Findings indicate poorer sentence recognition in children with NH and MBHL or UHL as SNR decreases. VRT results suggest that greater effort was expended when processing stimuli that were incorrectly identified. Increasing VRT with decreasing SNR for correct responses also supports greater effort in poorer acoustic conditions. The absence of significant hearing status differences suggests that VRT was not differentially affected by MBHL, UHL, or NH for children in this study.

Purpose To evaluate the nature of CDK5 hyperactivity in pancreatic cancer progression. Experimental Design We utilized genetic, biochemical, and molecular biology methods to investigate the nature and function of overexpression of CDK5 and its activators p35 and p39 during the progression of pancreatic cancer. Purpose Investigate the expression and function of CDK5 and its co-activators p35 and p39 in pancreatic cancer. Experimental Design Determine the genetic and biochemical cause of CDK5 hyperactivity in pancreatic cancer. Results Amplification of the CDK5 gene or either of its main activators, p35 and p39, was observed in 67% of human pancreatic ductal adenocarcinoma (PDAC). CDK5, p35 and p39 were rarely expressed in pancreatic ducts, while greater than 90% of PDACs had increased levels of CDK5 and p35. Increased levels of CDK5, p35 and p39 protein were observed in several pancreatic cancer cell lines. Inhibition of CDK5 kinase activity using a CDK5 dominant negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. Increased CDK5 kinase activity was also observed in immortalized human pancreatic cells (HPNE) expressing a mutant form of K-Ras (G12D) compared to HPNE cells expressing native K-Ras. G12D K-Ras increased cleavage of p35 to p25, a stable and greater activator of CDK5, thus implicating a role for CDK5 in early progression of PDAC. Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves MEK, PI3K or CDK5 decreased p25 protein levels. Conclusion These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells.

BackgroundEffective teamwork facilitates collective learning, which is integral to safety culture. There are no rigorous evaluations of the impact of team training on the four components of safety culture—reporting, just, flexible and learning cultures. We evaluated the impact of a year-long team training programme on safety culture in 24 hospitals using two theoretical frameworks.MethodsWe used two quasi-experimental designs: a cross-sectional comparison of hospital survey on patient safety culture (HSOPS) results from an intervention group of 24 hospitals to a static group of 13 hospitals and a pre-post comparison of HSOPS results within intervention hospitals. Dependent variables were HSOPS items representing the four components of safety culture; independent variables were derived from items added to the HSOPS that measured the extent of team training, learning and transfer. We used a generalised linear mixed model approach to account for the correlated nature of the data.Results59% of 2137 respondents from the intervention group reported receiving team training. Intervention group HSOPS scores were significantly higher than static group scores in three dimensions assessing the flexible and learning components of safety culture. The distribution of the adoption of team behaviours (transfer) varied in the intervention group from 2.8% to 31.0%. Adoption of team behaviours was significantly associated with odds of an individual reacting more positively at reassessment than baseline to nine items reflecting all four components of safety culture.ConclusionsTeam training can result in transformational change in safety culture when the work environment supports the transfer of learning to new behaviour.

The effect of readiness to change on treatment outcome was examined among 332 adolescents (45.6% male, 73.8% Caucasian), aged 12 through 17 (M = 14.6, SD = 1.5), with Major Depressive Disorder participating in the Treatment for Adolescents with Depression Study (TADS). TADS was a randomized clinical trial comparing the effectiveness of Fluoxetine, Cognitive Behavioral Therapy, their combination, and a pill placebo. An abbreviated Stages of Change Questionnaire was used to obtain four readiness to change scores: Precontemplation, Contemplation, Action and Maintenance. The association between each readiness score and depression severity across 12 weeks of acute treatment for depression, as measured by the Children's Depression Rating Scale-Revised, was examined. Although treatment response was not moderated by any of the readiness scores, baseline Action scores predicted outcome: higher Action scores were associated with better outcome Corresponding Author: Cara C. Lewis, M.S. 1227 Psychology Department, University of Oregon, Eugene, OR, 97403. Phone: (541) 346-5534. Fax: (541) 346-4911. clewis@uoregon.edu. Disclosure: Susan Silva is a consultant with Pfizer. John March is a consultant or scientific advisor to Pfizer, Lilly, Wyeth, GSK, Jazz, and MedAvante and holds stock in MedAvante; he receives research support from Lilly and study drug for an NIMH-funded study from Lilly and Pfizer; he is the author of the MASC. The other authors have no financial relationships to disclose. Publisher's Disclaimer:The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/pubs/journals/ccp NIH Public Access A recent literature review suggests that treatment for adolescent depression achieve response rates of approximately 60% (Weisz, McCarty & Valeri, 2006). Given an expected 40% treatment non-response rate, it would be useful to identify (1) factors that influence treatment response regardless of treatment modality (non-specific predictors), (2) factors associated with differential response to treatments (moderators), and (3) post-randomization factors that help explain outcome (mediators). Identification of the characteristics associated with treatment response will help determine for whom a given treatment works best. The rationale for the current study was based on the idea that treatments may be most effective when they "fit" the individual with respect to readiness to change. For example, psychotherapy, as compared to pharmacotherapy, may place more demands on the client to actively engage in treatment. Cognitive Behavioral Therapy (CBT) requires clients to colla...

BackgroundCurrent accelerometer technology allows for data collection using brief time sampling intervals (i.e., epochs). The study aims were to examine the role of epoch length on physical activity estimates and subsequent relationships with clinically-meaningful health outcomes in post-menopausal women.MethodsData was obtained from the Woman On the Move through Activity and Nutrition Study (n = 102). Differences in activity estimates presented as 60s and 10s epochs were evaluated using paired t-tests. Relationships with health outcomes were examined using correlational and regression analyses to evaluate differences by epoch length.ResultsInactivity, moderate- and vigorous-intensity activity (MVPA) were significantly higher and light-intensity activity was significantly lower (all P < 0.001) when presented as 10s epochs. The correlation between inactivity and self-reported physical activity was stronger with 10s estimates (P < 0.03); however, the regression slopes were not significantly different. Conversely, relationships between MVPA and body weight, BMI, whole body and trunk lean and fat mass, and femoral neck bone mineral density was stronger with 60s estimates (all P < 0.05); however, regression slopes were similar.ConclusionThese findings suggest that although the use of a shorter time sampling interval may suggestively reduce misclassification error of physical activity estimates, associations with health outcomes did not yield strikingly different results. Additional studies are needed to further our understanding of the ways in which epoch length contributes to the ascertainment of physical activity in research studies.Trial RegistrationClinical Trials Identifier: NCT00023543

BackgroundHost-species specificity of the human immunodeficiency virus (HIV) limits pathobiologic, diagnostic and therapeutic research investigations to humans and non-human primates. The emergence of humanized mice as a model for viral infection of the nervous system has overcome such restrictions enabling research for HIV-associated end organ disease including behavioral, cognitive and neuropathologic deficits reflective of neuroAIDS. Chronic HIV-1 infection of NOD/scid-IL-2Rgcnull mice transplanted with human CD34+ hematopoietic stem cells (CD34-NSG) leads to persistent viremia, profound CD4+ T lymphocyte loss and infection of human monocyte-macrophages in the meninges and perivascular spaces. Murine cells are not infected with virus.MethodsChanges in mouse behavior were measured, starting at 8 weeks after viral infection. These were recorded coordinate with magnetic resonance spectroscopy metabolites including N-acetylaspartate (NAA), creatine and choline. Diffusion tensor magnetic resonance imaging (DTI) was recorded against multispectral immunohistochemical staining for neuronal markers that included microtubule associated protein-2 (MAP2), neurofilament (NF) and synaptophysin (SYN); for astrocyte glial fibrillary acidic protein (GFAP); and for microglial ionized calcium binding adaptor molecule 1 (Iba-1). Oligodendrocyte numbers and integrity were measured for myelin associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG) antigens.ResultsBehavioral abnormalities were readily observed in HIV-1 infected mice. Longitudinal open field activity tests demonstrated lack of habituation indicating potential for memory loss and persistent anxiety in HIV-1 infected mice compared to uninfected controls. End-point NAA and creatine in the cerebral cortex increased with decreased MAG. NAA and glutamate decreased with decreased SYN and MAG. Robust inflammation reflected GFAP and Iba-1 staining intensities. DTI metrics were coordinate with deregulation of NF, Iba-1, MOG and MAG levels in the whisker barrel and MAP2, NF, MAG, MOG and SYN in the corpus callosum.ConclusionsThe findings are consistent with some of the clinical, biochemical and pathobiologic features of human HIV-1 nervous system infections. This model will prove useful towards investigating the mechanisms of HIV-1 induced neuropathology and in developing novel biomarkers and therapeutic strategies for disease.Electronic supplementary materialThe online version of this article (doi:10.1186/1750-1326-9-58) contains supplementary material, which is available to authorized users.

This study demonstrated the superiority of laparoscopy over conventional open surgery across all illness severity risk groups for common surgical procedures. The results in general show that laparoscopic surgery is safe, efficacious, and cost-effective compared with open surgery and suggest that laparoscopic surgery should be the procedure of choice for all common surgical procedures, regardless of illness severity.

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