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.

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.

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.

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.

'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.

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.

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.

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.

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 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.

Substituted Aminoacetamides as Novel Leads for Malaria Treatment.

Herein we describe the optimization of a phenotypic hit against Plasmodium falciparum based on an aminoacetamide scaffold. This led to N-(3-chloro-4-fluorophenyl)-2-methyl-2-{[4-methyl-3-(morpholinosulfonyl)phenyl]amino}propanamide (compound 28) with low-nanomolar activity against the intraerythrocytic stages of the malaria parasite, and which was found to be inactive in a mammalian cell counter-screen up to 25 µm. Inhibition of gametes in the dual gamete activation assay suggests that this family of compounds may also have transmission blocking capabilities. Whilst we were unable to optimize the aqueous solubility and microsomal stability to a point at which the aminoacetamides would be suitable for in vivo pharmacokinetic and efficacy studies, compound 28 displayed excellent antimalarial potency and selectivity; it could therefore serve as a suitable chemical tool for drug target identification.

"It's a nice country but it's not mine": Exploring the meanings attached to home, rurality and place for older lesbian, gay and bisexual adults.

An ageing population across European nations, including the United Kingdom, brings with it new challenges for health and social care services and precipitates social policy initiatives targeted at meeting the care and support needs of a rapidly expanding number of older people. Ageing in place is one such policy driver-policy efforts that seek to promote the maintenance of older citizens residing in their own homes for as long as possible with minimal state intervention. Current generations of older lesbian, gay and bisexual (LGB) people have endured homophobia throughout their life histories, and sexual identity can shape perceptions and experiences of ageing, including experiences of home life, community and place. Our objective is to examine the meanings attached to home and place for older LGB adults living independently across three dimensions: rural places as "home," connections to LGB communities, and social care provision in the home. We present interview findings from a mixed-methods study on the social inclusion of older LGB adults in Wales. Twenty-nine LGB-identifying adults (50-76 years) self-selected to participate in semistructured interviews between 2012 and 2013. Thematic findings from interviews indicate varying and contradictory meanings attached to home life in rural places, the importance of connection to communities of identity across geographical and online localities, and a high degree of ambivalence towards the prospect of receiving social care services in the home. We argue that a more nuanced understanding of the subjective meanings attached to home, rurality and community for older LGB people is needed to fully support LGB citizens to continue to live independently in their homes.

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.

Turning the Co-Production Corner: Methodological Reflections from an Action Research Project to Promote LGBT Inclusion in Care Homes for Older People.

Background: Older lesbian, gay, bisexual and trans (LGBT) residents are often invisible in long-term care settings. This article presents findings from a community-based action research project, which attempted to address this invisibility through co-produced research with LGBT community members. Particular Question: What conditions enable co-produced research to emerge in long-term residential care settings for older people? Aims of Project: To analyse outcomes and challenges of action-oriented, co-produced research in the given context. In particular, we explore how co-production as a collaborative approach to action-orientated research can emerge during the research/fieldwork process; and reflect critically on the ethics and effectiveness of this approach in advancing inclusion in context. METHODS: The project was implemented across six residential care homes in England. Reflections are based on qualitative evaluation data gathered pre- and post-project, which includes 37 interviews with care home staff, managers and community advisors (two of whom are co-authors). Results and Conclusions: We discuss how the co-production turn emerged during research and evaluate how the politics of this approach helped advance inclusion-itself crucial to well-being. We argue for the value of co-produced research in instigating organizational change in older people's care environments and of non-didactic storytelling in LGBT awareness-raising amongst staff.

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.

Developing inclusive residential care for older lesbian, gay, bisexual and trans (LGBT) people: An evaluation of the Care Home Challenge action research project.

There have been substantial achievements in legislative and human rights for lesbian, gay, bisexual and transgender (LGBT) older people and their visibility in health and social care has equally increased. These appear to have surpassed the ability of care services to meet their needs given documented concerns about the accessibility, inclusiveness and safety of care services particularly institutionalised care. This requires systemic change not easy to operationalise. This paper describes an action research initiative where six care homes belonging to a national care provider, collaborated to assess and develop their services with the support of local LGBT "Community Advisors" and academic partners. Framed within Rogers' (2003) change management framework and combined with a participatory leadership approach, a programme of intervention was implemented comprising structured activities around seven key areas thought to promote LGBT inclusion. A formal evaluation was conducted involving 35 pre- and post-intervention qualitative interviews with 18 people (community advisors; care home managers and senior managers). The findings are presented across three key themes (1) starting points on the journey; (2) challenges encountered along the journey (organisational and interpersonal); and (3) making change happen; opportunities, initiatives and gains. We make recommendations on the value of a programme approach for achieving tangible outcomes that demonstrate increased inclusion for older LGBT people living in long-term care settings.

Design and Synthesis of Orally Bioavailable Piperazine Substituted 4(1H)-Quinolones with Potent Antimalarial Activity: Structure-Activity and Structure-Property Relationship Studies.

Malaria deaths have been decreasing over the last 10-15 years, with global mortality rates having fallen by 47% since 2000. While the World Health Organization (WHO) recommends the use of artemisinin-based combination therapies (ACTs) to combat malaria, the emergence of artemisinin resistant strains underscores the need to develop new antimalarial drugs. Recent in vivo efficacy improvements of the historical antimalarial ICI 56,780 have been reported, however, with the poor solubility and rapid development of resistance, this compound requires further optimization. A series of piperazine-containing 4(1H)-quinolones with greatly enhanced solubility were developed utilizing structure-activity relationship (SAR) and structure-property relationship (SPR) studies. Furthermore, promising compounds were chosen for an in vivo scouting assay to narrow selection for testing in an in vivo Thompson test. Finally, two piperazine-containing 4(1H)-quinolones were curative in the conventional Thompson test and also displayed in vivo activity against the liver stages of the parasite.