Performance Measures Using Electronic Health Records: Five Case Studies

Presents the experiences of five provider organizations in developing, testing, and implementing four types of electronic quality-of-care indicators based on EHR data. Discusses challenges, and compares results with those from traditional indicators

PERFORMANCE EVALUATION OF THE PERMANENT NEW JERSEY SAFETY SHAPE BARRIER – UPDATE TO NCHRP 350 TEST NO. 4-12 (2214NJ-2)

Based on the proposed changes to the National Cooperative Highway Research Program (NCHRP) Report No. 350 guidelines, NCHRP Project 22-14(2) researchers deemed it appropriate to evaluate permanent safety shape barrier systems prior to finalizing the new crash testing procedures and guidelines. For this effort, the permanent New Jersey Safety Shape barrier was selected for evaluation. One full-scale vehicle crash test was performed on the longitudinal barrier system in accordance with the Test Level 4 (TL-4) requirements presented in the Update to NCHRP Report No. 350. For the permanent barrier testing program, a 10000S single unit truck was used. The permanent safety shape barrier provided an unacceptable safety performance when impacted by the single unit truck, thus failing to meet the proposed TL-4 requirements presented in the Update to NCHRP Report No. 350

DEVELOPMENT OF STANDARDS FOR PLACEMENT OF STEEL GUARDRAIL POSTS IN ROCK

A steel post W-beam guardrail system was developed for installation in rock-soil foundations. The guardrail system was constructed with a 2.66-mm (12-gauge) thick W-beam rail, 53.34 m in length. The W-beam guardrail was supported by twenty-seven W152x13.4 by 1,346-mm long steel posts, spaced at 1,905 mm on center. The posts were installed in drilled holes in concrete, constructed by drilling three 203-mm diameter holes on 165- mm centers to a depth of 610 mm. The drilled holes were backfilled with compacted ASTM C33 coarse aggregate, size no. 57. One full-scale vehicle crash test, using a 3⁄4-ton pickup truck, was performed on the W-beam guardrail system. The test was conducted and reported in accordance with the requirements specified in the National Cooperative Highway Research Program (NCHRP) Report No. 350, Recommended Procedures for the Safety Performance Evaluation of Highway Features. The safety performance of the W-beam guardrail system with post placed in rock was determined to be acceptable according to the Test Level 3 (TL-3) evaluation criteria specified in NCHRP Report No. 350. Further, guardrail post placement recommendations were also developed for situations where rock is located below the surface. These recommendations were developed through an analysis of bogie testing of posts

Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling

Atherosclerosis is primarily a disease of lipid metabolism and inflammation; however, it is also closely associated with endothelial extracellular matrix (ECM) remodelling, with fibronectin accumulating in the laminin–collagen basement membrane. To investigate how fibronectin modulates inflammation in arteries, we replaced the cytoplasmic tail of the fibronectin receptor integrin α5 with that of the collagen/laminin receptor integrin α2. This chimaera suppressed inflammatory signalling in endothelial cells on fibronectin and in knock-in mice. Fibronectin promoted inflammation by suppressing anti-inflammatory cAMP. cAMP was activated through endothelial prostacyclin secretion; however, this was ECM-independent. Instead, cells on fibronectin suppressed cAMP via enhanced phosphodiesterase (PDE) activity, through direct binding of integrin α5 to phosphodiesterase-4D5 (PDE4D5), which induced PP2A-dependent dephosphorylation of PDE4D5 on the inhibitory site Ser651. In vivo knockdown of PDE4D5 inhibited inflammation at athero-prone sites. These data elucidate a molecular mechanism linking ECM remodelling and inflammation, thereby identifying a new class of therapeutic targets.United States. National Institutes of Health (5R01HL75092)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (MR/J007412/1

Syndecan-4 controls lymphatic vasculature remodeling during embryonic development

The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4(-/-); Pecam1(-/-) double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.info:eu-repo/semantics/publishe

Randomized Controlled Pilot Trial of Mindfulness-Based Stress Reduction for Breast and Colorectal Cancer Survivors: Effects on Cancer-Related Cognitive Impairment

Purpose Cancer-related cognitive impairment (CRCI) is a common, fatigue-related symptom that disrupts cancer survivors’ quality of life. Few interventions for CRCI exist. As part of a randomized pilot study targeting cancer-related fatigue, the effects of mindfulness-based stress reduction (MBSR) on survivors’ cognitive outcomes were investigated. Methods Breast and colorectal cancer survivors (n = 71) with moderate-to-severe fatigue were randomized to MBSR (n = 35) or a fatigue education and support (ES; n = 36) condition. The Attentional Function Index (AFI) and the Stroop test were used to assess survivors’ cognitive function at baseline (T1), after the 8-week intervention period (T2), and 6 months later (T3) using intent-to-treat analysis. Mediation analyses were performed to explore mechanisms of intervention effects on cognitive functioning. Results MBSR participants reported significantly greater improvement on the AFI total score compared to ES participants at T2 (d = 0.83, p = 0.001) and T3 (d = 0.55, p = 0.021). MBSR also significantly outperformed ES on most AFI subscales, although both groups improved over time. MBSR produced greater Stroop accuracy rates relative to ES at T2 (r = 0.340, p = 0.005) and T3 (r = 0.280, p = 0.030), with improved accuracy over time only for the MBSR group. There were no significant differences in Stroop reaction time between groups. Improvements in mindfulness mediated the effect of group (e.g., MBSR vs. ES) on AFI total score at T2 and T3. Conclusions Additional randomized trials with more comprehensive cognitive measures are warranted to definitively assess the efficacy of MBSR for CRCI. Implications for Cancer Survivors This pilot study has important implications for all cancer survivors as it is the first published trial to show that MBSR offers robust and durable improvements in CRCI

Bovine tuberculosis disturbs parasite functional trait composition in African buffalo

Novel parasites can have wide-ranging impacts, not only on host populations, but also on the resident parasite community. Historically, impacts of novel parasites have been assessed by examining pairwise interactions between parasite species. However, parasite communities are complex networks of interacting species. Here we used multivariate taxonomic and trait-based approaches to determine how parasite community composition changed when African buffalo (Syncerus caffer) acquired an emerging disease, bovine tuberculosis (BTB). Both taxonomic and functional parasite richness increased significantly in animals that acquired BTB than in those that did not. Thus, the presence of BTB seems to catalyze extraordinary shifts in community composition. There were no differences in overall parasite taxonomic composition between infected and uninfected individuals, however. The trait-based analysis revealed an increase in direct-transmitted, quickly replicating parasites following BTB infection. This study demonstrates that trait-based approaches provide insight into parasite community dynamics in the context of emerging infections

Shear-induced Notch-Cx37-p27 axis arrests endothelial cell cycle to enable arterial specification

Establishment of a functional vascular network is rate-limiting in embryonic development, tissue repair and engineering. During blood vessel formation, newly generated endothelial cells rapidly expand into primitive plexi that undergo vascular remodeling into circulatory networks, requiring coordinated growth inhibition and arterial-venous specification. Whether the mechanisms controlling endothelial cell cycle arrest and acquisition of specialized phenotypes are interdependent is unknown. Here we demonstrate that fluid shear stress, at arterial flow magnitudes, maximally activates NOTCH signaling, which upregulates GJA4 (commonly, Cx37) and downstream cell cycle inhibitor CDKN1B (p27). Blockade of any of these steps causes hyperproliferation and loss of arterial specification. Re-expression of GJA4 or CDKN1B, or chemical cell cycle inhibition, restores endothelial growth control and arterial gene expression. Thus, we elucidate a mechanochemical pathway in which arterial shear activates a NOTCH-GJA4-CDKN1B axis that promotes endothelial cell cycle arrest to enable arterial gene expression. These insights will guide vascular regeneration and engineering

Randomized Controlled Pilot Trial of Mindfulness-Based Stress Reduction Compared to Psychoeducational Support for Persistently Fatigued Breast and Colorectal Cancer Survivors

Purpose Cancer-related fatigue (CRF) is a disruptive symptom for many survivors. Despite promising evidence for efficacy of Mindfulness-Based Stress Reduction (MBSR) in reducing CRF, no trials comparing it to an active comparator for fatigued survivors have been published. The purpose of this trial was to compare MBSR to psychoeducation for CRF and associated symptoms. Methods Breast (n=60) and colorectal (n=11) cancer survivors (stage 0–III) with clinically significant CRF after completing chemotherapy and/or radiation therapy an average of 28 months prior to enrollment were randomized to MBSR or psychoeducation/support groups (PES). MBSR focused on mindfulness training; PES focused on CRF self-management. Outcomes included CRF interference (primary), CRF severity and global improvement, vitality, depression, anxiety, sleep disturbance, and pain. Outcomes were assessed at baseline (T1), post-intervention (T2), and 6-month follow-up (T3) using intent-to-treat analysis. Results Between-group differences in CRF interference were not significant at any time point; however, there was a trend favoring MBSR (d=−0.46, p=0.073) at T2. MBSR participants reported significantly greater improvement in vitality (d=0.53, p=0.003) and were more likely to report CRF as moderately-to-completely improved compared to the PES group (χ2 (1)=4.1765, p=0.041) at T2. MBSR participants also reported significantly greater reductions in pain at T2 (d=0.53, p=0.014). In addition, both MBSR and PES produced moderate-to-large and significant within-group improvements in all fatigue outcomes, depression, anxiety, and sleep at T2 and T3 compared to T1. Conclusion MBSR and PES appear efficacious for CRF and related symptoms. Larger trials including a usual care arm are warranted

Genetic determinants of gut microbiota composition and bile acid profiles in mice.

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions