Abstract
Background
Data on risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors ...independently associated with COVID-19–associated hospitalizations.
Methods
Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March–23 June 2020 were identified from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization.
Results
Among 5416 adults, hospitalization rates (all reported as aRR 95% confidence interval) were higher among those with ≥3 underlying conditions (vs without) (5.0 3.9–6.3), severe obesity (4.4 3.4–5.7), chronic kidney disease (4.0 3.0–5.2), diabetes (3.2 2.5–4.1), obesity (2.9 2.3–3.5), hypertension (2.8 2.3–3.4), and asthma (1.4 1.1–1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45–64 years (vs 18–44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites).
Conclusions
Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
Severe obesity, chronic kidney disease, diabetes, obesity, hypertension, asthma, age ≥45 years, male sex, and non-Hispanic black and other race/ethnicity are associated with increased risk of coronavirus disease 2019–associated hospitalizations.
Combinations of anti-cancer drugs can overcome resistance and provide new treatments
. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to ...systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
Abstract
The GWAS Catalog delivers a high-quality curated collection of all published genome-wide association studies enabling investigations to identify causal variants, understand disease ...mechanisms, and establish targets for novel therapies. The scope of the Catalog has also expanded to targeted and exome arrays with 1000 new associations added for these technologies. As of September 2018, the Catalog contains 5687 GWAS comprising 71673 variant-trait associations from 3567 publications. New content includes 284 full P-value summary statistics datasets for genome-wide and new targeted array studies, representing 6 × 109 individual variant-trait statistics. In the last 12 months, the Catalog's user interface was accessed by ∼90000 unique users who viewed >1 million pages. We have improved data access with the release of a new RESTful API to support high-throughput programmatic access, an improved web interface and a new summary statistics database. Summary statistics provision is supported by a new format proposed as a community standard for summary statistics data representation. This format was derived from our experience in standardizing heterogeneous submissions, mapping formats and in harmonizing content. Availability: https://www.ebi.ac.uk/gwas/.
Physical literacy is an emerging construct in children's health promotion, and may impact their lifelong physical activity habits. However, recent data reveal that only a small portion of Canadian ...children are regularly physically active and/or meet sedentary behaviour guidelines. To our knowledge, no study has investigated the association between physical literacy and movement behaviour guidelines. Therefore, the purpose of this study was to examine the relationship between physical literacy scores in Canadian children who meet or do not meet physical activity and sedentary behaviour guidelines.
Children (n = 2956; 56.6% girls) aged 8-12 years from 10 Canadian cities had their physical literacy levels measured using the Canadian Assessment of Physical Literacy, which consists of four domains (Physical Competence; Daily Behaviour; Knowledge and Understanding; and Motivation and Confidence) that are aggregated to provide a composite physical literacy score. Physical activity levels were measured by pedometers, and sedentary behaviour was assessed through self-report questionnaire. Analyses were conducted separately for each guideline, comparing participants meeting versus those not meeting the guidelines. Comparisons were performed using MANOVA and logistic regression to control for age, gender, and seasonality.
Participants meeting physical activity guidelines or sedentary behaviour guidelines had higher physical literacy domain scores for Physical Competence and for Motivation and Confidence compared to those not meeting either guideline (both p < 0.0001). Participants had increased odds of meeting physical activity guidelines and sedentary behaviour guidelines if they met the minimum recommended level of the Physical Competence and Motivation and Confidence domains. Significant age (OR 0.9; 95% CI: 0.8, 0.9), gender (OR 0.4; 95% CI: 0.3, 0.5) and seasonality effects (OR 1.6; 95% CI: 1.2, 2.2 spring and OR 1.7; 95% CI: 1.2, 2.5 summer, reference winter) were seen for physical activity guidelines, and age (OR 0.8; 95% CI: 0.7, 0.8) and gender effects (OR 1.7; 95% CI: 1.4, 2.0) for sedentary behaviour guidelines. Knowledge and Understanding of physical activity principles was not related to guideline adherence in either model.
These cross-sectional findings demonstrate important associations between physical literacy and guideline adherence for physical activity and sedentary behaviour. Future research should explore the causality of these associations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The reality confronting ecosystem managers today is one of heterogeneous, rapidly transforming landscapes, particularly in the areas more affected by urban and agricultural development. A landscape ...management framework that incorporates all systems, across the spectrum of degrees of alteration, provides a fuller set of options for how and when to intervene, uses limited resources more effectively, and increases the chances of achieving management goals. That many ecosystems have departed so substantially from their historical trajectory that they defy conventional restoration is not in dispute. Acknowledging novel ecosystems need not constitute a threat to existing policy and management approaches. Rather, the development of an integrated approach to management interventions can provide options that are in tune with the current reality of rapid ecosystem change.
We report on a 32-year-old Italian man, his 5-year-old daughter, and his 3 1/2-year-old son, all of whom had congenital joint contractures. Each has severe ulnar deviation of fingers and soft-tissue ...contractures of both hands; and each had bilateral clubfeet at birth. The father is short in stature, as are the children, who also have delayed carpal ossification. The findings in this family suggest autosomal-dominant inheritance of the condition. The clinical features are consistent with the condition currently referred to as "distal" arthrogryposis.
Brain metastases are devastating complications of cancer. The blood-brain barrier (BBB), which protects the normal brain, morphs into an inadequately characterized blood-tumor barrier (BTB) when ...brain metastases form, and is surrounded by a neuroinflammatory response. These structures contribute to poor therapeutic efficacy by limiting drug uptake. Here, we report that experimental breast cancer brain metastases of low- and high permeability to a dextran dye exhibit distinct microenvironmental gene expression patterns. Astrocytic sphingosine-1 phosphate receptor 3 (S1P3) is upregulated in the neuroinflammatory response of the highly permeable lesions, and is expressed in patients' brain metastases. S1P3 inhibition functionally tightens the BTB in vitro and in vivo. S1P3 mediates its effects on BTB permeability through astrocytic secretion of IL-6 and CCL2, which relaxes endothelial cell adhesion. Tumor cell overexpression of S1P3 mimics this pathway, enhancing IL-6 and CCL-2 production and elevating BTB permeability. In conclusion, neuroinflammatory astrocytic S1P3 modulates BTB permeability.
Illnesses transmitted by food and water cause a major disease burden in the United States despite advancements in food safety, water treatment, and sanitation. We report estimates from a structured ...expert judgment study using 48 experts who applied Cooke's classical model of the proportion of disease attributable to 5 major transmission pathways (foodborne, waterborne, person-to-person, animal contact, and environmental) and 6 subpathways (food handler-related, under foodborne; recreational, drinking, and nonrecreational/nondrinking, under waterborne; and presumed person-to-person-associated and presumed animal contact-associated, under environmental). Estimates for 33 pathogens were elicited, including bacteria such as Salmonella enterica, Campylobacter spp., Legionella spp., and Pseudomonas spp.; protozoa such as Acanthamoeba spp., Cyclospora cayetanensis, and Naegleria fowleri; and viruses such as norovirus, rotavirus, and hepatitis A virus. The results highlight the importance of multiple pathways in the transmission of the included pathogens and can be used to guide prioritization of public health interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current physical literacy level of Canadian children is unknown. The Royal Bank of Canada (RBC) Learn to Play - Canadian Assessment of Physical Literacy (CAPL) project, which is anchored in the ...Canadian consensus statement definition of physical literacy, aimed to help establish the current physical literacy level of Canadian children.
The CAPL was used to assess the physical literacy (and component domains: Daily Behaviour, Physical Competence, Knowledge and Understanding, and Motivation and Confidence) of Canadian children aged 8-12 years. Data were collected from 11 sites across Canada, yielding a sample of 10,034 participants (5030 girls). Descriptive statistics by age and gender were calculated and percentile distributions of physical literacy scores, including each domain and individual measure, were derived.
The mean age of participants was 10.1 ± 1.2 years. Total physical literacy scores (out of 100) were on average 63.1 ± 13.0 for boys and 62.2 ± 11.3 for girls. For boys and girls respectively, domain scores were 19.9 ± 4.7 and 19.3 ± 4.1 (out of 32) for Physical Competence; 18.6 ± 7.9 and 18.5 ± 7.4 (out of 32) for Daily Behaviour; 12.7 ± 2.8 and 12.2 ± 2.6 (out of 18) for Motivation and Confidence; and 11.8 ± 2.8 and 12.2 ± 2.6 (out of 18) for Knowledge and Understanding. Physical Competence measures were on average 28.1 ± 8.4 cm (sit-and-reach flexibility), 33.5 ± 9.4 kg (grip strength, right + left), 23.4 ± 14.1 laps (Progressive Aerobic Cardiovascular Endurance Run PACER shuttle run), 61.8 ± 43.8 s (isometric plank), 19.0 ± 3.8 kg/m
(body mass index), 67.3 ± 10.8 cm (waist circumference), and 20.6 ± 3.9 out of 28 points for the Canadian Agility and Movement Skill Assessment (CAMSA), with scores for boys higher than girls and older children higher than younger children for grip strength, PACER, plank, and CAMSA score. Girls and younger children had better scores on the sit-and-reach flexibility than boys and older children. Daily pedometer step counts were higher in boys than girls (12,355 ± 4252 vs. 10,779 ± 3624), and decreased with age.
These results provide the largest and most comprehensive assessment of physical literacy of Canadian children to date, providing a "state of the nation" baseline, and can be used to monitor changes and inform intervention strategies going forward.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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