Funding Media, Strengthening Democracy: Grantmaking for the 21st Century

Despite the pervasiveness of media, the amount of philanthropic dollars in support of public interest media remains minuscule and, therefore largely ineffective. The report, based on a survey of the the funding sector, calls on philanthropists to embrace a practice of transparency and information sharing via technology, to determine how existing funds are being used and how they can best be leveraged to increase philanthropic impact within the media field

Differential regulation of key stages in early corneal wound healing by TGF-beta isoforms and their inhibitors

PURPOSE: Inhibition of TGF-beta reduces myofibroblast differentiation and fibrosis in the cornea. Determining the actions of distinct TGF-beta isoforms and their inhibitors during early corneal wound healing is an essential step in guiding therapeutic intervention. METHODS: Bovine serum-free corneal cell and wounded organ cultures were challenged with a range of concentrations of TGF-beta1, -beta2, and -beta3; IL-10; and neutralizing human monoclonal antibodies (mAbs) against TGF-beta1 (CAT-192) or -beta2, (CAT-152). Cultures were assessed for re-epithelialization, proliferation (cell counts and cresyl violet assay), morphology (histologic examination), repopulation of the area under the wound, and myofibroblast transformation (alpha-smooth muscle actin) between 0 and 5 days. RESULTS: TGF-beta1 delayed re-epithelialization, increased repopulation of the stroma, increased keratocyte proliferation and was the only isoform to promote myofibroblast differentiation. The anti-TGF-beta1 mAb, CAT-192 promoted re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-beta3 had little effect on re-epithelialization but reduced repopulation of the stroma. IL-10 promoted corneal re-epithelialization at low doses but inhibited this response at high doses. Stromal repopulation was prevented by all doses of IL-10. TGF-beta2 or the anti-TGF-beta2 mAb, CAT-152 had little effect on any repair parameter. CONCLUSIONS: The results confirm TGF-beta1 as the principal isoform in corneal wound healing and suggest that inhibition of the action of TGF-beta1 can promote corneal wound healing. Treatment with the anti-TGF-beta1 mAb CAT-192 accelerates corneal re-epithelialization but reduces cell repopulation of the stroma. The cytokines TGF-beta3 and IL-10 have opposing actions to that of TGF-beta1

Wellbeing and Nurture: Physical and Emotional Security in Childhood

While there is increasing concern about developing and reinforcing children’s physical and emotional security, researchers have been busy working out the actual mechanics, even at the cellular level, of how this can be achieved. This report will provide a concise update on what is known about optimising children’s wellbeing and security in childhood and far beyond. In examining the ways in which children grow and develop, we can learn from that because their physical and emotional wellbeing and therefore that of our future society will depend on it. This report represents what we have learned and we hope that it will contribute in a small way to the making of the brave new ‘post-Covid’ world

Mental Health Through Movement

Children’s mental health: ‘has become an issue of real concern, in the media and to both politicians and NHS leaders, over the last five years in particular. It has prompted numerous inquiries, reports, recommendations and pledges by politicians and NHS leaders to improve the situation’: https://www.theguardian.com/society/2018/nov/22/what-is-happening-withchildrens-mental-health On July 1st 2019, the Local Government Association released statistics to show that: ‘There were 205,720 cases where a child was identified as having a mental health issue in 2017/18, compared with 133,600 in 2014/15- up 54%’: https://www.local.gov.uk/about/news/councils-seeing-more-560-child-mentalhealth-cases-every-day It is within this context that the All-Party Parliamentary Group on A Fit and Healthy Childhood presents its 14th Report: ‘Positive Mental Health Through Movement’. With 1 in 10 children now having a mental health diagnosis and 1 in 4 an undiagnosed mental health issue, this, our third Report on the issue of child mental health, addresses the link between positive mental health and physical activity and movement experiences at a time when, paradoxically, today’s children and young people are more inactive and play less than ever before. The growing recognition of a link between mental health and movement is fortuitous because from September 2019, health education in English schools will be statutory alongside the expectation that they will offer their pupils at least 30 ‘active minutes’ per day. The APPG on A Fit and Healthy Childhood welcomes the change whilst recognising that those responsible for implementing the new strategy (including practitioners and families) will need guidance as they help children to develop individual strategies to address future adverse events and foster the positive sense of self that will enable them to lead fulfilled, healthy lives. This Report is therefore presented as a practical contribution to an essential debate. It offers new strategies against the persistence of historical and traditional ways of thinking; examines and collates best practice in the devolved Home Countries as well as the wider world and discusses exactly what is required to ensure that future child mental health strategy is holistic. It is respectful of equalities and is aware that the successful outcome of policies is entirely dependent upon the expertise and confidence of those tasked with the responsibility of delivering them. As the 21st century advances, we consider the effects of the digital age and its impact on children and young people’s mental health and wellbeing and the crucial role of parents and carers who want the best for their children in a societal climate where, all too often, fears of ‘nanny state’ meddling serve to isolate families who suffer in silence – until a disaster that may have been all too predictable and preventable overtakes them, making a private grief a public concern. The trajectory of progress in mental health policy has been ‘stop start’ rather than linear, with legislative change in 1959 and 1983, an increase in spending from 1997- 2010 and radical changes to child and adolescent mental health services (CAMHS) in 2000. The Wessely Independent Review of the Mental Health Act is another such milestone: https://www.gov.uk/government/groups/independent-review-of-the-mentalhealth-act The APPG on A Fit and Healthy Childhood anticipates that the Government will fulfil its pledge to parents, children and practitioners by introducing much needed mental health legislation - and that our trio of Reports and the holistic theme of this one will help to inform a strategy that works for 21st century children

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

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Localisation of receptors to estradiol, progesterone and androgen in the bovine cornea

Purpose: To investigate the density and spatial distribution of estradiol, progesterone and androgen receptors in corneal cryosections. Methods: Bovine corneas including the limbus were cryoprotected and snap frozen using isopentane cooled in liquid nitrogen. Cryosections of 10µm thickness were prepared and subjected to antibodies raised against receptors for estradiol, progesterone and androgen at dilutions of 1:10, 1:50 and 1:100 respectively. Staining was visualised using a Mouse ExtraAvidin® Peroxidase Staining Kit and nuclei were counterstained with bisbenzimide. Results: Assessment of tissue sections demonstrated immunostaining for estradiol, progesterone, and androgen receptors in the epithelium and in the keratocytes. Staining for all three receptors was nuclear and was detected in the limbal and peripheral regions of the cornea in both basal and suprabasal cell layers. With respect to the central corneal regions immunostaining was more diffuse within the cell layers. Immunostaining for all receptors was nuclear in the keratocytes throughout the corneal stroma. Conclusions: Estradiol, progesterone and androgen receptors are present in the epithelium and the stroma of the cornea and may be influenced by their ligands that we have previously identified in the tear film. It is likely that sex hormones may regulate cell-cell interactions during corneal wound healing