Traditional approaches for evaluating the impact of scientific research – mainly scholarship (i.e., publications, presentations) and grant funding – fail to capture the full extent of contributions that come from larger scientific initiatives. The Translational Science Benefits Model (TSBM) was developed to support more comprehensive evaluations of scientific endeavors, especially research designed to translate scientific discoveries into innovations in clinical or public health practice and policy-level changes. Here, we present the domains of the TSBM, including how it was expanded by researchers within the Implementation Science Centers in Cancer Control (ISC3) program supported by the National Cancer Institute. Next, we describe five studies supported by the Penn ISC3, each focused on testing implementation strategies informed by behavioral economics to reduce key practice gaps in the context of cancer care and identify how each study yields broader impacts consistent with TSBM domains. These indicators include Capacity Building, Methods Development (within the Implementation Field) and Rapid Cycle Approaches, implementing Software Technologies, and improving Health Care Delivery and Health Care Accessibility. The examples highlighted here can help guide other similar scientific initiatives to conceive and measure broader scientific impact to fully articulate the translation and effects of their work at the population level.

Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by less dense arrays. However, our study lacked power to make clear statements on the existence of hitherto untagged small-effect variants.

Six individuals with probable Alzheimer’s disease (AD) participated in a phase 1 study employing a repeated measures, parallel baseline design testing the hypothesis that error-free experience during word production practice combined with an acetyl cholinesterase inhibitor would improve confrontation naming ability. While acetyl cholinesterase inhibitors are safe and delay cognition decline associated with AD, improvement over baseline cognition is less evident; clinically significant cognitive deficits persist and progress. Both animal and clinical research strongly implicate acetylcholine in learning, a form of neuroplasticity. In clinical practice, however, people with AD are given cholinergic medications without concomitant systematic/targeted retraining. In this study six participants with probable AD and taking donepezil participated in targeted word production practice using an errorless learning strategy. Results showed that combining behavioral enrichment training and an acetyl cholinesterase inhibitor resulted in significant improvements in verbal confrontation naming of trained items for three of six participants. Differences in baseline dementia severity, living conditions, and medications may have influenced the training response. Detection of substantial treatment effects in 50% of subjects suggests further language treatment studies in AD in combination with an acetyl cholinesterase inhibitor are warranted and provide useful information on inclusion/exclusion criteria for use in subsequent studies. (JINS, 2009, 15, 311–322.)

Chalcopyrite-based devices show highest conversion efficiencies among present thin film architectures with values of 20% at laboratory scale. This outstanding performance has been achieved for quaternary Cu(Inx,Ga1-x)Se2 (x˜0.7) compound material. However, a strong correlation between the performance and the gallium content or, in other words, low versus high bandgap materials has been recognized. One critical issue in this discussion is the formation of a copper-depleted near-surface phase with 1:3:5 and 1:5:8 stoichiometries. In earlier reports, surface phases with corresponding compositions have been found on CuInSe2, CuGaSe2 and Cu(Inx,Ga1-x)Se2 thin films. These near-surface phases show a positive influence on the performance of cells based on low bandgap Cu(Inx,Ga1-x)Se2 material due to n-type inversion and band gap widening compared to bulk properties. A tendency towards a neutral or even a negative impact of the near-surface phase on wide band gap material (high gallium content) has recently been reported [1]. Nevertheless, the structural models of copper-poor chalcopyrite-related compounds have been controversially discussed in literature but a stannite-type structural model is most suitable as will be presented. In any case, the relation of the structural properties between chalcopyrite and 1:3:5 phases is crucial for the performance of related devices.

In this contribution we will report about the structural analysis of the Cu(Inx,Ga1-x)3Se5 solid solution series by means of anomalous x-ray scattering using synchrotron radiation, powder and single crystal neutron diffraction. Contributions of the isoelectronic species Cu+ and Ga3+ could be separated by these experiments. Bulk samples synthesized from the elements and heat treated at 650°C after the main reaction step - the latter in order to allow equilibrium structure formation - were investigated. Structural data like lattice parameters, tetragonal distortion and cation distribution were obtained for the complete Cu(Inx,Ga1-x)3Se5 solid solution series. The stannite-type structural model was assigned to all members of the investigated 1:3:5s which will be strengthened by simulations. We observed that the tetragonal distortion vanishes for compositions close to a gallium content as used for highest efficiency Cu(Inx,Ga1-x)Se2 devices. However, the tetragonal distortion depends critically on the cation distribution which is in turn controlled by the thermal history of the sample, as we have recently reported for pure CuGaSe2 [1]. This means that we can plot a direct correlation for the misfit between chalcopyrite and 1:3:5 phases depending on the gallium content and the thermal treatment of the considered thin films. These results will widen the understanding of the chalcopyrite-based thin film photovoltaic devices.

[1] S. Lehmann et al., Phys. Stat. Sol. A (in press)

Twenty-three chronic nonfluent aphasia patients with moderate or severe word-finding impairments and 11 with profound word-finding impairments received two novel picture-naming treatments. The intention treatment initiated picture-naming trials with a complex left-hand movement and was designed to enhance right frontal participation during word retrieval. The attention treatment required patients to view visual stimuli for picture-naming trials in their left hemispace and was designed to enhance right posterior perisylvian participation during word retrieval. Because the intention treatment addressed action mechanisms and nonfluent aphasia reflects difficulty initiating or maintaining action (i.e., language output), it was hypothesized that intention component of the treatment would enhance re-acquisition of picture naming more than the attention component. Patients with moderate and severe word-finding impairment showed gains with both treatments but greater incremental improvement from one treatment phase to the next with the intention than the attention treatment. Thus, the hypothesis that intention component would be a more active constituent than the attention component was confirmed for these patients. Patients with profound word-finding impairment showed some improvement with both treatments but no differential effects for the intention treatment. Almost all patients who showed treatment gains on either treatment also demonstrated generalization from trained to untrained items. (JINS, 2007, 13, 582–594.)

The need for research that is applicable to the most common health problems is well recognized. Some of this research will be in the area of primary care, and family doctors must contribute to the research for it to be effective in improving care. Using a sample of key informants from 10 different countries, this paper explores the extent to which family doctors are involved in research in the various regions of the globe. We find great variability in the level of research being conducted by family doctors at academic institutions and in the development of the community research structures, such as practice based research networks. Despite the problems, family doctors are involved in research in every region assessed, and there is room for optimism that this role will be substantially expanded.

This investigation reports the results of a pilot study concerning the application of principles of use-dependent learning developed in the motor rehabilitation literature as Constraint Induced Therapy to language rehabilitation in a group of individuals with chronic aphasia. We compared treatment that required forced use of the language modality, Constraint Induced Language Therapy, (CILT) to treatment allowing all modes of communication. Both treatments were administrated intensively in a massed practice paradigm, using the same therapeutic stimuli and tasks. Results suggest that whereas both interventions yielded positive outcomes, CILT participants showed more consistent improvement on standard aphasia measures and clinician judgments of narrative discourse. These findings suggest that CILT intervention may be a viable approach to aphasia rehabilitation. (JINS, 2006, 12, 843–852.)

There is compelling evidence for the early involvement of the hippocampal formation in the natural history of Alzheimer's disease (AD). The evidence comes from recent neuropathology, neuropsychology, and neuroimaging studies. AD-type histopathologic changes limited to the hippocampus have been described and may be seen in normal aging subjects. The sites of maximal neuronal loss in the hippocampal formation are in the CA1, subiculum, and entorhinal cortex. Minimally cognitively impaired (MCI) individuals (defined by ratings of functional capacity and psychiatric symptomatology) exhibit a neuropsychological profile that is distinct from that of the unimpaired elderly. Pathologic evidence suggests that most of these cases already have AD brain changes accentuated in the hippocampal region, and our own longitudinal studies reveal that 70% of this group develop dementia within a 4-year period. We have developed a negative-angle axial view designed to cut parallel to the anterior-posterior plane of the hippocampus. Using this modified axial plane of section in conjunction with computed tomography (CT) and magnetic resonance imaging (MRI), we estimated the prevalence of hippocampal atrophy in normal aging and across severity levels of cognitively impaired elderly patients. Longitudinal study shows that hippocompal atrophy is a sensitive and specific predictor of future AD for patients with MCI. MRI volume study of AD patients, controls, and MCI patients shows specific hippocampal volume loss in MCI. We conclude that the atrophic changes associated with early AD can be visualized using qualitative techniques and are readily quantifiable with volumetry. This article is not intended to be comprehensive, but to provide an overview of some of the structural neuroimaging data from our laboratory.