A support programme for caregivers of children with disabilities in Ghana: Understanding the impact on the wellbeing of caregivers

Background: Four fifths of the estimated 150 million children with disability in the world live in resource poor settings where the role of the family is crucial in ensuring that these children survive and thrive. Despite their critical role, evidence is lacking on how to provide optimal support to these families. This study explores the impact of a participatory training programme for caregivers delivered through a local support group, with a focus on understanding caregiver wellbeing. Methods: A qualitative longitudinal study was conducted to investigate the impact of a training programme, “getting to know cerebral palsy,” with caregivers on their wellbeing. Eighteen caregivers, from four districts, were interviewed up to three times over 14 months, to assess impact and the reasons for any changes. Results: Low levels of knowledge, high levels of stigma, physical and emotional exhaustion, and often difficult family relationships with social exclusion of the child and caregiver were common themes at the outset. Caregivers struggled to combine their caring and economic activities. This was exacerbated by the common absence of the father. Two months after completion of the training, their reported wellbeing had improved. The reasons for this were an improved understanding about their child's condition, positive attitudinal change towards their child, feelings of hope, and through the group support, a profound realisation that they are “not on their own.” While relationships within the family remained complex in many cases, the support group offered an important and alternative social support network. Conclusions: This study illustrates the many benefits of a relatively simple caregiver intervention, which has the potential to offer a mechanism to provide sustainable social support for caregivers and children with cerebral palsy. Any future programme needs to also address more structural issues, including stigma and discrimination, and strengthen approaches to family engagement

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Genetics and sex influence peripheral and central innate immune responses and blood-brain barrier integrity.

Lipopolysaccharide (LPS) is a stimulator of the innate immune system and is routinely used in animal models to study blood-brain barrier (BBB) dysfunction under inflammatory conditions. It is appreciated that both humans and mice have sexually dimorphic immune responses, which could influence the brain's response to a systemic inflammatory insult. Mouse strain is also an important factor that can contribute to pathophysiological responses to inflammatory stimuli. Therefore, we aimed to test whether BBB disruption and the associated cytokine profiles in response to LPS differed in male and female mice from two mouse strains most commonly used in blood-brain barrier studies: CD-1 and C57BL6/J (C57). Mice were treated with saline, a single injection of 0.3, or 3mg/kg LPS, or three injections of 3mg/kg LPS, and studied 28 hours after the first LPS injection. To assay BBB disruption, we utilized the tracer 99mTc-DTPA. A 23-plex panel of cytokines was assayed in brain and blood of the same cohort of mice, which allowed us to compare differences in the levels of individual cytokines as well as correlations among cytokines and 99mTc-DTPA uptake. We found that only the three-injection dose of LPS induced significant BBB disruption in all sexes and strains. The treatment, strain, and sex, as well as treatment-by- strain and treatment-by-sex interactions significantly contributed to the variance. The mean brain/serum ratios of 99mTc-DTPA in the three-injection LPS group were ranked CD-1 male < CD-1 female < C57 male < C57 female. There were significant sex and strain differences in cytokine profiles in brain and blood, and pro-inflammatory cytokines and chemokines in brain were most strongly correlated with 99mTc-DTPA brain/serum ratios

Effects of Ozone on Sickness and Depressive-like Behavioral and Biochemical Phenotypes and Their Regulation by Serum Amyloid A in Mice

Ozone (O3) is an air pollutant that primarily damages the lungs, but growing evidence supports the idea that O3 also harms the brain; acute exposure to O3 has been linked to central nervous system (CNS) symptoms such as depressed mood and sickness behaviors. However, the mechanisms by which O3 inhalation causes neurobehavioral changes are limited. One hypothesis is that factors in the circulation bridge communication between the lungs and brain following O3 exposure. In this study, our goals were to characterize neurobehavioral endpoints of O3 exposure as they relate to markers of systemic and pulmonary inflammation, with a particular focus on serum amyloid A (SAA) and kynurenine as candidate mediators of O3 behavioral effects. We evaluated O3-induced dose-, time- and sex-dependent changes in pulmonary inflammation, circulating SAA and kynurenine and its metabolic enzymes, and sickness and depressive-like behaviors in Balb/c and CD-1 mice. We found that 3 parts per million (ppm) O3, but not 2 or 1 ppm O3, increased circulating SAA and lung inflammation, which were resolved by 48 h and was worse in females. We also found that indoleamine 2,3-dioxygenase (Ido1) mRNA expression was increased in the brain and spleen 24 h after 3 ppm O3 and that kynurenine was increased in blood. Sickness and depressive-like behaviors were observed at all O3 doses (1–3 ppm), suggesting that behavioral responses to O3 can occur independently of increased SAA or neutrophils in the lungs. Using SAA knockout mice, we found that SAA did not contribute to O3-induced pulmonary damage or inflammation, systemic increases in kynurenine post-O3, or depressive-like behavior but did contribute to weight loss. Together, these findings indicate that acute O3 exposure induces transient symptoms of sickness and depressive-like behaviors that may occur in the presence or absence of overt pulmonary neutrophilia and systemic increases of SAA. SAA does not appear to contribute to pulmonary inflammation induced by O3, although it may contribute to other aspects of sickness behavior, as reflected by a modest effect on weight loss

Open government partnership global report - volume 1 : democracy beyond the ballot box

This volume reports on the world’s governance data, across multiple dimensions of democracy and openness. Reflecting a database of dozens of indicators from third-party sources across five policy dimensions (civic space, anti-corruption initiatives, open policy-making, access to information, and fiscal openness) this report compares 42 countries that have been in Open Government Partnership (OGP) for more than five years to non-OGP countries. Seventy-nine countries and a growing number of local governments, representing more than two billion people have joined the OGP to join forces, commit to reforms to open up government, and together ensure that public institutions work for citizens

Development and Validation of an Assessment of Regional Anesthesia Ultrasound Interpretation Skills

Interpretation of ultrasound images and knowledge of anatomy are essential skills for ultrasound-guided peripheral nerve blocks. Competency-based educational models promoted by the Accreditation Council for Graduate Medical Education require the development of assessment tools for the achievement of different competency milestones to demonstrate the longitudinal development of skills that occur during training. A rigorous study guided by psychometric principles was undertaken to identify and validate the domains and items in an assessment of ultrasound interpretation skills for regional anesthesia. A survey of residents, academic faculty, and community anesthesiologists, as well as video recordings of experts teaching ultrasound-guided peripheral nerve blocks, was used to develop short video clips with accompanying multiple choice-style questions. Four rounds of pilot testing produced a 50-question assessment that was subsequently administered online to residents, fellows, and faculty from multiple institutions. Test results from 90 participants were analyzed with Item Response Theory model fitting indicating that a 47-item subset of the test fits the model well (P = 0.11). There was a significant linear relation between expected and predicted item difficulty (P < 0.001). Overall test scores increased linearly with higher levels of formal anesthesia training, regional anesthesia training, number of ultrasound-guided blocks performed per year, and a self-rating of regional anesthesia skill (all P < 0.001). This study provides evidence for the reliability, content validity, and construct validity of a 47-item multiple choice-style online test of ultrasound interpretation skills for regional anesthesia, which can be used as an assessment of competency milestone achievement in anesthesiology training