HKSC Field Guide for Developing a Healthcare Knowledge Services Center

Knowledge is the foundation of our work as librarians; however, because it is intangible, we work directly with assets that result from knowledge. Content, people, and technology are the core knowledge assets. Knowledge assets are referenced throughout the HKSC Field Guide where we define a path to delivering knowledge services. Delivering the best content is achieved through the innovation and competencies of library professionals who leverage technologies to benefit their constituents. The result is excellent knowledge services. This field guide is organized in chapters that are aligned with modules of the HKSC Model Template. The HKSC Field Guide is laid out in a linear progression of activities, with simple commentary to encourage the reader’s thinking toward eventual outcomes and changes that are required to make a transition from a library setting to a Healthcare Knowledge Services Center (HKSC) operation. It is expected that the successful manager will make several passes through the entire guide, gaining a better understanding of all the pieces that must be in place for a strategic and successful plan. Each module/chapter provides descriptions to explain the module theme and to share ideas on how to proceed with the process. Following descriptions and guidance is a worksheet for taking notes and a checklist of tasks. The intent of each worksheet is to focus on a specific data collection, a strategic planning activity, and/or to note details describing required resources. Chapters conclude with a checklist for you to sign off on for tasks considered and/or completed. Some forms may not be completed until multiple passes have been made through the guide; managers are encouraged to refine and hone activities in fine-tuning their work. A separate document (in MS Word format) supplies both worksheets and checklists for you to edit electronically –or- to create separate editable documents in modular fashion

A simple method to derive speed for the endurance shuttle walk test

Background: The original method for determining endurance shuttle walk test (ESWT) speed involves components that are time consuming for clinicians. We sought to determine: (i) whether components described in the original method for determining ESWT speed held true and; (ii) the agreement between speeds derived using the original method and that equivalent to 85% of the peak speed achieved during the incremental shuttle walk test (ISWT). Methods: Patients with chronic obstructive pulmonary disease (COPD) performed two ISWTs and one ESWT on separate days, wearing a calibrated portable gas analysis unit. A retrospective analysis of these data allowed us to determine whether: (i) the peak rate of oxygen uptake (VO2peak) can be accurately estimated from the incremental shuttle walk distance (ISWD) and; (ii) ESWTs performed at a speed derived using the original method elicited 85% of VO2peak. Agreement between walks speeds was determined using Bland–Altman analysis. Results: Twenty-two participants (FEV1 48 ± 13% predicted, age 66 ± 8 yr) completed the study. The VO2peak estimated from the ISWD was less than that measured during the ISWT (mean difference −4.4; 95% confidence interval (CI), −6.0 to −2.9 ml• kg−1•min−1). The ESWT and ISWT elicited similar VO2peak (mean difference −0.2; 95% CI, −1.5 to 1.2 ml•kg−1•min−1). The mean difference (±limits of agreement) between ESWT speeds was 0.15 (±0.34) km•h−1. Conclusions: Components of the original method for determining the ESWT speed did not hold true in our sample. ESWT speed can be derived by calculating 85% of the peak speed achieved during the ISWT

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Activity of Dalbavancin against Bacillus anthracis In Vitro and in a Mouse Inhalation Anthrax Model▿

Bacillus anthracis, the causative agent of anthrax, can produce fatal disease when it is inhaled or ingested by humans. Dalbavancin, a novel, semisynthetic lipoglycopeptide, has potent activity, greater than that of vancomycin, against Gram-positive bacteria and a half-life in humans that supports once-weekly dosing. Dalbavancin demonstrated potent in vitro activity against B. anthracis (MIC range, ≤0.03 to 0.5 mg/liter; MIC50 and MIC90, 0.06 and 0.25 mg/liter, respectively), which led us to test its efficacy in a murine inhalation anthrax model. The peak concentrations of dalbavancin in mouse plasma after the administration of single intraperitoneal doses of 5 and 20 mg/kg of body weight were 15 and 71 mg/kg, respectively. At 20 mg/kg, the dalbavancin activity was detectable for 6 days after administration (terminal half-life, 53 h), indicating that long intervals between doses were feasible. The mice were challenged with 50 to 100 times the median lethal dose of the Ames strain of B. anthracis, an inoculum that kills untreated animals within 4 days. The efficacy of dalbavancin was 80 to 100%, as determined by the rate of survival at 42 days, when treatment was initiated 24 h postchallenge with regimens of 15 to 120 mg/kg every 36 h (q36h) or 30 to 240 mg/kg every 72 h (q72h). A regimen of ciprofloxacin known to protect 100% of animals was tested in parallel. Delayed dalbavancin treatment (beginning 36 or 48 h postchallenge) with 60 mg/kg q36h or 120 mg/kg q72h still provided 70 to 100% survival. The low MICs and long duration of efficacy in vivo suggest that dalbavancin may have potential as an alternative treatment or for the prophylaxis of B. anthracis infections

Acute phase protein quantitation in serum samples from healthy Atlantic bottlenose dolphins ( Tursiops truncatus

Acute phase proteins (APPs) have been studied in many companion and large animals and have been reported to have a differential sensitivity to traditional markers of inflammation. Studies have been performed indicating the conservation of these proteins as well as the application and cross-reactivity of automated assays among different species, but few reports have detailed APPs in marine mammal species. In the present study, automated assays were utilized to generate reference intervals for C-reactive protein, haptoglobin, and serum amyloid A using 44 serum samples from healthy Atlantic bottlenose dolphins (Tursiops truncatus). A total of 25 samples were obtained from dolphins under human care and 19 samples were obtained from free-ranging dolphins. Mild yet statistically significant differences were observed in levels of haptoglobin and serum amyloid A between these groups. The reference intervals from the combined groups were as follows: C-reactive protein 3.1-19.7 mg/l, haptoglobin 0-0.37 mg/ml, and serum amyloid A 17.5-42.9 mg/l. These baseline data should provide an important foundation for future studies of the application of APP quantitation in monitoring the health and stressors of dolphins under human care and with live capture of free-ranging dolphins