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The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder., (© 2024. The Author(s).)

Recent studies have found associations between obstructive sleep apnea and cognitive decline. The underlying mechanisms are still unclear. Here, we investigate the associations between changes in micro-architecture, specifically sleep spindles, and cognitive function in community-dwelling middle-aged and older adults, some with obstructive sleep apnea, with a focus on sex differences. A total of 125 voluntary participants (mean age 66.0 ± 6.4 years, 64 females) from a larger cohort (participants of the Brain in Motion Studies I and II) underwent 1 night of in-home polysomnography and a neuropsychological battery (sleep and cognitive testing were conducted within 2 weeks of each other). A semi-automatic computerized algorithm was used to score polysomnography data and detect spindle characteristics in non-rapid eye movement Stages 2 and 3 in both frontal and central electrodes. Based on their apnea-hypopnea index, participants were divided into those with no obstructive sleep apnea (apnea-hypopnea index < 5 per hr, n = 21), mild obstructive sleep apnea (5 ≥ apnea-hypopnea index < 15, n = 47), moderate obstructive sleep apnea (15 ≥ apnea-hypopnea index < 30, n = 34) and severe obstructive sleep apnea (apnea-hypopnea index ≥ 30, n = 23). There were no significant differences in spindle characteristics between the four obstructive sleep apnea severity groups. Spindle density and percentage of fast spindles were positively associated with some verbal fluency measures on the cognitive testing. Sex might be linked with these associations. Biological sex could play a role in the associations between spindle characteristics and some verbal fluency measures. Obstructive sleep apnea severity was not found to be a contributing factor in this non-clinical community-dwelling cohort., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia ( p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores ( p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Introduction: Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18 F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD., Methods: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion., Results: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions., Discussion: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment., Highlights: Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion., Competing Interests: The authors declare no conflicts of interest related to this research. The principal author confirms that all authors have read the manuscript, and the paper has not previously been published or is under consideration at another journal. The authors take full responsibility for the data, analyses, and interpretation, and the conduct of the research, and have full access to all the data and the right to publish it. All authors have agreed to the conditions noted on the authorship agreement form., (© 2024 The Author(s). Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The microbiome is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. The microbiome may influence transmission of pathogens by their vectors, such as mosquitoes or aquatic snails. We previously sequenced the bacterial 16S V4 ribosomal DNA of the hemolymph (blood) of Biomphalaria spp. snails, one of the vectors of the human blood fluke schistosome. We showed that snail hemolymph harbored an abundant and diverse microbiome. This microbiome is distinct from the water environment and can discriminate snail species and populations. As hemolymph bathes snail organs, we then investigated the heterogeneity of the microbiome in these organs., Results: We dissected ten snails for each of two different species ( B. alexandrina and B. glabrata ) and collected their organs (ovotestis, hepatopancreas, gut, and stomach). We also ground in liquid nitrogen four whole snails of each species. We sampled the water in which the snails were living (environmental controls). Sequencing the 16S V4 rDNA revealed organ-specific microbiomes. These microbiomes harbored a lower diversity than the hemolymph microbiome, and the whole-snail microbiome. The organ microbiomes tend to cluster by physiological function. In addition, we showed that the whole-snail microbiome is more similar to hemolymph microbiome., Conclusions: These results are critical for future work on snail microbiomes and show the necessity of sampling individual organ microbiomes to provide a complete description of snail microbiomes., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Background: A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Our objective was to determine potential improvements in the number needed to treat (NNT) and number of events prevented (NEP) using different risk models in patients eligible for risk stratification., Methods: A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2)., Results: The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%). Accordingly, the NEP was highest for the FRS at 406 and lowest for SCORE2 at 156., Conclusions: Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT but prevent fewer events at the population level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort., Methods and Results: A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40-69 while the models for older persons (OPs) were applied to 9885 individuals 70-89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men., Conclusion: The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions., Competing Interests: Conflict of interest: K.T. receives a Research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. KT holds a Chair in Family and Community Medicine Research in Primary Care at UHN and receives a research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. R.K. is an Associate Editor of JAMA. He receives support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (under award K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060022060). He also receives research support, through Yale, from Bristol-Myers Squibb and Novo Nordisk, unrelated to the current work. He is a co-inventor of U.S. Provisional Patent Applications 63/177 117, 63/428 569, 63/346 610, and 63/484 426. He is a co-founder of Evidence2Health, a precision health platform to improve evidence-based cardiovascular care. D.S.L. is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dyslipidemia management is a cornerstone in cardiovascular disease prevention and relies heavily on patient adherence to lifestyle modifications and medications. Numerous cholesterol patient education materials are available online, but it remains unclear whether these resources are suitable for the majority of North American adults given the prevalence of low health literacy. This review aimed to (1) identify printable cholesterol patient education materials through an online search, and (2) evaluate the readability, understandability, and actionability of each resource to determine its utility in practice., Methods and Results: We searched the MEDLINE database for peer-reviewed educational materials and the websites of Canadian and American national health organizations for gray literature. Readability was measured using the Flesch-Kincaid Grade Level, and scores between fifth- and sixth-grade reading levels were considered adequate . Understandability and actionability were scored using the Patient Education Materials Assessment Tool and categorized as superior (>80%), adequate (50%-70%), or inadequate (<50%). Our search yielded 91 results that were screened for eligibility. Among the 22 educational materials included in the study, 15 were identified through MEDLINE, and 7 were from websites. The readability across all materials averaged an 11th-grade reading level (Flesch-Kincaid Grade Level=11.9±2.59). The mean±SD understandability and actionability scores were 82.8±6.58% and 40.9±28.60%, respectively., Conclusions: The readability of online cholesterol patient education materials consistently exceeds the health literacy level of the average North American adult. Many resources also inadequately describe action items for individuals to self-manage their cholesterol, representing an implementation gap in cardiovascular disease prevention.

Semiconductor wafer manufacturing relies on the precise control of various performance metrics to ensure the quality and reliability of integrated circuits. In particular, GaN has properties that are advantageous for high voltage and high frequency power devices; however, defects in the substrate growth and manufacturing are preventing vertical devices from performing optimally. This paper explores the application of machine learning techniques utilizing data obtained from optical profilometry as input variables to predict the probability of a wafer meeting performance metrics, specifically the breakdown voltage (V bk ). By incorporating machine learning techniques, it is possible to reliably predict performance metrics that cause devices to fail at low voltage. For diodes that fail at a higher (but still below theoretical) breakdown voltage, alternative inspection methods or a combination of several experimental techniques may be necessary., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We previously performed a genome-wide association study (GWAS) to identify the genetic basis of praziquantel (PZQ) response in schistosomes, identifying two quantitative trait loci situated on chromosomes 2 and 3. We reanalyzed this GWAS using the latest (version 10) genome assembly showing that a single locus on chromosome 3, rather than two independent loci, determines drug response. These results reveal that PZQ response is monogenic and demonstrates the importance of high-quality genomic information., Competing Interests: The authors declare no conflict of interest.

Background: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated., Objective: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group., Methods: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated., Results: Overall, people with PD had a regionally smaller posterior lobe (d max  = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (d max  = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (d max  = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17)., Conclusions: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies., Objective: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs)., Design: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models., Setting: Population-based cohort study in Ontario, Canada., Participants: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014., Measurements: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years., Results: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02])., Limitation: Medication use was not available at the population level., Conclusion: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs., Primary Funding Source: Canadian Institutes of Health Research., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1345.

Photoemission electron microscopy (PEEM) is a unique and powerful tool for studying the electronic properties of materials and surfaces. However, it requires intense and well-controlled light sources with photon energies ranging from the UV to soft X-rays for achieving high spatial resolution and image contrast. Traditionally, many PEEMs were installed at synchrotron light sources to access intense and tunable soft X-rays. More recently, the maturation of solid-state lasers has opened a new avenue for laboratory-based PEEMs using laser-based UV light at lower photon energies. Here, we report on the characteristics of a laser-based UV light source that was recently integrated with a PEEM instrument. The system consists of a high repetition rate, tunable wavelength laser coupled to a harmonics generation module, which generates deep-UV radiation from 192 nm to 210 nm. We comment on the spectral characteristics and overall laser system stability, as well as on the effects of space charge within the PEEM microscope at high UV laser fluxes. Further, we show an example of imaging on gallium nitride, where the higher UV photon energy and flux of the laser provides considerably improved image quality, compared to a conventional light source. These results demonstrate the capabilities of laser-based UV light sources for advancing laboratory-based PEEMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice., (© 2023 The Authors.)

Genetic diversity within species represents a fundamental yet underappreciated level of biodiversity. Because genetic diversity can indicate species resilience to changing climate, its measurement is relevant to many national and global conservation policy targets. Many studies produce large amounts of genome-scale genetic diversity data for wild populations, but most (87%) do not include the associated spatial and temporal metadata necessary for them to be reused in monitoring programs or for acknowledging the sovereignty of nations or Indigenous peoples. We undertook a distributed datathon to quantify the availability of these missing metadata and to test the hypothesis that their availability decays with time. We also worked to remediate missing metadata by extracting them from associated published papers, online repositories, and direct communication with authors. Starting with 848 candidate genomic data sets (reduced representation and whole genome) from the International Nucleotide Sequence Database Collaboration, we determined that 561 contained mostly samples from wild populations. We successfully restored spatiotemporal metadata for 78% of these 561 data sets (n = 440 data sets with data on 45,105 individuals from 762 species in 17 phyla). Examining papers and online repositories was much more fruitful than contacting 351 authors, who replied to our email requests 45% of the time. Overall, 23% of our email queries to authors unearthed useful metadata. The probability of retrieving spatiotemporal metadata declined significantly as age of the data set increased. There was a 13.5% yearly decrease in metadata associated with published papers or online repositories and up to a 22% yearly decrease in metadata that were only available from authors. This rapid decay in metadata availability, mirrored in studies of other types of biological data, should motivate swift updates to data-sharing policies and researcher practices to ensure that the valuable context provided by metadata is not lost to conservation science forever., (© 2023 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Work in animal and human neuroscience has identified neural regions forming a network involved in the production of motivated, goal-directed behaviour. In particular, the nucleus accumbens and anterior cingulate cortex are recognized as key network nodes underlying decisions of whether to exert effort for reward, to drive behaviour. Previous work has convincingly shown that this cognitive mechanism, known as effort-based decision making, is altered in people with Parkinson's disease with a syndrome of reduced goal-directed behaviour-apathy. Building on this work, we investigated whether the neural regions implementing effort-based decision-making were associated with apathy in Parkinson's disease, and more importantly, whether changes to these regions were evident prior to apathy development. We performed a large, multimodal neuroimaging analysis in a cohort of people with Parkinson's disease (n = 199) with and without apathy at baseline. All participants had ∼2-year follow-up apathy scores, enabling examination of brain structure and function specifically in those with normal motivation who converted to apathy by ∼2-year follow-up. In addition, of the people with normal motivation, a subset (n = 56) had follow-up neuroimaging data, allowing for examination of the 'rate of change' in key nodes over time in those who did, and did not, convert to apathy. Healthy control (n = 54) data were also included to aid interpretation of findings. Functional connectivity between the nucleus accumbens and dorsal anterior cingulate cortex was higher in people with normal motivation who later converted to apathy compared to those who did not, whereas no structural differences were evident between these groups. In contrast, grey matter volume in these regions was reduced in the group with existing apathy. Furthermore, of those with normal motivation who had undergone longitudinal neuroimaging, converters to apathy showed a higher rate of change in grey matter volume within the nucleus accumbens. Overall, we show that changes in functional connectivity between nucleus accumbens and anterior cingulate cortex precedes apathy in people with Parkinson's disease, with conversion to apathy associated with higher rate of grey matter volume loss in nucleus accumbens, despite no baseline differences. These findings significantly add to an accumulating body of transdiagnostic evidence that apathy arises from disruption to key nodes within a network in which normal goal-directed behaviour is instantiated, and raise the possibility of identifying those at risk for developing apathy before overt motivational deficits have arisen., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events. Here, we assess LDL-C levels and threshold achievement among patients by lipid-lowering therapies (LLT) received post-AMI., Methods: A retrospective cohort study of patients identified with AMI between 2015 and 2019 was conducted using administrative health databases in Alberta, Canada. Patients were grouped by their highest-intensity LLT post-AMI (proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT; PCSK9i alone; ezetimibe + statin; statins (high, moderate, low intensity); or ezetimibe alone), and available LDL-C levels were examined in the year before and after LLT dispense date., Results: The cohort included 15,283 patients. In patients on PCSK9i + LLT, the median [95% confidence interval (CI)] LDL-C levels decreased from 2.7 (2.3-3.4) before to 0.9 (0.5-1.2) mmol/l after treatment, the largest decrease among treatment groups. In the ezetimibe + statin and high-intensity statin groups, median (95% CI) values after treatment were 1.5 (1.5-1.6) and 1.4 (1.4-1.4) mmol/l, respectively. The proportion of patients below the 1.8 mmol/l threshold increased by 77.7% in the PSCK9i + LLT group after treatment, compared to 45.4 and 32.4% in the ezetimibe + statin and high-intensity statin groups, respectively., Conclusions: Intensification with PCSK9i in AMI patients results in a greater proportion of patients achieving below the recommended LDL-C threshold versus statins and or ezetimibe alone. Increased focus on achieving below the LDL-C thresholds with additional LLT as required may benefit patient cardiovascular outcomes., (© 2022. The Author(s).)

Background: Parkinson's disease frequently causes communication impairments, but knowledge about the occurrence of new-onset stuttering is limited., Objectives: To determine the presence of acquired neurogenic stuttering and its relationship with cognitive and motor functioning in individuals with Parkinson's disease., Method: Conversation, picture description, and reading samples were collected from 100 people with Parkinson's disease and 25 controls to identify the presence of stuttered disfluencies (SD) and their association with neuropsychological test performance and motor function., Results: Participants with Parkinson's disease presented with twice as many stuttered disfluencies during conversation (2.2% ± 1.8%SD) compared to control participants (1.2% ± 1.2%SD; P  < 0.01). 21% of people with Parkinson's disease ( n  = 20/94) met the diagnostic criterion for stuttering, compared with 1/25 controls. Stuttered disfluencies also differed significantly across speech tasks, with more disfluencies during conversation compared to reading ( P  < 0.01). Stuttered disfluencies in those with Parkinson's disease were associated with longer time since disease onset ( P  < 0.01), higher levodopa equivalent dosage ( P  < 0.01), and lower cognitive ( P  < 0.01) and motor scores ( P  < 0.01)., Conclusion: One in five participants with Parkinson's disease presented with acquired neurogenic stuttering, suggesting that speech disfluency assessment, monitoring and intervention should be part of standard care. Conversation was the most informative task for identifying stuttered disfluencies. The frequency of stuttered disfluencies was higher in participants with worse motor functioning, and lower cognitive functioning. This challenges previous suggestions that the development of stuttered disfluencies in Parkinson's disease has purely a motoric basis., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

The aim of this study was to better understand the relation of schizotypy traits with sensory gating ability in a sample of community-dwelling individuals with high and low schizotypy traits. Sensory gating was assessed through the paired click paradigm and mid-latency evoked responses (i.e., P50, N100, P200), while schizotypy traits were assessed through the SPQ-BR which was used to classify participants into "high" and "low" schizotypy groups. Based on prior work, we hypothesized that those with the highest schizotypy scores would have reduced sensory gating ability. While this study does not show differences between relatively low and high schizotypy groups on sensory gating ability, it does suggest that our participants may have been experiencing deficits in attention allocation, a downstream cognitive processing measure. Scores on the SPQ-BR suggest that our sample was not close to the high end of the schizotypy traits which may help explain why no differences were found. This research shows the importance of including all levels of schizotypy ratings in clinical research as we can gain a clearer view of the impact of schizotypy on the brain and cognitive functioning in those with "high" levels of schizotypy. Additionally, this work highlights the importance of including measures of important factors such as impulsivity and sensation-seeking to better understand what aspects of schizotypy may be driving these sensory gating alterations reported in the literature., Competing Interests: All of the authors have no conflicts of interest to disclose., (© The Author(s) 2023.)

To improve the manufacturing process of GaN wafers, inexpensive wafer screening techniques are required to both provide feedback to the manufacturing process and prevent fabrication on low quality or defective wafers, thus reducing costs resulting from wasted processing effort. Many of the wafer scale characterization techniques-including optical profilometry-produce difficult to interpret results, while models using classical programming techniques require laborious translation of the human-generated data interpretation methodology. Alternatively, machine learning techniques are effective at producing such models if sufficient data is available. For this research project, we fabricated over 6000 vertical PiN GaN diodes across 10 wafers. Using low resolution wafer scale optical profilometry data taken before fabrication, we successfully trained four different machine learning models. All models predict device pass and fail with 70-75% accuracy, and the wafer yield can be predicted within 15% error on the majority of wafers., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Interventional neuroradiology procedures subject professionals who work in this area to high doses of ionizing radiation, and such exposure leads to a higher chance of occupational diseases related to this physical risk. Radiation protection practices aim to reduce the occurrence of such damage to the health of these workers., Objectives: To identify how the practice of radiation protection occurs in a multidisciplinary team of an interventional neuroradiology service in the state of Santa Catarina, Brazil., Methods: A qualitative, exploratory, and descriptive research conducted with nine health professionals from the multidisciplinary team. Non-participant observation and a survey form were used as data collection techniques. For data analysis, descriptive analysis based on absolute and relative frequency and content analysis were used., Results: Although some practices showed the use of radiation protection measures in practice, such as workers taking turns to perform procedures and continuous use of the lead apron as well as the mobile suspended protection, we found that most of the practices violate the principles of radiation protection. Among these inadequate radiological protection practices, the following aspects were observed: not wearing lead goggles, not using collimation to obtain the image, poor knowledge of the principles of radiation protection and biological effects of ionizing radiation, and non-use of an individual dosimeter., Conclusions: There was a lack of know-how of the multidisciplinary team working in interventional neuroradiology regarding the practice of radiation protection., Competing Interests: Conflicts of interest: None

Metformin has been used as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS), metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reduce insulin resistance and enhance peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as important. In the gut, metformin modulates the glucagon-like peptide- 1 (GLP-1) - gut-brain axis and impacts the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has the interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases, and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review, we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Angina with no obstructive coronary artery disease (ANOCA) is a common entity. There is still under-recognition of this condition, but it is unclear if the referral patterns for chest pain diagnosis have changed. We aimed to determine if the prevalence of patients diagnosed with ANOCA by means of coronary angiography has changed over time., Methods: A population-based cohort of patients who had their first coronary angiogram for a chest pain syndrome in Alberta from 1995 to 2020 was extracted retrospectively from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. A temporal trend analysis was performed to compare patients with ANOCA vs obstructive coronary artery disease (CAD), and the predictors of ANOCA were investigated., Results: In our analysis, 121,066 patients were included (26% ANOCA, 31% female, overall mean age 62 years). The percentages of ANOCA vs obstructive CAD ranged from 24.2% to 26.7% in all patients (P < 0.001), from 19.4% to 21.4% in patients with acute coronary syndromes (P = 0.002), and from 30.6% to 37.5% in patients with stable angina (P < 0.001). Independent predictors of ANOCA were female sex (odds ratio [OR] 3.34, 95% confidence interval [CI] 3.05-3.66), younger age (OR 0.96, 95% CI 0.95-0.96), history of atrial fibrillation (OR 2.18, 95% CI 1.73-2.73), and stable angina (vs myocardial infarction: OR 0.25, 95% CI 0.23-0.28; vs unstable angina: OR 0.79, 95% CI 0.70-0.89). Traditional cardiovascular risk factors were associated with obstructive CAD., Conclusions: There remained a high prevalence of ANOCA detected during invasive coronary angiography, which remained stable over time. This study demonstrates an opportunity to exclude obstructive CAD with less invasive testing, particularly in women., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: To reflect on the elements of nursing care management in radiological protection in interventional radiology., Methodology: A reflection paper based on national and international articles and laws addressing the nursing care management issue and radiological protection in interventional radiology., Results: From the conceptions of nursing care management and professional practice, the following elements were perceived in this management: expertise and applicability of the radiological protection principles, biological effects of ionizing radiation, occupational dose monitoring, personal and collective protective equipment, patient safety, training in radiological protection, quality assurance program., Conclusion: The management of nursing care in radiological protection in interventional radiology is implemented in an elementary way regarding care aimed at dose reduction, either for workers or patients. There is a need to recognize, understand and characterize the management of nursing care in this scenario.

Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy., Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors., Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001)., Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01178320.

Background: The Framingham Risk Score (FRS) and Pooled Cohort Equations (PCEs) overestimate risk in many contemporary cohorts., Objectives: This study sought to determine if recalibration of these scores using contemporary population-level data improves risk stratification for statin therapy., Methods: Five-year FRS and PCEs were recalibrated using a cohort of Ontario residents alive January 1, 2011, who were 30 to 79 years of age without cardiovascular disease. Scores were externally validated in a primary care cohort of routinely collected electronic medical record data from January 1, 2010, to December 31, 2014. The relative difference in mean predicted and observed risk, number of statins avoided, and number needed to treat with statins to reduce a cardiovascular event at 5 years were reported., Results: The FRS was recalibrated in 6,938,971 Ontario residents (51.6% women, mean age 48 years) and validated in 71,450 individuals (56.1% women, mean age 52 years). Recalibration reduced overestimation from 109% to 49% for women and 131% to 32% for men. The recalibrated FRS was estimated to reduce statin prescriptions in up to 26 per 1,000 low-risk women and 80 per 1,000 low-risk men, as well as reduce the number needed to treat from 61 to 47 in women and from 53 to 41 in men. In contrast, after recalibration of the PCEs, risk remained overestimated by 217% in women and 128% in men., Conclusions: Recalibration is a feasible solution to improve risk prediction but is dependent on the model being used. Recalibration of the FRS but not the PCEs reduced overestimation and may improve utilization of statins., Competing Interests: Funding Support and Author Disclosures This work was supported by funding from a Foundation Grant (FDN 143313 [to Jack V. Tu]) by the Canadian Institutes of Health Research. Additional funding was provided by another Canadian Institutes of Health Research Foundation Grant (FDN 154333). The funding source had no role in the study's design, conduct, or reporting. Dr Sud is funded by the Eliot Phillipson Clinician-Scientist Program at the University of Toronto, a Canadian Institute of Health Research Post-Doctoral Fellowship, and the SANSAR-Burgundy Young Investigator Award. Dr Austin is supported by a Mid-Career Investigator Award from the Heart and Stroke Foundation. Dr Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr Roifman is funded by the National New Investigator and Ontario Clinician Scientist Awards by the Heart and Stroke Foundation. Dr Tu receives a research scholar award from the Department of Family and Community Medicine at the University of Toronto. Dr Wijeysundera is supported by a Canada Research Chair in Structural Heart Disease Policy and Outcomes. Dr Ko is supported by the Jack Tu Chair in Cardiovascular Outcomes, Sunnybrook Hospital and University of Toronto. Dr Farkouh has received research grants support from Amgen, Novartis, and Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Individualised predictive models of cognitive decline require disease-monitoring markers that are repeatable. For wide-spread adoption, such markers also need to be reproducible at different locations. This study assessed the repeatability and reproducibility of MRI markers derived from a dementia protocol., Methods: Six participants were scanned at three different sites with a 3T MRI scanner. The protocol employed: T1-weighted (T1w) imaging, resting state functional MRI (rsfMRI), arterial spin labelling (ASL), diffusion-weighted imaging (DWI), T2-weighted fluid attenuation inversion recovery (FLAIR), T2-weighted (T2w) imaging, and susceptibility weighted imaging (SWI). Participants were scanned repeatedly, up to six times over a maximum period of five years. One participant was also scanned a further three times on sequential days on one scanner. Fifteen derived metrics were computed from the seven different modalities., Results: Reproducibility (coefficient of variation; CoV, across sites) was best for T1w derived grey matter, white matter and hippocampal volume (CoV < 1.5%), compared to rsfMRI and SWI derived metrics (CoV, 19% and 21%). For a given metric, long-term repeatability (CoV across time) was comparable to reproducibility, with short-term repeatability considerably better., Conclusions: Reproducibility and repeatability were assessed for a suite of markers calculated from a dementia MRI protocol. In general, structural markers were less variable than functional MRI markers. Variability over time on the same scanner was comparable to variability measured across different scanners. Overall, the results support the viability of multi-site longitudinal studies for monitoring cognitive decline., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Aotearoa New Zealand's population is ageing. Increasing life expectancy is accompanied by increases in prevalence of Alzheimer's Disease (AD) and ageing-related disorders. The multicentre Dementia Prevention Research Clinic longitudinal study aims to improve understanding of AD and dementia in Aotearoa, in order to develop interventions that delay or prevent progression to dementia. Comprising research clinics in Auckland, Christchurch and Dunedin, this multi-disciplinary study involves community participants who undergo biennial investigations informed by international protocols and best practice: clinical, neuropsychological, neuroimaging, lifestyle evaluations, APOE genotyping, blood collection and processing. A key research objective is to identify a 'biomarker signature' that predicts progression from mild cognitive impairment to AD. Candidate biomarkers include: blood proteins and microRNAs, genetic, neuroimaging and neuropsychological markers, health, cultural, lifestyle, sensory and psychosocial factors. We are examining a range of mechanisms underlying the progression of AD pathology (e.g. faulty blood-brain barrier, excess parenchymal iron, vascular dysregulation). This paper will outline key aspects of the Dementia Prevention Research Clinic's research, provide an overview of data collection, and a summary of 266 participants recruited to date. The national outreach of the clinics is a strength; the heart of the Dementia Prevention Research Clinics are its people., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Royal Society of New Zealand.)

We describe the New Zealand Parkinson's Progression Programme (NZP3), its goals, findings, and future plans. To date, 354 people with Parkinson's disease and 89 healthy older controls have participated over a 14-year period. A major focus of the programme has been the characterisation of current cognitive impairment, and the identification of biomarkers for its future emergence in people with Parkinson's. The programme has made significant contributions to the concept of mild cognitive impairment (MCI) in Parkinson's and the development and validation of standardised criteria for it. Brain imaging, both MRI and PET, has also been a focus, showing associations between increasing brain pathology and declining cognitive function. Additional biomarkers such as genetics, fluid biomarkers, eye movement, speech, and quantitative electroencephalography (EEG) are also under investigation. The programme has become a platform supporting many other avenues of research, from investigating the personal impacts of caregiver burden through to national-level epidemiology. To date, the programme has led to multiple journal publications and 17 completed and 9 ongoing PhDs, and many other postgraduate theses. It has led to the development of a skilled core of early-career through to senior researchers and clinicians. We discuss the future directions for the programme., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Royal Society of New Zealand.)

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09-0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01-0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06-0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, -0.31; 95% CI, -0.42 to -0.21) and African (beta coefficient, -0.26; 95% CI, -0.31 to -0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race- ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

Individuals with schizophrenia use on average twice as much caffeine than the healthy population, but the underlying cortical effects of caffeine in this population are still not well understood. Using resting electroencephalography (EEG) data, we can determine recurrent configurations of the electric field potential over the cortex. These configurations, referred to as microstates, are reported to be altered in schizophrenia and can give us insight into the functional dynamics of large-scale brain networks. In the current study, we use a placebo-controlled, randomized, double-blind, repeated-measures design to examine the effects of a moderate dose of caffeine (200mg) on microstate classes A, B, C, and D in a sample of individuals within the first five years of psychosis onset compared to healthy controls. The results support the reduction of microstate class C and D, as well as the increase of microstate class A and B in schizophrenia. Further, acute caffeine administration appears to exacerbate these group differences by reducing class D, and increasing occurrences of class A and B states in the patient group only. The current results support the hypothesis of a microstate class D reduction as an endophenotypic marker for psychosis and provide the first descriptive account of how caffeine is affecting these microstate classes in an early phase psychosis sample.

Individuals with schizophrenia use twice as much caffeine on average when compared to healthy controls. Knowing the high rates of consumption, and the potential negative effects of such, it is important we understand the cortical mechanisms that underlie caffeine use, and the consequences of caffeine use on neural circuits in this population. Using a randomized, placebo controlled, double-blind, repeated measures design, the current study examines caffeine's effects on resting electroencephalography (EEG) power in those who have been recently diagnosed with schizophrenia (SZ) compared to regular-using healthy controls (HC). Correlations between average caffeine consumption, withdrawal symptoms, drug related symptoms and clinical psychosis symptoms were measured and significant correlations with neurophysiological data were examined. Results showed caffeine had no effect on alpha asymmetry in the SZ group, although caffeine produced a more global effect on the reduction of alpha 2 power in the SZ group. Further, those with more positive symptoms were found to have a greater reduction in alpha 2 power following caffeine administration. Caffeine also reduced beta power during eyes closed and eyes open resting in HC, but only during eyes closed resting conditions in the SZ group. These findings provide a descriptive profile of the resting EEG state following caffeine administration in individuals with schizophrenia. The findings ultimately suggest caffeine does not affect alpha or beta power as readily in this population and a higher dose may be needed to achieve the desired effects, which may elucidate motivational factors for high caffeine use.

Parkinson’s disease affects millions worldwide with a large rise in expected burden over the coming decades. More easily accessible tools and techniques to diagnose and monitor Parkinson’s disease can improve the quality of life of patients. With the advent of new wearable technologies such as smart rings and watches, this is within reach. However, it is unclear what method for these new technologies may provide the best opportunity to capture the patient-specific severity. This study investigates which locations on the hand can be used to capture and monitor maximal movement/tremor severity. Using a Leap Motion device and custom-made software the volume, velocity, acceleration, and frequency of Parkinson’s (n = 55, all right-handed, majority right-sided onset) patients’ hand locations (25 joints inclusive of all fingers/thumb and the wrist) were captured simultaneously. Distal locations of the right hand, i.e., the ends of fingers and the wrist showed significant trends (p < 0.05) towards having the largest movement velocities and accelerations. The right hand, compared with the left hand, showed significantly greater volumes, velocities, and accelerations (p < 0.01). Supplementary analysis showed that the volumes, acceleration, and velocities had significant correlations (p < 0.001) with clinical MDS-UPDRS scores, indicating the potential suitability of using these metrics for monitoring disease progression. Maximal movements at the distal hand and wrist area indicate that these locations are best suited to capture hand tremor movements and monitor Parkinson’s disease.

Aims: Statins are first line therapy in people with diabetes. Little is known about real-world statin intensity use and low-density lipoprotein cholesterol (LDL-C) levels achieved. We aimed to describe statin intensity used, achievement of LDL-C targets, and factors associated with achieving targets among adults with diabetes., Methods: This population based (∼4.3 million), retrospective observational study, used clinical and administrative databases. Statin use by intensity, adherence, and achievement of LDL-C targets in adults with diabetes were described. Multiple logistic regression assessed the factors associated with achieving targets., Results: Out of 331,312 individuals with diabetes, 88% had an index LDL-C test. At follow up, 31% overall did not achieve LDL-C targets and overall adherence was 66%. Failure to achieve targets was 49%, 30%, and 25% in low-, moderate-, and high-intensity statin groups, respectively. Those who were older, males, had a history of myocardial infarction, stroke, congestive heart failure, renal disease, better adherence, and higher intensity statin users were more likely to achieve targets., Conclusions: One-third of people on statins did not achieve targets. Strategies to fill the gap between ideal and current levels of LDL-C achieved are needed if the benefits of statins demonstrated in trials are to be translated into practice., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age-related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6-month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO 2 max and 65 W), intensities that have been shown to be comparable to activities of daily life. Two hundred three low-active healthy men and women enrolled in the Brain in Motion study, completed a 6-month exercise intervention and underwent submaximal and maximal tests pre-/post-intervention. The intervention improved the gas exchange threshold and maximal oxygen consumption (VO 2 max), with no change in heart rate at VO 2 max, during the treadmill VO 2 max test. Heart rate and CVRi decreased from pre-intervention values during both relative (40% VO 2 max) and absolute (65 W) submaximal exercise tests. Blood flow velocity in the middle cerebral artery and CVCi increased post-intervention during 40% VO 2 max and 65 W. Changes in mean arterial pressure were found only during the absolute component (65 W). Our study demonstrates that aerobic exercise improves not only cardiorespiratory indices but also cerebrovascular function at submaximal workloads which may help to mitigate age-related declines in everyday life. Investigation of the mechanisms underlying the decline in cardiovascular and cerebrovascular capacity with aging has important implications for the maintenance of health and continued independence of older adults., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

To improve the manufacturing of vertical GaN devices for power electronics applications, the effects of defects in GaN substrates need to be better understood. Many non-destructive techniques including photoluminescence, Raman spectroscopy and optical profilometry, can be used to detect defects in the substrate and epitaxial layers. Raman spectroscopy was used to identify points of high crystal stress and non-uniform conductivity in a substrate, while optical profilometry was used to identify bumps and pits in a substrate which could cause catastrophic device failures. The effect of the defects was studied using vertical P-i-N diodes with a single zone junction termination extention (JTE) edge termination and isolation, which were formed via nitrogen implantation. Diodes were fabricated on and off of sample abnormalities to study their effects. From electrical measurements, it was discovered that the devices could consistently block voltages over 1000 V (near the theoretical value of the epitaxial layer design), and the forward bias behavior could consistently produce on-resistance below 2 mΩ cm 2 , which is an excellent value considering DC biasing was used and no substrate thinning was performed. It was found that high crystal stress increased the probability of device failure from 6 to 20%, while an inhomogeneous carrier concentration had little effect on reverse bias behavior, and slightly (~ 3%) increased the on-resistance (R on ). Optical profilometry was able to detect regions of high surface roughness, bumps, and pits; in which, the majority of the defects detected were benign. However a large bump in the termination region of the JTE or a deep pit can induce a low voltage catastrophic failure, and increased crystal stress detected by the Raman correlated to the optical profilometry with associated surface topography., (© 2022. The Author(s).)

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery (V¯ P ); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V¯ P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V¯ P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans., (Copyright © 2021. Published by Elsevier Inc.)

Young women with chronic kidney disease (CKD) have disproportionately increased risk of cardiovascular mortality. Reduced anti-Müllerian hormone (AMH) is linked to poor cardiovascular outcomes in the general population, but whether AMH is associated with increased cardiovascular risk in the high-risk CKD population is unknown. This study examined the association between AMH and vascular function, validated markers of cardiovascular risk, in women with CKD. An exploratory cross-sectional study was performed in 47 young women with CKD. Laboratory measurements of AMH were collected. Using standardized protocols, endothelial function was measured with brachial artery flow-mediated dilation and hyperemic velocity time integral. Arterial stiffness was measured with aortic augmentation index and pulse wave velocity. Multivariate linear regression analyses were utilized to evaluate the association between AMH levels and each measure of vascular health. Forty women (36 ± 7 years) with non-dialysis-dependent CKD and 7 women (38 ± 6 years) with dialysis-dependent CKD participated. AMH levels were inversely associated with age (p = 0.01) but not associated with eGFR (p = 0.59) or dialysis status (p = 0.97). AMH was associated with brachial artery flow-mediated dilation (R 2  = 0.21 [p = 0.03]) and aortic augmentation index (R 2  = 0.20 [p = 0.04]) in the non-dialysis-dependent participants, and with aortic augmentation index in all participants (R 2  = 0.18 [p = 0.03]). No association between AMH and any measure of vascular function was demonstrated in the dialysis-dependent participants. AMH levels are associated with impaired vascular function in young women with CKD and may be an important marker of future cardiovascular risk. Further investigation into this female-specific cardiovascular risk factor is warranted in this high-risk population., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Radiology technicians are exposed to occupational risks in their daily work. Among these, there are biological and ergonomic risks., Objectives: To describe the biological and ergonomic risks in the work process of radiology technicians in a conventional radiology service., Methods: This was a qualitative, descriptive, and exploratory research. Data collection was conducted through semi-structured interviews with 12 radiology technicians, participant observation, and consensual validation with nine workers. Content analysis was based on the assumptions of the thematic analysis., Results: Exposure to body fluids, contamination of work instruments by biological agents, no disinfection, and no use of personal protective equipment were found to be biological risks. Excessive weight manipulation, inappropriate physical structure, night work, and work instruments that do conform to the principles of body mechanics were identified as ergonomic risks., Conclusions: The mentioned occupational risks are related to the work conditions of the health service and to inadequate body positioning of radiology technicians., Competing Interests: Conflicts of interest: None

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer's dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer's disease., (© 2021. The Author(s).)

A primary characteristic of obstructive sleep apnea (OSA) is chronic exposure to intermittent hypoxia (IH) due to repeated upper airway obstruction. Chronic IH exposure is believed to increase OSA severity over time by enhancing the acute ventilatory response to hypoxia (AHVR), thus promoting ventilatory overshoot when apnea ends and perpetuation of apnea during sleep. Continuous positive airway pressure (CPAP), the gold-standard treatment of OSA, reduces the AHVR, believed to result from correction of IH. However, CPAP also corrects ancillary features of OSA such as intermittent hypercapnia, negative intrathoracic pressure and surges in sympathetic activity, which may also contribute to the reduction in AHVR. Therefore, the objective of this study was to investigate the impact of nocturnal oxygen therapy (to remove IH only) and CPAP (to correct IH and ancillary features of OSA) on AHVR in newly diagnosed OSA patients. Fifty-two OSA patients and twenty-two controls were recruited. The AHVR was assessed using a 5 min iscopanic-hypoxic challenge before, and after, treatment of OSA by nocturnal oxygen therapy and CPAP. Following baseline measurements, OSA patients were randomly assigned to nocturnal oxygen therapy (Oxygen, n = 26) or no treatment (Air; n = 26). The AHVR was re-assessed following two weeks of oxygen therapy or no treatment, after which all patients were treated with CPAP. The AHVR was quantified following ~4 weeks of adherent CPAP therapy (n = 40). Both nocturnal oxygen and CPAP treatments improved hypoxemia (p < 0.05), and, as expected, nocturnal oxygen therapy did not completely abolish respiratory events (i.e., apneas/hypopneas). Averaged across all OSA patients, nocturnal oxygen therapy did not change AHVR from baseline to post-oxygen therapy. Similarly, the AHVR was not altered pre- and post-CPAP (p > 0.05). However, there was a significant decrease in AHVR with both nocturnal oxygen therapy and CPAP in patients in the highest OSA severity quartile (p < 0.05). Nocturnal oxygen therapy and CPAP both reduce the AHVR in patients with the most severe OSA. Therefore, IH appears to be the primary mechanism producing ventilatory instability in patients with severe OSA via enhancement of the AHVR., (Copyright © 2021. Published by Elsevier Inc.)

Aims: Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome., Methods and Results: A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow-up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan-Meier analyses compared to those with no remodelling, log-rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction., Conclusions: Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long-term outcomes whereas change in left ventricular ejection fraction did not., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1ß/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions-within 30 days and, ideally, within 3 days-or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Brain structure abnormalities throughout the course of Parkinson's disease have yet to be fully elucidated., Objective: Using a multicenter approach and harmonized analysis methods, we aimed to shed light on Parkinson's disease stage-specific profiles of pathology, as suggested by in vivo neuroimaging., Methods: Individual brain MRI and clinical data from 2357 Parkinson's disease patients and 1182 healthy controls were collected from 19 sources. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effects models. Patients grouped according to Hoehn and Yahr stage were compared with age- and sex-matched controls. Within the patient sample, we investigated associations with Montreal Cognitive Assessment score., Results: Overall, patients showed a thinner cortex in 38 of 68 regions compared with controls (d max  = -0.20, d min  = -0.09). The bilateral putamen (d left  = -0.14, d right  = -0.14) and left amygdala (d = -0.13) were smaller in patients, whereas the left thalamus was larger (d = 0.13). Analysis of staging demonstrated an initial presentation of thinner occipital, parietal, and temporal cortices, extending toward rostrally located cortical regions with increased disease severity. From stage 2 and onward, the bilateral putamen and amygdala were consistently smaller with larger differences denoting each increment. Poorer cognition was associated with widespread cortical thinning and lower volumes of core limbic structures., Conclusions: Our findings offer robust and novel imaging signatures that are generally incremental across but in certain regions specific to disease stages. Our findings highlight the importance of adequately powered multicenter collaborations. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5-year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada., Methods: A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five-year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One-year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined., Results: There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5-year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1-year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03-6.26) per 100 person-years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45-15.20) per 100 person-years., Conclusions: This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)