Improving attainment? Interventions in education by the New Deal for Communities Programme

"The New Deal for Communities (NDC) Programme was announced in 1998 and designed to reduce gaps between some of the most deprived areas in England and the rest of the country... This report presents the findings of one element of the second phase of the evaluation of the NDC Programme: research in four case study NDC partnerships focusing on interventions and outcomes under the theme of education." - introduction

Interplay between P-glycoprotein-mediated efflux and cytochrome P4503A-mediated metabolism in the intestine

Intestinal metabolism and drug efflux are recognized as two important barriers to drug absorption. The interactions between these factors may also be an important consideration in evaluating the drug-drug interaction potential of a given compound. Presented here are mechanistic studies that examine the interaction between the most germane metabolic enzyme/efflux transporter pair: cytochrome P4503A (CYP3A) and P-glycoprotein (P-gp). In order to study this interaction, two model systems and two dual CYP3A/P-gp substrates were selected. The first model used was the CYP3A-expressing Caco-2 cell system. This system allowed for detailed mechanistic studies, with few confounding factors. The second system utilized was fresh mouse intestine (from P-gp competent and deficient mice) in a side-by-side diffusion chamber model. This model provided more physiologically relevant results with the caveat of increased complexity. The two drugs selected for study were terfenadine (an antihistamine) and loperamide (an antidiarrheal). In order to study the interplay between P-gp efflux and metabolism, the metabolism of each compound was measured during absorptive transport across Caco-2 cell monolayers and mouse tissue, in the presence or absence of P-gp activity. In the Caco-2 cell system, the results varied between the two compounds. Loperamide showed an increase in metabolism in the presence of the P-gp inhibitor GW918, while terfenadine showed no change. The lack of effect for terfenadine may be due to the action of a second transporter. In the mouse intestine, both compounds showed a higher metabolic rate in the absence of P-gp expression. For both systems, the effects were seen only within the low dose range, below about 50 [mu]M. This study also showed that terfenadine is metabolized about 60% by an enzyme that is inhibitable by quinidine (possibly CYP2D22) and only 40% by CYP3A in mouse intestine. The results presented in this dissertation indicate that P-gp efflux effectively decreases metabolism in intestine by decreasing intracellular concentrations. This conclusion is also supported by the pharmacokinetic modeling and simulations presented. The mechanistic information collected can provide insight into the nature of the CYP3A/P-gp interaction and can help in developing better models to predict in vivo intestinal drug-drug interactions

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach

Background: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the “Combined Diabetes and Renal Control Trial” (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. Methods: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. Results: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. Conclusions: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients

Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service [version 2; peer review: 2 approved]

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). The GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: Our mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Preparing Young Children for Kindergarten-Readiness and Life-Long Learning Through Play in the New Millennium

In this new millennium the first year of elementary school once meant for play and getting children acclimated to school life, Kindergarten , has become more and more focused on academic performance. Formal academic structured kindergarten programs are spreading rapidly across the United States, causing a push for academic preparation to be acknowledge during the younger years for children. This academic focus is targeting children younger than five years of age, which are the years children are growing rapidly physical, socially, emotionally, and cognitively. These years are also the times where young children are enjoying life experiences in their world of learning through their routine play activities. The key method to prepare young children for kindergarten readiness in the new millennium is to continue allowing young children to be exposed to academic concepts through adult facilitated interactive play activities. The literature review supports the importance of young children\u27s play activities and how play can introduce and allow young children to develop the academic concepts needed in the kindergarten structure classroom. The project provides awareness for the parents/guardians and early childhood educators/preschool teachers of what components are needed to provide a playful academic concept building environment for young children. Also within the project there are concept skills checklists and several suggested play activities that are age-appropriate and developmentally appropriate for young children from birth through four years