Content Validity of the Geriatric Depression Scale in Inpatient Health Care Settings

The content validity of the Geriatric Depression Scale (GDS) for use in inpatient health care settings was evaluated. Clinical experience has shown that one or more questions may not be appropriate in such settings. These questions ask about behaviors or feelings with which the examinee may not be able to identify with because they have been in an inpatient setting during the past week. Twenty-five Subject Matter Experts (SMEs) evaluated the GDS-30 as to whether each item appropriately assesses the construct of depression for inpatients in a medical care setting. SMEs were identified by an online search of the Florida Division of Medical Quality Assurance database; inclusion criteria are presented. Nineteen SMEs held a Ph.D. and six held a Psy.D. Years of post-licensure practice experience ranged from 10 to 48 years with a mean of 23.12 years (SD = 10.07). Using the Content Validity Ratio, four questions emerged as inappropriate (statistically significant at, or below, an alpha level of .025). The lack of content validity of these questions necessitates their omission when psychometrically assessing depression in elderly inpatients. Recommended revised cutoff values are presented. Utilizing the recommended modification to the GDS presented here should reduce false positives when psychometrically assessing depression in elderly inpatients

Basic Atomic Physics

Contains reports on five research projects.National Science Foundation Grant PHY 96-024740National Science Foundation Grant PHY 92-21489U.S. Navy - Office of Naval Research Contract N00014-96-1-0484Joint Services Electronics Program Grant DAAHO4-95-1-0038National Science Foundation Grant PHY95-14795U.S. Army Research Office Contract DAAHO4-94-G-0170U.S. Army Research Office Contract DAAG55-97-1-0236U.S. Army Research Office Contract DAAH04-95-1-0533U.S. Navy - Office of Naval Research Contract N00014-96-1-0432National Science Foundation Contract PHY92-22768David and Lucile Packard Foundation Grant 96-5158National Science Foundation Grant PHY 95-01984U.S. Army Research OfficeU.S. Navy - Office of Naval Research Contract N00014-96-1-0485AASERT N00014-94-1-080

Basic Atomic Physics

Contains reports on five research projects.Joint Services Electronics Program Grant DAAH04-95-1-0038National Science Foundation Grant PHY 92-21489U.S. Navy - Office of Naval Research Grant N00014-90-J-1322National Science Foundation Grant PHY95-14795Charles S. Draper Laboratory Contract DL-H-484775U.S. Army Research Office Contract DAAH04-94-G-0170U.S. Army Research Office Contract DAAH04-95-1-0533U.S. Navy - Office of Naval Research Contract N00014-89-J-1207U.S. Navy - Office of Naval Research Contract N000014-96-1-0432David and Lucile Packard Foundation Grant 96-5158National Science Foundation Grant PHY95-01984U.S. Army - Office of ResearchU.S. Navy - Office of Naval Research Contract N00014-96-1-0485U.S. Navy - Office of Naval Research AASERT N00014-94-1-080

CXCR4 Mediated Chemotaxis Is Regulated by 5T4 Oncofetal Glycoprotein in Mouse Embryonic Cells

5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process important during embryonic development and metastatic spread of epithelial tumors. Investigation of the transcriptional changes in early ES differentiation showed upregulation of CXCL12 and down-regulation of a cell surface protease, CD26, which cleaves this chemokine. CXCL12 binds to the widely expressed CXCR4 and regulates key aspects of development, stem cell motility and tumour metastasis to tissues with high levels of CXCL12. We show that the 5T4 glycoprotein is required for optimal functional cell surface expression of the chemokine receptor CXCR4 and CXCL12 mediated chemotaxis in differentiating murine embryonic stem cells and embryo fibroblasts (MEF). Cell surface expression of 5T4 and CXCR4 molecules is co-localized in differentiating ES cells and MEF. By contrast, differentiating ES and MEF derived from 5T4 knockout (KO) mice show only intracellular CXCR4 expression but infection with adenovirus encoding mouse 5T4 restores CXCL12 chemotaxis and surface co-localization with 5T4 molecules. A series of chimeric constructs with interchanged domains of 5T4 and the glycoprotein CD44 were used to map the 5T4 sequences relevant for CXCR4 membrane expression and function in 5T4KO MEF. These data identified the 5T4 transmembrane domain as sufficient and necessary to enable CXCR4 cell surface expression and chemotaxis. Furthermore, some monoclonal antibodies against m5T4 can inhibit CXCL12 chemotaxis of differentiating ES cells and MEF which is not mediated by simple antigenic modulation. Collectively, these data support a molecular interaction of 5T4 and CXCR4 occurring at the cell surface which directly facilitates the biological response to CXCL12. The regulation of CXCR4 surface expression by 5T4 molecules is a novel means to control responses to the chemokine CXCL12 for example during embryogenesis but can also be selected to advantage the spread of a 5T4 positive tumor from its primary site

Genome-Wide Identification of Transcriptional Start Sites in the Plant Pathogen Pseudomonas syringae pv. tomato str. DC3000

RNA-Seq has provided valuable insights into global gene expression in a wide variety of organisms. Using a modified RNA-Seq approach and Illumina's high-throughput sequencing technology, we globally identified 5′-ends of transcripts for the plant pathogen Pseudomonas syringae pv. tomato str. DC3000. A substantial fraction of 5′-ends obtained by this method were consistent with results obtained using global RNA-Seq and 5′RACE. As expected, many 5′-ends were positioned a short distance upstream of annotated genes. We also captured 5′-ends within intergenic regions, providing evidence for the expression of un-annotated genes and non-coding RNAs, and detected numerous examples of antisense transcription, suggesting additional levels of complexity in gene regulation in DC3000. Importantly, targeted searches for sequence patterns in the vicinity of 5′-ends revealed over 1200 putative promoters and other regulatory motifs, establishing a broad foundation for future investigations of regulation at the genomic and single gene levels

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

Knowledge of prevalent RV types, antibody responses, and populations at risk based on age and genetics may guide the development of vaccines or other novel therapies against this important respiratory pathogen.Longitudinal data from the Childhood Origins of ASThma (COAST) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for rhinovirus A (RV-A) and RV-C (3 types each) were determined using a novel polymerase chain reaction-based assay. We pooled data from 14 study cohorts in the United States, Finland, and Australia and used mixed-effects logistic regression to identify factors related to the proportion of RV-C versus RV-A detection.In COAST, RV-A and RV-C infections were similarly common in infancy, while RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (pRhinovirus C (RV-C) can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing.To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses.</div

Co-limitation towards lower latitudes shapes global forest diversity gradients

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Soft tissue reconstruction and osteotomies for pes planovalgus correction

The correction of the flexible pes planovalgus foot and ankle is a complicated and somewhat controversial topic. After conservative methods fail, there is a wide range of possible soft tissue and bony procedures. The appropriate work up and understanding of the pathomechanics are vital to the correct choice of procedures to correct these deformities. Once the work up and procedure selection are done, the operation must also be technically performed well and with efficiency, as most often the condition is corrected with a variety of procedures. This article discusses some of the most common procedures necessary to fully correct the pes planovalgus foot and discusses the authors\u27 technique and pearls

Deformity correction of the midfoot/hindfoot/ankle

The correction of the deformed arthritic foot and ankle is a complicated and somewhat controversial topic. After conservative methods fail, there is a wide range of possible bony procedures and arthrodesis that maybe performed. The appropriate work up and understanding of the pathomechanics is vital to the correct choice of procedures to correct these deformities. Once the work up and procedure selection is done, the operation must also be technically performed well and with efficiency, as most often the condition is corrected with a variety of procedures. This article discusses some of the most common procedures necessary to fully correct deformity of the midfoot, hindfoot, and ankle. This article will also discuss the authors\u27 technique and pearls