From Research to Knowledge Translation: Co-Producing Resources to Raise Awareness of Meals on Wheels in England.

BACKGROUND: Meals on Wheels (MoWs) could help adults with care and support needs continue living independently. However, many people are not aware that the service still exists in England, or that it could provide benefits beyond nutrition. OBJECTIVE: Working with an existing advisory group of six people with lived experience of MoWs (an adult who uses MoWs and people who have referred a family member to MoWs), this work aimed to co-produce knowledge translation resources (two infographics and a film) to raise awareness of MoWs and their benefits. METHODS: Four participatory online workshops were held in May-July 2023, to establish perceived high-priority themes from recent qualitative research that should be included in the resources, and preferences about message content, language, design, and how the resources should be disseminated. FINDINGS: The most important perceived MoWs benefits that the group agreed should be included in the resources were: the importance of a nutritious meal that requires no preparation; the service's reliability/consistency; the importance of interactions in reducing social isolation, and; the ease to commence the service. The group highlighted the need for language to be nontechnical and invitational, and for images to relate to respective messages, and be inclusive of anyone who could benefit from MoWs. Several routes for dissemination were proposed, highlighting the need to disseminate to the NHS, social care organisations and community groups. CONCLUSION: These co-produced resources could enhance adult social care delivery in England, as raising awareness of MoWs and their benefits could increase referral rates, so that more adults with care and support needs can benefit from the service. PATIENT OR PUBLIC CONTRIBUTION: An advisory group of people with lived experience of MoWs (users of the service and family referrers) participated in the workshops, extensively discussed the findings of earlier research, co-produced the knowledge translation resources, and advised on the implications and future dissemination steps. The group also provided informal feedback on a draft of this manuscript.

Actives from MMV Open Access Boxes? A suggested way forward.

It is estimated that more than 1 billion people across the world are affected by a neglected tropical disease (NTD) that requires medical intervention. These diseases tend to afflict people in areas with high rates of poverty and cost economies billions of dollars every year. Collaborative drug discovery efforts are required to reduce the burden of these diseases in endemic regions. The release of "Open Access Boxes" is an initiative launched by Medicines for Malaria Venture (MMV) in collaboration with its partners to catalyze new drug discovery in neglected diseases. These boxes are mainly requested by biology researchers across the globe who may not otherwise have access to compounds to screen nor knowledge of the workflow that needs to be followed after identification of actives from their screening campaigns. Here, we present guidelines on how to move such actives beyond the hit identification stage, to help in capacity strengthening and enable a greater impact of the initiative.

The discovery and evaluation of 3-amino-2(1H)-pyrazinones as a novel series of selective p38α MAP kinase inhibitors.

The discovery and optimisation of a novel series of potent and selective p38α inhibitors is described. Evaluating the structure-activity relationship of an aminoalkyl substituent at the 3 position of the 2(1H)-pyrazinone core, p38α potency was increased 20000-fold. The most advanced compound (25) demonstrated excellent in vivo properties suitable for an inhaled route of administration.

Reluctant educators and self-advocates: Older trans adults' experiences of health-care services and practitioners in seeking gender-affirming services.

BACKGROUND: Trans-identifying individuals experience unique barriers and challenges in negotiating health-care systems due to the cisnormative attitudes and practices which obstruct the receipt of trans-inclusive care. To date, there has been little exploration of older trans consumers' experiences of contemporary health-care services when seeking to transition medically in later life. OBJECTIVES: Qualitative findings are presented from a study of trans ageing and trans-related health and social care needs in Wales, UK (2016-18). The objectives are to (1) examine supportive and obstructive points of interaction with health-care professionals, and (2) identify key learning messages for improving trans-related health care from the perspectives of trans-identifying adults in later life. DESIGN: Trans-identifying participants self-selected to take part in two interviews-a life-history interview and a semi-structured interview. Interview data were analysed thematically using the framework method approach. SETTING AND PARTICIPANTS: This paper focuses on the accounts of 19 participants (50-74 years of age) who identified as trans and were seeking to transition medically in mid- to later life. RESULTS: Findings indicate how older trans patients are positioned as reluctant educators for GPs in primary care settings and illustrate the transphobic practices and cisnormative assumptions encountered across health-care interactions and systems that impede their journey of transitioning in later life. DISCUSSION AND CONCLUSIONS: Messages from this study speak to the importance of improving professionals' knowledge of gender identity diversity across the life course and making changes at a systemic level in redressing cisnormative assumptions and systems that reinforce inequities on the basis of gender identity.

Older People in the Context of COVID-19: A European Perspective.

The Coronavirus pandemic and associated measures for the protection of the public have impacted differently on different parts of the population and across different nations. In many areas, COVID-19 has also either exacerbated already existing or created new inequalities in relation to specific parts of the population. Older individuals are one group in society that has been widely impacted, while social isolation/shielding measures have placed them in higher risk of loneliness, isolation, financial deprivation and mental health challenges, to name a few. This commentary reflects on such inequalities across four European nations (the United Kingdom (UK), Republic of Ireland, Finland, Spain) and draws attention to the critical role of Gerontological Social Work (GSW), while emphasizing the ways in which social work can intervene. First, we identify common concerns for the rights of older people that span across all four nations, and second, we identify significant roles for GSW practitioners at the individual, community and policy levels and conclude with a call for GSW in these four nations to be reimagined in a time of global crisis.

Susceptibility Testing of Medically Important Parasites.

In the last 2 decades, renewed attention to neglected tropical diseases (NTDs) has spurred the development of antiparasitic agents, especially in light of emerging drug resistance. The need for new drugs has required in vitro screening methods using parasite culture. Furthermore, clinical laboratories sought to correlate in vitro susceptibility methods with treatment outcomes, most notably with malaria. Parasites with their various life cycles present greater complexity than bacteria, for which standardized susceptibility methods exist. This review catalogs the state-of-the-art methodologies used to evaluate the effects of drugs on key human parasites from the point of view of drug discovery as well as the need for laboratory methods that correlate with clinical outcomes.

2,3,8-Trisubstituted Quinolines with Antimalarial Activity.

Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P. falciparum NF54 (IC50 = 22 nM) and low cytotoxicity. We performed a detailed evaluation of the substituents to improve the metabolic stability and solubility liabilities of the original hit and identified derivatives with enhanced physicochemical and/or PK properties and that maintained biological activity. However the high potency was not retained on testing against drug resistant plasmodium strains.

Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.

BACKGROUND: In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. METHODS: The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. RESULTS: This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC50 < 1 µM) and selectivity (SI > 10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. CONCLUSION: A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical library against blood-stage P. falciparum. Emphasis was placed on chemical novelty whereby computational clustering, data mining of known anti-malarial chemotypes and the application of relaxed physicochemical filters, were key to the process. This led to the selection of 15 chemical series from which ten confirmed their activity when newly synthesized sample were tested.

Antimalarial drug discovery - the path towards eradication.

Malaria is a disease that still affects a significant proportion of the global human population. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. This article highlights the current mainstay treatments alongside a selection of emerging new clinical molecules from the portfolio of Medicines for Malaria Venture (MMV) and our partners. In each case, the key highlights from each research phase are described to demonstrate how these new potential medicines were discovered. Given the increased focus of the community on eradicating the disease, the strategy for next generation combination medicines that will provide such potential is explained.

Open source drug discovery - a limited tutorial.

Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantial.

Evaluating real-world emissions from in-use buses and taxis using on-road remote sensing.

Assessing real-world emissions from buses and taxis is vital to comprehend their impact on urban air quality. Such vehicles differ significantly from the majority of the fleet owing to their higher mileage rates. However, few studies have focused on specifically assessing the emissions from this segment of the vehicle fleet. In this context, this study evaluated the real-world emissions of nitrogen oxides (NOx) from in-use buses and taxis in Dublin, Ireland, using crossroad remote sensing technology. The remote sensing system was deployed at strategic locations throughout the city to capture on-road emissions from passing vehicles. The collected data included vehicle related information such as emission standard, make, and mileage, and pollutants including NOx. Based on this data, analysis was aimed to understand the impact of Euro emission standard, ambient temperature, mileage, and make of the vehicle on NOx emissions. The results reveal that the average emissions from taxis reduce by 37% from Euro 5 to Euro 6b, and average emissions from Euro 6 buses are 87% lower compared to Euro 5. The trends in emission factors (EFs) of buses and taxis were similar during summer and winter sampling. Moreover, on comparing the emissions from the top five taxi manufacturers, different trends in the emission factors were observed. Finally, the study found that the effect of vehicle mileage on emissions was unclear for both buses and taxis. In any case, these findings provide valuable insights into the real-world emission performance of the existing fleet of buses and taxis in Dublin and highlight the need for targeted measures to reduce emissions from these vehicles. The results can assist policymakers and urban planners in formulating evidence-based strategies to improve air quality in Dublin and other cities facing similar challenges.

"There isn't anybody else like me around here": the insider-outsider status of LGBT residents in housing with care schemes for older people.

The intersections between aging, social minority status and housing needs in later life is a neglected area of sociological exploration, even more so for older people who identify as lesbian, gay, bisexual and trans (LGBT). Recent sociological findings indicate that older LGBT people in housing schemes stress the importance of bonding social capital and look to other people in their social networks who reflect their identities and experiences as sources of support. In this paper, we examine the insider-outsider status occupied by older LGBT residents living in housing schemes that provide some form of care and support, for example extra care and independent living schemes. We present qualitative findings generated from a mixed-methods study of social inclusion practices in housing with care in England and Wales (UK) (2019-22). In this study 15 LGBT residents participated in semi-structured interviews (55-79 years of age) across a total of 31 interviews. Through a queer gerontological lens we examine how older LGBT people are socially situated within mainstream housing schemes in which they experience partial visibility while also encountering exclusionary pressures that locate them as "the other." This insider-outsider status undermines the premise of housing with care schemes to provide safe, secure spaces to grow old. We discuss three core themes: (1) how LGBT residents navigate their outsider status in scheme life and how the intersection of disability and minority status amplifies this social location; (2) the exclusionary practices exercised by other residents that reinforce boundaries of sexual and gender normalcy; and, (3) the heightened importance of maintaining external social connections among LGBT residents. We conclude by introducing an alternative notion of marginal aging and expanding on the implications for housing providers, reflecting on their responsibilities for promoting and maintaining queer-friendly environments.

The impact of COVID-19 lockdown measures on older residents' social connections and everyday wellbeing within housing schemes that provide care and support in England and Wales.

The COVID-19 pandemic and the lockdown measures imposed as a result affected the lives of people in all parts of society across the world. In 2020, during the first UK national lockdown, older adults (aged 70 years and over) were told to 'shield' within their homes, as they were regarded as being at higher risk of serious COVID-19 infection compared to other age groups. This paper explores older adults' experiences of COVID-19 lockdown measures whilst living in housing with care schemes for older people. The purpose is to examine the impact of the lockdown measures on scheme life including social connections amongst residents and their general everyday wellbeing during this time. We present qualitative findings based on interviews with 72 residents who took part in longitudinal and cross-sectional interviews across 26 housing with care schemes. Data were analysed using a thematic framework approach to examine specifically their experiences of living in housing with care schemes during the 2020 UK lockdown. The paper highlights that COVID-19 restrictions had a detrimental impact on the social connections and interactions of older residents living in housing with care schemes, as well as on their feelings of autonomy and independence. Despite this, residents adapted and coped with self-isolation restrictions and sought out positive ways to maintain social contact with others inside and outside to the scheme. We further highlight the tensions that providers of housing for older adults faced in promoting residents' autonomy and connectedness whilst also trying to provide a safe living environment and protect residents from risk of COVID-19 infection. Our findings apply not only to a pandemic situation but to the broader understanding of how housing with care for older adults must navigate between autonomy and support.

Constructions of lesbian, gay, bisexual and queer identities among young people in contemporary Australia.

This paper focuses on young people's construction of lesbian, gay, bisexual and queer (LGBQ) identities in contemporary Australia. Through the perspectives of young people, it seeks to position their understanding of LGBQ identities alongside current theoretical and empirical debates about the individual and social significance attached to these identity frames. In this qualitative study, 28 young people (aged 18 to 26 years) shared their stories of identifying as LGBQ through online, face-to-face or telephone interviews. The findings highlight how varying elements of LGBQ identities continue to have currency within this group and how young people adopt and refer to these terms interchangeably and in tandem. This is balanced alongside an awareness of both the limitations of lesbian, gay, bisexual and queer identity categories and of the homophobic discourses informing these subject positions. The paper concludes by arguing that health and social care professionals have a integral role to play in supporting LGBQ youth through a process of co-authorship - to work in partnership to construct more enabling self-stories that transcend restrictive identity frames.

Loneliness, coping practices and masculinities in later life: Findings from a study of older men living alone in England.

While much attention has been given to loneliness as a public health and societal problem less consideration has been given to men's experiences, particularly in later life, and there is a limited evidence based on what works with supporting older men to counteract the impact of loneliness on their mental and social wellbeing. In this paper, we focus on the experiences of older men living alone in the community. Between 2017-2018 72 men residing in England (65-95 years) took part in the study and shared their accounts of experiencing and addressing loneliness on an everyday basis. We generated qualitative data through semi-structured interviews. Interview data were analysed thematically using the framework analysis approach. We present and discuss findings on the difficulties older men experience in responding to and discussing loneliness and the range of coping practices men applied within their home environments. Three core themes are presented: 1. Maintaining silence around loneliness and distress; 2. Getting on with it versus feeling stuck in loneliness and, 3. Temporary remedies and distractions from loneliness from within the home. Across men's accounts, 'the home' is constructed as a space of biographical connections with others as well as a restrictive environment of separation from others. In relation to help-seeking and efforts to break silence surrounding loneliness, the findings speak to the ways in which masculinities and social expectations attached to male roles complicate older men's varying attempts at help-seeking and underpin some of their everyday methods of coping with loneliness. The findings reiterate the importance of targeted individual support for older men, particularly for those feeling frozen in loneliness. Facilitators of group-based support for older men need to recognise the different and potentially conflicting positions older male service users may adopt in relation to help-seeking that are configured around masculine ideals but in diverging ways.

The Impact of Living in Housing With Care and Support on Loneliness and Social Isolation: Findings From a Resident-Based Survey.

Background and Objectives: Housing with care is often lauded as a way to combat loneliness and social isolation in later life. This study examined whether housing with care created better outcomes for residents in terms of loneliness and social isolation than they might expect if they were living in the community. Research Design and Methods: A survey was distributed to residents of housing with care as part of the Diversity in Care Environments project. It was designed to enable comparison with the English Longitudinal Study of Ageing. Propensity score matching was applied to identify the effect of housing with care residence on loneliness and social isolation. Results: People living in housing with care had lower levels of loneliness than would be expected if they lived in the general community, with an average treatment effect on the treated (ATT) of -0.407 (95% CI = -0.601, -0.214). In contrast, social isolation was found to be slightly higher for residents than would be expected if they were in the community (ATT = 0.134 [95% CI = 0.022, 0.247]). Higher social isolation appears driven by less frequent contact with friends and reduced organizational membership rather than any difference in contact with family and children. Discussion and Implications: Our research has shown a positive impact on subjective social experiences from housing with care residence, despite a slight increase in objective social isolation. The findings underscore the importance of looking at loneliness and social isolation as distinct concepts as well as the effectiveness of housing with care at improving later-life outcomes.

'It's not just about the dinner; it's about everything else that we do': A qualitative study exploring how Meals on Wheels meet the needs of self-isolating adults during COVID-19.

Meals on Wheels (MoWs), a service offered by local authorities in England, deliver meals to older, housebound and/or vulnerable adults, who might otherwise not be able to acquire and prepare their own meals. Research suggests that MoWs provide benefits beyond nutrition. Little is known about the actual interactions between service providers and clients, particularly during the COVID-19 pandemic. The aim of this small-scale, formative study was to explore MoWs service providers' experiences and their perceptions around the benefits and challenges faced by the service, and understand how these experiences changed during the first UK national lockdown. Semi-structured interviews were conducted in September 2020 with 18 service providers of MoWs (drivers who deliver the meals, service coordinators and managers) in two local authorities in England, and analysed thematically. Participants indicated that benefits of the service encompassed those to clients (e.g. welfare checks, encouraging independence and identifying and addressing isolation and loneliness), employees (e.g. sense of pride, rewarding relationships with clients) and the wider community (e.g. reducing pressures on families), and described MoWs as the 'fourth emergency service' (e.g. being the first responders to emergency situations). Participants identified several challenges faced by the MoWs service, including organisational challenges (e.g. funding cuts and closures, lack of appropriate publicity to raise awareness of the service) and restrictions on time spent with clients. The pandemic and lockdown resulted in increased demand on resources, concerns about client and staff wellbeing and uncertainty about how the service will cope if lockdowns continue. These findings provide important insights regarding the wide benefits of MoWs and the challenges the service faces, which can be used as the formative research base to guide future interventions and policies to protect vulnerable adults, not only during the COVID-19 pandemic, but beyond.

The Pandemic Response Box─Accelerating Drug Discovery Efforts after Disease Outbreaks.

The current Covid-19 pandemic has underlined the need for a more coordinated and forward-looking investment in the search for new medicines targeting emerging health care threats. Repositioning currently approved drugs is a popular approach to any new emerging disease, but it represents a first wave of response. Behind this would be a second wave of more specifically designed therapies based on activities against specific molecular targets or in phenotypic assays. Following the successful deployment and uptake of previous open access compound collections, we assembled the Pandemic Response Box, a collection of 400 compounds to facilitate drug discovery in emerging infectious disease. These are based on public domain information on chemotypes currently in discovery and early development which have been shown to have useful activities and were prioritized by medicinal chemistry experts. They are freely available to the community as a pharmacological test set with the understanding that data will be shared rapidly in the public domain.

An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials.

The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others.

Older LGBT+ health inequalities in the UK: setting a research agenda.

Lesbian, gay, bisexual and trans+ (LGBT+) people report poorer health than the general population and worse experiences of healthcare particularly cancer, palliative/end-of-life, dementia and mental health provision. This is attributable to: (a) social inequalities, including 'minority stress'; (b) associated health-risk behaviours (eg, smoking, excessive drug/alcohol use, obesity); (c) loneliness and isolation, affecting physical/mental health and mortality; (d) anticipated/experienced discrimination and (e) inadequate understandings of needs among healthcare providers. Older LGBT+ people are particularly affected, due to the effects of both cumulative disadvantage and ageing. There is a need for greater and more robust research data to support growing international and national government initiatives aimed at addressing these health inequalities. We identify seven key research strategies: (1) Production of large data sets; (2) Comparative data collection; (3) Addressing diversity and intersectionality among LGBT+ older people; (4) Investigation of healthcare services' capacity to deliver LGBT+ affirmative healthcare and associated education and training needs; (5) Identification of effective health promotion and/or treatment interventions for older LGBT+ people, and subgroups within this umbrella category; (6) Development of an (older) LGBT+ health equity model; (7) Utilisation of social justice concepts to ensure meaningful, change-orientated data production which will inform and support government policy, health promotion and healthcare interventions.