Faith-Based Partnerships from the Perspective of the Schools: An exploratory study of partnership benefits and challenges in Philadelphia District Schools - Executive Summary

In the spring of 2008, the School District of Philadelphia (SDP) asked Research for Action to conduct an exploratory study of partnerships between faith-based organizations and schools. The goal of the study was to understand the types of supports and benefits schools receive from their faith-based partners as well as the range of outcomes and impacts that result from these partnerships. This study was based on interviews at 23 schools and surveys received from 54% of all SDP schools. The study found that although nearly half (44%) of schools in the sample had a faith-based partner, the remainder were struggling to create or maintain a partnership (27%) or had never attempted to develop a faith-based partnership (29%). Faith-based partnerships in this study also varied in their complexity, ranging from one-time events to partnerships that provided multiple services, such as use of facilities, monetary donations, mentoring, parental engagement and tutoring services. Although principals cited some challenges to their partnership related to time, funding, staffing, and retaining a consistent volunteer base, most principals also reported positive benefits from these partnerships. Principals at most schools with active faith-based partnerships believed these programs helped improve students' motivation, self-esteem, goal setting, and/or conflict resolution skills

Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model.

BackgroundToca 511 (vocimagene amiretrorepvec) is a retroviral replicating vector encoding an optimized yeast cytosine deaminase (CD). Tumor-selective expression of CD converts the prodrug, 5-fluorocytosine (5-FC), into the active chemotherapeutic, 5-fluorouracil (5-FU). This therapeutic approach is being tested in a randomized phase II/III trial in recurrent glioblastoma and anaplastic astrocytoma (NCT0241416). The aim of this study was to identify the immune cell subsets contributing to antitumor immune responses following treatment with 5-FC in Toca 511-expressing gliomas in a syngeneic mouse model.MethodsFlow cytometry was utilized to monitor and characterize the immune cell infiltrate in subcutaneous Tu-2449 gliomas in B6C3F1 mice treated with Toca 511 and 5-FC.ResultsTumor-bearing animals treated with Toca 511 and 5-FC display alterations in immune cell populations within the tumor that result in antitumor immune protection. Attenuated immune subsets were exclusive to immunosuppressive cells of myeloid origin. Depletion of immunosuppressive cells temporally preceded a second event which included expansion of T cells which were polarized away from Th2 and Th17 in the CD4+ T cell compartment with concomitant expansion of interferon gamma-expressing CD8+ T cells. Immune alterations correlated with clearance of Tu-2449 subcutaneous tumors and T cell-dependent protection from future tumor challenge.ConclusionsTreatment with Toca 511 and 5-FC has a concentrated effect at the site of the tumor which causes direct tumor cell death and alterations in immune cell infiltrate, resulting in a tumor microenvironment that is more permissive to establishment of a T cell mediated antitumor immune response

Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity.

BackgroundProdrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.MethodsHere we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor models, employing both human glioma xenografts in immunodeficient hosts and syngeneic murine gliomas in immunocompetent hosts.ResultsIn both models, a single injection of replicating vector followed by prodrug administration achieved long-term survival benefit. In the immunodeficient model, tumors recurred repeatedly, but bioluminescence imaging of tumors enabled tailored scheduling of multicycle prodrug administration, continued control of disease burden, and long-term survival. In the immunocompetent model, complete loss of tumor signal was observed after only 1-2 cycles of prodrug, followed by long-term survival without recurrence for >300 days despite discontinuation of prodrug. Long-term survivors rejected challenge with uninfected glioma cells, indicating immunological responses against native tumor antigens, and immune cell depletion showed a critical role for CD4+ T cells.ConclusionThese results support dual mechanisms of action contributing to the efficacy of RRV-mediated prodrug-activator gene therapy: long-term tumor control by prodrug conversion-mediated cytoreduction, and induction of antitumor immunity

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Improving mental health and psychosocial wellbeing in humanitarian settings: Reflections on research funded through R2HC

From Springer Nature via Jisc Publications RouterMajor knowledge gaps remain concerning the most effective ways to address mental health and psychosocial needs of populations affected by humanitarian crises. The Research for Health in Humanitarian Crisis (R2HC) program aims to strengthen humanitarian health practice and policy through research. As a significant portion of R2HC’s research has focused on mental health and psychosocial support interventions, the program has been interested in strengthening a community of practice in this field. Following a meeting between grantees, we set out to provide an overview of the R2HC portfolio, and draw lessons learned. In this paper, we discuss the mental health and psychosocial support-focused research projects funded by R2HC; review the implications of initial findings from this research portfolio; and highlight four remaining knowledge gaps in this field. Between 2014 and 2019, R2HC funded 18 academic-practitioner partnerships focused on mental health and psychosocial support, comprising 38% of the overall portfolio (18 of 48 projects) at a value of approximately 7.2 million GBP. All projects have focused on evaluating the impact of interventions. In line with consensus-based recommendations to consider a wide range of mental health and psychosocial needs in humanitarian settings, research projects have evaluated diverse interventions. Findings so far have both challenged and confirmed widely-held assumptions about the effectiveness of mental health and psychosocial interventions in humanitarian settings. They point to the importance of building effective, sustained, and diverse partnerships between scholars, humanitarian practitioners, and funders, to ensure long-term program improvements and appropriate evidence-informed decision making. Further research needs to fill knowledge gaps regarding how to: scale-up interventions that have been found to be effective (e.g., questions related to integration across sectors, adaptation of interventions across different contexts, and optimal care systems); address neglected mental health conditions and populations (e.g., elderly, people with disabilities, sexual minorities, people with severe, pre-existing mental disorders); build on available local resources and supports (e.g., how to build on traditional, religious healing and community-wide social support practices); and ensure equity, quality, fidelity, and sustainability for interventions in real-world contexts (e.g., answering questions about how interventions from controlled studies can be transferred to more representative humanitarian contexts).All studies described here were funded by Elrha’s Research for Health in Humanitarian Crises (R2HC) Programme, which aims to improve health outcomes by strengthening the evidence base for public health interventions in humanitarian crises.14pubpu

Introduction: reconsidering the region in India: mobilities, actors and development politics

In this introduction to a special issue on ‘Reconsidering the Region in India’, we aim to develop a synthetic and theoretically nuanced account of the multifarious ways in which the idea of region has been imbricated in diverse spatial, political, cultural and socio-economic configurations. We draw from various bodies of anthropological, geographic and historical literature to elaborate on three themes that we believe are central to understanding contemporary processes of region-making in India: trans-regional mobilities and connections; the actors who produce and perform regional imaginaries; and changing regional politics of development.IS

Acute Cardiovascular and Metabolic Responses to Three Modes of Treadmill Exercise in Older Adults with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative condition characterized by muscle tremors, rigidity and dyskinesis leading to balance and gait abnormalities that could alter physiologic responses during exercise. Locomotion on an aquatic treadmill (ATM) or anti-gravity treadmill (AGTM) may be a safe alternative to exercise on a traditional land treadmill (LTM) in those with PD. PUPROSE: To determine the acute cardiovascular and metabolic responses to three different modes of treadmill exercise in older adults diagnosed with Parkinson’s disease. METHODS: Eight adults diagnosed with PD (68 ± 3 years of age) completed one exercise session on an LTM, one session on an ATM, and one session on an AGTM at 50% body weight. Participants walked from 1 to 3 mph in 0.5 mph increments at 0% grade during each exercise session. Heart rate (HR), energy expenditure (EE), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured at rest and during steady-state exercise at each speed on each treadmill. Rate of perceived exertion was also measured during steady-state exercise. Rate pressure product (RPP) was calculated. RESULTS: All variables, with the exception of DBP, increased as speed increased across all treadmill modes (p \u3c 0.001). Between treadmill modes across all speeds, EE was statistically different (p = 0.025). There was a significant interaction effect for mode and speed for HR (p \u3c 0.001) and RPP (p = 0.003). At all speeds except 1.5 mph, HR was higher on the LTM versus the AGTM (p \u3c 0.05). CONCLUSION: Exercising on an ATM or an AGTM elicits similar physiologic responses to exercise on an LTM in adults with P

Changes in Balance, Gait and Motor Skills Following Treadmill Exercise in Adults with Parkinson’s Disease

Locomotion on an aquatic treadmill or anti-gravity treadmill may be a safe and effective alternative to exercise on a traditional land treadmill in those with Parkinson’s disease as the removal of body weight in these environments may allow the participant to exercise with less concern of falling at higher speeds before reaching volitional fatigue. PURPOSE: To determine the training effects of three different treadmill modalities on dynamic balance, gait, and fine motor control in older adults diagnosed with Parkinson’s disease. METHODS: Ten adults diagnosed with Parkinson’s disease (70 ± 5 years of age) completed 8 exercise sessions (4 weeks, 2x/week) each separately on a land treadmill, aquatic treadmill, and anti-gravity treadmill at 50% body weight. Two weeks separated each intervention and the order was randomized. A 4-week control period occurred at the start of the study in which no treadmill exercise was performed. Each exercise session included a 2-minute warm-up and 30 minutes at a moderate intensity. Before and after each intervention, balance, gait and fine motor control were measured. Dynamic balance and gait were assessed using a Timed-Up-and-Go test and Performance Oriented Mobility Assessment (POMA). Fine motor control was assessed with the Purdue Pegboard Test. RESULTS: The gait assessment of the POMA was significant across all time points (p = 0.028). All other variables were statistically similar (p \u3e 0.05) across all time points. CONCLUSION: Exercising on a traditional land treadmill, aquatic treadmill, or anti-gravity treadmill for 60 min/week for 4 weeks at a moderate intensity did not alter balance, gait or fine motor control in adults with Parkinson’s disease