The 2004 Claremont Debate: Lipsey vs. Scriven

While there is little disagreement about the need for, and value of, program evaluation, there remain major disagreements in the field about best practices (Donaldson & Lipsey, in press). For example, Donaldson and Scriven (2003) invited a diverse group of evaluators to Claremont in 2001 to share their visions for “how we should practice evaluation” in the new millennium. Theorists and practitioners discussed a wide range of views and evaluation approaches, many at odds with one another, on how best to improve evaluation practice (e.g., the experimental paradigm, evaluation as a transdiscipline, results-oriented management, empowerment evaluation, fourth generation evaluation, inclusive evaluation, theory-driven evaluation and the like). In response to some of the heated exchanges, Mark (2003) noted “it seems ironic when evaluators who espouse inclusion, empowerment, and participation would like to exclude, disempower, and see no participation by evaluators who hold different views.” Hefurther concluded that whatever peace has been achieved in the so-call quantitative-qualitative paradigm wars remains an uneasy peace

Choosing an Evaluation Theory: A Supplement to Evaluation Roots (3rd Edition)

Background: Unlike scientific theories, evaluation theories are prescriptive: a set of actions and approaches that should be followed when conducting an evaluation. While evaluation theorists have offered a variety of writings describing their theories and approaches, few have offered a specific outline of what the theory looks like in practice. Thus, Alkin and Christie formulated a book to aid evaluators in how to apply theories in evaluations (Alkin & Christie, forthcoming). This book culminates in a series of prototypes that outline each theory’s goals, appropriate contexts, prescriptions, and observable actions in application. Purpose: In order to aid evaluators in applying theories, this article seeks to provide a basis for comparison that can be used to help evaluators select which theory would be most appropriate in their practice. Setting: This comparison can be applied in any setting where evaluations fit the context prescribed by each of the theories. Intervention: Not applicable. Research Design: Not applicablre. Data Collection and Analysis: Not applicable. Findings: In order for theories to influence practice effectively, theories must be displayed in a way that allows for easy comparison. This comparison of three theory prototypes demonstrates that prototypes can be an effective way for selecting a prescriptive theory when conducting an evaluation. Keywords: prescriptive theories; practice; empowerment evaluation; learning centered model; developmental evaluatio

The response of VEGF-stimulated endothelial cells to angiostatic molecules is substrate-dependent

BACKGROUND: The microenvironment surrounding cells can exert multiple effects on their biological responses. In particular the extracellular matrix surrounding cells can profoundly influence their behavior. It has been shown that the extracellular matrix composition in tumors is vastly different than that found in normal tissue with increased amounts of certain matrices such as collagen I. It has been previously demonstrated that VEGF stimulation of endothelial cells growing on type I collagen results in the induction of bcl-2 expression and enhanced endothelial cell survival. We sought to investigate whether this increased endothelial cell survival resulted in the failure of angiostatic molecules to inhibit angiogenesis. RESULTS: We now demonstrate that VEGF-induced survival on collagen I impairs the ability of three known angiostatic molecules, TSP-1, IP-10 and endostatin to inhibit endothelial cell proliferation. Apoptosis of endothelial cells, growing on collagen I, induced by TSP-1 and IP-10 was also inhibited following VEGF stimulation. In contrast, endostatin induced apoptosis in these same cells. Further analysis determined that endostatin did not decrease the expression of bcl-2 nor did it increase activation of caspase-3 in the presence of VEGF. Alternatively, it appeared that in the presence of VEGF, endostatin induced the activation of caspase-8 in endothelial cells grown on collagen I. Furthermore, only endostatin had the ability to inhibit VEGF-induced sprout formation in collagen I gels. CONCLUSION: These data suggest that TSP-1, IP-10 and endostatin inhibit endothelial cells via different mechanisms and that only endostatin is effective in inhibiting angiogenic activities in the presence of collagen I. Our results suggest that the efficacy of angiostatic treatments may be impaired depending on the context of the extracellular matrix within the tumor environment and thus could impede the efficacy of angiostatic therapies

Should first-line empiric treatment strategies cover coagulase-negative staphylococcal infections in severely malnourished or HIV-infected children in Kenya?

BACKGROUND: Bloodstream infection is a common cause of morbidity in children aged andlt;5 years in developing countries. In studies reporting bacteremia in Africa, coagulase-negative Staphylococci (CoNS) are commonly isolated. However, it is currently unclear whether children who are highly susceptible to infection because of severe acute malnutrition (SAM) or HIV should be treated with antimicrobials specifically to cover CoNS. We aimed to determine the clinical significance of CoNS amongst children admitted to a rural hospital in Kenya in relation to nutritional and HIV status. METHODS: Systematically collected clinical and microbiological surveillance data from children aged 6-59 months admitted to Kilifi County Hospital (2007-2013) were analysed. Multivariable regression was used to test associations between CoNS isolation from blood cultures and SAM (MUAC andlt;11.5cm or nutritional oedema (kwashiorkor)), and HIV serostatus; and among children with SAM or HIV, associations between CoNS isolation and mortality, duration of hospitalization and clinical features. RESULTS: CoNS were isolated from blood culture in 906/13,315 (6.8%) children, of whom 135/906 (14.9%) had SAM and 54/906 (6.0%) were HIV antibody positive. CoNS isolation was not associated with SAM (MUACandlt;11.5cm (aOR 1.11, 95% CI 0.88-1.40) or kwashiorkor (aOR 0.84, 95% CI 0.48-1.49)), or a positive HIV antibody test (aOR 1.25, 95% CI 0.92-1.71). Among children with SAM or a positive HIV antibody test, CoNS isolation was not associated with mortality or prolonged hospitalization. CONCLUSION: In a large, systematic study, there was no evidence that antimicrobial therapy should specifically target CoNS amongst children with SAM or HIV-infection or exposure

Phospholipids Trigger Cryptococcus neoformans Capsular Enlargement during Interactions with Amoebae and Macrophages

A remarkable aspect of the interaction of Cryptococcus neoformans with mammalian hosts is a consistent increase in capsule volume. Given that many aspects of the interaction of C. neoformans with macrophages are also observed with amoebae, we hypothesized that the capsule enlargement phenomenon also had a protozoan parallel. Incubation of C. neoformans with Acanthamoeba castellanii resulted in C. neoformans capsular enlargement. The phenomenon required contact between fungal and protozoan cells but did not require amoeba viability. Analysis of amoebae extracts showed that the likely stimuli for capsule enlargement were protozoan polar lipids. Extracts from macrophages and mammalian serum also triggered cryptococcal capsular enlargement. C. neoformans capsule enlargement required expression of fungal phospholipase B, but not phospholipase C. Purified phospholipids, in particular, phosphatidylcholine, and derived molecules triggered capsular enlargement with the subsequent formation of giant cells. These results implicate phospholipids as a trigger for both C. neoformans capsule enlargement in vivo and exopolysaccharide production. The observation that the incubation of C. neoformans with phospholipids led to the formation of giant cells provides the means to generate these enigmatic cells in vitro. Protozoan- or mammalian-derived polar lipids could represent a danger signal for C. neoformans that triggers capsular enlargement as a non-specific defense mechanism against potential predatory cells. Hence, phospholipids are the first host-derived molecules identified to trigger capsular enlargement. The parallels apparent in the capsular response of C. neoformans to both amoebae and macrophages provide additional support for the notion that certain aspects of cryptococcal virulence emerged as a consequence of environmental interactions with other microorganisms such as protists

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Age and distraction are determinants of performance on a novel visual search task in aged Beagle dogs

Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention

Nasal Accumulation and Metabolism of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration in an Adolescent Rat Model

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the drug and its first-pass metabolites – 11-hydroxy-Δ9-THC (11-OH-THC) and 11-nor-9-carboxy-Δ9-THC (11-COOH-THC) – in nasal mucosa, lungs, plasma, and brain (olfactory bulb and cerebellum) at various time points after exposure. Apparent maximal THC concentration and area under the curve were ∼5 times higher in nasal mucosa than in lungs and 50–80 times higher than in plasma. Concentrations of 11-OH-THC were also greater in nasal mucosa and lungs than other tissues, whereas 11-COOH-THC was consistently undetectable. Experiments with microsomal preparations confirmed local metabolism of THC into 11-OH-THC (not 11-COOH-THC) in nasal mucosa and lungs. Finally, whole-body exposure to THC deposited substantial amounts of THC (∼150 mg/g) on fur but suppressed post-exposure grooming in rats of both sexes. The results indicate that THC absorption and metabolism in nasal mucosa and lungs, but probably not gastrointestinal tract, contribute to the pharmacological effects of aerosolized THC in male and female rats