Evaluating Program Impact: Our Approach to Performance Assessment

Discerning and communicating the impact of grantmaking and other programmatic contributions are essential to fulfilling the Rockefeller Brothers Fund's (RBF) mission as well as our commitment to stewardship, transparency, and accountability. The Fund's board and staff have found that engaging policymakers on the results and insights gained from our grantmaking, informing the public about our grantees' work, and attracting additional donors to promising institutions and approaches are key activities that help build a more just, sustainable, and peaceful world.In order to bring additional rigor to the Fund's approach to program impact assessment, a committee of RBF trustees and staff was established in March 2012. Based on our experience, the state of evaluation in philanthropy, and a review of literature and activity in the field, the Impact Assessment Committee developed a set of principles to guide our impact assessment approach, defined terms for the purposes of RBF discussions, established several points for evaluation activities in the life cycle of a grantmaking program, and identified opportunities to embed impact assessment in the Fund's regular institutional processes. The Fund establishes its programs in fields and places that reflect its mission and the evolution of its longstanding interests, along with an analysis of the changing global context. The key elements of the RBF's approach to assessing program impact are as follows:* The board approves program guidelines that lay the foundation for the Fund's grantmaking within a program. Guidelines include a preamble that presents the vision and rationale for each program, ambitious long-term goals, and strategies that articulate specific actions the Fund will support to achieve progress toward these goals. They provide guidance to staff and grantseekers about what the RBF is prepared to fund.* A program framework summary, derived from the guidelines, is developed for internal use and includes indicators of progress. These indicators identify anticipated changes in understanding, behavior, capacity, public engagement, or public policy that would demonstrate that program strategies are contributing to realizing program goals.* Within each program, evaluation activities occur on an ongoing basis. Monitoring of the field and of individual grants draws on regular staff engagement and grantee reporting; program reviews, conducted every three to five years by program staff, provide an opportunity to engage the board in a strategic review of progress—often resulting in updated program strategies; impact assessments are conducted by external consultants after five or more years as strategies mature.* The annual institutional calendar provides a variety of opportunities for the board and staff to discuss and review programmatic impact at different points each year and across several years.This approach to impact assessment reflects emerging practices in the field and is consistent with the Fund's values and grantmaking approaches. The committee believes that the approach effectively supports program learning, guides program development, and enhances the impact of the Fund's grantmaking

Evaluating Program Impact: Our Approach to Performance Assessment Abridged Version

Discerning and communicating the impact of grantmaking and other programmatic contributions are essential to fulfilling the Rockefeller Brothers Fund's mission as well as our commitment to stewardship, transparency, and accountability. The Fund's board and staff have found that engaging policymakers on the results and insights gained from our grantmaking, informing the public about our grantees' work, and attracting additional donors to promising institutions and approaches are key activities that help build a more just, sustainable, and peaceful world.In order to bring additional rigor to the Fund's approach to program impact assessment an impact assessment committee, comprised of RBF trustees and staff, was established in March 2012. This committee continued the work of the Fund's 2003 Foundation Performance Assessment Committee that provided guidance to efforts to streamline internal processes, solicit grantee feedback on the RBF's funding approach, and conduct program reviews at regular intervals to assess program impact. The task for the 2012 Impact Assessment Committee was to further define and embed regular program review and impact assessment activities in the Fund's institutional processes in a manner that supports its program approach and grantmaking style.Principles and Conclusions to Guide the Fund's Approach to ImpactThe Impact Assessment Committee developed the following principles to guide the Fund's approach to impact assessment.* The Fund's impact assessment approach is rooted in its mission and its program goals and reflects and supports the RBF grantmaking style as captured in its program statement. It must be flexible enough to work across the Fund's six programs and their respective evolving contexts.* Given the nature of the RBF's grantmaking, a wide range of indicators and information is needed to understand the impact the Fund is having on a field or issue.* The Fund's approach to impact assessment is action-oriented. It enables staff and trustees to better understand the effectiveness of our grantmaking in light of the context in which our grantees are working, make mid-course corrections as necessary, and identify opportunities to share our insights with external audiences.* Impact assessments focus on the contribution of the Fund's grantmaking to a field or issue over the long term; staff monitor indicators of progress over the near and medium term.* The impact assessment process should add value to Fund and grantee work, not create administrative and financial burdens

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence

Curriculum-based outdoor learning for children aged 9-11: A qualitative analysis of pupils’ and teachers’ views

The relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects, and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers’, teachers’ and pupils’ views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9–11) in South Wales, United Kingdom. We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n = 3) and teachers (n = 10) and focus groups with pupils aged 9–11 (n = 10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils’ engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers’ job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture

Wnt4 Enhances Murine Hematopoietic Progenitor Cell Expansion Through a Planar Cell Polarity-Like Pathway

Background: While the role of canonical (b-catenin-mediated) Wnt signaling in hematolymphopoiesis has been studied extensively, little is known of the potential importance of non-canonical Wnt signals in hematopoietic cells. Wnt4 is one of the Wnt proteins that can elicit non-canonical pathways. We have previously shown that retroviral overexpression of Wnt4 by hematopoietic cells increased thymic cellularity as well as the frequency of early thymic progenitors and bone marrow hematopoietic progenitor cells (HPCs). However, the molecular pathways responsible for its effect in HPCs are not known. Methodology/Principal Findings: Here we report that Wnt4 stimulation resulted in the activation of the small GTPase Rac1 as well as Jnk kinases in an HPC cell line. Jnk activity was necessary, while b-catenin was dispensable, for the Wnt4-mediated expansion of primary fetal liver HPCs in culture. Furthermore, Jnk2-deficient and Wnt4 hemizygous mice presented lower numbers of HPCs in their bone marrow, and Jnk2-deficient HPCs showed increased rates of apoptosis. Wnt4 also improved HPC activity in a competitive reconstitution model in a cell-autonomous, Jnk2-dependent manner. Lastly, we identified Fz6 as a receptor for Wnt4 in immature HPCs and showed that the absence of Wnt4 led to a decreased expression of four polarity complex genes. Conclusions/Significance: Our results establish a functional role for non-canonical Wnt signaling in hematopoiesis throug

DAF-16 and Δ9 Desaturase Genes Promote Cold Tolerance in Long-Lived Caenorhabditis elegans age-1 Mutants

In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS) pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Δ9 desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Δ9 desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546) mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546) mutants is predominantly due to the Δ9 desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic