bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum S100B level increases after running but not cycling exercise
Authors: Stocchero Cintia Mussi Alvim , Oses Jean Pierre , Cunha Giovani Santos , Martins Jocelito Bijoldo , Brum Liz Marina , Zimmer Eduardo Rigon , Souza Diogo Onofre , Portela Luis Valmor , Reischak-Oliveira Álvaro
Published: September 2013

The objective of this study was to investigate the effect of running versus cycling exercises upon serum S100B levels and typical markers of skeletal muscle damage such as creatine kinase (CK), aspartate aminotransferase (AST) and myoglobin (Mb). Although recent work demonstrates that S100B is highly expressed and exerts functional properties in skeletal muscle, there is no previous study that tries to establish a relationship between muscle damage and serum S100B levels after exercise. We conducted a cross-sectional study on 13 male triathletes. They completed 2 submaximal exercise protocols at anaerobic threshold intensity. Running was performed on a treadmill with no inclination (RUN) and cycling (CYC) using a cycle-simulator. Three blood samples were taken before (PRE), immediately after (POST) and 1 h after exercise for CK, AST, Mb and S100B assessments. We found a significant increase in serum S100B levels and muscle damage markers in RUN POST compared with RUN PRE. Comparing groups, POST S100B, CK, AST and Mb serum levels were higher in RUN than CYC. Only in RUN, the area under the curve (AUC) of serum S100B is positively correlated with AUC of CK and Mb. Therefore, immediately after an intense exercise such as running, but not cycling, serum levels of S100B protein increase in parallel with levels of CK, AST and Mb. Additionally, the positive correlation between S100B and CK and Mb points to S100B as an acute biomarker of muscle damage after running exercise.
ASYMPTOTIC EVALUATION OF BOSONIC PROBABILITY AMPLITUDES IN LINEAR UNITARY NETWORKS IN THE CASE OF LARGE NUMBER OF BOSONS
Authors: SHCHESNOVICH V. S.
Published: September 2013

An asymptotic analytical approach is proposed for bosonic probability amplitudes in unitary linear networks, such as the optical multiport devices for photons. The asymptotic approach applies for large number of bosons N ≫ M in the M-mode network, where M is finite. The probability amplitudes of N bosons unitarily transformed from the input modes to the output modes of a unitary network are approximated by a multidimensional integral with the integrand containing a large parameter (N) in the exponent. The integral representation allows an asymptotic estimate of bosonic probability amplitudes up to a multiplicative error of order 1/N by the saddle point method. The estimate depends on solution of the scaling problem for the M × M-dimensional unitary network matrix: to find the left and right diagonal matrices which scale the unitary matrix to a matrix which has specified row and column sums (equal, respectively, to the distributions of bosons in the input and output modes). The scaled matrices give the saddle points of the integral. For simple saddle points, an explicit formula giving the asymptotic estimate of bosonic probability amplitudes is derived. Performance of the approximation and the scaling of the relative error with N are studied for two-mode network (the beam splitter), where the saddle-points are roots of a quadratic and an exact analytical formula for the probability amplitudes is available, and for three-mode network (the tritter).
ENTREPRENEURS IN THE DARK: THE IMPACT OF FRAGILE AND HYBRID GOVERNANCE ON LEBANESE ENTREPRENEURSHIP — A CASE-STUDY OF THE ELECTRICITY SECTOR
Authors: STEL NORA
Published: September 2013

This article studies the relationship between governance and entrepreneurship, with a specific focus on Lebanon. In Lebanon, fragility and hybridity — manifested in violent conflict and sectarian oligopolies — undermine entrepreneurial activities, among others through its impact on electricity supply. It is found here that hybrid governance results in inflated electricity prices and reduced electricity reliability, undermining business competitiveness and limiting innovative entrepreneurship. The article's contributions lie in providing a deeper understanding of entrepreneurship in fragile states and showing not merely that, but precisely how, governance matters for developmental entrepreneurship.
MINORITY BUSINESS NETWORKS AS SOURCES OF SOCIAL CAPITAL FOR MINORITY FIRMS
Authors: BLOUNT IAN Y. , SMITH DELMONIZE A. , HILL JAMES A.
Published: September 2013

Much of our understanding concerning minority-owned firms is based on nascent entrepreneurial businesses. Therefore, it is difficult to answer the question of how a minority-owned firm's age and size may influence the social capital derived from a minority business network. We utilize a resource-dependence perspective to hypothesize that the social capital derived from participation in a minority business network will be negatively related to the minority-owned firm's age and size. We find that firm size (as measured by revenue and number of employees) is negatively related with social capital derived from the minority business network. Our findings may help minority business owners understand the relative value of membership in minority business networks before committing limited resources.
Late Permian aeolian sand seas from the Polish Upper Rotliegend Basin in the context of palaeoclimatic periodicity
Authors: Kiersnowski Hubert
Published: September 2013

A study of a Permian aeolian depositional system in the Polish Upper Rotliegend Basin (PURB) is described and is placed in the wider context of similar studies of the German, Dutch and UK parts of the Southern Permian Basin (SPB). Aeolian complexes in the PURB consist of several stacked erg units inter-bedded with fluvial and playa deposits. These deposits are grouped into seven main units: six predominantly aeolian and one fluvial. The separate aeolian units were considered as representative of the changing pattern of palaeowinds directions. The correlations of wind mean directions assisted in the development of a new depositional model for part of the Eastern Erg aeolian complex within the PURB.
Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth
Authors: Engevik Melinda A. , Aihara Eitaro , Montrose Marshall H. , Shull Gary E. , Hassett Daniel J. , Worrell Roger T.
Published: September 2013

Changes in the intestinal microbiota have been linked to diabetes, obesity, inflammatory bowel disease, and Clostridium difficile ( C. difficile)-associated disease. Despite this, it remains unclear how the intestinal environment, set by ion transport, affects luminal and mucosa-associated bacterial composition. Na+/H+-exchanger isoform 3 (NHE3), a target of C. difficile toxin B, plays an integral role in intestinal Na+absorption. Thus the NHE3-deficient mouse model was chosen to examine the effect of pH and ion composition on bacterial growth. We hypothesized that ion transport-induced change in the intestinal environment would lead to alteration of the microbiota. Region-specific changes in ion composition and pH correlated with region-specific alteration of luminal and mucosal-associated bacteria with general decreases in Firmicutes and increases in Bacteroidetes members. Bacteroides thetaiotaomicron ( B. thetaiotaomicron) increased in NHE3−/−terminal ileum and was examined in vitro to determine whether altered Na+was sufficient to affect growth. Increased in vitro growth of B. thetaiotaomicron occurred in 43 mM Na+correlating with the NHE3−/−mouse terminal ileum [Na+]. NHE3−/−terminal ileum displayed increased fut2 mRNA and fucosylation correlating with B. thetaiotaomicron growth. Inoculation of B. thetaiotaomicron in wild-type and NHE3−/−terminal ileum organoids displayed increased fut2 and fucosylation, indicating that B. thetaiotaomicron alone is sufficient for the increased fucosylation seen in vivo. These data demonstrate that loss of NHE3 alters the intestinal environment, leading to region-specific changes in bacteria, and shed light on the growth requirements of some gut microbiota members, which is vital for creating better treatments of complex diseases with an altered gut microbiota.
Digestion of epithelial tight junction proteins by the commensalClostridium perfringens
Authors: Pruteanu Mihaela , Shanahan Fergus
Published: September 2013

The enteric microbiota contributes to the pathogenesis of inflammatory bowel disease, but the pathways involved and bacterial participants may vary in different hosts. We previously reported that some components of the human commensal microbiota, particularly Clostridium perfringens ( C. perfringens), have the proteolytic capacity for host matrix degradation and reduce transepithelial resistance. Here, we examined the C. perfringens-derived proteolytic activity against epithelial tight junction proteins using human intestinal epithelial cell lines. We showed that the protein levels of E-cadherin, occludin, and junctional adhesion molecule 1 decrease in colonic cells treated with C. perfringens culture supernatant. E-cadherin ectodomain shedding in C. perfringens-stimulated intestinal epithelial cells was detected with antibodies against the extracellular domain of E-cadherin, and we demonstrate that this process occurs in a time- and dose-dependent manner. In addition, we showed that the filtered sterile culture supernatant of C. perfringens has no cytotoxic activity on the human intestinal cells at the concentrations used in this study. The direct cleavage of E-cadherin by the proteases from the C. perfringens culture supernatant was confirmed by C. perfringens supernatant-induced in vitro degradation of the human recombinant E-cadherin. We conclude that C. perfringens culture supernatant mediates digestion of epithelial cell junctional proteins, which is likely to enable access to the extracellular matrix components by the paracellular pathway.
Individuals with medial knee osteoarthritis show neuromuscular adaptation when perturbed during walking despite functional and structural impairments
Authors: Kumar Deepak , Swanik Charles (Buz) , Reisman Darcy S. , Rudolph Katherine S.
Published: September 2013

Neuromuscular control relies on sensory feedback that influences responses to changing external demands, and the normal response is for movement and muscle activation patterns to adapt to repeated perturbations. People with knee osteoarthritis (OA) are known to have pain, quadriceps weakness, and neuromotor deficits that could affect adaption to external perturbations. The aim of this study was to analyze neuromotor adaptation during walking in people with knee OA ( n = 38) and controls ( n = 23). Disability, quadriceps strength, joint space width, malalignment, and proprioception were assessed. Kinematic and EMG data were collected during undisturbed walking and during perturbations that caused lateral translation of the foot at initial contact. Knee excursions and EMG magnitudes were analyzed. Subjects with OA walked with less knee motion and higher muscle activation and had greater pain, limitations in function, quadriceps weakness, and malalignment, but no difference was observed in proprioception. Both groups showed increased EMG and decreased knee motion in response to the first perturbation, followed by progressively decreased EMG activity and increased knee motion during midstance over the first five perturbations, but no group differences were observed. Over 30 trials, EMG levels returned to those of normal walking. The results illustrate that people with knee OA respond similarly to healthy individuals when exposed to challenging perturbations during functional weight-bearing activities despite structural, functional, and neuromotor impairments. Mechanisms underlying the adaptive response in people with knee OA need further study.
CD95L Cell Surface Cleavage Triggers a Prometastatic Signaling Pathway in Triple-Negative Breast Cancer
Authors: Malleter Marine , Tauzin Sébastien , Bessede Alban , Castellano Rémy , Goubard Armelle , Godey Florence , Levêque Jean , Jézéquel Pascal , Campion Loic , Campone Mario , Ducret Thomas , MacGrogan Gaëtan , Debure Laure , Collette Yves , Vacher Pierre , Legembre Patrick
Published: September 2013

Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here, we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other patients with breast cancer. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility due to the formation of an unconventional CD95-containing receptosome called the motility-inducing signaling complex. The formation of this complex was instrumental for Nox3-driven reactive oxygen species generation. Mechanistic investigations revealed a Yes–Orai1–EGFR–PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a prometastatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis. Cancer Res; 73(22); 6711–21. ©2013 AACR.
Approaches for Assessing and Discovering Protein Interactions in Cancer
Authors: Mohammed Hisham , Carroll Jason S.
Published: September 2013

Significant insight into the function of proteins can be delineated by discovering and characterizing interacting proteins. There are numerous methods for the discovery of unknown associated protein networks, with purification of the bait (the protein of interest) followed by mass spectrometry as a common theme. In recent years, advances have permitted the purification of endogenous proteins and methods for scaling down starting material. As such, approaches for rapid, unbiased identification of protein interactomes are becoming a standard tool in the researchers toolbox, rather than a technique that is only available to specialists. This review will highlight some of the recent technical advances in proteomic-based discovery approaches, the pros and cons of various methods and some of the key findings in cancer-related systems. Mol Cancer Res; 11(11); 1295–302. ©2013 AACR.
Estimating the Range of Obesity Treatment Response Variability in Humans: Methods and Illustrations
Authors: Kaiser Kathryn A. , Gadbury Gary L.
Published: September 2013

Background/Aims: The rising prevalence of human obesity worldwide has focused research on a variety of interventions that result in highly varied degrees of weight loss (WL). The advent of genomic testing has quantified estimates of both the contribution of genetic factors to the development of obesity as well as racial/ethnic variation of risk alleles across subpopulations. More recent studies have examined genetic associations with effectiveness of WL interventions, but to date are unable to explain a large proportion of the variance observed. Methods: We describe and provide two illustrations of statistical methods to estimate upper and lower bounds of WL treatment response heterogeneity (TRH) in the absence of genotypic data, using published summary statistics and a raw data set from WL studies. Results: Thirty-two studies had some evidence of a positive mean treatment effect with respect to the control intervention. Twelve of these 32 studies reported WL TRH. Of these 12, 3 demonstrated an estimated proportion of >5% of the sampled population having an outcome opposite the mean effect. In the raw data set, bounds estimations for change in waist circumference revealed tighter ranges in men than women. Conclusion: Future studies may be able to take advantage of multiple approaches, including the method we describe, to identify and quantify the presence of TRH in studies of WL or related outcomes.
Impact of Informing Overweight Individuals about the Role of Genetics in Obesity: An Online Experimental Study
Authors: Lippa Natalie C. , Sanderson Saskia C.
Published: September 2013

Background/Aims: Increasing public awareness of obesity genetics could have beneficial or harmful effects on overweight individuals. This study examined the impact of genetic information on weight-related cognitions as well as interest in personalized genetic information about obesity among overweight individuals. Methods: Online survey respondents (n = 655) were randomly assigned to read either genetic, gene-environment, or nongenetic obesity causal information. Fifty-two percent of the participants were female, 82.4% were White, 45% had an annual income of USD <40,000, and the mean BMI was 32.5. Internalized weight stigma was measured using the Weight Bias Internalization Scale. Results: Participants in the genetic and gene-environment conditions were more likely to believe genetics increase obesity risk than participants in the nongenetic condition (both p < 0.05); however, they did not differ regarding internalized weight stigma. Sixty-four percent of the participants expressed interest in receiving personalized genetic information about their obesity risk. Conclusion: Dissemination of information about obesity genetics may have neither a beneficial nor a harmful impact on how overweight individuals perceive themselves. Some overweight individuals may be interested in receiving personalized genetic information. The actual effects of obesity genetic information being incorporated into public health messages and of personalized genetic information on obesity prevention and treatment interventions remain to be seen.
Genetics of Food Intake Self-Regulation in Childhood: Literature Review and Research Opportunities
Authors: Faith Myles S. , Carnell Susan , Kral Tanja V.E.
Published: September 2013

Pediatric obesity results from a daily energy imbalance between intake and expenditure, an imbalance potentially as slight as ∼30-50 kcal/day (e.g., a few extra sips of cola or bites of a cookie). That an ‘energy gap' so small may be so powerful suggests the importance of understanding mechanisms of food intake self-regulation (FISR). This review focuses on 4 behavioral indices of FISR in childhood: (1) eating in the absence of hunger; (2) eating rate; (3) caloric compensation and satiety responsiveness, and (4) food responsiveness. Evidence from pediatric samples around the world indicates that these traits are associated with body mass index, are heritable, and are linked to polymorphisms in the FTO gene. We review these data, also discussing their relevance to practical issues of parental feeding styles, portion sizes, and health literacy and numeracy. Research gaps and opportunities for future investigation are discussed. Multidisciplinary approaches and study designs that can address gene-environment interactions are needed to advance the science of FISR and stimulate new avenues for childhood obesity prevention.
Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program
Authors: Wang Yingying , Wang Anthony , Donovan Sharon M. , Teran-Garcia Margarita ,   and the STRONG Kids Research Team
Published: September 2013

Background/Aims: The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. Methods: Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. Results: Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. Conclusion: Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes.
Transcriptional Repressor HipB Regulates the Multiple Promoters in Escherichia coli
Authors: Lin Chun-Yi , Awano Naoki , Masuda Hisako , Park Jung-Ho , Inouye Masayori
Published: September 2013

HipB is a DNA-binding protein in Escherichia coli and negatively regulates its own promoter by binding to the palindromic sequences [TATCCN8GGATA (N represents any nucleotides)] on the hipBA promoter. For such sequences, bioinformatic analysis revealed that there are a total of 39 palindromic sequences (TATCCN(x)GGATA: N is any nucleotides and x is the number of nucleotides from 1 to 30) in the promoter regions of 33 genes on the E. coli genome. Notably, eutH and fadH have two and three TATCCN(x)GGATA palindromic sequences located in their promoters, respectively. Another significant finding was that a palindromic sequence was also identified in the promoter region of hipAB locus, known to be involved in the RelA-dependent persister cell formation in bacteria. Here, we demonstrated that HipB binds to the palindromic structures in the eutH, fadH, as well as the relA promoter regions and represses their expressions. We further demonstrated that HipA enhances the repression of the relA promoter activity by HipB. This effect was not observed with D291A HipA mutant which was previously shown to lack an ability to interact with HipB, indicating that HipA enhances the HipB's repressor activity through direct interaction with HipB.
Transforming Growth Factor-β–Activated Kinase 1 Regulates Angiogenesis via AMP-Activated Protein Kinase-α1 and Redox Balance in Endothelial Cells
Authors: Zippel Nina , Malik Randa Abdel , Frömel Timo , Popp Rüdiger , Bess Elke , Strilic Boris , Wettschureck Nina , Fleming Ingrid , Fisslthaler Beate
Published: September 2013

Objective—

Transforming growth factor-β–activated kinase 1 (TAK1) is a mitogen-activated protein 3-kinase and an AMP-activated protein kinase (AMPK) kinase in some cell types. Although TAK1
−/−
mice display defects in developmental vasculogenesis, the role of TAK1 in endothelial cells has not been investigated in detail.

Approach and Results—

TAK1 downregulation (small interfering RNA) in human endothelial cells attenuated proliferation without inducing apoptosis and diminished endothelial cell migration, as well as tube formation. Cytokine- and vascular endothelial growth factor (VEGF)–induced endothelial cell sprouting in a modified spheroid assay were abrogated by TAK1 downregulation. Moreover, VEGF–induced endothelial sprouting was impaired in aortic rings from mice lacking TAK1 in endothelial cells (TAK
ΔEC
). TAK1 inhibition and downregulation also inhibited VEGF–stimulated phosphorylation of several kinases, including AMPK. Proteomic analyses revealed that superoxide dismutase 2 (SOD2) expression was reduced in TAK1-deficient endothelial cells, resulting in attenuated hydrogen peroxide production but increased mitochondrial superoxide production. Endothelial cell SOD2 expression was also attenuated by AMPK inhibition and in endothelial cells from AMPKα1
−/−
mice but was unaffected by inhibitors of c-Jun N-terminal kinase, p38, extracellular signal–regulated kinase 1/2, or phosphatidylinositol 3-kinase/Akt. Moreover, the impaired endothelial sprouting from TAK
ΔEC
aortic rings was abrogated in the presence of polyethylene glycol-SOD, and tube formation was normalized by the overexpression of SOD2. A similar rescue of angiogenesis was observed in polyethylene glycol-SOD–treated aortic rings from mice with endothelial cell–specific deletion of the AMPKα1.

Conclusions—

These results establish TAK1 as an AMPKα1 kinase that regulates vascular endothelial growth factor–induced and cytokine-induced angiogenesis by modulating SOD2 expression and the superoxide anion:hydrogen peroxide balance.
Exome Sequencing and Directed Clinical Phenotyping Diagnose Cholesterol Ester Storage Disease Presenting as Autosomal Recessive Hypercholesterolemia
Authors: Stitziel Nathan O. , Fouchier Sigrid W. , Sjouke Barbara , Peloso Gina M. , Moscoso Alessa M. , Auer Paul L. , Goel Anuj , Gigante Bruna , Barnes Timothy A. , Melander Olle , Orho-Melander Marju , Duga Stefano , Sivapalaratnam Suthesh , Nikpay Majid , Martinelli Nicola , Girelli Domenico , Jackson Rebecca D. , Kooperberg Charles , Lange Leslie A. , Ardissino Diego , McPherson Ruth , Farrall Martin , Watkins Hugh , Reilly Muredach P. , Rader Daniel J. , de Faire Ulf , Schunkert Heribert , Erdmann Jeanette , Samani Nilesh J. , Charnas Lawrence , Altshuler David , Gabriel Stacey , Kastelein John J.P. , Defesche Joep C. , Nederveen Aart J. , Kathiresan Sekar , Hovingh G. Kees
Published: September 2013

Objective—

Autosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in
LDLRAP1
. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in
LDLRAP1
or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family.

Approach and Results—

We used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in
LIPA
that segregated with the diagnosis of hypercholesterolemia. Because homozygosity for mutations in
LIPA
is known to cause cholesterol ester storage disease, we performed directed follow-up phenotyping by noninvasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of cholesterol ester storage disease. Given previous suggestions of cardiovascular disease risk in heterozygous
LIPA
mutation carriers, we genotyped E8SJM in >27 000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance.

Conclusions—

By integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent cholesterol ester storage disease in the affected individuals from this kindred and addressed an outstanding question about risk of cardiovascular disease in
LIPA
E8SJM heterozygous carriers.
Portfolio of Clinical Research in Adult Cardiovascular Disease as Reflected in ClinicalTrials.gov
Authors: Alexander Karen P. , Kong David F. , Starr Aijing Z. , Kramer Judith , Chiswell Karen , Tasneem Asba , Califf Robert M.
Published: September 2013

Background

Cardiovascular medicine is widely regarded as a vanguard for evidence‐based drug and technology development. Our goal was to describe the cardiovascular clinical research portfolio from ClinicalTrials.gov.

Methods and Results

We identified 40 970 clinical research studies registered between 2007 and 2010 in which patients received diagnostic, therapeutic, or other interventions per protocol. By annotating 18 491 descriptors from the National Library of Medicine's Medical Subject Heading thesaurus and 1220 free‐text terms to select those relevant to cardiovascular disease, we identified studies that related to the diagnosis, treatment, or prevention of diseases of the heart and peripheral arteries in adults (n=2325 [66%] included from review of 3503 potential studies). The study intervention involved a drug in 44.6%, a device or procedure in 39.3%, behavioral intervention in 8.1%, and biological or genetic interventions in 3.0% of the trials. More than half of the trials were postmarket approval (phase 4, 25.6%) or not part of drug development (no phase, 34.5%). Nearly half of all studies (46.3%) anticipated enrolling 100 patients or fewer. The majority of studies assessed biomarkers or surrogate outcomes, with just 31.8% reporting a clinical event as a primary outcome.

Conclusions

Cardiovascular studies registered on ClinicalTrials.gov span a range of study designs. Data have limited verification or standardization and require manual processes to describe and categorize studies. The preponderance of small and late‐phase studies raises questions regarding the strength of evidence likely to be generated by the current portfolio and the potential efficiency to be gained by more research consolidation.
THRIVE Score Predicts Ischemic Stroke Outcomes and Thrombolytic Hemorrhage Risk in VISTA
Authors: Flint Alexander C. , Faigeles Bonnie S. , Cullen Sean P. , Kamel Hooman , Rao Vivek A. , Gupta Rishi , Smith Wade S. , Bath Philip M. , Donnan Geoffrey A. ,   VISTA Steering Committee (VISTA-Acute) members, Lees K.R. , Alexandrov A. , Bath P.M. , Bluhmki E. , Bornstein N. , Claesson L. , Davis S.M. , Donnan G. , Diener H.C. , Fisher M. , Gregson B. , Grotta J. , Hacke W. , Hennerici M.G. , Hommel M. , Kaste M. , Lyden P. , Marler J. , Muir K. , Sacco R. , Shuaib A. , Teal P. , Wahlgren N.G. , Warach S. , Weimar C.
Published: September 2013

Background and Purpose—

In previous studies, the Totaled Health Risks in Vascular Events (THRIVE) score has shown broad utility, allowing prediction of clinical outcome, death, and risk of hemorrhage after tissue-type plasminogen activator (tPA) treatment, irrespective of the type of acute stroke therapy applied to the patient.

Methods—

We used data from the Virtual International Stroke Trials Archive to further validate the THRIVE score in a large cohort of patients receiving tPA or no acute treatment, to confirm the relationship between THRIVE and hemorrhage after tPA, and to compare the THRIVE score with several other available outcome prediction scores.

Results—

The THRIVE score strongly predicts clinical outcome (odds ratio, 0.55 for good outcome [95% CI, 0.53–0.57];
P
<0.001), mortality (odds ratio, 1.57 [95% confidence interval, 1.50–1.64];
P
<0.001), and risk of intracerebral hemorrhage after tPA (odds ratio, 1.34 [95% confidence interval, 1.22–1.46];
P
<0.001). The relationship between THRIVE score and outcome is not influenced by the independent relationship of tPA administration and outcome. In receiver operator characteristic curve analysis, the THRIVE score was superior to several other available outcome prediction scores in the prediction of clinical outcome and mortality.

Conclusions—

The THRIVE score is a simple-to-use tool to predict clinical outcome, mortality, and risk of hemorrhage after thrombolysis in patients with ischemic stroke. Despite its simplicity, the THRIVE score performs better than several other outcome prediction tools. A free Web calculator for the THRIVE score is available at
http://www.thrivescore.org
.
Barrier Layers in the Tropical South Atlantic: Mean Dynamics and Submesoscale Effects*
Authors: Veneziani Milena , Griffa Annalisa , Garraffo Zulema , Mensa Jean A.
Published: September 2013

Barrier layers are generated when the surface mixed layer is shallower than the layer where temperature is well mixed, in geographical regions where salinity plays a key role in setting up upper-ocean density stratification. In the tropical oceans, thick barrier layers are also found in a latitude range where spiraling trajectories from surface in situ drifters suggest the presence of predominantly cyclonic submesoscale-like vortices. The authors explore these dynamical processes and their interplay in the present paper, focusing on the tropical South Atlantic Ocean and using a high-resolution modeling approach. The objective is threefold: to investigate the mean dynamics contributing to barrier-layer formation in this region, to study the distribution and seasonality of submesoscale features, and to verify whether and how the submesoscale impacts barrier-layer thickness. The model used is the Regional Ocean Modeling System (ROMS) in its Adaptive Grid Refinement in Fortran (AGRIF) online-nested configuration with a horizontal resolution ranging between 9 and 1 km. The simulated circulation is first described in terms of mean and submesoscale dynamics, and the associated seasonal cycle. Mechanisms for barrier-layer formation are then investigated. The results confirm previous hypotheses by Mignot et al. on the relevance of enhanced winter mixing deepening the isothermal layer, whereas the salinity stratification is sustained by advection of surface fresh waters and subsurface salinity maxima. Finally, submesoscale effects on barrier-layer thickness are studied, quantifying their contribution to vertical fluxes of temperature and salinity. Submesoscale vortices associated with salinity fronts are found to have a significant effect, producing thicker barrier layers (by ~20%–35%) and a shallower mixed layer because of their restratifying effect on salinity.
An Expanded VVP Technique to Resolve Primary and Environmental Circulations in Hurricanes
Authors: Harasti Paul R.
Published: September 2013

An expansion of the volume velocity processing (VVP) single-Doppler radar analysis method is presented for use with hurricanes. The so-called hurricane VVP (HVVP) method connects the estimated coefficients of a second-order Taylor series expansion of the wind field to the kinematic properties of a wind model that assumes axisymmetry of the tangential and radial wind and a vertically varying environmental flow. HVVP extracts the average radial profiles of these wind components between 1.0- and 3.5-km altitudes along with two parametric indicators of axisymmetry. A new method is thus provided to simultaneously monitor the trends in lower-tropospheric hurricane and environmental winds near landfall. In addition, novel kinematic approximations between the radial variations of the tangential and radial winds developed for HVVP will be of interest to the hurricane research community.

Estimates of bias caused by expected average deviations of the true wind from the assumed wind model suggest that the HVVP method is capable of estimating the maximum wind magnitude of the primary circulation and the environmental wind components to within ~10% and ~2 m s−1 accuracy, respectively, while the radar is located beyond a distance of 2.5 times the radius of maximum wind from the circulation center. An application of the HVVP method to a case study of Hurricane Bret (1999) shows good agreement between the results from two WSR-88D radars located on opposite sides of the storm and a pseudo triple-Doppler radar wind analysis that included NOAA airborne Doppler radar observations.
The Community Development Progress and Evaluation Tool: Assessing community development fieldwork / Un outil pour évaluer les stages en développement communautaire: Le Community Development Progress and Evaluation Tool
Authors: Boudreau Mary Lou , Donnelly Catherine A.
Published: September 2013

Background.

Both the Canadian Association of Occupational Therapists (CAOT) and World Federation of Occupational Therapists (WFOT) fieldwork guidelines promote fieldwork experiences that build community capacity. Yet, no existing tool that assesses the unique skills of community development fieldwork could be identified within or outside of occupational therapy.

Purpose.

This article describes the development of the Community Development Progress and Evaluation Tool (CD-PET), an assessment of community development fieldwork in occupational therapy.

Tool Development.

The CD-PET was developed in five distinct phases: (a) literature review, (b) identification of a theoretical framework, (c) tool construction, (d) pilot testing, and (e) ongoing refinement. Focus groups yielded input from preceptors and students. Once developed, the assessment was pilot tested with feedback received through an online survey completed by preceptors and students. Key enablement skills identified in Enabling Occupation II provided the foundation for the tool.

Implication.

The CD-PET is a student assessment and learning tool for occupational therapy students and preceptors that supports learning in the key enablement skills that are used in community development fieldwork.
Choice in Multitasking
Authors: Katidioti Ioanna , Taatgen Niels A.
Published: September 2013

Objective:

The objective was to establish the nature of choice in cognitive multitasking.

Background:

Laboratory studies of multitasking suggest people are rational in their switch choices regarding multitasking, whereas observational studies suggest they are not. Threaded cognition theory predicts that switching is opportunistic and depends on availability of cognitive resources.

Method:

A total of 21 participants answered e-mails by looking up information (similar to customer service employees) while being interrupted by chat messages. They were free to choose when to switch to the chat message. We analyzed the switching behavior and the time they needed to complete the primary mail task.

Results:

When participants are faced with a delay in the e-mail task, they switch more often to the chat task at high-workload points. Choosing to switch to the secondary task instead of waiting makes them slower. It also makes them forget the information in the e-mail task half of the time, which slows them down even more.

Conclusion:

When many cognitive resources are available, the probability of switching from one task to another is high. This does not necessarily lead to optimal switching behavior.

Application:

Potential applications of this research include the minimization of delays in task design and the inability or discouragement of switching in high-workload moments.
Cable Screens in Hazardous Areas
Authors: Towle Chris
Published: September 2013

This article considers the requirements for bonding the screens of field cables used in intrinsically safe systems. The possible safety hazard created by potential differences within plant structures is explored, and the recommendation for single-point bonding justified. Figures which illustrate the techniques recommended for commonly occurring installations complete the article
M180 Amelogenin Processed by MMP20 is Sufficient for Decussating Murine Enamel
Authors: Pugach M.K. , Suggs C. , Li Y. , Wright J.T. , Kulkarni A.B. , Bartlett J.D. , Gibson C.W.
Published: September 2013

Amelogenin (AMELX) and matrix metalloproteinase-20 (MMP20) are essential for proper enamel development. Amelx and Mmp20 mutations cause amelogenesis imperfecta. MMP20, a protease secreted by ameloblasts, is responsible for processing enamel proteins, including AMELX, during the secretory stage of enamel formation. Of at least 16 different amelogenin splice products, the most abundant isoform found in murine ameloblasts and developing enamel is the M180 protein. To understand the role of MMP20 processing of M180 AMELX, we generated AmelxKO/ Mmp20KO (DKO) mice with an amelogenin (M180Tg) transgene. We analyzed the enamel phenotype by SEM to determine enamel structure and thickness, µCT, and by nanoindentation to quantify enamel mechanical properties. M180Tg/DKO mouse enamel had 37% of the hardness of M180Tg/ AmelxKO teeth and demonstrated a complete lack of normal prismatic architecture. Although molar enamel of M180Tg/ AmelxKO mice was thinner than WT, it had similar mechanical properties and decussating enamel prisms, which were abolished by the loss of MMP20 in the M180Tg/DKO mice. Retention of the C-terminus or complete lack of this domain is unable to rescue amelogenin null enamel. We conclude that among amelogenins, M180 alone is sufficient for normal enamel mechanical properties and prism patterns, but that additional amelogenin splice products are required to restore enamel thickness.
Low-cost process monitoring for polymer extrusion
Authors: Deng Jing , Li Kang , Harkin-Jones Eileen , Price Mark , Fei Minrui , Kelly Adrian , Vera-Sorroche Javier , Coates Phil , Brown Elaine
Published: September 2013

Polymer extrusion is regarded as an energy-intensive production process, and the real-time monitoring of both energy consumption and melt quality has become necessary to meet new carbon regulations and survive in the highly competitive plastics market. The use of a power meter is a simple and easy way to monitor energy, but the cost can sometimes be high. On the other hand, viscosity is regarded as one of the key indicators of melt quality in the polymer extrusion process. Unfortunately, viscosity cannot be measured directly using current sensory technology. The employment of on-line, in-line or off-line rheometers is sometimes useful, but these instruments either involve signal delay or cause flow restrictions to the extrusion process, which is obviously not suitable for real-time monitoring and control in practice. In this paper, simple and accurate real-time energy monitoring methods are developed. This is achieved by looking inside the controller, and using control variables to calculate the power consumption. For viscosity monitoring, a ‘soft-sensor’ approach based on an RBF neural network model is developed. The model is obtained through a two-stage selection and differential evolution, enabling compact and accurate solutions for viscosity monitoring. The proposed monitoring methods were tested and validated on a Killion KTS-100 extruder, and the experimental results show high accuracy compared with traditional monitoring approaches.
The current practice of lift traffic design using calculation and simulation
Authors: Al-Sharif Lutfi , Al-Adem Mohamed D
Published: September 2013

Lift traffic design can employ calculation or simulation methods. Calculation can be split into main categories: analytical equation-based methods and numerical methods. Simulation can be split into discrete event simulation and time-slice simulation. These methods vary in the level of computational complexity, as well as their ability to arrive at a value for the required performance parameters with acceptable accuracy and under the general case. Moreover, the repeatability of the results is an important consideration, as well as the simplicity and calculation time of the method used. This technical note provides a general overview of each of the four methods. It also discusses the suitable areas of application of each of the methods, showing the strengths and weaknesses of each of the four methods. This technical note concludes by outlining the current hybrid method used by designers in lift traffic design, whereby one of the calculation methods is used to find a starting arrangement and then the design is fine tuned using one of the simulation methods (e.g. changing speed, capacity of the lifts as well as the group control algorithm) in order to achieve the required average passenger waiting time and average passenger transit time.

Practical application: This technical note provides a blueprint to lift traffic designers for the lift traffic design process. It emphasises the fact that calculation and simulation are not mutually exclusive methodologies, and shows how they complement each other, where the former provides a starting design and the latter allows the designer to fine tune the lift traffic design.
Hypothyroidism and Iodine Deficiency in an Infant Requiring Total Parenteral Nutrition
Authors: Clarridge Katherine Elizabeth , Conway Erin E. , Bucuvalas John
Published: September 2013

While iodine deficiency remains a relatively rare cause of thyroid dysfunction in the United States, little is known about iodine status and deficiency in children requiring parenteral nutrition (PN). This population may be at an elevated risk of thyroid dysregulation and neurodevelopmental sequelae due to low concentrations in typical PN formulations. Furthermore, with the widespread practice of switching from iodine‐based antiseptics to chlorhexadine, previous inadvertent sources of iodine are being eliminated as well.
Development and Psychometric Evaluation of a German Version of the PROMIS® Item Banks for Satisfaction With Participation
Authors: Nagl Michaela , Gramm Lukas , Heyduck Katja , Glattacker Manuela , Farin Erik
Published: September 2013

The Patient Reported Outcomes Measurement Information System (PROMIS) initiative aims to provide reliable and precise item banks measuring patient-reported outcomes in different health domains. The aim of the present work was to provide a German translation of the PROMIS item banks for satisfaction with participation and to psychometrically test these German versions. Cognitive interviews followed a forward–backward translation. Distribution characteristics, unidimensionality, Rasch model fit, reliability, construct validity, and internal responsiveness were tested in 262 patients with chronic low back pain undergoing rehabilitation. Results for the final 13- and 10-item German static scales (Satisfaction with Participation in Social Roles–German version [PSR-G] and Satisfaction for Participation in Discretionary Social Activities–German version [PSA-G]) regarding unidimensionality were satisfactory. The scales are reliable and show good Rasch model fit and distribution characteristics. Both scales are sensitive to small to moderate clinical changes, and we observed initial proof of construct validity. These German versions of the Satisfaction with Participation scales can be recommended to assess participation in a clinical context. The scales’ applicability in other contexts should be examined.
Becoming cruel
Authors: Weierstall Roland , Haer Roos , Banholzer Lilli , Elbert Thomas
Published: September 2013

Appetitive aggression – a rewarding perception of the perpetration of violence – seems to be an adaptation common to adverse conditions. Children raised within armed groups may develop attitudes and values that favour harming others when socialized within a combat force. Combatants who joined an armed force early in their lives should, therefore, perceive aggression in a more appetitive way than those who were recruited later. We interviewed 95 former members of armed groups operating in the eastern part of the Democratic Republic of the Congo. Those combatants that were having higher levels of appetitive aggression were those who joined a rebel force earlier in life. Surprisingly, neither the amount of military training nor the amount of time spent in the forces had a significant effect on the level of appetitive aggression. Our results show that when civil socialization is replaced by socialization within an armed group early in life, self-regulation of appetitive aggression may become deficient, leading to a higher propensity towards cruelty.
Association of Psychosocial Factors and Heart Rate Variability in Heart Failure Patients
Authors: Kao Chi-Wen , Tseng Li-Fang , Lin Wei-Shiang , Cheng Shu-Meng
Published: September 2013

The purpose of this study was to examine the association of psychosocial factors (depression, social support, and health-related quality of life) with heart rate variability (HRV) in patients with heart failure. The sample comprised 91 outpatients from a medical center. Data were collected using the Beck Depression Inventory–II, Medical Outcomes Study (MOS) Social Support Survey, and Minnesota Living With Heart Failure Questionnaire. HRV was measured in terms of time-domain parameters from a 24-hr ambulatory Holter electrocardiogram. After adjusting for demographic and clinical variables, quality of life and social support were significantly associated with HRV. HRV (time-domain measures) was significantly higher in patients who perceived better quality of life and more social support. Our findings suggest that nurses could screen early for patients’ risk of adverse psychosocial conditions and suggest online or other social supportive interventions to help at-risk patients minimize the negative associations with HRV.