Charitable Trust Research Articles

HIV-1 transmission dynamics among people who inject drugs on the US/Mexico border during the COVID-19 pandemic: a prospective cohort study

We examined HIV prevalence and transmission dynamics among people who inject drugs in the U.S./Mexico border region during the COVID-19 pandemic. People who inject drugs aged ≥18 years from 3 groups were recruited: people who inject drugs who live in San Diego (SD) and engaged in cross-border drug use in Tijuana, Mexico (SD CBDUs), and people who inject drugs in SD and Tijuana (TJ) who did not engage in cross-border drug use (NCBDUs). We computed HIV prevalence at baseline and bivariate incidence-density rates (IR) at 18-month follow-up. Bayesian phylogenetic analysis was used to identify local transmission clusters, estimate their age, and effective reproductive number (Re) over time within the clusters. At baseline (n=612), 26% of participants were female, 9% engaged in sex work, and HIVprevalencewas 8% (4% SD CBDU, 4% SD NCBDU, 16% TJ NCBDU). Nine HIV seroconversions occurred over 18 months, IR: 1.357 per 100 person-years (95% CI: 0.470, 2.243); 7 in TJ NCBDU and 2 in SD CBDU. Out of 16 identified phylogenetic clusters, 9 (56%) had sequences from both the U.S. and Mexico (mixed-country). The age of three youngest mixed-country dyads (2018-2021) overlapped with the COVID-related US-Mexico border closure in 2020. One large mixed-country cluster (N=15) continued to grow during the border closure (Re=4.8, 95% Highest Posterior Density (HPD) 1.5-9.1) with 47% engaging in sex work. Amidst the COVID-19 pandemic and the border closure, cross-border HIV clusters grew. Efforts to end the HIV epidemic in the U.S. should take into account cross-border HIV-1 transmission from Tijuana. Mobile harm reduction services and coordination with municipal HIV programs to initiate anti-retroviral therapy and pre-exposure prophylaxisis are needed to reduce transmission. This research was supported by the James B. Pendleton Charitable Trust and the San Diego Center for AIDS Research.

Zedra Fiduciary Services (UK) Ltd v Attorney General: the contemporary Scope of the Statutory Cy‐près Doctrine

Historically, the cy‐près doctrine required that, upon the substantive alteration of a charitable trust, the new purposes should be ‘as near as possible’ to the old. This is no longer the case. Subject to section 67(3) of the Charities Act 2011, the redrafting court or Charity Commission must have regard to factors other than proximity of purpose. Zedra Fiduciary Services (UK) Ltd v Attorney General is the first high‐level authority to consider the meaning of the statute, and, with it, the scope of the contemporary statutory cy‐près doctrine. This note argues that the Court of Appeal read down the statutory factors conservatively, prioritising fidelity to the original objects of the trust. The note considers the method of the Court and suggests that a more creative approach might have been taken. Finally, the note considers the impact of the authority on the Charity Commission's routine, day‐to‐day cy‐près casework .

Restricted Philanthropic Gifts: Paradigm Clash between Law and Practice or Simply a Muddle?

Restricted philanthropic gifts are becoming more common, yet their legal characterisation is unsettled. Moreover, other than from anecdotal evidence, it is unclear how charities treat such gifts in practice. This article investigates the potential legal characterisations of restricted gifts and identifies the charitable trust as a commonly preferred construction by the courts. It then examines original empirical interview evidence from charities to show that, contrary to legal expectations, charities do not typically treat restricted gifts as being on charitable trust, but rather as being subject to an agreement or an extra-legal set of agreed norms with donors. This indicates a move away from a publicly regulated arrangement (the charitable trust) to private ordering arrangements, which has implications for the pursuit of public goals and the degree of power afforded to donors over social, cultural and environmental projects.

Abstract 4128: Biofield therapy suppressed invasion and metastases of human pancreatic cancer

Abstract The NIH categorizes Biofield Therapy (BT) as therapeutic approaches within energy medicine that involve using the body's energy field (biofield) for therapeutic benefit. Although controversial, in some cases devices have been developed that mimic the electromagnetic fields (EMF) that are emitted from people when delivering BTs. We previously reported that BT significantly inhibited the growth of pancreatic cancer cells and liver metastasis in their relevant animal models mediated in part through modification of the cell cycle, reductions in cell voltage potentials, and down regulation of PI3K/Akt pathways. We expanded this research to examine the potential role of BT in anti-invasiveness in human pancreatic ductal adenocarcinoma (PDAC) cells and animal models. We found that PANC-1 cells treated with BT (15 min) displayed 55% less invading cells than that of untreated incubator control and sham control cells (P < 0.001). Similar results were observed in human PDAC L3.7 cells and mouse pancreatic cancer KPCY cells. These experiments were replicated 8 times for Panc-1 cells and 4 times for L3.7 cells. Additionally, migration capacity was tested using the transwell migration and scratch assays. Consistent with the result of cell invasion assays, BT treatment also led to significant reduction of migration of PANC-1 and L3.7 cells by 34% and 41%, respectively, compared to sham controls. Two additional therapists independently replicated the anti-invasiveness and anti-migratory effects of BT on these PDAC cells. This suggests the replicability of these findings across studies and therapists. In a repeated PANC-1 mouse orthotopic model, we found that only a third of BT treated mice had visible liver nodules whereas liver metastasis was observed in more than half of mice in the untreated colony control and sham control groups. Furthermore, BT treatment significantly reduced liver tumor burden by 73% compared to that of the sham control group (p < 0.05), which was similar to that observed in the previous study. Similar to the prior PANC-1 mouse model, in the current study BT treatment had only a moderate impact on the growth of primary pancreatic tumor. We assessed certain markers indicative of cell status as well as pathways associated with migration and invasion and these will be presented at the meeting. Our findings suggest that exposure to BT reduced cellular invasion and migration processes and profoundly reduced metastasis of pancreatic tumor in an animal model. This study is in part supported by Emerald Gate Charitable Trust. Citation Format: Peiying Yang, Sharmistha Chakraborty, Phuong Nguyen, Defeng Deng, Andrew Cusimano, Daoyan Wei, Lorenzo Cohen. Biofield therapy suppressed invasion and metastases of human pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4128.

Managing <i>Waqf</i> Land in Indonesia: ANP-Driven Strategies

This study aims to elaborate on the main problems of developing <i>waqf</i> (perpetual charitable trust) land in Indonesia and provide identifiable empirical results of the main problem, solutions, and strategy as a framework to guide stakeholders to produce policy recommendations appropriately using the Analytical Networking Process (ANP) approach. Several steps were followed: decomposition, model quantification, and result analysis. The initial data was collected through a literature review, focus group discussion, and in-depth interviews. This data was used to construct an ANP framework, which was then analyzed using <i>Superdecision</i> software to obtain conclusions. This study found that the most considerable aspect regarding <i>waqf</i> land development in Indonesia was the managerial issue. Unprofessional management has become a top priority. The <i>waqf</i> institution should increase its responsibility to the public, which is the highest rank of solution regarding the <i>waqf</i> land problems. This research also derived the strategy recommendations: reforming and strengthening <i>waqf</i> regulation.

Piercing the corporate veil—the trust connection

Abstract The principle of separate legal entity which forms the basic foundation of company law provides for the company as a separate legal entity. This results in the formation of a veil, so to say, that protects the liability of the directors or other related companies from incurring liability. Under the Doctrine of Piercing the Corporate Veil, the said veil can be disregarded in certain circumstances. Historically, this principle has been restricted to companies incorporated under statute. However, recently, a High Court of India applied the doctrine to a Charitable Trust which is a non-corporate body. With Courts of India not providing any contours or sound reasoning towards the extension of the doctrine to non-corporate bodies, this article examines the application of the doctrine on charitable trusts, the flaws and problems that arise from such application and the possible solutions for the same while tracing evolved and developing jurisprudence surrounding the doctrine in taxation cases and trusts.

The Charge of the Light Cy-près

Abstract The cy-près doctrine empowers courts to rescue funds held on a frustrated charitable trust by applying them to a different purpose. In Zedra Fiduciary Services (UK) Ltd v HM Attorney General [2023] EWCA Civ 133, the Court of Appeal upheld a decision applying the funds of a substantial and unusual charitable trust towards relieving the UK’s national debt. In this article, we offer a brief history of the trust before considering the Court of Appeal’s judgment. We argue that the decision is justified, but reveals flaws in legislative reforms, which have sought to create more flexibility in the doctrine.

A263 IRONING OUT THE DETAILS: CROHN’S DISEASE PATIENT DERIVED MACROPHAGES ARE MORE SUSCEPTIBLE TO FERROPTOSIS

Abstract Background Death of intestinal epithelial cells is ubiquitous in Crohn’s disease (CD) but the death of immune cells such as macrophages is less explored. We have found that monocyte derived macrophages from patients with active CD are more susceptible to H2O2-induced cytotoxicity but the form of regulated cell death these cells undergo remains to be elucidated. Selenium (Se)—a common micronutrient deficiency in patients with CD—is used in the synthesis of selenoproteins that have antioxidant properties (e.g., glutathione peroxidases (GPx)) and are highly expressed in macrophages. Whether Se deficiency plays a role in the increased cytotoxicity also remains to be elucidated. Aims To determine the form of cell death of macrophages in response to H2O2-induced cytotoxicity and whether selenium deficiency plays a role in the increased susceptibility to H2O2-induced cytotoxicity. Methods Blood collected from healthy volunteers and patients with active CD was analyzed for serum GPx activity. Monocytes isolated by plastic adherence were treated with M-CSF (10ng/ml, 7d) to derive macrophages. Macrophages were treated with H2O2 (500μm, 2h) and lactate dehydrogenase release was measured. GPX1, SLC7A11 and PTGS2 mRNA expression were determined by qPCR. The presence of cleaved caspase 3 was determined by immunoblotting and IL-1β by ELISA. Lipid peroxidation a marker of ferroptosis was assessed by staining macrophages with Bodipy C-11 (± liproxstatin-1, an inhibitor of ferroptosis). Results CD macrophages were two times more susceptible to H2O2-evoked cell death. In response to H2O2 macrophages did not express cleaved caspase 3 or IL-1β, but there was an induction of ferroptosis markers (SLC7A11 and PTGS2). Moreover, lipid peroxidation was induced and could be blocked with liproxstatin-1. Dietary Se intake did not differ between groups but serum GPx activity was greater in patients with CD compared to control. In contrast, GPX1 mRNA expression and GPx1 protein expression were decreased in CD macrophages compared to healthy controls. Conclusions Macrophages derived from patients with CD are inherently more sensitive to ferroptosis potentially through reduced GPx1 expression. Future studies warrant testing if GPx1 prevents ferroptotic macrophage cell death and if it holds therapeutic relevance in CD pathophysiology. Funding Agencies Helmsley Charitable Trust, Crohn's and Colitis Foundation of America

A261 INVESTIGATING THE RELATIONSHIP BETWEEN AIR POLLUTION AND BIOMARKERS OF CROHN’S DISEASE IN CANADA

Abstract Background The cause of Crohn's disease (CD) remains unclear. Studies suggest a potential connection between CD and air pollution, with a higher occurrence of CD found in areas with higher pollution levels. Aims Our study sought to explore this potential connection by investigating the relationship between components of air pollution and biomarkers indicative of CD risk. Methods In total, 2,256 healthy first-degree relatives of patients with CD were recruited as part of the CCC-GEM Project. We assessed baseline samples of gut permeability using the urinary fractional excretion ratio of lactulose-to-mannitol (LMR), subclinical inflammation via fecal calprotectin (FCP), and stool microbiome using 16S-rRNA sequencing. Air pollutant (n=8) concentrations were obtained from the National Air Pollution Surveillance Database. We used postal code to estimate air pollutant exposure via inverse distance weighting, averaging data for one (pollutant1-month), three (pollutant3-months), and twelve months (pollutant12-months) prior to recruitment. We used generalized estimating equation models to find associations between pollutant exposure and LMR, FCP, and microbiome composition, adjusting for age, sex, air pollutant seasonality, familial income, and familial relationships. Significance was set at pampersand:003C0.05, and false discovery rate (q) correction was applied to microbiome analysis. Results We observed a negative association between particulate matter (PMµg/m3), PM101-month, and PM103-months and LMR (β=-0.06[-0.09, -0.01], p=6.0×10-3 and β=-0.05[-0.07, -0.01], p=7.6×10-4), and a positive association between PM103-months and FCP (β=0.05[0.001, 0.10], p=0.04). 12-month pollutant exposure was associated with seven microbial taxa in a logit model. Notably, Carbon monoxide (CO)12-months was associated with Oscillospiraceae UCG_003 (β=3.49[1.53, 5.46], q=0.03). PM2512-months was associated with Marvinbryantia (β=0.12[0.06, 0.18], q=0.02). PM1012-months was associated with Moryella (β=0.07[0.03, 0.10], q=0.02). Nitrogen dioxide (NO)12-months was associated with Coprobacter and Ruminococcaceae UBA1819 (β=0.05[0.02, 0.07], q=0.03 and β=0.05[0.02, 0.08], q=0.04). NOX12-months was also associated with Ruminococcaceae_UBA1819 as well as Intestinimonas (β=0.03[0.01, 0.04], q=0.04 and β=0.03[0.01, 0.04], q=0.02). Conclusions Air pollutant exposure was associated with biomarkers of gut inflammation, barrier function, and microbiome composition. A shorter exposure (1/3 months) primarily affected FCP and LMR, while longer-term exposure (12 months) exerted a discernible impact on the microbiome. These findings suggest that exposure to air pollution may modulate the gut barrier function, inflammation, and the gut microbiome, biomarkers that are associated with the development of CD. Funding Agencies Crohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III, Leona M. and Harry B. Helmsley Charitable Trust, Dr. Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases

A68 PERCEPTIONS OF ADOLESCENTS AND YOUNG ADULTS WITH INFLAMMATORY BOWEL DISEASE REGARDING A BIOPSYCHOSOCIAL TRANSITION INTERVENTION: A QUALITATIVE STUDY

Abstract Background The transition from the pediatric to adult care healthcare system for adolescents and young adults (AYAs) with inflammatory bowel disease (IBD) is complex. This group requires support to prepare for and adapt to adult care due to the manifestation of the disease, expectations for self-management, and simultaneous life transitions. To address this need, a multi-site randomized controlled trial (RCT) is being conducted to evaluate the impact of a multimodal transition intervention on functional, clinical, and psychosocial outcomes for AYAs with IBD. An embedded qualitative study explored participants’ perspectives of the intervention's acceptability and appropriateness to support the translation of findings into practice. Aims Using in-depth individual qualitative interviews with a purposive sample of AYAs in both the intervention and control arms of the RCT, this qualitative study aimed to understand AYAs’ experiences preparing for and undergoing service transitions, developing self-management skills, and engaging with the intervention. Methods Semi-structured interviews were held via videoconference with 21 AYAs aged 16-18 years participating in the RCT (intervention arm n=11; control arm n=10) in Toronto, Canada. Purposive sampling was used to recruit AYAs with diverse demographic and clinical characteristics at different stages of the healthcare transition. Interviews were audio-recorded, transcribed verbatim, and analyzed using an inductive approach to reflexive thematic analysis. Results The analysis yielded four overarching themes related to 1) individual, familial, and system-level factors promoting transition readiness, 2) areas of strength and areas for growth regarding self-management skill development, 3) perceptions of the multimodal transition intervention, including barriers and facilitators to engagement, and 4) recommendations for future transition care, including refinement of the intervention. Findings to date indicate the criticality of considering AYAs’ support systems, learning styles, and communication preferences when designing and implementing transition interventions. The qualitative data analysis is ongoing, and the full results will be presented. Conclusions The perspectives of AYAs with IBD can inform the development and refinement of clinical interventions, ensuring they are tailored to recipients’ unique needs and preferences and promote engagement and skill development during pediatric-adult transitions. Funding Agencies CCCThe Leona M. and Harry B. Helmsley Charitable Trust

Understanding the current acute aortic syndrome (AAS) pathways-The Collaborative Acute Aortic Syndrome Project (CAASP) protocol.

Acute aortic syndrome (AAS) is an emergency associated with high peri-hospital mortality rates. Variable clinical presentation makes timely diagnosis challenging and such delays in diagnosis directly impact patient outcomes. The aims of the Collaborative Acute Aortic Syndrome Project (CAASP) are to characterise and evaluate the current AAS pathways of a cohort of hospitals in the UK, USA and New Zealand to determine if patient outcomes are influenced by the AAS pathway (time to hospital admission, diagnosis and management plan) and demographic, social, geographic and patient-specific factors (clinical presentation and comorbidities). The objectives are to describe different AAS pathways and time duration between hospital admission to diagnosis and management plan instigation, and to compare patient outcomes between pathways. The study is a multicentre, retrospective service evaluation project of adult patients diagnosed on imaging with AAS. It will be coordinated by the UK National Interventional Radiology Trainee Research (UNITE) network and Vascular and Endovascular Research Network (VERN) in conjunction with The Aortic Dissection Charitable Trust (TADCT). All AAS cases diagnosed on imaging between 1st January 2018 to 1st June 2021 will be included and followed-up for 6 months. Eligibility criteria include aortic dissection (AD) Type A, Type B, non A/B, penetrating aortic ulcer, and intramural haematoma. Exclusion criteria are non-AAS pathology, acute on chronic AAS, and age<18. This project will evaluate patient demographics, timing of presentation, patient symptoms, risk factors for AD, physical examination findings, timing to imaging and treatment, hospital stay, and mortality. Univariate and multivariate analysis will be used to identify predictors associated with prolonged time to diagnosis or treatment and mortality at 30 days.

Repeat placental growth factor-based testing in women with suspected preterm pre-eclampsia (PARROT-2): a multicentre, parallel-group, superiority, randomised controlled trial

Placental growth factor (PlGF)-based testing has high diagnostic accuracy for predicting pre-eclampsia needing delivery, significantly reducing time to diagnosis and severe maternal adverse outcomes. The clinical benefit of repeat PlGF-based testing is unclear. We aimed to determine whether repeat PlGF-based testing (using a clinical management algorithm and nationally recommended thresholds) reduces adverse perinatal outcomes in pregnant individuals with suspected preterm pre-eclampsia. In this multicentre, parallel-group, superiority, randomised controlled trial, done in 22 maternity units across England, Scotland, and Wales, we recruited women aged 18 years or older with suspected pre-eclampsia between 22 weeks and 0 days of gestation and 35 weeks and 6 days of gestation. Women were randomly assigned (1:1) to revealed repeat PlGF-based testing or concealed repeat testing with usual care. The intervention was not masked to women or partners, or clinicians or data collectors, due to the nature of the trial. The trial statistician was masked to intervention allocation. The primary outcome was a perinatal composite of stillbirth, early neonatal death, or neonatal unit admission. The primary analysis was by the intention-to-treat principle, with a per-protocol analysis restricted to women managed according to their allocation group. The trial was prospectively registered with the ISRCTN registry, ISRCTN 85912420. Between Dec 17, 2019, and Sept 30, 2022, 1253 pregnant women were recruited and randomly assigned treatment; one patient was excluded due to randomisation error. 625 women were allocated to revealed repeat PlGF-based testing and 627 women were allocated to usual care with concealed repeat PlGF-based testing (mean age 32·3 [SD 5·7] years; 879 [70%] white). One woman in the concealed repeat PlGF-based testing group was lost to follow-up. There was no significant difference in the primary perinatal composite outcome between the revealed repeat PlGF-based testing group (195 [31·2%]) of 625 women) compared with the concealed repeat PlGF-based testing group (174 [27·8%] of 626 women; relative risk 1·21 [95% CI 0·95-1·33]; p=0·18). The results from the per-protocol analysis were similar. There were four serious adverse events in the revealed repeat PlGF-based testing group and six in the concealed repeat PlGF-based testing group; all serious adverse events were deemed unrelated to the intervention by the site principal investigators and chief investigator. Repeat PlGF-based testing in pregnant women with suspected pre-eclampsia was not associated with improved perinatal outcomes. In a high-income setting with a low prevalence of adverse outcomes, universal, routine repeat PlGF-based testing of all individuals with suspected pre-eclampsia is not recommended. Tommy's Charity, Jon Moulton Charitable Trust, and National Institute for Health and Care Research Guy's and St Thomas' Biomedical Research Centre.

Lethal means counseling can help prevent suicide by firearms

Pointing to the need for effective suicide risk screenings by health care professionals, especially given that more than half of suicide deaths in 2022 involved firearms, a new article published Jan. 23 by The Pew Charitable Trust addresses the need for lethal means counseling for people at risk of suicide and with access to guns.

P677 The Oxford Anti-TNF Study of Immunogenicity and Sustained Response (OASIS-IBD): Analysis of 40,000 Patient Years of Anti-TNF Use

Abstract Background Anti-TNF therapy is established as a mainstay in IBD management. Recent data raise controversies regarding efficacy of these agents, sustainability of response, and identification of factors that may influence outcomes, including dose escalation and need for long-term concurrent immunosuppression (Lancet Gastro.Hep.2019;4:341). Methods We report a retrospective cohort study of 699 IBD patients on anti-TNF at our centre between 2005-2022. Clinical data were obtained from patient records and pharmacy database (TABLE 1). Primary outcomes were overall loss of response (LOR) at any timepoint; and secondary LOR (after an initial clinical response to therapy). Cox regression analysis was performed to identify variables independently affecting outcome. Kaplan-Meyer survival curves were constructed to demonstrate overall response rates (persistence on drug) and secondary LOR (Figure 1a-d). Dose adjustments were made proactively in a Virtual Clinic. Results 204 patients had a diagnosis of ulcerative colitis (UC), 481 Crohn’s Disease (CD) and 14 IBD-unclassified. 126 patients received both infliximab (IFX) and adalimumab (ADA). Median duration on IFX was 42 months (range 0-204); median duration on ADA was 48.5 months (range 0-180). 48% of patients on IFX underwent dose escalation, as did 40% on ADA. Overall, 58 patients (7.6%) remained on treatment at 120 months. Overall survival rates for IFX at 12 months were 83% (82%CD vs. 82%UC); and at 36 months were 71% (69%CD vs. 74%UC). Overall survival rates for ADA at 12 months were 84% (89%CD vs. 59%UC); and at 36 months were 72% (78% CD vs. 42% UC) (Figure 1a-b). Secondary LOR rates for IFX at 12 months were 6% (5%CD vs. 9%UC); and at 36 months were 16% (15%CD vs.19%UC). Secondary LOR rates for ADA at 12 months were 7% (5%CD vs. 19%UC); and at 36 months were 16% (12% CD vs. 42% UC) (Figure 1c-d). There was no difference in survival analysis for IFX between CD and UC. On Cox regression analysis, for IFX, immunomodulation was associated with reduction in overall LOR (HR=0.48, p=1.07e-05) but not secondary LOR (HR=0.78, p=0.31) (Figure 1e-f). For ADA, outcomes were better for CD vs. UC for both overall LOR (HR=0.35, p=3.29e-07) and secondary LOR (HR=0.35, p=9.99e-05). Conclusion We demonstrate encouraging response rates in the first three years of therapy, with a small proportion remaining on therapy beyond 120 months. Survival rates on IFX were similar for UC and CD, but for ADA were significantly lower in UC. Secondary LOR was not affected by immunomodulation. Further analysis of relation to drug levels, dose escalation and genotyping is underway. This work was supported by The Leona M &amp; Harry B Helmsley Charitable Trust.

Out-of-pocket payment and financial risk protection for breast cancer treatment: a prospective study from India

Available data on cost of cancer treatment, out-of-pocket payment and reimbursement are limited in India. We estimated the treatment costs, out-of-pocket payment, and reimbursement in a cohort of breast cancer patients who sought treatment at a publicly funded tertiary cancer care hospital in India. A prospective longitudinal study was conducted from June 2019 to March 2022at Tata Memorial Centre (TMC), Mumbai. Data on expenditure during each visit of treatment was collected by a team of trained medical social workers. The primary outcome variables were total cost (TC) of treatment, out-of-pocket payment (OOP), and reimbursement. TC included cost incurred by breast cancer patients during treatment at TMC. OOP was defined as the total cost incurred at TMC less of reimbursement. Reimbursement was any form of financial assistance (cashless or repayment), including social health insurance, private health insurance, employee health schemes, and assistance from charitable trusts, received by the patients for breast cancer treatment. Of the 500 patients included in the study, 45 discontinued treatment (due to financial or other reasons) and 26 died during treatment. The mean TC of breast cancer treatment was ₹258,095/US$3531 (95% CI: 238,225, 277,934). Direct medical cost (MC) accounted for 56.3% of the TC. Systemic therapy costs (₹50,869/US$696) were higher than radiotherapy (₹33,483/US$458) and surgery costs (₹25,075/US$343). About 74.4% patients availed some form of financial assistance at TMC; 8% patients received full reimbursement. The mean OOP for breast cancer treatment was ₹186,461/US$2551 (95% CI: 167,666, 205,257), accounting for 72.2% of the TC. Social health insurance (SHI) had a reasonable coverage (33.1%), followed by charitable trusts (29.6%), employee health insurance (5.1%), private health insurance (4.4%) and 25.6% had no reimbursement. But SHI covered only 40.1% of the TC of treatment compared to private health insurance that covered as much as 57.1% of it. Both TC and OOP were higher for patients who were younger, belonged to rural areas, had a comorbidity, were diagnosed at an advanced stage, and were from outside Maharashtra. In India, the cost and OOP for breast cancer treatment are high and reimbursement for the treatment flows from multiple sources. Though many of the patients receive some form of reimbursement, it is insufficient to prevent high OOP. Hence both wider insurance coverage as well as higher cap of the insurance packages in the health insurance schemes is suggested. Allowing for the automatic inclusion of cancer treatment in SHI can mitigate the financial burden of cancer patients in India. This work was funded by an extramural grant from the Women's Cancer Initiative and the Nag Foundation and an intramural grant from the International Institute of Population Sciences, Mumbai.

Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers.

Accurate detection of graft-versus-host disease (GVHD) is a major challenge in the management of patients undergoing hematopoietic stem cell transplantation (HCT). Here, we demonstrated the use of circulating cell-free DNA (cfDNA) for detection of tissue turnover and chronic GVHD (cGVHD) in specific organs. We established a cocktail of tissue-specific DNA methylation markers and used it to determine the concentration of cfDNA molecules derived from the liver, skin, lungs, colon, and specific immune cells in 101 patients undergoing HCT. Patients with active cGVHD showed elevated concentrations of cfDNA, as well as tissue-specific methylation markers that agreed with clinical scores. Strikingly, transplanted patients with no clinical symptoms had abnormally high levels of tissue-specific markers, suggesting hidden tissue turnover even in the absence of evident clinical pathology. An integrative model taking into account total cfDNA concentration, monocyte/macrophage cfDNA levels and alanine transaminase was able to correctly identify GVHD with a specificity of 86% and precision of 89% (AUC of 0.8). cfDNA markers can be used for the detection of cGVHD, opening a window into underlying tissue dynamics in patients that receive allogeneic stem cell transplants. This work was supported by grants from the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, The Israel Science Foundation, the Waldholtz/Pakula family, the Robert M. and Marilyn Sternberg Family Charitable Foundation and the Helmsley Charitable Trust (to YD).

Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen.

BACKGROUNDVaccination is typically administered without regard to site of prior vaccination, but this factor may substantially affect downstream immune responses.METHODSWe assessed serological responses to initial COVID-19 vaccination in baseline seronegative adults who received second-dose boosters in the ipsilateral or contralateral arm relative to initial vaccination. We measured serum SARS-CoV-2 spike-specific Ig, receptor-binding domain-specific (RBD-specific) IgG, SARS-CoV-2 nucleocapsid-specific IgG, and neutralizing antibody titers against SARS-CoV-2.D614G (early strain) and SARS-CoV-2.B.1.1.529 (Omicron) at approximately 0.6, 8, and 14 months after boosting.RESULTSIn 947 individuals, contralateral boosting was associated with higher spike-specific serum Ig, and this effect increased over time, from a 1.1-fold to a 1.4-fold increase by 14 months (P < 0.001). A similar pattern was seen for RBD-specific IgG. Among 54 pairs matched for age, sex, and relevant time intervals, arm groups had similar antibody levels at study visit 2 (W2), but contralateral boosting resulted in significantly higher binding and neutralizing antibody titers at W3 and W4, with progressive increase over time, ranging from 1.3-fold (total Ig, P = 0.007) to 4.0-fold (pseudovirus neutralization to B.1.1.529, P < 0.001).CONCLUSIONSIn previously unexposed adults receiving an initial vaccine series with the BNT162b2 mRNA COVID-19 vaccine, contralateral boosting substantially increases antibody magnitude and breadth at times beyond 3 weeks after vaccination. This effect should be considered during arm selection in the context of multidose vaccine regimens.FUNDINGM.J. Murdock Charitable Trust, OHSU Foundation, NIH.

The Reform of Charitable Constitutional Purposes: Should Australia Follow England’s Path in Aligning Charitable Trusts and Corporations?

The Reform of Charitable Constitutional Purposes: Should Australia Follow England’s Path in Aligning Charitable Trusts and Corporations?

Digital Empowerment:Transforming Rural Women through Digital Marketing Skills in the District of Fatehgarh Sahib

Women empowerment means giving equal power and opportunities to women as men without any kind of discrimination. The role of NGOs has shifted from merely ‘gap-filling’ to ‘capacity building and empowerment’. Mehar Baba Charitable Trust, Bassi Pathana, Punjab, India has beenselected by CFLI1for the project. This project has helped women in many ways to lead from the front and be part of decision-making at the local level. This project aimed at empowering rural women in Fatehgarh Sahib through the acquisition of digital marketing skills.The study is based on primary and secondary sources of data collection. The present study analyses and evaluates the implementation of the project and itsimpact on the society. The findings highlight that involving stakeholders from the mobilization to follow-up processes has a long-term impact on society as a whole. Women broke the chains of their traditional roles and stepped out of their four walls to learn new skills and set an example for other women in society. By assessing the current knowledge and challenges faced by these women, a tailored training program was developed and implemented. Additionally, it explored the role of mentorship and support networks in sustaining their success. The findings from this research will inform future scalability and replication of the project in other regions

In search of a non-anthropocentric middle-range theory of the firm: On how the Patagonia Purpose Trust granted a controlling stake to nature

Patagonia, an outdoor clothing company thrust into the limelight by a New York Times full-page ad that in 2001 invited customers not to buy its own gear, has recently responded to the inherently low capacity of firms to supply ecosystem services. Since the firm is a generic term encompassing many different bundles of property rights, the specific mechanism of the Patagonia Purpose Trust is researched to find whether it has plausibly locked the company in on preserving ecosystems through its environmentally driven community investment, product re-design, and supply chain overhaul. A mechanism-based methodology is employed, organizing the units of observation in keeping with a formal ontology and benchmarking Patagonia's mechanism against the generic templates of a corporation and a charitable Trust to highlight what is distinct about Patagonia. The findings are that, in a nutshell, Patagonia's mechanism consists of: 1) increasing the opportunity cost of not redressing a breach of purpose by designating an ascertained beneficiary with an unequivocal interest in Nature's preservation; 2) offsetting fiduciaries' influence on asset management with a countervailing mechanism; and 3) designing a procedure centered on the renewal of credible co-trustees to keep checking on fiduciaries in the long run.