Evaluators as Conduits and Supports for Foundation Learning

Evaluators play a critical role in supporting philanthropic learning, programming, and strategy, but evaluation and learning in philanthropy is often limited in ways that impede deeper resonance and impact. Most philanthropic evaluation is focused on the needs of individual foundations, knowledge sharing with the broader field is limited, and foundations struggle to integrate evaluation and learning as a management tool. This article makes the case that evaluators and funders can do more to build the collective capacity of evaluators working in philanthropy in order to enhance their contributions to community change. This article also examines the ways that evaluation in philanthropy is evolving, lays out root causes of its limitations, and looks at emerging tools, techniques, and lessons that showcase new ways evaluators and funders are working together to strengthen practice

Differential role of ICAM ligands in determination of human memory T cell differentiation

BACKGROUND: Leukocyte Function Antigen-1 (LFA-1) is a primary adhesion molecule that plays important roles in T cell activation, leukocyte recirculation, and trans-endothelial migration. By applying a multivariate intracellular phospho-proteomic analysis, we demonstrate that LFA-1 differentially activates signaling molecules. RESULTS: Signal intensity was dependent on both ICAM ligand and LFA-1 concentration. In the presence of CD3 and CD28 stimulation, ICAM-2 and ICAM-3 decreased TGFβ1 production more than ICAM-1. In long-term differentiation experiments, stimulation with ICAM-3, CD3, and CD28 generated IFNγ producing CD4+CD45RO+CD62L-CD11a(Bright)CD27- cells that had increased expression of intracellular BCL2, displayed distinct chemokine receptor profiles, and exhibited distinct migratory characteristics. Only CD3/CD28 with ICAM-3 generated CD4+CD45RO+CD62L-CD11a(Bright)CD27- cells that were functionally responsive to chemotaxis and exhibited higher frequencies of cells that signaled to JNK and ERK1/2 upon stimulation with MIP3α. Furthermore, these reports identify that the LFA-1 receptor, when presented with multiple ligands, can result in distinct T cell differentiation states and suggest that the combinatorial integration of ICAM ligand interactions with LFA-1 have functional consequences for T cell biology. CONCLUSION: Thus, the ICAM ligands, differentially modulate LFA-1 signaling in T cells and potentiate the development of memory human T cells in vitro. These findings are of importance in a mechanistic understanding of memory cell differentiation and ex vivo generation of memory cell subsets for therapeutic applications

A Rare Case Report of a Testicular Germ-Cell Tumor (GCT) Metastasis Mimicking Pancreatic Malignancy

Introduction: Testicular germ cell tumors (TGCT), evenly divided into two histologic types, seminomas and nonseminomas, are the most common malignancy among males between ages 15 to 44 years [1, 2]. The incidence of TGCT in the U.S. has increased over the past 20 years, being attributed to chronic exposure environmental risk factors (i.e. pesticides and plastic component polyvinyl chloride) in addition to genetic predisposition [1, 3-6]. Description: We report of an unusual case of retroperitoneal metastatic GCT clinically simulating a pancreatic lymphoma. A 31-year-old male presented with a 2-month history of abdominal pain in the right upper quadrant, 40-pound weight loss, nausea, episodes of emesis and decreased appetite. Abdominal computed tomography scan showed a large heterogenous mass measuring 11 x 8 cm in close proximity to the head and body of the pancreas. This tumor encased portions of the celiac trunk, superior mesenteric artery, splenic, superior mesenteric and portal veins. Additional solid masses measuring 8.2 cm and 10 x 8.8 cm were noted inferior to porta hepatis and medial to the left kidney, respectively. Given the tumor distribution, patient was suspected of having pancreatic lymphoma and underwent endoscopic ultrasound-guided tissue sampling of the tumor. Microscopic examination of the biopsy revealed solid nests of infiltrative malignant epitheloid cells characterized by nuclear pleomorphisms and hyperchromatic nuclei with focal necrotic and apoptotic debris. Immunohistochemical stains revealed positive pancytokeratin and SALL4, a transcription factor specific for embryonic cell pluripotency and an immunohistochemical marker for TGCT [7]. Laboratory tests revealed elevated serum levels of alpha fetoprotein (AFP = 57.8 ng/ml; reference: 10-20 ng/ml), lactate dehydrogenase (LDH = 2919 units/L; reference:106-242 units/L) and beta human chronic gonadotrophin (β-hCG =1458 IU/L; reference: 0-3 IU/L). Both microscopic and laboratory findings are consistent with metastatic retroperitoneal GCT. Subsequent clinical history and physical exam of the patient revealed a right testicular solid mass measuring 13.3 x 7.8 x 10.7 cm. Patient was aware of this progressively enlarging right testicular mass for the past 5-years, but had not undergone previous evaluation. Patient’s family history is negative for TGCT and denied undergoing orchiopexy for cryptorchidism during his childhood. Patient has been working in a plastic manufacturing company with exposure to endocrine disrupting chemicals, a potential exogenous risk factor for his TGCT [5]. Conclusion: Final diagnosis was “Stage IIIA-Testicular GCT-Low-risk” based on the primary and metastatic sites involvement and serum tumor marker levels. The patient underwent radical orchiectomy of the right testicle followed by 4 cycles of chemotherapy with etoposide/cisplatin/bleomycin for the remaining retroperitoneal tumors. The five-year progression-free and overall survival rate for our patient are 89% and 92%, respectively [1]. This case highlights an unusual presentation of retroperitoneal GCT metastasis and the need to include the following differentials of lymphoma, sarcoma, and GCT for retroperitoneal masses with lymphadenopathy

Trematodes of the Great Barrier Reef, Australia: emerging patterns of diversity and richness in coral reef fishes

The Great Barrier Reef holds the richest array of marine life found anywhere in Australia, including a diverse and fascinating parasite fauna. Members of one group, the trematodes, occur as sexually mature adult worms in almost all Great Barrier Reef bony fish species. Although the first reports of these parasites were made 100 years ago, the fauna has been studied systematically for only the last 25 years. When the fauna was last reviewed in 1994 there were 94 species known from the Great Barrier Reef and it was predicted that there might be 2,270 in total. There are now 326 species reported for the region, suggesting that we are in a much improved position to make an accurate prediction of true trematode richness. Here we review the current state of knowledge of the fauna and the ways in which our understanding of this fascinating group is changing. Our best estimate of the true richness is now a range, 1,100–1,800 species. However there remains considerable scope for even these figures to be incorrect given that fewer than one-third of the fish species of the region have been examined for trematodes. Our goal is a comprehensive characterisation of this fauna, and we outline what work needs to be done to achieve this and discuss whether this goal is practically achievable or philosophically justifiable

Galaxy Pairs in the Sloan Digital Sky Survey - III: Evidence of Induced Star Formation from Optical Colours

We have assembled a large, high quality catalogue of galaxy colours from the Sloan Digital Sky Survey Data Release 7, and have identified 21,347 galaxies in pairs spanning a range of projected separations (r_p < 80 h_{70}^{-1} kpc), relative velocities (\Delta v < 10,000 km/s, which includes projected pairs that are essential for quality control), and stellar mass ratios (from 1:10 to 10:1). We find that the red fraction of galaxies in pairs is higher than that of a control sample matched in stellar mass and redshift, and demonstrate that this difference is likely due to the fact that galaxy pairs reside in higher density environments than non-paired galaxies. We detect clear signs of interaction-induced star formation within the blue galaxies in pairs, as evidenced by a higher fraction of extremely blue galaxies, along with blueward offsets between the colours of paired versus control galaxies. These signs are strongest in close pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v < 200 km/s), diminish for more widely separated pairs (r_p > 60 h_{70}^{-1} kpc and \Delta v < 200 km/s) and disappear for close projected pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v > 3000 km/s). These effects are also stronger in central (fibre) colours than in global colours, and are found primarily in low- to medium-density environments. Conversely, no such trends are seen in red galaxies, apart from a small reddening at small separations which may result from residual errors with photometry in crowded fields. When interpreted in conjunction with a simple model of induced starbursts, these results are consistent with a scenario in which close peri-centre passages trigger induced star formation in the centres of galaxies which are sufficiently gas rich, after which time the galaxies gradually redden as they separate and their starbursts age.Comment: 17 pages. Accepted for publication in MNRA

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD, therefore reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionization tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function

Hierarchically Porous Gd3+-Doped CeO2 Nanostructures for the Remarkable Enhancement of Optical and Magnetic Properties

Rare earth ion-doped CeO2 has attracted more and more attention because of its special electrical, optical, magnetic, or catalytic properties. In this paper, a facile electrochemical deposition route was reported for the direct growth of the porous Gd-doped CeO2. The formation process of Gd-doped CeO2 composites was investigated. The obtained deposits were characterized by SEM, EDS, XRD, and XPS. The porous Gd3+- doped CeO2 (10 at% Gd) displays a typical type I adsorption isotherm and yields a large specific surface area of 135 m2/g. As Gd3+ ions were doped into CeO2 lattice, the absorption spectrum of Gd3+-doped CeO2 nanocrystals exhibited a red shift compared with porous CeO2 nanocrystals and bulk CeO2, and the luminescence of Gd3+-doped CeO2 deposits was remarkably enhanced due to the presence of more oxygen vacancies. In addition, the strong magnetic properties of Gd-doped CeO2 (10 at% Gd) were observed, which may be caused by Gd3+ ions or more oxygen defects in deposits. In addition, the catalytic activity of porous Gd-doped CeO2 toward CO oxidation was studied

Bilateral vestibulopathy and age:experimental considerations for testing dynamic visual acuity on a treadmill

Introduction: Bilateral vestibulopathy (BVP) can affect visual acuity in dynamic conditions, like walking. This can be assessed by testing Dynamic Visual Acuity (DVA) on a treadmill at different walking speeds. Apart from BVP, age itself might influence DVA and the ability to complete the test. The objective of this study was to investigate whether DVA tested while walking, and the drop-out rate (the inability to complete all walking speeds of the test) are significantly influenced by age in BVP-patients and healthy subjects. Methods: Forty-four BVP-patients (20 male, mean age 59 years) and 63 healthy subjects (27 male, mean age 46 years) performed the DVA test on a treadmill at 0 (static condition), 2, 4 and 6 km/h (dynamic conditions). The dynamic visual acuity loss was calculated as the difference between visual acuity in the static condition and visual acuity in each walking condition. The dependency of the drop-out rate and dynamic visual acuity loss on BVP and age was investigated at all walking speeds, as well as the dependency of dynamic visual acuity loss on speed. Results: Age and BVP significantly increased the drop-out rate (p ≤ 0.038). A significantly higher dynamic visual acuity loss was found at all speeds in BVP-patients compared to healthy subjects (p < 0.001). Age showed no effect on dynamic visual acuity loss in both groups. In BVP-patients, increasing walking speeds resulted in higher dynamic visual acuity loss (p ≤ 0.036). Conclusion DVA tested while walking on a treadmill, is one of the few “close to reality” functional outcome measures of vestibular function in the vertical plane. It is able to demonstrate significant loss of DVA in bilateral vestibulopathy patients. However, since bilateral vestibulopathy and age significantly increase the drop-out rate at faster walking speeds, it is recommended to use age-matched controls. Furthermore, it could be considered to use an individual “preferred” walking speed and to limit maximum walking speed in older subjects when testing DVA on a treadmill

SpiroZin1: A Reversible and pH-Insensitive, Reaction-Based, Red-Fluorescent Probe for Imaging Biological Mobile Zinc

A reversible, reaction-based sensor for biological mobile zinc was designed, prepared, and characterized. The sensing mechanism of this probe is based on the zinc-induced, ring-opening reaction of spirobenzopyran to give a cyanine fluorophore that emits in the deep-red region of the electromagnetic spectrum. This probe is not activated by protons and operates efficiently in aqueous solution at pH 7 and high ionic strength. The mechanism of this reaction was studied by using a combination of kinetics experiments and DFT calculations. The biocompatibility of the probe was demonstrated in live HeLa cells.National Institute of General Medical Sciences (U.S.) (Grant GM 65519)Swiss National Science Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (1S0RR13886-01