Classroom Level Effects of Children’s Prior Participation in Child Care

Previous research indicates that children who spend many hours in early child care exhibit more externalizing behavior problems than children who spend less time in child care. Concern has been expressed regarding the cumulative effect of these problem behaviors on elementary school classes. We collected information about children’s child-care histories from parents of first through fourth graders (N = 429) and about classroom functioning from their teachers (N = 31). We analyzed associations between the proportion of children in the class who had spent many hours in care prior to school entry and teachers’ reports of the time they spent in instruction and management, the difficulty they had in teaching and managing the class and the frequency of students’ positive and negative behavior in the classroom. No significant associations were found to support the contention that prior child-care participation negatively affects classroom functioning

Designing out Medical Error: An Interdisciplinary Approach to the Design of Healthcare Equipment

Medical error is an internationally recognised problem, with major financial and human costs (Gray; 2003, de Vries; et.al. 2008). The design of hospital equipment, devices and environments can contribute to the problem. Clinical staff often have to cope with confusing interfaces and equipment, making their tasks difficult and potentially dangerous. There are calls to rethink the approach to design in healthcare. Design should acknowledge the real world issues users face in the hospital environment. A collaborative approach is required to understand these issues, (Karsh & Scanlon, 2007). This paper outlines the methodologies used in two interdisciplinary case study projects, revealing the importance of a clear set of working methods and detailing the approach taken at each point. The resulting designs aim to better support healthcare processes, reducing the instance of medical error and ultimately saving lives

Latitude gradient influences the age of onset of rheumatoid arthritis : a worldwide survey

The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10A degrees increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 +/- 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p <0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p <0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p <0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.Peer reviewe

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Background Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations

Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: a systematic review

Background: The evidence base for testing thiopurine methyltransferase (TPMT) enzymatic activity or genotype before thiopurine therapy is unclear. Purpose: To examine the sensitivity and specificity of TPMT genotyping with reference to TPMT enzymatic activity, thiopurine harms reduction with pretesting, and association of thiopurine toxicity with TPMT status in adults and children with chronic inflammatory diseases. Data Sources: MEDLINE, EMBASE, the Cochrane Library, and Healthstar from inception to December 2010; and BIOSIS and Genetics Abstracts to May 2009 were searched. Study Selection: Two reviewers screened records and identified relevant studies in English. Data Extraction: One author extracted, and another independently verified, data on patient characteristics, outcomes, and risks of bias. Data Synthesis: 54 observational studies and one RCT were included.Insufficient evidence addressed pre-testing effectiveness. Genotyping sensitivity to identify patients with low and intermediate TPMT enzymatic activity ranged from 70.33% to 86.15% (95% CI, lower bound 54.52% to 70.88%; upper bound 78.50% to 96.33%). There is sparse data of genotype sensitivity to identify patients with low to absent enzymatic activity. Genotyping specificity approached 100%. Compared with noncarriers, heterozygous and homozygous genotypes were associated with leukopenia (OR 4.29, 95% CI 2.67, 6.89; OR 20.84, 95% CI 3.42, 126.89, respectively). Compared with intermediate or normal activities, low TPMT enzymatic activity was significantly associated with myelotoxicity and leukopenia. Limitations: Available evidence is not rigorous and underpowered to detect a difference in outcomes. Conclusions: Insufficient evidence addresses TPMT pre-testing effectiveness in patients with chronic inflammatory diseases. Estimates of sensitivity of genotyping are imprecise. Evidence confirms known associations of leukopenia and/or myelotoxicity with reduced TPMT activity or variant genotype.This project was funded under Contract No. HHSA290-2007-10059-I (EPCIII) from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services.The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality, the National Center for Complementary and Alternative Medicine, National Institute of Health or the U.S. Department of Health and Human Services

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7