Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

Active School Day implementation increased student moderate-to-vigorous physical activity levels by 24% and decreased sedentary time during school at modest cost.

The induction of proinflammatory proteins in stimulated endothelial cells (EC) requires activation of multiple transcription programs. The homeobox transcription factor HOXA9 has an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules (ELAM) E-selectin and vascular cell adhesion molecule 1 (VCAM-1). However, the mechanism underlying stimulus-dependent activation of HOXA9 is completely unknown. Here, we elucidate the molecular mechanism of HOXA9 activation by tumor necrosis factor alpha (TNF-␣) and show an unexpected requirement for arginine methylation by protein arginine methyltransferase 5 (PRMT5). PRMT5 was identified as a TNF-␣-dependent binding partner of HOXA9 by mass spectrometry. Small interfering RNA (siRNA)-mediated depletion of PRMT5 abrogated stimulus-dependent HOXA9 methylation with concomitant loss in E-selectin or VCAM-1 induction. Chromatin immunoprecipitation analysis revealed that PRMT5 is recruited to the E-selectin promoter following transient HOXA9 binding to its cognate recognition sequence. PRMT5 induces symmetric dimethylation of Arg140 on HOXA9, an event essential for E-selectin induction. In summary, PRMT5 is a critical coactivator component in a newly defined, HOXA9-containing transcription complex. Moreover, stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response.

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IntroductionIntake of sugar-sweetened beverages (SSBs) is associated with negative health effects. Access to healthy beverages may be promoted by policies such as the Healthy Beverage Executive Order (HBEO) established by former Boston mayor Thomas M. Menino, which directed city departments to eliminate the sale of SSBs on city property. Implementation consisted of “traffic-light signage” and educational materials at point of purchase. This study evaluates the impact of the HBEO on changes in beverage availability.MethodsResearchers collected data on price, brand, and size of beverages for sale in spring 2011 (899 beverage slots) and for sale in spring 2013, two years after HBEO implementation (836 beverage slots) at access points (n = 31) at city agency locations in Boston. Nutrient data, including calories and sugar content, from manufacturer websites were used to determine HBEO beverage traffic-light classification category. We used paired t tests to examine change in average calories and sugar content of beverages and the proportion of beverages by traffic-light classification at access points before and after HBEO implementation.ResultsAverage beverage sugar grams and calories at access points decreased (sugar, −13.1 g; calories, −48.6 kcal; p<.001) following the implementation of the HBEO. The average proportion of high-sugar (“red”) beverages available per access point declined (−27.8%, p<.001). Beverage prices did not change over time. City agencies were significantly more likely to sell only low-sugar beverages after the HBEO was implemented (OR = 4.88; 95% CI, 1.49–16.0).DiscussionPolicies such as the HBEO can promote community-wide changes that make healthier beverage options more accessible on city-owned properties.

Objective Magnetic resonance imaging (MRI) is pivotal in the assessment of early sacroiliitis in children. We aimed to evaluate the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac (SI) joints. Methods Eight hospitals each contributed up to 20 cases of consecutively imaged children and adolescents with juvenile idiopathic arthritis and suspected sacroiliitis. Studies were independently reviewed by 3 experienced musculoskeletal pediatric radiologists. Local assessments of global impression and lesions were coded from the local radiology reports by 2 study team members. Test properties of local reports were calculated using the central imaging team’s majority as the reference standard. Results For 120 evaluable subjects, the median age was 14 years, half of the cases were male, and median disease duration at the time of imaging was 0.8 years (interquartile range 0–2). Sensitivity of local reports for inflammation was high, 93.5% (95% confidence interval [95% CI] 78.6–99.2), and specificity was moderate, 69.7% (95% CI 59.0–79.0), but positive predictive value (PPV) was low, 51.8% (95% CI 38.0–65.3). Twenty‐seven cases (23%) had active inflammation reported locally but rated normal at the central reading, 19 (70%) with subsequent medication changes. The sensitivity of local reports detecting structural damage was low, 45.7% (95% CI 28.8–63.4), and specificity was high, 88.2% (95% CI 79.4–94.2); PPV was low, 61.5% (95% CI 40.6–79.8). Conclusion Substantial variation exists in the interpretation of inflammatory and structural lesions at the SI joints in children. To reliably identify pathology, additional training in the MRI appearance of the maturing SI joint is greatly needed.

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We found modest reductions in the percentage of higher-sodium prepackaged products across community institutions. Community-level interventions may increase availability of lower-sodium products in the food supply.