increase risk of ischaemic stroke and myocardial infarction (MI) in UK primary care patients prescribed clopidogrel. DESIGN: Retrospective cohort analysis. SETTING: Primary care practices in the UK from January 1999 to September 2017. PARTICIPANTS: 7483 European-ancestry adults from the UK Biobank study with genetic and linked primary care data, aged 36-79 years at time of first clopidogrel prescription. INTERVENTIONS: Clopidogrel prescription in primary care, mean duration 2.6 years (range 2 months to 18 years). MAIN OUTCOME MEASURE: Hospital inpatient-diagnosed ischaemic stroke, MI or angina while treated with clopidogrel. RESULTS: 28.7% of participants carried at least one CYP2C19 LoF variant. LoF carriers had higher rates of incident ischaemic stroke while treated with clopidogrel compared with those without the variants (8 per 1000 person-years vs 5.2 per 1000 person-years; HR 1.53, 95% CIs 1.04 to 2.26, p=0.031). LoF carriers also had increased risk of MI (HR 1.14, 95% CI 1.04 to 1.26, p=0.008). In combined analysis LoF carriers had increased risk of any ischaemic event (stroke or MI) (HR 1.17, 95% CI 1.06 to 1.29, p=0.002). Adjustment for aspirin coprescription produced similar estimates. In lifetables using observed incidence rates, 22.5% (95% CI 14.4% to 34.0%) of CYP2C19 LoF carriers on clopidogrel were projected to develop an ischaemic stroke by age 79 (oldest age in the study), compared with 15.4% (95% CI 11.4% to 20.5%) in non-carriers, that is, 7.1% excess stroke incidence in LoF carriers by age 79. CONCLUSIONS: A substantial proportion of the UK population carry genetic variants that reduce metabolism of clopidogrel to its active form. In family practice patients on clopidogrel, CYP2C19 LoF variants are associated with substantially higher incidence of ischaemic events. Genotype-guided selection of antiplatelet medications may improve outcomes in patients carrying CYP2C19 genetic variants.
Subject(s)
Brain Ischemia , Stroke , Adult , Aged , Brain Ischemia/epidemiology , Brain Ischemia/genetics , Clopidogrel/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Genotype , Humans , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Primary Health Care , Retrospective Studies , Stroke/drug therapy , Stroke/epidemiology , Stroke/genetics , Treatment Outcome , United Kingdom/epidemiologyABSTRACT
AIMS: Rising sea-level following the Last Glacial Maximum lead to fragmentation of coastal limpet populations between islands of the Archipelago of Madeira. This fragmentation is reinforced by recent heavy exploitation reducing effective population size on Madeira Island. We use the limpet P. aspera to understand how the role of processes at different time scales (i.e. changes in the sea level and overexploitation) can influence the genetic composition of an extant species, relating these processes to reproductive phenology and seasonal shifts in ocean currents. LOCATION: Madeira Island, Porto Santo and Desertas (Archipelago of Madeira, NE Atlantic Ocean). TAXON: The limpet Patella aspera. METHODS: Twelve microsatellite genetic markers were used. A power analysis was used to evaluate the power of the microsatellite markers to detect a signal of population differentiation. Long-term past migrations were assessed using a Bayesian Markov Montecarlo approach in the software MIGRATE-n to estimate mutation-scaled migration rates (M = m/µ; m, probability of a lineage immigrating per generation; µ, mutation rate). Two scenarios were evaluated using an Approximate Bayesian Computation (ABC) in the software DIYABC 2.1 (i) Scenario 1: considered a population scenario from a reduced Ne at time t3 to a higher Ne at time t2; and (ii) Scenario 2 considering a reduction of Ne from a time t3 to a time t2. RESULTS: Colonization of the archipelago by Portuguese settlers six centuries ago probably led to an important decrease in the genetic diversity of the species (Ne). Contemporary gene flow strongly support a pattern of high asymmetric connectivity explained by the reproductive phenology of the species and spatio-temporal seasonal changes in the ocean currents. Spatio-temporal reconstructions using Bayesian methods, including coalescent and Approximate Bayesian Computation (ABC) approaches, suggest changes in the migration patterns from highly symmetric to highly asymmetric connectivity with subtle population differentiation as consequence of post-glacial maximum sea level rise during the Holocene. MAIN CONCLUSIONS: Our results suggest that anthropogenic activity could have had serious effects on the genetic diversity of heavily exploited littoral species since the end of the Pleistocene, probably accelerating in recent years.
Subject(s)
Genetic Variation , Patella , Atlantic Ocean , Bayes Theorem , Genetics, Population , PortugalABSTRACT
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.
Subject(s)
Dementia , Frailty , Hypertension , Hypotension, Orthostatic , Aged , Blood Pressure , Dementia/epidemiology , HumansABSTRACT
OBJECTIVE: 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. METHODS: 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: 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. CONCLUSIONS: 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.
Subject(s)
COVID-19 , Anxiety/epidemiology , Cross-Sectional Studies , Depression , Humans , Mental Health , Pandemics , SARS-CoV-2ABSTRACT
The understanding of the mechanical fixation behavior of coatings is crucial for a better comprehension of the bonding systems, especially at the interface between the mortar and the substrate. Physical adherence is related, among other things, to the contents of the materials used in the roughcast and mortar coatings, due to the colloidal water penetration into the pores of the substrate. This work evaluated the influence of different lime solution additions replacing the kneading water in the preparation of roughcast and mortar coatings. Two types of substrates were investigated:ceramic bricks and concrete blocks. Three wall masonry panels were constructed, with dimensions of 220 × 180 cm2, one of concrete block and two of ceramic bricks, followed by the application of roughcast and mortar coating with an average thickness of 5 mm and 20 mm, respectively. Direct tensile bond strength tests were performed and the results, with a 95% confidence level, showed that substrate ceramic and treatment in the roughcast exhibited a better behavior regarding the distribution of the tensile bond strength of the tested specimens. However, no significant differences of the amount of addition used (0%, 5%, 10% and 15%) on the tensile bond strength were observed.