Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.

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.

Point-of-care ultrasound associated with shorter length of stay than computed tomography for renal colic.

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.

Calcium-channel blockers: Clinical outcome associations with reported pharmacogenetics variants in 32 000 patients.

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.

Change detection versus change localization for faces, houses, and words.

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.

Point-of-care ultrasound may expedite diagnosis and revascularization of occult occlusive myocardial infarction.

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.

NiTi SMA Superelastic Micro Cables: Thermomechanical Behavior and Fatigue Life under Dynamic Loadings.

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.

Early maladaptive schemas and COVID-19 anxiety: The mediational role of mistrustfulness and vulnerability to harm and illness.

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.

Path analysis from COVID-19 perceptions to psychological health: The roles of critical distance and mastery.

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.

Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and pharmacoepidemiologic study.

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 = <0.001-0.013) in males in BLSA. In ADNI, we found a modest sex-specific effect indicating that lower serum concentrations of CA and CDCA were associated with faster brain atrophy (FDR p = 0.049) in males.Step 2: In the Clinical Practice Research Datalink (CPRD) dataset, covering >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.

Potentially inappropriate prescribing in dementia, multi-morbidity and incidence of adverse health outcomes.

IMPORTANCE: treatment of dementia in individuals with comorbidities is complex, leading to potentially inappropriate prescribing (PIP). The impact of PIP in this population is unknown. OBJECTIVE: to estimate the rate of PIP and its effect on adverse health outcomes (AHO). DESIGN: retrospective cohort. SETTING: primary care electronic health records linked to hospital discharge data from England. SUBJECTS: 11,175 individuals with dementia aged over 65 years in 2016 and 43,463 age- and sex-matched controls. METHODS: Screening Tool of Older Persons' Prescriptions V2 defined PIP. Logistic regression tested associations with comorbidities at baseline, and survival analyses risk of incident AHO, adjusted for age, gender, deprivation and 14 comorbidities. RESULTS: the dementia group had increased risk of PIP (73% prevalence; odds ratio [OR]: 1.92; confidence interval [CI]: 83-103%; P < 0.01) after adjusting for comorbidities. Most frequent PIP criteria were related to anti-cholinergic drugs and therapeutic duplication. Risk of PIP was higher in patients also diagnosed with coronary-heart disease (odds OR: 2.17; CI: 1.91-2.46; P < 0.01), severe mental illness (OR: 2.09; CI: 1.62-2.70; P < 0.01); and depression (OR: 1.81; CI: 1.62-2.01; P < 0.01). During follow-up (1 year), PIP was associated with increased all-cause mortality (hazard ratio: 1.14; CI: 1.02-1.26; P < 0.02), skin ulcer and pressure sores (hazard ratio: 1.66; CI: 1.12-2.46; P < 0.01), falls (hazard ratio: 1.37; CI: 1.15-1.63; P < 0.01), anaemia (hazard ratio: 1.61; CI: 1.10-2.38; P < 0.02) and osteoporosis (hazard ratio: 1.62; CI: 1.02-2.57; P < 0.04). CONCLUSION: patients with dementia frequently receive PIPs, and those who do are more likely to experience AHO. These results highlight the need to optimise medication in dementia patients, especially those with comorbidities.

COVID-19 Inventory and Mental Health: Preliminary Analysis.

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.

Blood pressure in frail older adults: associations with cardiovascular outcomes and all-cause mortality.

BACKGROUND: Blood pressure (BP) management in frail older people is challenging. An randomised controlled trial of largely non-frail older people found cardiovascular and mortality benefit with systolic (S) BP target <120 mmHg. However, all-cause mortality by attained BP in routine care in frail adults aged above 75 is unclear. OBJECTIVES: To estimate observational associations between baseline BP and mortality/cardiovascular outcomes in a primary-care population aged above 75, stratified by frailty. METHODS: Prospective observational analysis using electronic health records (clinical practice research datalink, n = 415,980). We tested BP associations with cardiovascular events and mortality using competing and Cox proportional-hazards models respectively (follow-up ≤10 years), stratified by baseline electronic frailty index (eFI: fit (non-frail), mild, moderate, severe frailty), with sensitivity analyses on co-morbidity, cardiovascular risk and BP trajectory. RESULTS: Risks of cardiovascular outcomes increased with SBPs >150 mmHg. Associations with mortality varied between non-frail <85 and frail 75-84-year-olds and all above 85 years. SBPs above the 130-139-mmHg reference were associated with lower mortality risk, particularly in moderate to severe frailty or above 85 years (e.g. 75-84 years: 150-159 mmHg Hazard Ratio (HR) mortality compared to 130-139: non-frail HR = 0.94, 0.92-0.97; moderate/severe frailty HR = 0.84, 0.77-0.92). SBP <130 mmHg and Diastolic(D)BP <80 mmHg were consistently associated with excess mortality, independent of BP trajectory toward the end of life. CONCLUSIONS: In representative primary-care patients aged ≥75, BP <130/80 was associated with excess mortality. Hypertension was not associated with increased mortality at ages above 85 or at ages 75-84 with moderate/severe frailty, perhaps due to complexities of co-existing morbidities. The priority given to aggressive BP reduction in frail older people requires further evaluation.

Predicting incident delirium diagnoses using data from primary-care electronic health records.

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.

Association of blood pressure with clinical outcomes in older adults with chronic kidney disease.

BACKGROUND: in chronic kidney disease (CKD), hypertension is associated with poor outcomes at ages <70 years. At older ages, this association is unclear. We tested 10-year mortality and cardiovascular outcomes by clinical systolic blood pressure (SBP) in older CKD Stages 3 and 4 patients without diabetes or proteinuria. METHODS: retrospective cohort in population representative primary care electronic medical records linked to hospital data from the UK. CKD staged by CKD-EPI equation (≥2 creatinine measurements ≥90 days apart). SBPs were 3-year medians before baseline, with mean follow-up 5.7 years. Cox competing models accounted for mortality. RESULTS: about 158,713 subjects with CKD3 and 6,611 with CKD4 met inclusion criteria. Mortality increased with increasing CKD stage in all subjects aged >60. In the 70 plus group with SBPs 140-169 mmHg, there was no increase in mortality, versus SBP 130-139. Similarly, SBPs 140-169 mmHg were not associated with increased incident heart failure, stroke or myocardial infarctions. SBPs <120 mmHg were associated with increased mortality and cardiovascular risk. At ages 60-69, there was increased mortality at SBP <120 and SBP >150 mmHg.Results were little altered after excluding those with declining SBPs during 5 years before baseline, or for longer-term outcomes (5-10 years after baseline). CONCLUSIONS: in older primary care patients, CKD3 or 4 was the dominant outcome predictor. SBP 140-169 mmHg having little additional predictive value, <120 mmHg was associated with increased mortality. Prospective studies of representative older adults with CKD are required to establish optimum BP targets.

Hemispheric asymmetry in holistic processing of words.

Holistic processing has been regarded as a hallmark of face perception, indicating the automatic and obligatory tendency of the visual system to process all face parts as a perceptual unit rather than in isolation. Studies involving lateralized stimulus presentation suggest that the right hemisphere dominates holistic face processing. Holistic processing can also be shown with other categories such as words and thus it is not specific to faces or face-like expertize. Here, we used divided visual field presentation to investigate the possibly different contributions of the two hemispheres for holistic word processing. Observers performed same/different judgment on the cued parts of two sequentially presented words in the complete composite paradigm. Our data indicate a right hemisphere specialization for holistic word processing. Thus, these markers of expert object recognition are domain general.

U.K. Foot and Mouth Disease: A Systemic Risk Assessment of Existing Controls.

This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted 'features, events, and processes' (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system.

A systems approach to the policy-level risk assessment of exotic animal diseases: network model and application to classical swine fever.

Exotic animal diseases (EADs) are characterized by their capacity to spread global distances, causing impacts on animal health and welfare with significant economic consequences. We offer a critique of current import risk analysis approaches employed in the EAD field, focusing on their capacity to assess complex systems at a policy level. To address the shortcomings identified, we propose a novel method providing a systematic analysis of the likelihood of a disease incursion, developed by reference to the multibarrier system employed for the United Kingdom. We apply the network model to a policy-level risk assessment of classical swine fever (CSF), a notifiable animal disease caused by the CSF virus. In doing so, we document and discuss a sequence of analyses that describe system vulnerabilities and reveal the critical control points (CCPs) for intervention, reducing the likelihood of U.K. pig herds being exposed to the CSF virus.

Trajectories of cognitive change following stroke: stepwise decline towards dementia in the elderly.

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.

The relation between holistic processing as measured by three composite tasks and face processing: A latent variable modeling approach.

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.