Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease

The R6/2 mouse is a popular model of Huntington’s disease (HD) because of its rapid progression and measurable behavioral phenotype. Yet current behavioral phenotyping methods are usually univariate (e.g., latency to fall from a rotarod) and labor intensive. We used a force-plate actometer and specialized computer algorithms to partition the data into topographically specific behavioral categories that were sensitive to HD-like abnormalities. Seven R6/2 male mice and 7 wild type (WT) controls were placed in a 42 cm X 42 cm force-plate actometer for 20-min recording sessions at 6–7, 8–9, 10–11 and 12–13 weeks of age. Distance traveled, number of wall rears, and number of straight runs (traveling 175 mm or more in 1.5 s) were reduced in R6/2 relative to WT mice at all ages tested. Low mobility bouts (each defined as remaining continuously in a virtual circle of 15 mm radius for 5 s) were increased in R6/2 mice at 6–7 wk and beyond. Independent of body weight, force off-load during wall rears was reduced in R6/2 mice except at 6–7 wk. Power spectra of force variation during straight runs indicated an age-related progressive loss of rhythmicity in R6/2 compared to WT, suggesting gait dysrhythmia and dysmetria. Collectively, these data, which extend results obtained with other widely different behavioral phenotyping methods, document a multifaceted syndrome of motor abnormalities in R6/2 mice. We suggest, moreover, that the force-plate actometer offers a high-throughput tool for screening drugs that may affect symptom expression in R6/2 or other HD model mice

Pharmacist Contributions to the U.S. Health Care System

Objective: The overall goal for this study was to conduct a segment analysis of the pharmacist workforce during 2009 based upon time spent in medication providing and in patient care services. Methods: Data for this study were obtained from the 2009 National Pharmacist Workforce Survey in which a random sample of 3,000 pharmacists was selected. Cluster analysis was used for identifying pharmacist segments and descriptive statistics were used for describing and comparing segments.Results: Of the 2,667 surveys that were presumed to be delivered to a pharmacist, 1,395 were returned yielding a 52.3% overall response rate. Of these, 1,200 responses were usable for cluster analysis. Findings from this study revealed five segments ofpharmacists: (1) Medication Providers, (2) Medication Providers who also Provide Patient Care, (3) Other Activity Pharmacists, (4) Patient Care Providers Who also Provide Medication, and (5) Patient Care Providers. The results showed that, in 2009, 41% of U.S. pharmacists were devoted wholly to medication providing (Medication Providers). Forty-three percent of pharmacists contributed significantly to patient care service provision (Medication Providers who also Provide Patient Care, Patient Care Providers who also Provide Medication, and Patient Care Providers) and the remaining 16% (Other Activity Pharmacists) contributed most of their time to business / organization management, research, education, and other health-system improvement activities. Conclusions: Based on the findings, we propose that the pharmacy profession currently has, and will continue to build, capacity for contributing to the U.S. health care system in new roles for which they have been identified. However, as shifts in professional roles occur, a great deal of capacity is required related to new service provision. Resources are scarce, so an understanding of the most appropriate timing for making such changes can lead to cost-effective use of limited resources for improving patient care

Gray space \u3ci\u3eand\u3c/i\u3e green space proximity associated with higher anxiety in youth with autism

This study used ZIP code level data on children\u27s health (National Survey of Children\u27s Health, 2012) and land cover (National Land Cover Database, 2011) from across the United States to investigate connections between proximity to green space (tree canopy), gray space (impervious surfaces), and expression of a critical co-morbid condition, anxiety, in three groups of youth: children diagnosed with autism spectrum disorder (ASD, n=1501), non-ASD children with special healthcare needs (CSHCN, n=15,776), and typically developing children (n=53,650). Both impervious surface coverage and tree canopy coverage increased the risk of severe anxiety in youth with autism, but not CSHCN or typical children. Children with ASD might experience the stress-reducing benefits of nature differently than their typically developing peers. More research using objective diagnostic metrics at finer spatial scales would help to illuminate complex relationships between green space, anxiety, and other co-morbid conditions in youth with ASD

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

etuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9–11.4) and 8.9 (90% CI = 2.7–15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6–40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC

The global pharmacy workforce: a systematic review of the literature

The importance of health workforce provision has gained significance and is now considered one of the most pressing issues worldwide, across all health professions. Against this background, the objectives of the work presented here were to systematically explore and identify contemporary issues surrounding expansion of the global pharmacy workforce in order to assist the International Pharmaceutical Federation working group on the workforce