Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items

The use of global health items permits an efficient way of gathering general perceptions of health. These items provide useful summary information about health and are predictive of health care utilization and subsequent mortality. Analyses of 10 self-reported global health items obtained from an internet survey as part of the Patient-Reported Outcome Measurement Information System (PROMIS) project. We derived summary scores from the global health items. We estimated the associations of the summary scores with the EQ-5D index score and the PROMIS physical function, pain, fatigue, emotional distress, and social health domain scores. Exploratory and confirmatory factor analyses supported a two-factor model. Global physical health (GPH; 4 items on overall physical health, physical function, pain, and fatigue) and global mental health (GMH; 4 items on quality of life, mental health, satisfaction with social activities, and emotional problems) scales were created. The scales had internal consistency reliability coefficients of 0.81 and 0.86, respectively. GPH correlated more strongly with the EQ-5D than did GMH (r = 0.76 vs. 0.59). GPH correlated most strongly with pain impact (r = −0.75) whereas GMH correlated most strongly with depressive symptoms (r = −0.71). Two dimensions representing physical and mental health underlie the global health items in PROMIS. These global health scales can be used to efficiently summarize physical and mental health in patient-reported outcome studies

Real-time smart and standalone vision/IMU navigation sensor

In this paper, we present a smart, standalone, multi-platform stereo vision/IMU-based navigation system, providing ego-motion estimation. The real-time visual odometry algorithm is run on a nano ITX single-board computer (SBC) of 1.9 GHz CPU and 16-core GPU. High-resolution stereo images of 1.2 megapixel provide high-quality data. Tracking of up to 750 features is made possible at 5 fps thanks to a minimal, but efficient, features detection–stereo matching–feature tracking scheme runs on the GPU. Furthermore, the feature tracking algorithm benefits from assistance of a 100 Hz IMU whose accelerometer and gyroscope data provide inertial features prediction enhancing execution speed and tracking efficiency. In a space mission context, we demonstrate robustness and accuracy of the real-time generated 6-degrees-of-freedom trajectories from our visual odometry algorithm. Performance evaluations are comparable to ground truth measurements from an external motion capture system

Necdin, a Negative Growth Regulator, Is a Novel STAT3 Target Gene Down-Regulated in Human Cancer

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines. These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin

Inhibition of Serine Palmitoyl Transferase I Reduces Cardiac Ceramide Levels and Increases Glycolysis Rates following Diet-Induced Insulin Resistance

Objective: Diet-induced obesity (DIO) leads to an accumulation of intra-myocardial lipid metabolites implicated in causing cardiac insulin resistance and contractile dysfunction. One such metabolite is ceramide, and our aim was to determine the effects of inhibiting de novo ceramide synthesis on cardiac function and insulin stimulated glucose utilization in mice subjected to DIO. Materials and Methods: C57BL/6 mice were fed a low fat diet or subjected to DIO for 12 weeks, and then treated for 4 weeks with either vehicle control or the serine palmitoyl transferase I (SPT I) inhibitor, myriocin. In vivo cardiac function was assessed via ultrasound echocardiography, while glucose metabolism was assessed in isolated working hearts. Results: DIO was not associated with an accumulation of intra-myocardial ceramide, but rather, an accumulation of intra-myocardial DAG (2.63±0.41 vs. 4.80±0.97 nmol/g dry weight). Nonetheless, treatment of DIO mice with myriocin decreased intra-myocardial ceramide levels (50.3±7.7 vs. 26.9±2.7 nmol/g dry weight) and prevented the DIO-associated increase in intra-myocardial DAG levels. Interestingly, although DIO impaired myocardial glycolysis rates (7789±1267 vs. 2671±326 nmol/min/g dry weight), hearts from myriocin treated DIO mice exhibited an increase in glycolysis rates. Conclusions: Our data reveal that although intra-myocardial ceramide does not accumulate following DIO, inhibition of de novo ceramide synthesis nonetheless reduces intra-myocardial ceramide levels and prevents the accumulation of intra-myocardial DAG. These effects improved the DIO-associated impairment of cardiac glycolysis rates, suggesting that SPT I inhibition increases cardiac glucose utilization. © 2012 Ussher et al.published_or_final_versio

Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD

Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing prevalence worldwide. The primary aim of this study was to identify genes and gene ontologies associated with COPD severity. Gene expression profiling was performed on total RNA extracted from lung tissue of 18 former smokers with COPD. Class comparison analysis on mild (n = 9, FEV1 80–110% predicted) and moderate (n = 9, FEV1 50–60% predicted) COPD patients identified 46 differentially expressed genes (p<0.01), of which 14 genes were technically confirmed by quantitative real-time-PCR. Biological replication in an independent test set of 58 lung samples confirmed the altered expression of ten genes with increasing COPD severity, with eight of these genes (NNMT, THBS1, HLA-DPB1, IGHD, ETS2, ELF1, PTGDS and CYRBD1) being differentially expressed by greater than 1.8 fold between mild and moderate COPD, identifying these as candidate determinants of COPD severity. These genes belonged to ontologies potentially implicated in COPD including angiogenesis, cell migration, proliferation and apoptosis. Our secondary aim was to identify gene ontologies common to airway obstruction, indicated by impaired FEV1 and KCO. Using gene ontology enrichment analysis we have identified relevant biological and molecular processes including regulation of cell-matrix adhesion, leukocyte activation, cell and substrate adhesion, cell adhesion, angiogenesis, cell activation that are enriched among genes involved in airflow obstruction. Exploring the functional significance of these genes and their gene ontologies will provide clues to molecular changes involved in severity of COPD, which could be developed as targets for therapy or biomarkers for early diagnosis

The Reinforcing Therapist Performance (RTP) experiment: Study protocol for a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Rewarding provider performance has been recommended by the Institute of Medicine as an approach to improve the quality of treatment, yet little empirical research currently exists that has examined the effectiveness and cost-effectiveness of such approaches. The aim of this study is to test the effectiveness and cost-effectiveness of providing monetary incentives directly to therapists as a method to improve substance abuse treatment service delivery and subsequent client treatment outcomes.</p> <p>Design</p> <p>Using a cluster randomized design, substance abuse treatment therapists from across 29 sites were assigned by site to either an implementation as usual (IAU) or pay-for-performance (P4P) condition.</p> <p>Participants</p> <p>Substance abuse treatment therapists participating in a large dissemination and implementation initiative funded by the Center for Substance Abuse Treatment.</p> <p>Intervention</p> <p>Therapists in both conditions received comprehensive training and ongoing monitoring, coaching, and feedback. However, those in the P4P condition also were given the opportunity to earn monetary incentives for achieving two sets of measurable behaviors related to quality implementation of the treatment.</p> <p>Outcomes</p> <p>Effectiveness outcomes will focus on the impact of the monetary incentives to increase the proportion of adolescents who receive a targeted threshold level of treatment, months that therapists demonstrate monthly competency, and adolescents who are in recovery following treatment. Similarly, cost-effectiveness outcomes will focus on cost per adolescent receiving targeted threshold level of treatment, cost per month of demonstrated competence, and cost per adolescent in recovery.</p> <p>Trial Registration</p> <p>Trial Registration Number: NCT01016704</p

Perinatal mental ill health - the experiences of women from ethnic minority groups

This study aimed to investigate ethnic minority women’s experiences and opinions of perinatal mental health problems and the provision of perinatal mental health support services. An exploratory survey was undertaken using a questionnaire. Quantitative data were analysed using descriptive statistics and a simple thematic analysis was used for the qualitative data. A total of 51 responses from women of 14 different ethnic minority backgrounds were analysed. Women from minority ethnic groups face barriers to seeking help for perinatal mental ill health as a result of ongoing stigma and the poor attitudes and behaviours of health professionals and inappropriately designed services. Future interventions should focus on providing adequate cultural competency for health care professionals and ensure that all women are able to access culturally appropriate spaces to talk and be listened to within community settings and wider services

A cloud-based enhanced differential evolution algorithm for parameter estimation problems in computational systems biology

This is a post-peer-review, pre-copyedit version of an article published in Cluster Computing. The final authenticated version is available online at: https://doi.org/10.1007/s10586-017-0860-1[Abstract] Metaheuristics are gaining increasing recognition in many research areas, computational systems biology among them. Recent advances in metaheuristics can be helpful in locating the vicinity of the global solution in reasonable computation times, with Differential Evolution (DE) being one of the most popular methods. However, for most realistic applications, DE still requires excessive computation times. With the advent of Cloud Computing effortless access to large number of distributed resources has become more feasible, and new distributed frameworks, like Spark, have been developed to deal with large scale computations on commodity clusters and cloud resources. In this paper we propose a parallel implementation of an enhanced DE using Spark. The proposal drastically reduces the execution time, by means of including a selected local search and exploiting the available distributed resources. The performance of the proposal has been thoroughly assessed using challenging parameter estimation problems from the domain of computational systems biology. Two different platforms have been used for the evaluation, a local cluster and the Microsoft Azure public cloud. Additionally, it has been also compared with other parallel approaches, another cloud-based solution (a MapReduce implementation) and a traditional HPC solution (a MPI implementation)Ministerio de Economía y Competitividad; DPI2014-55276-C5-2-RMinisterio de Economía y Competitividad; TIN2013-42148-PMinisterio de Economía y Competitividad; TIN2016-75845-PXunta de Galicia ; R2016/045Xunta de Galicia; GRC2013/05