Harnessing Collaborative Technologies: Helping Funders Work Together Better

This report was produced through a joint research project of the Monitor Institute and the Foundation Center. The research included an extensive literature review on collaboration in philanthropy, detailed analysis of trends from a recent Foundation Center survey of the largest U.S. foundations, interviews with 37 leading philanthropy professionals and technology experts, and a review of over 170 online tools.The report is a story about how new tools are changing the way funders collaborate. It includes three primary sections: an introduction to emerging technologies and the changing context for philanthropic collaboration; an overview of collaborative needs and tools; and recommendations for improving the collaborative technology landscapeA "Key Findings" executive summary serves as a companion piece to this full report

Foundation Giving for Nonprofit and Philanthropic Infrastructure 2004-2012

In the special report Foundation Giving for Nonprofit and Philanthropic Infrastructure 2004-2012, Foundation Center presents the first-ever analysis of U.S. foundation support globally for nonprofit and philanthropic infrastructure organizations and services. This analysis spans nine years of funding, encompassing 717 different funders and 12,200 grants. It finds that a set of the largest U.S. foundations provided $134 million in support for nonprofit and philanthropic infrastructure organizations, networks, and services in 2012; since 2004, their support has totaled more than$1 billion. About 41% of this giving funded philanthropy-specific organizations and networks -- from the Mexican Center for Philanthropy to Grantmakers for Effective Organizations. The other 59% targeted a range of organizations and activities -- from funding nonprofit-related research at major universities and think tanks to providing operating and project support to Foundation Center. This special report was created with funding from the William and Flora Hewlett Foundation

Depression of the ULF geomagnetic pulsation related to ionospheric irregularities

We consider a depression in intensity of ULF magnetic pulsations, which is observed on the ground surface due to appearance of the irregularities in the ionosphere. It is supposed that oblique Alfven waves in the ULF frequency range are downgoing from the magnetosphere and the horizontal irregularities of ionospheric conductivity are created by upgoing atmospheric gravity waves from seismic source. Unlike the companion paper by Molchanov et al. (2003), we used a simple model of the ionospheric layer but took into consideration the lateral inhomogeneity of the perturbation region in the ionosphere. It is shown that ULF intensity could be essentially decreased for frequencies f = 0.001-0.1 Hz at nighttime but the change is negligible at daytime in coincidence with observational results

Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) ablation limits offspring viability and growth in mice

Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta+/− breeders generated viable Sgta−/− offspring, but at less than Mendelian expectancy. Sgta−/− breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta−/− (vs WT, Sgta+/− P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta−/−. Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta−/−. Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The Education Collaboration Fund: Possibilities and Limitations of Pooled Funds

· Raising money for a pooled fund is time consuming and requires expertise with the funding topic and the target audience. Yet the process of shopping around a pooled fund or collaborative concept can be valuable in its own right, even if most do not participate. · Shared interest around a topic or community is a necessary but insufficient reason for participating in a pooled fund. A pooled fund provides an opportunity for individuals and family foundations to learn and grow as donors. · Someone with passion, organizational skills, and persistence needs to drive the process forward or it will likely fall by the wayside. The gap between “emerging” and “organized” philanthropy is real, but may be ameliorated through technology. · Vehicle choice is straightforward: The underlying public charity and administrative processing can be handled by a donor-advised fund at a community foundation or federation, financial services firm, or intermediary

The intersection of AR signalling and COVID-19

A cluster of unexplained pneumonia in late-2019 was the preface to a rapid-spreading global health crisis sparked by emergence of a novel coronavirus (SARS-CoV-2). Since its emergence, the highly contagious SARS-CoV-2 illness Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and triggered a rapid scientific movement to map case statistics, understand disease pathophysiology and find efficacious treatments for this insidious disease. Clinical case studies consistently report that being male is a major risk factor for COVID-19 morbidity and mortality. In one study covering 1099 adults admitted to 552 mainland China hospitals, 70% of patients requiring ventilation support in intensive care were biologically male (Guan et al, 2020, N Eng J Med). This was corroborated in reports of COVID-19 mortality across 38 countries, where the fatality rate of men was 1.7-fold higher than women (Scully et al, 2020, Nat Rev Immunol). Albeit, in paediatric studies this gender gap was not evident; prepubescent females and males were equally impacted by mild/moderate COVID-19 (Wu et al, 2020, JAMA Netw Open). These observations of distinct sex-specific disparities in the course of COVID-19 disease have triggered rigorous inquiry into the role of sex hormones in driving SARS-CoV-2 virus susceptibility and illness severity. Evolving evidence suggests male sex hormones, androgens, regulate the SARS-CoV-2 receptor, Angiotensin-Converting Enzyme 2 (ACE2), and co-receptor, Type II Transmembrane Serine Protease (TMPRSS2), which facilitate SARS-CoV-2 entry and infection of host cells. Furthermore, the host’s sex hormone milieu influences the immune response mounted in response to SARS-CoV-2 respiratory infection and the release inflammatory cytokines including interleukin-6 (IL-6) which is markedly elevated in severe COVID-19 infection and exhibits excessive secretion in males. In conclusion, the emerging intersection between androgens and COVID-19 may pave the way for hormone rationalised therapies to effectively lower disease severity across patients affected by severe COVID-19 illness

Next Gen Donors: Shaping the Future of Philanthropy

GrantCraft is pleased to partner with 21/64 and the Johnson Center for Philanthropy at Grand Valley State University in this analysis of their research on next generation donors.A relatively small group of Generation Xers and Millennials will inherit over $40 trillion in wealth, much of that designated for philanthropy. In first-of-its-kind research, the Johnson Center and 21/64 examined a key segment of the next generation of major donors in the United States. Through a national online survey and in-depth interviews, they explored themes including philanthropic orientation, priorities, strategies, decision-making, and activities.21/64 and the Johnson Center invited GrantCraft to do a parallel analysis of its interviews to draw out the "practical wisdom" of 30 next generation major donors. This GrantCraft companion guide captures what study participants found to be distinctive about themselves and their peers. It aims to increase understanding and stimulate discussion about Gen X and Millennial major donors -- the generations that have the potential to be the most significant philanthropists in history.HighlightsHunger for engagement: grantees, families, peers, other fundersNew ways of learning: ideas, approaches, and peopleImportance of now: deep interest in applying their skills sooner rather than laterWhat's in the Guide?In their own words: GrantCraft joined 21/64 and the Johnson Center for Philanthropy in listening to and reflecting upon the voices of a selected group of major donors in their 20s and 30s.Hunger for engagement: In their interviews, study participants expressed a desire to be hands-on philanthropists -- with their grant recipients, their approach to issues, their families, their peers, and other funders.New ways of learning: Generation X and Millennial interviewees described generational differences in the ways they learn about new ideas, approaches, and people.Importance of now: This group of next generation donors highlighted their deep interest in helping and applying their skills sooner rather than later.How to use this guide: These starter questions can be used to promote dialogue for audiences including next generation donors; family, community, and private foundations; donor advised funds; philanthropy networks; advisors; and researchers

Targeting Fat-secreted Hormones: A Novel Therapeutic Approach for Advanced Prostate Cancer

Therapies targeting the androgen axis (ATT) are used as mainstay treatments against advanced prostate cancer (PCa), starving prostate tumours of growth-promoting androgens. While ATTs are initially effective in slowing disease progression and extending patient survival, tumours inevitably develop treatment resistance. A further complication is that ATTs induce metabolic dysfunction in patients, seen in increased blood lipids, glucose and insulin, and elevated circulating adipose tissue-secreted hormone leptin. Along with the rapid rise in serum leptin induced by ATTs, we uncovered that leptin, and its signalling receptor (LEPR), are concomitantly increased in PCa cells and patient tumours exposed to ATTs, as is observed in patient samples of advanced metastatic and castrate resistant PCa. Given the major crossover between leptin/ LEPR signalling and several cancer-promoting hallmark pathways, including growth, proliferation, angiogenesis, inflammation, metabolism and migration, we hypothesised that the leptin axis is an attractive therapeutic target, particularly in advanced PCa where mainstay treatments fail. We aimed to assess the preclinical efficacy of leptin signalling blockade in preventing the growth and progression of advanced PCa, using Allo-aca, a proven safe, potent and specific LEPR antagonist. Allo-aca (1 mg/kg/d s.c.) efficacy to slow PCa progression was tested in male Nude mice bearing s.c. LNCaP tumour xenografts and surgically castrated at ~50 ng/mL serum prostate-specific antigen (PSA). PSA, tumour size and micro-environment changes (oxygenation, perfusion (VevoLAZR photoacoustic/ ultrasound imaging)) were assessed as markers of progression/ efficacy. LEPR antagonism by Allo-aca markedly suppressed tumour xenograft growth, observed in a 4-fold increase in tumour doubling time and 2-fold decrease in endpoint tumour mass and volume, vs vehicle. Therapeutic window and ‘survival’ were significantly extended, with 2-fold slower time to ethical endpoint in Allo-aca-treated mice. Gross changes in the tumour phenotype and vascularisation were observed, with Allo-aca-treated tumours paler than vehicle control xenografts which were typically bloody and highly vascularised. RNAseq analysis corroborated reduced tumour vascularity, and highlighted altered tumour pathways of apoptosis, transcription/translation, and energetics as potential mechanisms underpinning the marked anti-tumour efficacy of Allo-aca. Our findings highlight that LEPR blockade in combination with androgen axis inhibition represents a promising new therapeutic strategy, vital in the management of advanced PCa