This study examines the association between objectively measured access to green space, frequency of green space use, physical activity, and the probability of being overweight or obese in the city ...of Bristol, England. Data from the 2005 Bristol Quality of Life in your Neighbourhood survey for 6821 adults were combined with a comprehensive GIS database of neighbourhood and green space characteristics. A range of green space accessibility measures were computed. Associations between accessibility and the odds of respondents achieving a recommended 30min or more of moderate activity five times a week, or being overweight or obese, were examined using logistic regression. Results showed that the reported frequency of green space use declined with increasing distance. The study also found that respondents living closest to the type of green space classified as a Formal park were more likely to achieve the physical activity recommendation and less likely to be overweight or obese. The association with physical activity, but not with overweight or obesity, remained after adjustment for respondent characteristics, area deprivation, and a range of characteristics of the neighbourhood environment. The findings suggest that the provision of good access to green spaces in urban areas may help promote population physical activity.
Living in a greener neighbourhood may reduce the risk of developing incident cardiovascular disease, but evidence is limited by reliance on cross-sectional comparisons. We use data from a ...longitudinal study with a time-independent measure of risk to explore the association between exposure to greenspace and cardiovascular disease.
Data was from the European Prospective Investigation of Cancer Norfolk UK cohort, baseline 1993-1997 (n = 24,420). Neighbourhoods were defined as 800m radius zones around participants' home, according to their home postcode (zip code) in the year 2000. Greenspace exposure was identified using classified satellite imagery. Adjusted Cox proportional hazards regression examined associations between greenspace and incident cardiovascular disease. Mediation analysis assessed if physical activity mediated associations, whilst modification by rurality, socio-economic status and age was explored.
The mean age of participants was 59.2 years at baseline, 54.7% were female, and mean follow-up time was 14.5 years. Individuals living in the greenest neighbourhood quartile had a 7% lower relative hazard of developing cardiovascular disease than other neighbourhoods (HR 0.93; 95% CI 0.88, 0.97; p = 0.003) after adjusting for age, sex, BMI, prevalent diabetes and socio-economic status (SES). Physical activity did not mediate the relationship (greenest compared to the least green quartile HR 0.99; 95% CI 0.97, 1.01; p = 0.416). Models predicted incidence of cardiovascular disease in the least green neighbourhoods (19.4% greenspace on average) would fall by 4.8% (95% CI 1.6%, 8.2% p = 0.003) if they were as green as the average neighbourhood (59.0% greenspace). Occupation moderated the relationship, whereby exposure to greenspace was not associated with incident CVD for participants engaged in manual occupations.
Greener home neighbourhoods may protect against risk of cardiovascular disease even after accounting for SES, whilst the mechanism does not appear to be strongly associated with physical activity. Putative causal mechanisms require investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the ...association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort.
In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry.
In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not ...been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases. Using EEG, local field potential (LFP), and unit recordings in rats, we show that anteroposterior propagation of neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal cortical spindles during NREM sleep. This coordination is selectively disrupted in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and impaired slow-wave propagation in the model culminate in deficient ripple-spindle coordination and disrupted spike timing, potentially as a consequence of interneuronal abnormalities reflected by reduced parvalbumin expression. These data further define the interrelationships among slow-wave, spindle, and ripple events, indicating that sleep disturbances may be associated with state-dependent decoupling of hippocampal and cortical circuits in psychiatric diseases.
► Abnormal neurodevelopment leads to fragmented NREM sleep in the MAM-E17 model ► Delta wave and spindle abnormalities match patterns of altered parvalbumin expression ► Spindle phase-locked units in frontal cortex fire during CA1 ripples in normal NREM ► Mistimed limbic-cortical oscillations during fragmented NREM may impair cognition
A restless pillow makes a ruffled mind? Investigating sleep architecture and associated neural network activity in an animal model of schizophrenia, Phillips et al. propose a new sleep-dependent mechanism for cognitive deficits in neuropsychiatric disease.
Objectives The aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values. Background LDL-C is routinely estimated by the ...Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients. Methods We examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl. Results Patients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl). Conclusions The Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥70 mg/dl, and therefore additional evaluation is warranted in high-risk patients.
Many youth fail to meet the recommended guidelines for physical activity. Walking and cycling, forms of active travel, have the potential to contribute significantly towards overall physical activity ...levels. Recent research examining the associations between physical activity and the environment has shown that environmental factors play a role in determining behaviour in children and adolescents. However, links between the environment and active travel have received less attention.
Twenty four studies were identified which examined the associations between the environment (perceived or objectively measured) and active travel among youth aged 5-18 years. Findings were categorised according to the location of the environmental measure examined; attributes of the neighbourhood, destination and the route between home and destination.
Results from the reviewed studies indicated that youth active travel is positively associated with social interactions, facilities to assist active travel and urban form in the neighbourhood as well as shorter route length and road safety en-route. A conceptual framework is presented which highlights the associations between active travel behaviours and environmental factors, drawing upon both existing and hypothesised relationships.
We provide a review of the available literature and present a novel theoretical framework that integrates the environment into the wider decision making process around travel choices for children and adolescents. Further work should explore associations where gaps in understanding have been identified, and account for the main moderators of behaviour so hypothesised associations can be confirmed.
IMPORTANCE: Nursing home residents have been disproportionately affected by coronavirus disease 2019 (COVID-19). Prevention recommendations emphasize frequent testing of health care personnel and ...residents, but additional strategies are needed. OBJECTIVE: To develop a reproducible index of nursing home crowding and determine whether crowding was associated with COVID-19 cases and mortality in the first months of the COVID-19 epidemic. DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included more than 78 000 residents across more than 600 nursing homes in Ontario, Canada, and was conducted from March 29 to May 20, 2020. EXPOSURES: The nursing home crowding index equaled the mean number of residents per bedroom and bathroom. MAIN OUTCOMES AND MEASURES: The cumulative incidence of COVID-19 cases confirmed by a validated nucleic acid amplification assay and mortality per 100 residents; the introduction of COVID-19 into a home (≥1 resident case) was a negative tracer. RESULTS: Of 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78 607 residents (women, 54 160 68.9%; age ≥85 years, 42 919 54.6%). A total of 5218 residents (6.6%) developed COVID-19 infection, and 1452 (1.8%) died of COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes; 4496 infections (86%) occurred in 63 homes (10%). The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 homes (50%) had a high crowding index (≥2). Incidence in high crowding index homes was 9.7% vs 4.5% in low crowding index homes (P < .001), while COVID-19 mortality was 2.7% vs 1.3%, respectively (P < .001). The likelihood of COVID-19 introduction did not differ (high = 31.3% vs low = 30.2%; P = .79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with an increased incidence of infection (relative risk RR = 1.73, 95% CI, 1.10-2.72) and mortality (RR, 1.69; 95% CI, 0.99-2.87). A propensity score analysis yielded similar conclusions for infection (RR, 2.09; 95% CI, 1.30-3.38) and mortality (RR, 1.83; 95% CI, 1.09-3.08). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 998 COVID-19 cases (19.1%) and 263 deaths (18.1%). CONCLUSIONS AND RELEVANCE: In this cohort of Canadian nursing homes, crowding was common and crowded homes were more likely to experience larger and deadlier COVID-19 outbreaks.
Large-scale surveys of single-cell gene expression have the potential to reveal rare cell populations and lineage relationships but require efficient methods for cell capture and mRNA sequencing. ...Although cellular barcoding strategies allow parallel sequencing of single cells at ultra-low depths, the limitations of shallow sequencing have not been investigated directly. By capturing 301 single cells from 11 populations using microfluidics and analyzing single-cell transcriptomes across downsampled sequencing depths, we demonstrate that shallow single-cell mRNA sequencing (~50,000 reads per cell) is sufficient for unbiased cell-type classification and biomarker identification. In the developing cortex, we identify diverse cell types, including multiple progenitor and neuronal subtypes, and we identify EGR1 and FOS as previously unreported candidate targets of Notch signaling in human but not mouse radial glia. Our strategy establishes an efficient method for unbiased analysis and comparison of cell populations from heterogeneous tissue by microfluidic single-cell capture and low-coverage sequencing of many cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genetic analysis was applied to different regions of renal-cell cancers. The lesions noted in the tumor were not found in every sample, and regions of the tumor had different gene-expression ...patterns. This suggests that extrapolation from results of a single biopsy may be problematic.
Large-scale sequencing analyses of solid cancers have identified extensive heterogeneity between individual tumors.
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Genetic intratumor heterogeneity has also been shown
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and can contribute to treatment failure and drug resistance. Intratumor heterogeneity may have important consequences for personalized-medicine approaches that commonly rely on single tumor-biopsy samples to portray tumor mutational landscapes. Studies comparing mutational profiles of primary tumors and associated metastatic lesions
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or local recurrences
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have provided evidence of intratumor heterogeneity at nucleotide resolution. Intratumor heterogeneity within primary tumors and associated metastatic sites has not been systematically characterized by next-generation sequencing. We applied exome sequencing, chromosome aberration analysis, . . .
RNA-guided CRISPR-Cas9 endonucleases are widely used for genome engineering, but our understanding of Cas9 specificity remains incomplete. Here, we developed a biochemical method (SITE-Seq), using ...Cas9 programmed with single-guide RNAs (sgRNAs), to identify the sequence of cut sites within genomic DNA. Cells edited with the same Cas9-sgRNA complexes are then assayed for mutations at each cut site using amplicon sequencing. We used SITE-Seq to examine Cas9 specificity with sgRNAs targeting the human genome. The number of sites identified depended on sgRNA sequence and nuclease concentration. Sites identified at lower concentrations showed a higher propensity for off-target mutations in cells. The list of off-target sites showing activity in cells was influenced by sgRNP delivery, cell type and duration of exposure to the nuclease. Collectively, our results underscore the utility of combining comprehensive biochemical identification of off-target sites with independent cell-based measurements of activity at those sites when assessing nuclease activity and specificity.
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