'It's satisfying but destructive': A qualitative study on the experience of bedtime procrastination in new career starters.

BACKGROUND: Bedtime procrastination, the volitional delay of going to bed without any external circumstances causing the delay, is linked to multiple indicators of inadequate sleep. Intervening to reduce bedtime procrastination may be an important avenue to improve sleep outcomes, yet the phenomenon remains poorly understood in populations at risk for bedtime procrastination. New career starters, those who have graduated from tertiary education and started a new full-time job within the past 12 months, may be susceptible to problematic bedtime procrastination and are at an opportune time for a 'fresh start' to change behaviour. AIMS: The objectives of this study were to understand how bedtime procrastination is experienced and perceived by new career starters, to identify the enablers and barriers to behaviour change in new career starters and to explore themes for future interventions. MATERIALS & METHODS: Data were collected through in-depth semi-structured interviews with 28 participants. RESULTS: Inductive thematic analysis was used to find seven themes: (1) negative feelings before and during bedtime procrastination; (2) wanting to versus knowing I shouldn't; (3) difficulty falling asleep; (4) influence of automatic processes; (5) consequences of bedtime procrastination; (6) lack of self-control and (7) technology captures late-night attention. Participants emphasised the need for me-time, self-negotiation to continue procrastinating and knowledge of the value of sleep. DISCUSSION & CONCLUSION: Findings suggest that bedtime procrastination involves both reflective and automatic cognitive processes. Future interventions would benefit from a dual-process approach, using cognitive and behavioural techniques to reduce bedtime procrastination.

Direct Admission to Hospital for Children in the United States.

One in four unscheduled hospital admissions for children and adolescents in the United States occurs via direct admission, defined as hospital admission without first receiving care in the hospital's emergency department. The purpose of this policy statement is to present recommendations to optimize the quality and safety of this hospital admission approach for children. Recommendations included in this policy statement provide guidance related to: (i) direct admission written guidelines, (ii) clear systems of communication between members of the health care team and with families of children requiring admission, (iii) triage systems to identify patient acuity and disease severity, (iv) identification of hospital resources needed to support direct admission systems of care, (v) consideration of patient populations that may be at increased risk of adverse outcomes during the hospital admission process, (vi) addressing the relevance of local factors and resources, and (vii) ongoing evaluation of direct admission processes and outcomes. The recommendations included in this policy statement are intended to support the implementation of safe direct admission processes and to foster awareness of outcomes associated with this common portal of hospital admission.

Go to bed! A systematic review and meta-analysis of bedtime procrastination correlates and sleep outcomes.

Bedtime procrastination is defined as the volitional delay of going to bed, without any external circumstances causing the delay, and is associated with inadequate sleep. Alleviating bedtime procrastination is an important target for interventions promoting adequate sleep, yet the correlates of bedtime procrastination are poorly understood. This study examined (1) correlates of bedtime procrastination, and (2) strength and direction of the association between bedtime procrastination and sleep outcomes. Six databases (CINAHL, EMBASE, PsychINFO, PubMed, Scopus, Web of Science) were searched from inception to September 2021 against pre-determined eligibility criteria. Forty-three studies were included (GRADE = low). Meta-analysis revealed that bedtime procrastination had a moderate negative association with self-control (z = -0.39; CI: -0.45, -0.29) and a moderate positive association with evening chronotype (z = 0.43; CI: 0.32, 0.48). Furthermore, bedtime procrastination was moderately negatively associated with sleep duration (z = -0.31; CI: -0.37, -0.24), sleep quality (z = -0.35; CI: -0.42, -0.27) and moderately positively associated with daytime fatigue (z = 0.32; CI: 0.25, 0.38). Further high-quality studies are needed to identify causal relationships between bedtime procrastination and correlates, as well as bedtime procrastination and sleep. Future work will guide the development of interventions targeting bedtime procrastination for improved sleep outcomes. STUDY REGISTRATION: PROSPERO registration number CRD42021248891.

Major Adverse Cardiac Events With Immune Checkpoint Inhibitors: A Pooled Analysis of Trials Sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program.

PURPOSE: Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients. METHODS: We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute-Cancer Therapy Evaluation Program for National Cancer Institute-sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti-programmed cell death protein-1 (anti-PD-1)/programmed cell death-ligand 1 (anti-PD-L1) alone or with additional anticancer therapies. RESULTS: A total of 6,925 participants received anti-PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti-PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti-PD-(L)1 + targeted therapies compared with anti-PD-(L)1 + anti-cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti-PD-(L)1-based combination therapies versus single-agent anti-PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis. CONCLUSION: Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non-ICI-based anticancer therapies with anti-PD-(L)1 treatments is needed.

Guidance for Structuring a Pediatric Intermediate Care Unit.

The purpose of this policy statement is to update the 2004 American Academy of Pediatrics clinical report and provide enhanced guidance for institutions, administrators, and providers in the development and operation of a pediatric intermediate care unit (IMCU). Since 2004, there have been significant advances in pediatric medical, surgical, and critical care that have resulted in an evolution in the acuity and complexity of children potentially requiring IMCU admission. A group of 9 clinical experts in pediatric critical care, hospital medicine, intermediate care, and surgery developed a consensus on priority topics requiring updates, reviewed the relevant evidence, and, through a series of virtual meetings, developed the document. The intended audience of this policy statement is broad and includes pediatric critical care professionals, pediatric hospitalists, pediatric surgeons, other pediatric medical and surgical subspecialists, general pediatricians, nurses, social workers, care coordinators, hospital administrators, health care funders, and policymakers, primarily in resource-rich settings. Key priority topics were delineation of core principles for an IMCU, clarification of target populations, staffing recommendations, and payment.

A stellar stream remnant of a globular cluster below the metallicity floor.

Stellar ejecta gradually enrich the gas out of which subsequent stars form, making the least chemically enriched stellar systems direct fossils of structures formed in the early Universe1. Although a few hundred stars with metal content below 1,000th of the solar iron content are known in the Galaxy2-4, none of them inhabit globular clusters, some of the oldest known stellar structures. These show metal content of at least approximately 0.2% of the solar metallicity [Formula: see text]. This metallicity floor appears universal5,6, and it has been proposed that protogalaxies that merged into the galaxies we observe today were simply not massive enough to form clusters that survived to the present day7. Here we report observations of a stellar stream, C-19, whose metallicity is less than 0.05% of the solar metallicity [Formula: see text]. The low metallicity dispersion and the chemical abundances of the C-19 stars show that this stream is the tidal remnant of the most metal-poor globular cluster ever discovered, and is significantly below the purported metallicity floor: clusters with significantly lower metallicities than observed today existed in the past and contributed their stars to the Milky Way halo.

Tired and stressed: Examining the need for sleep.

A key feature of circadian rhythms is the sleep/wake cycle. Sleep causes reduced responsiveness to the environment, which puts animals in a particularly vulnerable state; yet sleep has been conserved throughout evolution, indicating that it fulfils a vital purpose. A core function of sleep across species has not been identified, but substantial advances in sleep research have been made in recent years using the genetically tractable model organism, Drosophila melanogaster. This review describes the universality of sleep, the regulation of sleep, and current theories on the function of sleep, highlighting a historical and often overlooked theory called the Free Radical Flux Theory of Sleep. Additionally, we summarize our recent work with short-sleeping Drosophila mutants and other genetic and pharmacological tools for manipulating sleep which supports an antioxidant theory of sleep and demonstrates a bi-directional relationship between sleep and oxidative stress.

Criteria for Critical Care Infants and Children: PICU Admission, Discharge, and Triage Practice Statement and Levels of Care Guidance.

OBJECTIVES: To update the American Academy of Pediatrics and Society of Critical Care Medicine's 2004 Guidelines and levels of care for PICU. DESIGN: A task force was appointed by the American College of Critical Care Medicine to follow a standardized and systematic review of the literature using an evidence-based approach. The 2004 Admission, Discharge and Triage Guidelines served as the starting point, and searches in Medline (Ovid), Embase (Ovid), and PubMed resulted in 329 articles published from 2004 to 2016. Only 21 pediatric studies evaluating outcomes related to pediatric level of care, specialized PICU, patient volume, or personnel. Of these, 13 studies were large retrospective registry data analyses, six small single-center studies, and two multicenter survey analyses. Limited high-quality evidence was found, and therefore, a modified Delphi process was used. Liaisons from the American Academy of Pediatrics were included in the panel representing critical care, surgical, and hospital medicine expertise for the development of this practice guidance. The title was amended to "practice statement" and "guidance" because Grading of Recommendations, Assessment, Development, and Evaluation methodology was not possible in this administrative work and to align with requirements put forth by the American Academy of Pediatrics. METHODS: The panel consisted of two groups: a voting group and a writing group. The panel used an iterative collaborative approach to formulate statements on the basis of the literature review and common practice of the pediatric critical care bedside experts and administrators on the task force. Statements were then formulated and presented via an online anonymous voting tool to a voting group using a three-cycle interactive forecasting Delphi method. With each cycle of voting, statements were refined on the basis of votes received and on comments. Voting was conducted between the months of January 2017 and March 2017. The consensus was deemed achieved once 80% or higher scores from the voting group were recorded on any given statement or where there was consensus upon review of comments provided by voters. The Voting Panel was required to vote in all three forecasting events for the final evaluation of the data and inclusion in this work. The writing panel developed admission recommendations by level of care on the basis of voting results. RESULTS: The panel voted on 30 statements, five of which were multicomponent statements addressing characteristics specific to PICU level of care including team structure, technology, education and training, academic pursuits, and indications for transfer to tertiary or quaternary PICU. Of the remaining 25 statements, 17 reached consensus cutoff score. Following a review of the Delphi results and consensus, the recommendations were written. CONCLUSIONS: This practice statement and level of care guidance manuscript addresses important specifications for each PICU level of care, including the team structure and resources, technology and equipment, education and training, quality metrics, admission and discharge criteria, and indications for transfer to a higher level of care. The sparse high-quality evidence led the panel to use a modified Delphi process to seek expert opinion to develop consensus-based recommendations where gaps in the evidence exist. Despite this limitation, the members of the Task Force believe that these recommendations will provide guidance to practitioners in making informed decisions regarding pediatric admission or transfer to the appropriate level of care to achieve best outcomes.

Executive Summary: Criteria for Critical Care of Infants and Children: PICU Admission, Discharge, and Triage Practice Statement and Levels of Care Guidance.

This is an executive summary of the 2019 update of the 2004 guidelines and levels of care for PICU. Since previous guidelines, there has been a tremendous transformation of Pediatric Critical Care Medicine with advancements in pediatric cardiovascular medicine, transplant, neurology, trauma, and oncology as well as improvements of care in general PICUs. This has led to the evolution of resources and training in the provision of care through the PICU. Outcome and quality research related to admission, transfer, and discharge criteria as well as literature regarding PICU levels of care to include volume, staffing, and structure were reviewed and included in this statement as appropriate. Consequently, the purposes of this significant update are to address the transformation of the field and codify a revised set of guidelines that will enable hospitals, institutions, and individuals in developing the appropriate PICU for their community needs. The target audiences of the practice statement and guidance are broad and include critical care professionals; pediatricians; pediatric subspecialists; pediatric surgeons; pediatric surgical subspecialists; pediatric imaging physicians; and other members of the patient care team such as nurses, therapists, dieticians, pharmacists, social workers, care coordinators, and hospital administrators who make daily administrative and clinical decisions in all PICU levels of care.

A bidirectional relationship between sleep and oxidative stress in Drosophila.

Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep.

Multi-Stakeholder Informed Guidelines for Direct Admission of Children to Hospital.

OBJECTIVES: To develop pediatric direct admission guidelines and prioritize outcomes to evaluate the safety and effectiveness of hospital admission processes. STUDY DESIGN: We conducted deliberative discussions at 1 children's hospital and 2 community hospitals, engaging parents of hospitalized children and inpatient, outpatient, and emergency department physicians and nurses to identify shared and dissenting perspectives regarding direct admission processes and outcomes. Discussions were audio-recorded, professionally transcribed, and analyzed using a general inductive approach. We then convened a national panel to prioritize guideline components and outcome measures using a RAND/UCLA Modified Delphi approach. RESULTS: Forty-eight stakeholders participated in 6 deliberative discussions. Emergent themes related to effective multistakeholder communication, resources needed for high quality direct admissions, written direct admission guidelines, including criteria to identify children appropriate for and inappropriate for direct admission, and families' needs. Building on these themes, Delphi panelists endorsed 71 guideline components as both appropriate and necessary at children's hospitals and community hospitals and 13 outcomes to evaluate hospital admission systems. Guideline components include (1) pre-admission communication, (2) written guidelines, (3) hospital resources to optimize direct admission processes, (4) special considerations for pediatric populations that may be at particular risk of nosocomial infection and/or stress in emergency departments, (5) communication with families referred for direct admission, and (6) quality reviews to evaluate admission systems. CONCLUSIONS: These direct admission guidelines can be adapted by hospitals and health systems to inform hospital admission policies and protocols. Multistakeholder engagement in evaluation of hospital admission processes may improve transitions of care and health system integration.

Antibiotic Prescribing Patterns Across the Continuum of Care for Children Hospitalized With Community-Acquired Pneumonia.

OBJECTIVES: The aim of this study was to describe the variation in antibiotic prescribing practices for uncomplicated community-acquired pneumonia across the continuum of care for hospitalized pediatric patients to better inform future efforts at standardizing antibiotic therapy throughout a single hospitalization. METHODS: This is a retrospective cohort study involving 4 hospitals caring for children aged 3 months to 18 years, hospitalized between January 1, 2011, and December 31, 2012, with diagnosis of uncomplicated pneumonia and without complex chronic medical conditions.Data collected include antibiotics prescribed before hospitalization, at the emergency department (ED) encounter, during hospitalization, and at hospital discharge. RESULTS: Six hundred nine children met inclusion criteria, with a mean age of 5.3 years and median length of stay of 2 days. Emergency department providers prescribed narrow-spectrum therapy 27% of the time, whereas discharging providers prescribed narrow-spectrum therapy 56% of the time. Third- and fourth-generation cephalosporins were less often prescribed in the preadmission setting and at discharge but were more often prescribed in the ED and inpatient setting. There was an association between inpatient prescription of broad-spectrum antibiotics when a blood culture was obtained, when broad-spectrum antibiotics were prescribed in the ED, and with increasing length of stay. CONCLUSION: Broad-spectrum antibiotic therapy for community-acquired pneumonia, especially third- and fourth-generation cephalosporins, often originates in the ED. When initiated in this setting, it is likely to be continued in the inpatient setting.

A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells.

Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found that Drosophila melanogaster Fmr1 mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria. Fmr1 mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.

period-Regulated Feeding Behavior and TOR Signaling Modulate Survival of Infection.

Most metazoans undergo dynamic, circadian-regulated changes in behavior and physiology. Currently, it is unknown how circadian-regulated behavior impacts immunity against infection. Two broad categories of defense against bacterial infection are resistance, control of microbial growth, and tolerance, control of the pathogenic effects of infection. Our study of behaviorally arrhythmic Drosophila circadian period mutants identified a novel link between nutrient intake and tolerance of infection with B. cepacia, a bacterial pathogen of rising importance in hospital-acquired infections. We found that infection tolerance in wild-type animals is stimulated by acute exposure to dietary glucose and amino acids. Glucose-stimulated tolerance was induced by feeding or direct injection; injections revealed a narrow window for glucose-stimulated tolerance. In contrast, amino acids stimulated tolerance only when ingested. We investigated the role of a known amino-acid-sensing pathway, the TOR (Target of Rapamycin) pathway, in immunity. TORC1 is circadian regulated and inhibition of TORC1 decreased resistance, as in vertebrates. Surprisingly, inhibition of the less well-characterized TOR complex 2 (TORC2) dramatically increased survival, through both resistance and tolerance mechanisms. This work suggests that dietary intake on the day of infection by B. cepacia can make a significant difference in long-term survival. We further demonstrate that TOR signaling mediates both resistance and tolerance of infection and identify TORC2 as a novel potential therapeutic target for increasing survival of infection.

Use of Intermittent vs Continuous Pulse Oximetry for Nonhypoxemic Infants and Young Children Hospitalized for Bronchiolitis: A Randomized Clinical Trial.

IMPORTANCE: Clinical practice guidelines for managing infants and children hospitalized for bronchiolitis recommend only obtaining intermittent or "spot check" pulse oximetry readings for those who show clinical improvement. The effect of such monitoring is currently unknown. OBJECTIVE: To determine the effect of intermittent vs continuous pulse oximetry monitoring on hospital length of stay among nonhypoxemic infants and young children hospitalized for bronchiolitis. DESIGN, SETTING, AND PARTICIPANTS: Randomized, parallel-group, superiority clinical trial of otherwise healthy infants and children 2 years of age or younger hospitalized for bronchiolitis during the period from 2009 to 2014 at 1 of 4 children's hospitals in the United States. Parents or guardians were blinded to allocation assignment until informed consent was obtained; study personnel and outcome assessors were not. INTERVENTIONS: Patients were randomly assigned to undergo continuous or intermittent pulse oximetry monitoring (ie, pulse oximetry measurements were obtained along with a scheduled check of vital signs or for clinical suspicion of deterioration) during hospitalization when oxygen saturation levels were 90% or higher. MAIN OUTCOMES AND MEASURES: Length of hospital stay was the primary outcome. Secondary outcome measures included duration of supplemental oxygen use and rate of escalation of care (defined as transfer to an intensive care unit). RESULTS: A total of 449 infants and young children were screened for inclusion; 288 infants and young children were excluded, resulting in 161 patients who were enrolled in the study (80 patients underwent continuous monitoring, and 81 patients intermittent). The mean length of stay did not differ based on pulse oximetry monitoring strategy (48.9 hours [95% CI, 41.3-56.5 hours] for continuous monitoring vs 46.2 hours [95% CI, 39.1-53.3 hours] for intermittent monitoring; P = .77). The rates of escalation of care and duration of supplemental oxygen use did not differ between groups. CONCLUSIONS AND RELEVANCE: Intermittent pulse oximetry monitoring of nonhypoxemic patients with bronchiolitis did not shorten hospital length of stay and was not associated with any difference in rate of escalation of care or use of diagnostic or therapeutic measures. Our results suggest that intermittent pulse oximetry monitoring can be routinely considered in the management of infants and children hospitalized for bronchiolitis who show clinical improvement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01014910.

Evaluating the use of blood cultures in the management of children hospitalized for community-acquired pneumonia.

BACKGROUND: Blood cultures are often recommended for the evaluation of community-acquired pneumonia (CAP). However, institutions vary in their use of blood cultures, and blood cultures have unclear utility in CAP management in hospitalized children. OBJECTIVE: To identify clinical factors associated with obtaining blood cultures in children hospitalized with CAP, and to estimate the association between blood culture obtainment and hospital length of stay (LOS). METHODS: We performed a multicenter retrospective cohort study of children admitted with a diagnosis of CAP to any of four pediatric hospitals in the United States from January 1, 2011-December 31, 2012. Demographics, medical history, diagnostic testing, and clinical outcomes were abstracted via manual chart review. Multivariable logistic regression evaluated patient and clinical factors for associations with obtaining blood cultures. Propensity score-matched Kaplan-Meier analysis compared patients with and without blood cultures for hospital LOS. RESULTS: Six hundred fourteen charts met inclusion criteria; 390 children had blood cultures obtained. Of children with blood cultures, six (1.5%) were positive for a pathogen and nine (2.3%) grew a contaminant. Factors associated with blood culture obtainment included presenting with symptoms of systemic inflammatory response syndrome (OR 1.78, 95% CI 1.10-2.89), receiving intravenous hydration (OR 3.94, 95% CI 3.22-4.83), receiving antibiotics before admission (OR 1.49, 95% CI 1.17-1.89), hospital admission from the ED (OR 1.65, 95% CI 1.05-2.60), and having health insurance (OR 0.42, 95% CI 0.30-0.60). In propensity score-matched analysis, patients with blood cultures had median 0.8 days longer LOS (2.0 vs 1.2 days, P < .0001) without increased odds of readmission (OR 0.94, 95% CI 0.45-1.97) or death (P = .25). CONCLUSIONS: Obtaining blood cultures in children hospitalized with CAP rarely identifies a causative pathogen and is associated with increased LOS. Our results highlight the need to refine the role of obtaining blood cultures in children hospitalized with CAP.

Early cerebral small vessel disease and brain volume, cognition, and gait.

OBJECTIVE: Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). METHODS: Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). RESULTS: Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. INTERPRETATION: Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life.