Motor Timing Intraindividual Variability in Amnestic Mild Cognitive Impairment and Cognitively Intact Elders at Genetic Risk for Alzheimer’s Disease

Introduction: Intraindividual variability (IIV) in motor performance has been shown to predict future cognitive decline. The apolipoprotein E-epsilon 4 (APOE-ε4) allele is also a well-established risk factor for memory decline. Here, we present novel findings examining the influence of the APOE-ε4 allele on the performance of asymptomatic healthy elders in comparison to individuals with amnestic MCI (aMCI) on a fine motor synchronization, paced finger-tapping task (PFTT). Method: Two Alzheimer’s disease (AD) risk groups, individuals with aMCI (n = 24) and cognitively intact APOE-ε4 carriers (n = 41), and a control group consisting of cognitively intact APOE-ε4 noncarriers (n = 65) completed the Rey Auditory Verbal Learning Test and the PFTT, which requires index finger tapping in synchrony with a visual stimulus (interstimulus interval = 333 ms). Results: Motor timing IIV, as reflected by the standard deviation of the intertap interval (ITI), was greater in the aMCI group than in the two groups of cognitively intact elders; in contrast, all three groups had statistically equivalent mean ITI. No significant IIV differences were observed between the asymptomatic APOE-ε4 carriers and noncarriers. Poorer episodic memory performance was associated with greater IIV, particularly in the aMCI group. Conclusions: Results suggest that increased IIV on a fine motor synchronization task is apparent in aMCI. This IIV measure was not sensitive in discriminating older asymptomatic individuals at genetic risk for AD from those without such a genetic risk. In contrast, episodic memory performance, a well-established predictor of cognitive decline in preclinical AD, was able to distinguish between the two cognitively intact groups based on genetic risk

Publication bias in clinical trials

This is the protocol for a review and there is no abstract. The objectives are as follows: To summarise evidence of publication bias for trials of health care interventions.Output Type: Protoco

Physical Activity Reduces Hippocampal Atrophy in Elders at Genetic Risk for Alzheimer\u27s Disease

We examined the impact of physical activity (PA) on longitudinal change in hippocampal volume in cognitively intact older adults at varying genetic risk for the sporadic form of Alzheimer\u27s disease (AD). Hippocampal volume was measured from structural magnetic resonance imaging (MRI) scans administered at baseline and at an 18-month follow-up in 97 healthy, cognitively intact older adults. Participants were classified as High or Low PA based on a self-report questionnaire of frequency and intensity of exercise. Risk status was defined by the presence or absence of the apolipoprotein E-epsilon 4 (APOE-ε4) allele. Four subgroups were studied: Low Risk/High PA (n = 24), Low Risk/Low PA (n = 34), High Risk/High PA (n = 22), and High Risk/Low PA (n = 17). Over the 18 month follow-up interval, hippocampal volume decreased by 3% in the High Risk/Low PA group, but remained stable in the three remaining groups. No main effects or interactions between genetic risk and PA were observed in control brain regions, including the caudate, amygdala, thalamus, pre-central gyrus, caudal middle frontal gyrus, cortical white matter (WM), and total gray matter (GM). These findings suggest that PA may help to preserve hippocampal volume in individuals at increased genetic risk for AD. The protective effects of PA on hippocampal atrophy were not observed in individuals at low risk for AD. These data suggest that individuals at genetic risk for AD should be targeted for increased levels of PA as a means of reducing atrophy in a brain region critical for the formation of episodic memories

Dual energy X-ray absorptiometry compared with anthropometry in relation to cardio-metabolic risk factors in a young adult population: Is the ‘Gold Standard’ tarnished?

Background and Aims: Assessment of adiposity using dual energy x-ray absorptiometry (DXA) has been considered more advantageous in comparison to anthropometryfor predicting cardio-metabolic risk in the older population, by virtue of its ability to distinguish total and regional fat. Nonetheless, there is increasing uncertainty regarding the relative superiority of DXA and little comparative data exist in young adults. This study aimed to identify which measure of adiposity determined by either DXA or anthropometry is optimal within a range of cardio-metabolic risk factors in young adults. Methods and Results: 1138 adults aged 20 years were assessed by DXA and standard anthropometry from the Western Australian Pregnancy Cohort (Raine) Study. Cross-sectional linear regression analyses were performed. Waist to height ratio was superior to any DXA measure with HDL-C. BMI was the superior model in relation to blood pressure than any DXA measure. Midriff fat mass (DXA) and waist circumference were comparable in relation to glucose. For all the other cardio-metabolic variables, anthropometricand DXA measures were comparable. DXA midriff fat mass compared with BMI or waist hip ratio was the superior measure for triglycerides, insulin and HOMA-IR. Conclusion: Although midriff fat mass (measured by DXA) was the superior measure with insulin sensitivity and triglycerides, the anthropometricmeasures were better or equal with various DXA measures for majority of the cardio-metabolic risk factors. Our findings suggest, clinical anthropometry is generally as useful as DXA in the evaluation of the individual cardio-metabolic risk factors in young adults

Projected changes in area of the Sundarban mangrove forest in Bangladesh due to SLR by 2100

The Sundarbans mangrove ecosystem, located in India and Bangladesh, is recognized as a global priority for biodiversity conservation and is an important provider of ecosystem services such as numerous goods and protection against storm surges. With global mean sea-level rise projected as up to 0.98m or greater by 2100 relative to the baseline period (1985-2005), the Sundarbans – mean elevation presently approximately 2 m above mean sea-level – is under threat from inundation and subsequent wetland loss; however the magnitude of loss remains unclear. We used remote and field measurements, geographic information systems and simulation modelling to investigate the potential effects of three sea-level rise scenarios on the Sundarbans within coastal Bangladesh. We illustrate how the Sea Level Affecting Marshes Model (SLAMM) is able to reproduce the observed area losses for the period 2000-2010. Using this calibrated model and assuming that mean sea-level is a better proxy than the SLAMM assumed mean lower low water for Mangrove area delineation, the estimated mangrove area net losses (relative to year 2000) are 81-178 km2, 111-376 km2 and 583-1393 km2 for relative sea-level rise scenarios to 2100 of 0.46m, 0.75m and 1.48m, respectively and net subsidence of ±2.5 mm/year. These area losses are very small (<10 percent of present day area) and significantly smaller than previous research has suggested. Our simulations also suggest that erosion rather than inundation may remain the dominant loss driver to 2100 under certain scenarios of sea-level rise and net subsidence. Only under the highest scenarios does inundation due to sea-level rise become the dominant loss process

Both Paraoxonase-1 Genotype and Activity Do Not Predict the Risk of Future Coronary Artery Disease; the EPIC-Norfolk Prospective Population Study

Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study. Methodology/Principal Findings: Cases (n = 1138) were apparently healthy men and women aged 45-79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7 +/- 645.3 versus 62.6 +/- 645.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p < 0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84-1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63-0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p < 0.0001) and more linearly predicted CAD risk (0.79[0.64-0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoprotein A-l (0.94[0.74-1.18], p-trend = 0.3). Conclusions/Significance: This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesi

Assessment of strategies for switching patients from olanzapine to risperidone: A randomized, open-label, rater-blinded study

<p>Abstract</p> <p>Background</p> <p>In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone.</p> <p>Methods</p> <p>In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued.</p> <p>Results</p> <p>The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; <it>p </it>< 0.0001) and in PANSS positive (-3.0; <it>p </it>< 0.0001), negative (-0.9; <it>p </it>= 0.171) and anxiety/depression (-1.4; <it>p </it>= 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal.</p> <p>Conclusion</p> <p>When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00378183</p

Exposure Assessment in the National Children’s Study: Introduction

The science of exposure assessment is relatively new and evolving rapidly with the advancement of sophisticated methods for specific measurements at the picogram per gram level or lower in a variety of environmental and biologic matrices. Without this measurement capability, environmental health studies rely on questionnaires or other indirect means as the primary method to assess individual exposures. Although we use indirect methods, they are seldom used as stand-alone tools. Analyses of environmental and biologic samples have allowed us to get more precise data on exposure pathways, from sources to concentrations, to routes, to exposure, to doses. They also often allow a better estimation of the absorbed dose and its relation to potential adverse health outcomes in individuals and in populations. Here, we make note of various environmental agents and how best to assess exposure to them in the National Children’s Study—a longitudinal epidemiologic study of children’s health. Criteria for the analytical method of choice are discussed with particular emphasis on the need for long-term quality control and quality assurance measures

A globally relevant change taxonomy and evidence-based change framework for land monitoring

A globally relevant and standardized taxonomy and framework for consistently describing land cover change based on evidence is presented, which makes use of structured land cover taxonomies and is underpinned by the Driver-Pressure-State-Impact-Response (DPSIR) framework. The Global Change Taxonomy currently lists 246 classes based on the notation 'impact (pressure)', with this encompassing the consequence of observed change and associated reason(s), and uses scale-independent terms that factor in time. Evidence for different impacts is gathered through temporal comparison (e.g., days, decades apart) of land cover classes constructed and described from Environmental Descriptors (EDs; state indicators) with pre-defined measurement units (e.g., m, %) or categories (e.g., species type). Evidence for pressures, whether abiotic, biotic or human-influenced, is similarly accumulated, but EDs often differ from those used to determine impacts. Each impact and pressure term is defined separately, allowing flexible combination into 'impact (pressure)' categories, and all are listed in an openly accessible glossary to ensure consistent use and common understanding. The taxonomy and framework are globally relevant and can reference EDs quantified on the ground, retrieved/classified remotely (from ground-based, airborne or spaceborne sensors) or predicted through modelling. By providing capacity to more consistently describe change processes-including land degradation, desertification and ecosystem restoration-the overall framework addresses a wide and diverse range of local to international needs including those relevant to policy, socioeconomics and land management. Actions in response to impacts and pressures and monitoring towards targets are also supported to assist future planning, including impact mitigation actions

A globally relevant change taxonomy and evidence-based change framework for land monitoring

A globally relevant and standardized taxonomy and framework for consistently describing land cover change based on evidence is presented, which makes use of structured land cover taxonomies and is underpinned by the Driver-Pressure-State�Impact-Response (DPSIR) framework. The Global Change Taxonomy currently lists 246 classes based on the notation ‘impact (pressure)’, with this encompassing the consequence of observed change and associated reason(s), and uses scale-independent terms that factor in time. Evidence for different impacts is gathered through temporal comparison (e.g., days, decades apart) of land cover classes constructed and described from Environmental Descriptors (EDs; state indicators) with pre-defined measurement units (e.g., m, %) or categories (e.g., species type). Evidence for pressures, whether abiotic, biotic or human-influenced, is similarly accumulated, but EDs often differ from those used to determine impacts. Each impact and pressure term is defined separately, allowing flexible combination into ‘impact (pressure)’ categories, and all are listed in an openly accessible glossary to ensure consistent use and common understanding. The taxonomy and framework are globally relevant and can reference EDs quantified on the ground, retrieved/classified remotely (from groundbased, airborne or spaceborne sensors) or predicted through modelling. By providing capacity to more consistently describe change processes—including land degradation, desertification and ecosystem restoration—the overall framework addresses a wide and diverse range of local to international needs including those relevant to policy, socioeconomics and land management. Actions in response to impacts and pressures and monitoring towards targets are also supported to assist future planning, including impact mitigation actions