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As part of a drug discovery program, 4-pyrazin-2-yl-1H-pyrrole-2-carboxamides were accessed along with a number of bicyclic analogues. Routes to these compounds were largely absent from the scientific literature. The synthesis of a 4-(pyrazin-2-yl)-1H-pyrrole-2-carboxamide and several fused bicyclic analogues all using standard procedures (SNAr, borylation, C–C cross couplings, hydrolysis, amide bond formation, cyclisation, halogenation, and alkylation) from readily available starting materials is reported. The synthetic sequences range from 4–12 steps per final compound, with yields of isolated intermediates ranging from 20 to ∼100%.

The city of Hawassa is growing fast, driven by construction of a flagship industrial park that is expected to attract up to 60,000 workers by 2021, mostly young women, arriving without families or dependents, and living off very low wages. Along with these young women, female-headed households; divorced, separated and widowed women; elderly women; and women with disabilities all face severe/acute shelter vulnerabilities. These groups are most likely to struggle to access both formal and informal shelter, related to their below-average income levels but also to other forms of bias and discrimination. This paper draws out key findings on gender and housing from a collaborative study investigating shelter provision in Hawassa, part of a wider research study on inclusive cities in East Africa led by the International Institute for Environment and Development (IIED). It aims to highlight specific constraints faced by women in accessing shelter, and around such issues as informality, safety and security, and infrastructure provision.

Chemical probes are valuable tools to explore the function of proteins. Incorporation of electrophiles into small molecules enables covalent capture of protein interactions and provides access to powerful technologies including chemoproteomic profiling and reactive fragment screening. Current approaches have been largely limited to protein pockets containing cysteine, so establishing strategies to target other amino acid residues is essential to expanding the applicability across the proteome. Here, we profiled sulfur(VI) fluorides (SVI-F) as reactive functionalities that can modify multiple residues including Lys, Tyr, His and Ser, thus offering utility for targeting almost any protein. These studies provided an in-depth understanding of SVI-F functionalities, including hydrolytic stability, protein reactivity and utility in chemoproteomics. Such insights offer a valuable guide for the prospective design of SVI-F-containing ligands for various chemical biology workflows and illustrate the wide range of proteins that SVI-Fs can capture, thus highlighting the opportunity for SVI-Fs to expand the liganded proteome.

Chemoresistance poses a great barrier to breast cancer treatment and is thought to correlate with increased matrix stiffness. We developed two-dimensional (2D) polyacrylamide (PAA) and three-dimensional (3D) alginate in vitro models of tissue stiffness that mimic the stiffness of normal breast and breast cancer. We then used these to compare cell viability in response to chemotherapeutic treatment. In both 2D and 3D we observed that breast cancer cell growth and size was increased at a higher stiffness corresponding to tumours compared to normal tissue. When chemotherapeutic response was measured, a specific differential response in cell viability was observed for gemcitabine in 2 of the 7 breast cancer cell lines investigated. MCF7 and T-47D cell lines showed gemcitabine resistance at 4 kPa compared to 500 Pa. These cell lines share a common phenotype of progesterone receptor (PGR) expression and, indeed, pre-treatment with the selective progesterone receptor modulator (SPRM) mifepristone abolished resistance to gemcitabine at high stiffness. Our data reveals that combined treatment with SPRMs may therefore help in reducing resistance to gemcitabine in stiffer breast tumours which are PGR positive.

IntroductionFrailty refers to a multifaceted age-related loss of physiological reserve. Aside from the immediate challenges it presents, it is also associated with various adverse health outcomes. Given our ageing population, the healthcare and societal costs resulting from frailty present a significant and growing public health challenge. Rapidly accumulating evidence suggests that resistance exercise combined with protein supplementation can reverse frailty in older adults. However, translation of these findings into practice has proven difficult, due to either a lack of clarity regarding the interventions used or the use of interventions not suitable for widespread implementation. There remains an absence of evidence-based programmes suitable for delivery to frail older adults in the community.Methods and analysisThis paper outlines the protocol for a study to examine the effect of a novel programme of exercise and protein supplementation. This intervention has been developed by an expert consensus group, specifically for delivery to frail older adults in a group setting in the community. The study will take the form of a within-subjects non-randomised trial. Participants will be assessed at baseline, then following an 8-week period of regular activity, then following the 8-week intervention. Frailty (according to the Fried Frailty criteria) will be the primary outcome measure, along with a range of secondary outcome measures (including physical performance measures, body mass composition, psychosocial assessments and frailty-related biomarkers). If shown to be feasible to implement and effective at reversing frailty, the Diet and Exercise for FRAILty (DEFRAIL) intervention may facilitate more widespread participation in resistance exercise for frail older adults.Ethics and disseminationThis study received ethical approval from the Research Ethics committees of both the Health Service Executive South-Eastern Area and Waterford Institute of Technology. Its findings will be disseminated through journal publications, conference presentations and other forms of public engagement.Trial registration numberISRCTN46458028; Pre-results.

Background Our Integrated Care Hub has been operating since mid-2017 providing patient-centred multidisciplinary team (MDT) care operating via a number of specialised care pathways. There has been an early emphasis on the response to crisis presentations and with the introduction of the Hub we now have an extensive and organised response to such presentations. We wanted to assess does this system result in earlier referral of the ‘Crisis’ patient to an Integrated Care Hub. Methods We performed a retrospective quantitative analysis of data comparing two time-periods January to June 2018 with January to April 2019 (year-to-date). The number and type of MDT contacts were classified into 4 categories: Immediate Crisis (would present to the Emergency Department within 48 hrs if not reviewed), Emerging Crisis (would present to the Emergency Department within 2 weeks if not reviewed), Stable Situation (needs optimisation), Stable Situation (no intervention). Data were extracted from File-Maker Pro. Results There were 424 MDT contacts in January-June 2018 compared with 658 MDT contacts in the year-to-date 2019. The number of patients in these time-periods presenting in ‘Immediate Crisis’ was reduced in the year-to-date 2019 - 4.41% when compared to the same time-period in 2018 – 11.79%. There was a similar reduction in ‘Emerging’ Crisis presentations in these time-periods: 15.65% in 2019 vs. 24.29% in 2018. While the patients attending that were classified as Stable Situation (needs optimisation) increased in 2019 compared to 2018 – 66.57% vs. 47.88%. Conclusion We can see from our data that the creation of our Integrated Care Hub has resulted in an increased demand for our service, however, interestingly we have found that the crisis patient load has, in fact, decreased. This suggests that we are influencing referral patterns by both recognising and intervening at an earlier stage to manage, stabilise and reverse crisis in these patients in an organised manner within the MDT.

Background The development of an Integrated Care Hub has resulted in a complete review of the triage system for older people referred to our service. Our aim was to develop a multidisciplinary triage process (MTP) to ensure patients are seen by the right person at the right time for a First Contact Assessment (FCA). Methods A quantitative retrospective analysis of referrals and frequency of multidisciplinary team input from January 2018 – June 2018, highlighted the majority of patients were seen for FCA by the staff nurse. This subsequently resulted in onward referrals to Allied Health Professionals within the ‘Hub’, and patients attended for multiple visits. A working group was formed to address these issues. This resulted in the development of the MTP where patients are triaged by the Multidisciplinary team (MDT) and allocated to the most appropriate team member based on the referring information. Following the introduction of this triage process, data analysed from November 2018 - April 2019 highlighted its impact on our service. Results In the first reference period the proportion of patients seen for FCA by each discipline was as follows; Staff nurse (SN) 53%, Clinical Nurse Specialist (CNS) 18%, Occupational Therapist (OT) 16% and Physiotherapist 9%. In the second reference period the proportions changed to the following; SN 12%, CNS 31%, OT 33%, Physiotherapist 20% and Dietitian 4%. It has reduced the number of patient visits to the ‘Hub’ and the waiting times to see the right person within the team. Conclusion Empowering supported MDT members to triage and the use of this new MTP has resulted in patients having rapid access to the most appropriate team member for FCA. It has resulted in a change in the distribution of the caseload to ensure patients are seen by the right person within the team, and at the right time for early patient centred intervention.

Background The Occupational Therapy (OT) service in the integrated care HUB team was established in January 2018. Prior to this, there was an established memory clinic, however with inconsistent access to OT. The streamlining and structuring of memory clinics further highlighted the need for post-diagnostic support for example individual sessions focusing on memory education and practical strategies to enable independence in daily activities. The integration of OT enabled person-centred strategies to be provided to individuals experiencing memory loss. Methods A retrospective analysis was completed comparing the number of OT memory patient contacts between January to June 2018 and November 2018 to April 2019 also reflecting the memory care pathway developed during this period. OT assessed all new patients experiencing memory difficulties that impacted on functional activities to initiate referral process. In April 2018, the Memory Technology Resource Room (MTRR) opened and the OT HUB using to facilitate patient contacts. The design/implementation of cognitive rehabilitation groups in May 2018 added another step to pathway. Dementia cafés were established in public cafés in the city and county area, sponsored by local care provider, also supported by HUB team. Feedback was gathered from surveys given to individuals, carers and HUB team in the Café and MTRR. Results From January to June 2018 there were 50 memory streamed patient contacts completed by the OT. From November 2018 to April 2019, 206 patient contacts were completed. These include both individual and group cognition focused sessions. Positive qualitative feedback was retrieved from attendees to MTRR and Café all indicating at least one positive outcome from post-diagnostic supports and services. Conclusion A multi-domain cognitive OT service when initiated by an integrated care HUB proves to be an effective and acceptable memory care pathway. The development of this holistic pathway enabled the person to be seen in the right place, at the right stage of their journey with memory difficulties.

Micronuclei represent the cellular attempt to compartmentalize DNA to maintain genomic integrity threatened by mitotic errors and genotoxic events. Some micronuclei show aberrant nuclear envelopes (NEs) that collapse, generating damaged DNA that can promote complex genome alterations. However, ruptured micronuclei also provide a pool of cytosolic DNA that can stimulate antitumor immunity, revealing the complexity of micronuclear impact on tumor progression. The ESCRT-III (Endosomal Sorting Complex Required for Transport-III) complex ensures NE reseals during late mitosis and is repaired in interphase. Therefore, ESCRT-III activity maybe crucial for maintaining the integrity of other genomic structures enclosed by a NE. ESCRT-III activity at the NE is coordinated by the subunit CHMP7. We show that CHMP7 and ESCRT-III protect against the genomic instability associated with micronuclei formation. Loss of ESCRT-III activity increases the population of micronuclei with ruptured NEs, revealing that its NE repair activity is also necessary to maintain micronuclei integrity. Surprisingly, aberrant accumulation of ESCRT-III are found at the envelope of most acentric collapsed micronuclei, suggesting that ESCRT-III is not recycled efficiently from these structures. Moreover, CHMP7 depletion relieves micronuclei from the aberrant accumulations of ESCRT-III. CHMP7-depleted cells display a reduction in micronuclei containing the DNA damage marker RPA and a sensor of cytosolic DNA. Thus, ESCRT-III activity appears to protect from the consequence of genomic instability in a dichotomous fashion: ESCRT-III membrane repair activity prevents the occurrence of micronuclei with weak envelopes, but the aberrant accumulation of ESCRT-III on a subset of micronuclei appears to exacerbate DNA damage and sustain proinflammatory pathways.

1.AbstractMicronuclei represent the cellular attempt to compartmentalize DNA to maintain genomic integrity threatened by mitotic errors and genotoxic events. Micronuclei show aberrant nuclear envelopes that collapse, generating damaged DNA and promoting complex genome alterations. However, ruptured micronuclei also provide a pool of cytosolic DNA that stimulates anti-tumour immunity, revealing the complexity of micronuclei impact on tumour progression.The ESCRT-III complex ensures nuclear envelope (NE) resealing during late mitosis and NE repair in interphase. Therefore, ESCRT-III activity maybe crucial for maintaining the integrity of other genomic structures enclosed by a nuclear envelope. ESCRT-III activity at the nuclear envelope is coordinated by the subunit CHMP7.We show that CHMP7 and ESCRT-III protects against the genomic instability associated with micronuclei formation. Loss of ESCRT-III activity increases the population of micronuclei with ruptured nuclear envelopes, in interphase cells. Surprisingly, ESCRT-III is retained at acentric micronuclei suggesting that ESCRT-III cannot repair these structures. Depletion of CHMP7 expression removes ESCRT-III accumulations at ruptured micronuclei, and removes the population of micronuclei with damaged DNA also containing a sensor for cytosolic DNA.Thus, ESCRT-III activity appears to protect from the consequence of genomic instability in a dichotomous fashion. Membrane repair activity prevents the occurrence of MN with weak envelopes; conversely, aberrant membrane remodelling at micronuclei generates a steady state pool of cytosolic DNA that may contribute to sustaining pro-inflammatory pathways in cancer cells.

In 2018 the World Health Organisation listed influenza pandemics as one of the top threats to global health. Influenza pandemics occur as a result of the emergence of antigenically distinct strains, which arise due to genomic re-assortment or through the acquisition of mutations. The resulting strains have different antigenic make-ups and implicate the ability of the immune system to respond quickly following infection. Particular HLA class II allomorphs including HLA-DRB1*07:01 have been linked with the occurrence of severe influenza infections and non-response to the influenza vaccine. However, other allomorphs such as HLA-DRB1*11:01 have been shown to be protective in viral diseases such as HIV and HCV, and might be important for influenza infection. The mechanism surrounding these associations of influenza infection and HLA class II molecules expression is unclear. As some individuals expressing particular HLA allomorphs are at a greater risk of developing severe influenza infection, further investigation into the mechanism of this association is warranted. Through stimulating T cells from donors expressing HLA-DRB1*11:01 or HLA-DRB1*07:01 with an influenza epitope (HA) derived from pandemic and epidemic influenza strains, we determined the level of cross-reactivity, phenotype and polyfunctionality of the responding CD4+ specific T cells. We have compared different allomorphs and provide the first insight into the molecular basis of influenza epitope recognition by different HLA class II allomorphs, and its functional impact.

Graphical abstract, Highlights • PARG and PARP inhibition both radiosensitize. • PARP and PARG inhibition both alter the DNA damage response following irradiation (IR). • PARP and PARG inhibition both alter homologous recombination following IR. • Only PARG inhibition induces rapid activation of non-homologous end-joining post-IR. • Only inhibition of PARG causes accumulation of cells in metaphase post-IR., Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the lack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radiosensitize. Further, PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed resolution of RAD51 foci compared with control cells. However, only PARG inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK) and perturbed mitotic progression. This suggests that PARG has additional functions in the cell compared with inhibition of PARP1/2/3, likely via reversal of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose) (PAR) has a different consequence to inhibiting PAR addition. Overall, our data are consistent with previous genetic findings, reveal new insights into the function of PAR metabolism following IR and demonstrate for the first time the therapeutic potential of PARG inhibitors as radiosensitizing agents.

Highlights • A synthetic lethal screen for Poly(ADP-ribose)glycohydrolase (PARG) is presented. • SiRNA and the PARG inhibitors Gallotannin and PDD00017273 are used. • PARG is synthetically lethal with BRCA1, BRCA2, PALB2, FAM175A (ABRAXAS) and BARD1. • PARG inhibition induces DNA damage, stalled replication forks and homologous recombination. • The data support the validity of PARG as a target for therapy., Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks. Here we use siRNA to show a synthetic lethal relationship between PARG and BRCA1, BRCA2, PALB2, FAM175A (ABRAXAS) and BARD1. In addition, we demonstrate that MCF7 cells depleted of these proteins are sensitive to Gallotannin and a novel and specific PARG inhibitor PDD00017273. We confirm that PARG inhibition increases endogenous DNA damage, stalls replication forks and increases homologous recombination, and propose that it is the lack of homologous recombination (HR) proteins at PARG inhibitor-induced stalled replication forks that induces cell death. Interestingly not all genes that are synthetically lethal with PARP result in sensitivity to PARG inhibitors, suggesting that although there is overlap, the functions of PARP and PARG may not be completely identical. These data together add further evidence to the possibility that single treatment therapy with PARG inhibitors could be used for treatment of certain HR deficient tumours and provide insight into the relationship between PARP, PARG and the processes of DNA repair.

There are few evaluations of social capital interventions in developing countries. By drawing on qualitative research this paper presents the strengths and weaknesses of an intervention in Cali, Colombia in light of the development of social capital as a tool for public policy. Key strengths of the intervention are that it aimed to benefit the wider community by reducing violence and that it aimed to build bonding, bridging, and linking social capital. Even in a context of high violence, an external agency can help develop social capital by promoting realistic, context-sensitive interventions that work with existing community structures and engage with the state.

With growing recognition of the social determinants of health, social capital is an increasingly important concept in international health research. Although there is relatively little experience of measuring social capital, particularly in developing countries, there are now a number of studies that allow the identification of some key issues that need to be considered when measuring social capital. After summarizing definitions and the rise of interest in the link between social capital and health, measures used in key studies of social capital and health are presented. Some important issues are then considered: obtaining a sufficiently comprehensive measure which empirically captures the latest theoretical developments in the field (particularly the concepts of cognitive, structural, bonding and bridging social capital); moving from the individual to the ecological level; consideration of confounding factors, and validity and reliability.

This article uses a social capital framework to analyse the strategies employed by two low–income communities in Guatemala City to improve their physical and social environment. The case studies provide examples of poor communities, without access to any form of insurance or welfare benefits, struggling to achieve neighbourhood development. They also demonstrate the way in which strategies can be defined by the issue of land tenure. Key strategies for development were found to be mobilization through community organization, informal links (including clientelistic relations) with powerful groups, and protest. The author concludes that social capital (within communities and between stakeholders) and some degree of security (land tenure) are critical ingredients for communities to develop effective strategies for neighbourhood development with other stakeholders.

This paper describes and discusses the role of different international agencies (including UNICEF and the World Bank) and NGOs in supporting development in El Mezquital, a settlement formed from a land invasion in Guatemala City the mid-1980s. It draws on interviews with the inhabitants and with staff from supporting agencies. The support from these international agencies and NGOs allowed considerable improvements in infrastructure and service provision, and supported important processes of community empowerment and greater status and possibilities for women. However, the paper also describes the limitations of this support, including the limited scope for participation, the projects that were planned and never implemented and the problems that the international support failed to resolve. It also describes the resentment from groups within the community with regard to what was achieved.

Social exclusion is a relatively new term currently in use in Europe to describe both the circumstances of marginalization and the processes that lead to marginalization. Social exclusion tends to be rooted in multiple forms of deprivation, related to issues such as employment status, housing, rights, education, gender or race, and is thus comprehensive in nature. There is an ongoing debate regarding the relevance of the concept to developing countries: given the differences in social and economic development between developed and developing countries, some critics argue that social exclusion is not an exportable concept. This paper seeks to review these arguments and analyze the policy implications, suggesting a possible way forward using the Sustainable Livelihoods Framework, involving multi-dimensional programs that prioritize human development and welfare, and which address exclusionary processes.

This paper describes the history of the community in El Mezquital, from the land invasion in the mid 1980s, through its consolidation and growth, until the present, drawing principally on interviews with the inhabitants and staff from supporting agencies. It analyzes the development of the different, and sometimes conflicting, community organizations and compares their different mandates and objectives. It shows important processes of community empowerment, the changing role of women and community self-help initiatives. It also describes how, in much of the settlement, basic infrastructure and services were in place and of good quality. However, it also highlights the lack of employment opportunities, how many people still live in overcrowded conditions, and the problems of violence, drug addiction and street children. It also highlights the inadequacies on the part of government agencies - including their incapacity to respond to the needs of the community, their under-estimation of community capacity and the attempts at political manipulation.

The "Learn Not to Burn" prevention program is a burn prevention curriculum sponsored by the North Carolina Jaycee Burn Center, the State Department of Public Instruction, and the North Carolina Department of Insurance Fire and Rescue Division. The goal of the program is to reduce burn-related deaths and injuries in North Carolina through burn prevention education by making the "Learn Not to Burn" curriculum available to primary school children across the state at no cost to the schools. The curriculum instrument is a reusable notebook that provides a means for teachers to integrate burn prevention into regular class subject areas. At the time of initiation of this study approximately 70% of the school systems in North Carolina had been provided with the "Learn Not to Burn" curriculum. Language: en

BackgroundThere are few studies of mental ill health among young people in developing countries.AimsTo measure the prevalence of common mental disorders among low-income young people in the city of Cali, Colombia and to examine associations with violence and social capital.MethodThe Self-Reporting Questionnaire was administered to 1057 young people aged 15–25 years. Social capital, violence, alcoholism and socio-demographic variables were also measured.ResultsWe found 255 young people (24%) with common mental disorders. Being a woman, having limited education and experiencing high levels of violence were the main risk factors for common mental disorders. Social capital did not emerge as a risk factor.ConclusionsA large burden of mental ill health among young people was found; this requires urgent interventions and more research on the mechanisms which link mental health and violence.

Mental ill health forms an increasingly significant part of the burden of disease in developing countries. The growing interest in social risk factors for mental health coincides with the development of social capital research which may further inform the social model of mental health. The objective of the study reported here was to discover if there is an independent association between social capital and mental health when taking into account an array of demographic and violence variables. A total of 1168 youth (15-25 years) in a low income community in Cali, Colombia were surveyed. Mental health was measured by a 20 item self-report questionnaire. The instrument used to measure social capital covered structural and cognitive social capital. Twenty-four per cent of the sample were probable cases of mental ill health. Females had a prevalence rate three times higher than males. Using a model which considered demographic and social capital measures as potential risk factors for mental ill health, the significant risk factors emerged as being female, having limited schooling, working in the informal sector, being a migrant, and having low trust in people. The 'classic' poverty type variables (poor education and employment) were more important than social capital, as was the commonly dominant risk factor for mental ill health-being a woman. When violence factors were added to the model, the 'trust' factor fell out and the most important risk factors became (in descending order of importance): being female; no schooling/incomplete primary; and being a victim of violence. The dominance of poverty related factors, as opposed to social capital, prompts renewed attention to the explanatory mechanisms that link income inequality and poor mental health.

Immunodominant T cell responses are important for virus clearance. However, the identification of immunodominant T cell peptide+HLA glycoprotein epitopes has been hindered by the extent of HLA polymorphism and the limitations of predictive algorithms. A simple, systematic approach has been used here to screen for new, immunodominant CD8+ T cell epitopes. The analysis targeted healthy HLA-A2+ and HLA-A2- donors. While M158A2 was consistently detected in all individual samples in our study, the response to this epitope was only immunodominant in three out of eight while, for the other five, prominent CD8+ T cell responses tended to focus on various peptides from the influenza nucleoprotein (NP) that were not presented by HLA-A2. In all the tested 7 A2- individuals, immunodominant responses all focused on NP. Importantly, most novel, immunodominant T cell epitopes identified by our study would not have been predicted by the current prediction programs as they are either too long or lacking typical HLA binding motifs. Our data stress the importance of systematic analysis for discovering HLA-dependent, immunodominant CD8+ T cell epitopes derived from viruses and tumors. Focusing on HLA-A2 and predictive algorithms may be too limiting as we seek to develop targeted immunotherapy and vaccine strategies that depend on T cell-mediated immunity.

O NE of the most significant trends of our times is the movement toward the enrichment of adult life. Leisure in this country is in-creasing, almost by accident. Out of the scientific study of adult learning, under Dr. Thorndike's direction, emerged the hopeful words, "One is never too old to learn." Books and magazine articles bear such inspiring captions as Life Begins at Forty, More Power to You, Dare To Live, Time To Live, Leisure in the Modern World, The Wise Use of Leisure, and A Challenge to Leisure. In fifty years the eight-hour workday, the Saturday afternoon holiday, the two weeks' vacation, and daylight saving time have brought leisure to millions. Nevertheless it is only about ten years ago that any large number of ordinary people began to think about leisure as a possession like food or wealth which, used well, would bring health and enjoyment; used ill, would bring misery and degeneration. Dorothy Canfield Fisher has said that leisure, if badly used, is either an active poison or a stupefying opiate, but, if well used, is the raw material out of which the deepest, most vivid, most enduring satisfactions can be shaped. A change has taken place in the moral status of leisure. The busy bee is no longer held to be an adequate moral guide; the butterfly is not regarded as immoral. Leisure is thought of as an end, desirable in itself, and not as deriving its value merely from its utility in increasing one's capacity for work. The old proverb said, "The Devil finds work for idle hands to do." It expressed a traditional suspicion of leisure, which was natural in a world in which supplies were scanty and hard to obtain. But in our world supplies are not scanty and production can easily be increased. The old proverb is irrelevant. It is God, not the Devil, who must direct leisure. When leisure takes its proper place in the esteem of mankind it will effect nothing less than a fundamental and beneficent transformation of the whole character of civilized life. To promote this transformation of the whole character of civilized life should be one of the chief aims of education and of