Dendritic Cells Limit Fibro-Inflammatory Injury in NASH

PubMed Central

Henning, Justin R.; Graffeo, Christopher S.; Rehman, Adeel; Fallon, Nina C.; Zambirinis, Constantinos P.; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Saeed, Usama Bin; Rao, Raghavendra S.; Badar, Sana; Quesada, Juan P.; Acehan, Devrim; Miller, George

2013-01-01

Non-alcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DC) are antigen presenting cells with an emerging role in hepatic inflammation. We postulated that DC are important in the progression of NASH. We found that intrahepatic DC expand and mature in NASH liver and assume an activated immune-phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibro-inflammation. Our mechanistic studies support a regulatory role for DC in NASH by limiting sterile inflammation via their role in clearance of apoptotic cells and necrotic debris. We found that DC limit CD8+ T cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion Our findings support a role for DC in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. PMID:23322710

Computing Nash equilibria through computational intelligence methods

NASA Astrophysics Data System (ADS)

Pavlidis, N. G.; Parsopoulos, K. E.; Vrahatis, M. N.

2005-03-01

Nash equilibrium constitutes a central solution concept in game theory. The task of detecting the Nash equilibria of a finite strategic game remains a challenging problem up-to-date. This paper investigates the effectiveness of three computational intelligence techniques, namely, covariance matrix adaptation evolution strategies, particle swarm optimization, as well as, differential evolution, to compute Nash equilibria of finite strategic games, as global minima of a real-valued, nonnegative function. An issue of particular interest is to detect more than one Nash equilibria of a game. The performance of the considered computational intelligence methods on this problem is investigated using multistart and deflection.

Controversies in the Diagnosis and Management of NAFLD and NASH.

PubMed

Rinella, Mary E; Loomba, Rohit; Caldwell, Stephen H; Kowdley, Kris; Charlton, Michael; Tetri, Brent; Harrison, Stephen A

2014-04-01

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.

Local Nash equilibrium in social networks.

PubMed

Zhang, Yichao; Aziz-Alaoui, M A; Bertelle, Cyrille; Guan, Jihong

2014-08-29

Nash equilibrium is widely present in various social disputes. As of now, in structured static populations, such as social networks, regular, and random graphs, the discussions on Nash equilibrium are quite limited. In a relatively stable static gaming network, a rational individual has to comprehensively consider all his/her opponents' strategies before they adopt a unified strategy. In this scenario, a new strategy equilibrium emerges in the system. We define this equilibrium as a local Nash equilibrium. In this paper, we present an explicit definition of the local Nash equilibrium for the two-strategy games in structured populations. Based on the definition, we investigate the condition that a system reaches the evolutionary stable state when the individuals play the Prisoner's dilemma and snow-drift game. The local Nash equilibrium provides a way to judge whether a gaming structured population reaches the evolutionary stable state on one hand. On the other hand, it can be used to predict whether cooperators can survive in a system long before the system reaches its evolutionary stable state for the Prisoner's dilemma game. Our work therefore provides a theoretical framework for understanding the evolutionary stable state in the gaming populations with static structures.

Local Nash Equilibrium in Social Networks

NASA Astrophysics Data System (ADS)

Zhang, Yichao; Aziz-Alaoui, M. A.; Bertelle, Cyrille; Guan, Jihong

2014-08-01

Nash equilibrium is widely present in various social disputes. As of now, in structured static populations, such as social networks, regular, and random graphs, the discussions on Nash equilibrium are quite limited. In a relatively stable static gaming network, a rational individual has to comprehensively consider all his/her opponents' strategies before they adopt a unified strategy. In this scenario, a new strategy equilibrium emerges in the system. We define this equilibrium as a local Nash equilibrium. In this paper, we present an explicit definition of the local Nash equilibrium for the two-strategy games in structured populations. Based on the definition, we investigate the condition that a system reaches the evolutionary stable state when the individuals play the Prisoner's dilemma and snow-drift game. The local Nash equilibrium provides a way to judge whether a gaming structured population reaches the evolutionary stable state on one hand. On the other hand, it can be used to predict whether cooperators can survive in a system long before the system reaches its evolutionary stable state for the Prisoner's dilemma game. Our work therefore provides a theoretical framework for understanding the evolutionary stable state in the gaming populations with static structures.

Local Nash Equilibrium in Social Networks

PubMed Central

Zhang, Yichao; Aziz-Alaoui, M. A.; Bertelle, Cyrille; Guan, Jihong

2014-01-01

Nash equilibrium is widely present in various social disputes. As of now, in structured static populations, such as social networks, regular, and random graphs, the discussions on Nash equilibrium are quite limited. In a relatively stable static gaming network, a rational individual has to comprehensively consider all his/her opponents' strategies before they adopt a unified strategy. In this scenario, a new strategy equilibrium emerges in the system. We define this equilibrium as a local Nash equilibrium. In this paper, we present an explicit definition of the local Nash equilibrium for the two-strategy games in structured populations. Based on the definition, we investigate the condition that a system reaches the evolutionary stable state when the individuals play the Prisoner's dilemma and snow-drift game. The local Nash equilibrium provides a way to judge whether a gaming structured population reaches the evolutionary stable state on one hand. On the other hand, it can be used to predict whether cooperators can survive in a system long before the system reaches its evolutionary stable state for the Prisoner's dilemma game. Our work therefore provides a theoretical framework for understanding the evolutionary stable state in the gaming populations with static structures. PMID:25169150

How Do Doctors Diagnose NAFLD and NASH?

MedlinePlus

... NAFLD and NASH, such as overweight or obesity insulin resistance high levels of triglycerides or abnormal levels of ... NASH, such as an enlarged liver signs of insulin resistance such as darkened skin patches over your knuckles, ...

The Hopeful Traveler Jay Bryan Nash.

ERIC Educational Resources Information Center

Jessup, Harvey M., Comp.

This book is one of a series of publications preserving the best writing and speeches of outstanding leaders of the American Alliance for Health, Physical Education, Recreation and Dance. Jay Bryan Nash was one of the founders of the Alliance. The speeches and essays by Nash in this collection are, for the most part, appearing in published form…

NARSTO SOS99NASH WIND PROFILER DATA

Atmospheric Science Data Center

2018-04-16

NARSTO SOS99NASH WIND PROFILER DATA Project Title:  NARSTO ... Platform:  Ground Station Instrument:  Wind Profiler Location:  Nashville, Tennessee Spatial ... Data Guide Documents:  SOS99Nash Wind Profiler Guide Related Data:  Southern Oxidants ...

Jay B. Nash.

ERIC Educational Resources Information Center

Jable, J. Thomas

1985-01-01

Jay B. Nash's accomplishments and professional service have long been recognized by physical educators. This article examines the major forces and events that made him one of the most important leaders in American physical education. (MT)

Pre-Collegiate Teachers and Gary Nash

ERIC Educational Resources Information Center

Sesso, Gloria

2009-01-01

In this article, the author recalls the time she met Gary Nash at UCLA on July 13, 1992, when they began the work of creating the National Standards in History. Professor Nash was the leader in the development of the United States History Standards. In creating the Standards, they were to focus on Historical Thinking. They needed to organize the…

Nash Social Welfare in Multiagent Resource Allocation

NASA Astrophysics Data System (ADS)

Ramezani, Sara; Endriss, Ulle

We study different aspects of the multiagent resource allocation problem when the objective is to find an allocation that maximizes Nash social welfare, the product of the utilities of the individual agents. The Nash solution is an important welfare criterion that combines efficiency and fairness considerations. We show that the problem of finding an optimal outcome is NP-hard for a number of different languages for representing agent preferences; we establish new results regarding convergence to Nash-optimal outcomes in a distributed negotiation framework; and we design and test algorithms similar to those applied in combinatorial auctions for computing such an outcome directly.

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

PubMed

Rockstroh, Jürgen Kurt

2017-04-01

Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

Pathophysiology of NASH: perspectives for a targeted treatment

PubMed Central

Marra, Fabio; Lotersztajn, Sophie

2013-01-01

Non alcoholic steatohepatitis (NASH) is the more severe form of nonalcoholic fatty liver disease. In NASH, fatty liver, hepatic inflammation, hepatocyte injury and fibrogenesis are associated, and thi condition may eventually lead to cirrhosis. Current treatment of NASH relies on the reduction of body weight and increase in physical activity, but there is no pharmacologic treatment approved as yet. Emerging data indicate that NASH progression results from parallel events originating from the liver as well as from the adipose tissue, the gut and the gastrointestinal tract. Thus, dysfunction of the adipose tissue through enhanced flow of free fatty acids and release of adipocytokines, and alterations in the gut microbiome generate proinflammatory signals that underly NASH progression. Additional ‘extrahepatic hits’ include dietary factors and gastrointestinal hormones. Within the liver, hepatocyte apoptosis, ER stress and oxidative stress are key contributors to hepatocellular injury. In addition, lipotoxic mediators and danger signals activate Kupffer cells which initiate and perpetuate the inflammatory response by releasing inflammatory mediators that contribute to inflammatory cell recruitment and development of fibrosis. Inflammatory and fibrogenic mediators include chemokines, the cannabinoid system, the inflammasome and activation of pattern-recognition receptors. Here we review the major mechanisms leading to appearance and progression of NASH, focusing on both extrahepatic signals and local inflammatory mechanisms, in an effort to identify the most promising molecular targets for the treatment of this condition. PMID:23394092

Nash equilibrium and evolutionary dynamics in semifinalists' dilemma.

PubMed

Baek, Seung Ki; Son, Seung-Woo; Jeong, Hyeong-Chai

2015-04-01

We consider a tournament among four equally strong semifinalists. The players have to decide how much stamina to use in the semifinals, provided that the rest is available in the final and the third-place playoff. We investigate optimal strategies for allocating stamina to the successive matches when players' prizes (payoffs) are given according to the tournament results. From the basic assumption that the probability to win a match follows a nondecreasing function of stamina difference, we present symmetric Nash equilibria for general payoff structures. We find three different phases of the Nash equilibria in the payoff space. First, when the champion wins a much bigger payoff than the others, any pure strategy can constitute a Nash equilibrium as long as all four players adopt it in common. Second, when the first two places are much more valuable than the other two, the only Nash equilibrium is such that everyone uses a pure strategy investing all stamina in the semifinal. Third, when the payoff for last place is much smaller than the others, a Nash equilibrium is formed when every player adopts a mixed strategy of using all or none of its stamina in the semifinals. In a limiting case that only last place pays the penalty, this mixed-strategy profile can be proved to be a unique symmetric Nash equilibrium, at least when the winning probability follows a Heaviside step function. Moreover, by using this Heaviside step function, we study the tournament by using evolutionary replicator dynamics to obtain analytic solutions, which reproduces the corresponding Nash equilibria on the population level and gives information on dynamic aspects.

Nash equilibrium and evolutionary dynamics in semifinalists' dilemma

NASA Astrophysics Data System (ADS)

Baek, Seung Ki; Son, Seung-Woo; Jeong, Hyeong-Chai

2015-04-01

We consider a tournament among four equally strong semifinalists. The players have to decide how much stamina to use in the semifinals, provided that the rest is available in the final and the third-place playoff. We investigate optimal strategies for allocating stamina to the successive matches when players' prizes (payoffs) are given according to the tournament results. From the basic assumption that the probability to win a match follows a nondecreasing function of stamina difference, we present symmetric Nash equilibria for general payoff structures. We find three different phases of the Nash equilibria in the payoff space. First, when the champion wins a much bigger payoff than the others, any pure strategy can constitute a Nash equilibrium as long as all four players adopt it in common. Second, when the first two places are much more valuable than the other two, the only Nash equilibrium is such that everyone uses a pure strategy investing all stamina in the semifinal. Third, when the payoff for last place is much smaller than the others, a Nash equilibrium is formed when every player adopts a mixed strategy of using all or none of its stamina in the semifinals. In a limiting case that only last place pays the penalty, this mixed-strategy profile can be proved to be a unique symmetric Nash equilibrium, at least when the winning probability follows a Heaviside step function. Moreover, by using this Heaviside step function, we study the tournament by using evolutionary replicator dynamics to obtain analytic solutions, which reproduces the corresponding Nash equilibria on the population level and gives information on dynamic aspects.

Near-Nash targeting strategies for heterogeneous teams of autonomous combat vehicles

NASA Astrophysics Data System (ADS)

Galati, David G.; Simaan, Marwan A.

2008-04-01

Military strategists are currently seeking methodologies to control large numbers of autonomous assets. Automated planners based upon the Nash equilibrium concept in non-zero sum games are one option. Because such planners inherently consider possible adversarial actions, assets are able to adapt to, and to some extent predict, potential enemy actions. However, these planners must function properly both in cases in which a pure Nash strategy does not exist and in scenarios possessing multiple Nash equilibria. Another issue that needs to be overcome is the scalability of the Nash equilibrium. That is, as the dimensionality of the problem increases, the Nash strategies become unfeasible to compute using traditional methodologies. In this paper we introduce the concept of near-Nash strategies as a mechanism to overcome these difficulties. We then illustrate this concept by deriving the near-Nash strategies and using these strategies as the basis for an intelligent battle plan for heterogeneous teams of autonomous combat air vehicles in the Multi-Team Dynamic Weapon Target Assignment model.

Serum uric acid concentrations and fructose consumption are independently associated with NASH in children and adolescents.

PubMed

Mosca, Antonella; Nobili, Valerio; De Vito, Rita; Crudele, Annalisa; Scorletti, Eleonora; Villani, Alberto; Alisi, Anna; Byrne, Christopher D

2017-05-01

Recent research has suggested that dietary fructose intake may increase serum uric acid (UA) concentrations. Both UA concentration and fructose consumption maybe also increase in NAFLD. It is not known whether dietary fructose consumption and UA concentration are independently associated with non-alcoholic steatohepatitis (NASH). Our aim was to investigate the factors associated with NASH in children and adolescents with proven NAFLD, and to test whether UA concentrations and fructose consumption are independently associated with NASH. Obese children with NAFLD were studied (n=271). NASH was diagnosed by a NAFLD activity score ⩾5 and the fatty liver inhibition of progression (FLIP) algorithm. Fructose consumption (g/day) was assessed by food frequency questionnaire, and UA (mg/dl) was measured in serum. Binary logistic regression with adjustment for covariates and potential confounders was undertaken to test factors independently associated with NASH. NASH occurred in 37.6% of patients. Hyperuricaemia (UA ⩾5.9mg/dl) was present in 47% of patients with NASH compared with 29.7% of non-NASH patients (p=0.003). Both UA concentration (OR=2.488, 95% CI: 1.87-2.83, p=0.004) and fructose consumption (OR=1.612, 95% CI 1.25-1.86, p=0.001) were independently associated with NASH, after adjustment for multiple (and all) measured confounders. Fructose consumption was independently associated with hyperuricaemia (OR=2.021, 95% CI: 1.66-2.78, p=0.01). These data were confirmed using the FLIP algorithm. Both dietary fructose consumption and serum UA concentrations are independently associated with NASH. Fructose consumption was the only factor independently associated with serum UA concentration. Currently, it is not known whether dietary fructose consumption and uric acid (UA) concentration are linked with non-alcoholic steatohepatitis (NASH) in children and adolescents. Our aim was to test whether UA concentrations and fructose consumption are independently associated with

 The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women.

PubMed

Simental-Mendía, Luis E; Simental-Mendía, Esteban; Rodríguez-Hernández, Heriberto; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

2016-01-01

 Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH.

Design and rationale for a real-world observational cohort of patients with nonalcoholic fatty liver disease: The TARGET-NASH study.

PubMed

Barritt, A S; Gitlin, Norman; Klein, Samuel; Lok, Anna S; Loomba, Rohit; Malahias, Laura; Powell, Margaret; Vos, Miriam B; Weiss, L Michael; Cusi, Kenneth; Neuschwander-Tetri, Brent A; Sanyal, Arun

2017-10-01

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. NAFLD comprises the spectrum from simple steatosis (nonalcoholic fatty liver, NAFL), to steatosis with inflammation (nonalcoholic steatohepatitis, NASH). Current primary therapy recommended for NAFLD is weight loss induced by lifestyle modification. The difficulty in achieving this has led to robust pharmacological therapy development. While new drugs may show efficacy in selected phase II/III clinical trial populations, their real-world effectiveness is unknown. TARGET-NASH is a 5-year, longitudinal, observational study of patients with NAFLD designed to evaluate the effectiveness of clinical practice interventions and provide practical information unobtainable in registration trials. A biological specimen repository is included in TARGET-NASH for translational studies of genomics and biomarkers of disease activity. Patients are enrolling at adult and pediatric sites representing multiple specialties. All patients being managed for NAFLD are eligible, whereas those in other NASH registries or clinical trials will be excluded. Enrolled patients range in age from 6 and up and will have 3years of clinical data reviewed. Patient comorbidities, concomitant medications, disease progression and off-label interventions will be assessed, and adverse outcomes, monitored. Confirming the use, safety and effectiveness of NAFLD interventions in children and adults and establishing pragmatic methods of assessing disease progression under real-world conditions are key study outcomes. Ultimately, TARGET-NASH will establish a large, diverse registry of NAFLD patients at academic and community practices to be leveraged to improve health and reduce development of cirrhosis and hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Single non-invasive model to diagnose non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

PubMed

Otgonsuren, Munkhzul; Estep, Michael J; Hossain, Nayeem; Younossi, Elena; Frost, Spencer; Henry, Linda; Hunt, Sharon; Fang, Yun; Goodman, Zachary; Younossi, Zobair M

2014-12-01

Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD). A liver biopsy is considered the "gold standard" for diagnosing/staging NASH. Identification of NAFLD/NASH using non-invasive tools is important for intervention. The study aims were to: develop/validate the predictive performance of a non-invasive model (index of NASH [ION]); assess the performance of a recognized non-invasive model (fatty liver index [FLI]) compared with ION for NAFLD diagnosis; determine which non-invasive model (FLI, ION, or NAFLD fibrosis score [NFS]) performed best in predicting age-adjusted mortality. From the National Health and Nutrition Examination Survey III database, anthropometric, clinical, ultrasound, laboratory, and mortality data were obtained (n = 4458; n = 861 [19.3%] NAFLD by ultrasound) and used to develop the ION model, and then to compare the ION and FLI models for NAFLD diagnosis. For validation and diagnosis of NASH, liver biopsy data were used (n = 152). Age-adjusted Cox proportional hazard modeling estimated the association among the three non-invasive tests (FLI, ION, and NFS) and mortality. FLI's threshold score > 60 and ION's threshold score > 22 had similar specificity (FLI = 80% vs ION = 82%) for NAFLD diagnosis; FLI < 30 (80% sensitivity) and ION < 11 (81% sensitivity) excluded NAFLD. An ION score > 50 predicted histological NASH (92% specificity); the FLI model did not predict NASH or mortality. The ION model was best in predicting cardiovascular/diabetes-related mortality; NFS predicted overall or diabetes-related mortality. The ION model was superior in predicting NASH and mortality compared with the FLI model. Studies are needed to validate ION. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Quantum gambling based on Nash-equilibrium

NASA Astrophysics Data System (ADS)

Zhang, Pei; Zhou, Xiao-Qi; Wang, Yun-Long; Liu, Bi-Heng; Shadbolt, Pete; Zhang, Yong-Sheng; Gao, Hong; Li, Fu-Li; O'Brien, Jeremy L.

2017-06-01

The problem of establishing a fair bet between spatially separated gambler and casino can only be solved in the classical regime by relying on a trusted third party. By combining Nash-equilibrium theory with quantum game theory, we show that a secure, remote, two-party game can be played using a quantum gambling machine which has no classical counterpart. Specifically, by modifying the Nash-equilibrium point we can construct games with arbitrary amount of bias, including a game that is demonstrably fair to both parties. We also report a proof-of-principle experimental demonstration using linear optics.

Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

PubMed

Duarte, S M B; Stefano, J T; Miele, L; Ponziani, F R; Souza-Basqueira, M; Okada, L S R R; de Barros Costa, F G; Toda, K; Mazo, D F C; Sabino, E C; Carrilho, F J; Gasbarrini, A; Oliveira, C P

2018-04-01

The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the

Nash Receives 2004 David Perlman Award for Excellence in Science Writing

NASA Astrophysics Data System (ADS)

Elmer-DeWitt, Philip; Nash, J. Madeleine

2004-07-01

J. Madeleine Nash received the David Perlman Award for Excellence in Science Writing at the AGU Joint Assembly Honors Ceremony, which was held on 19 May 2004, in Montreal, Canada. Nash was honored for ``Fireproofing the Forests,'' an article that appeared in the 18 August 2003 edition of Time Magazine. ``It is an honor to present AGU's 2004 David Perlman Award to Madeleine Nash, a senior contributor to Time Magazine and, if I may say so, one of the great science writers of her generation.''

A novel role of astrocyte elevated gene-1 (AEG-1) in regulating nonalcoholic steatohepatitis (NASH).

PubMed

Srivastava, Jyoti; Robertson, Chadia L; Ebeid, Kareem; Dozmorov, Mikhail; Rajasekaran, Devaraja; Mendoza, Rachel; Siddiq, Ayesha; Akiel, Maaged A; Jariwala, Nidhi; Shen, Xue-Ning; Windle, Jolene J; Subler, Mark A; Mukhopadhyay, Nitai D; Giashuddin, Shah; Ghosh, Shobha; Lai, Zhao; Chen, Yidong; Fisher, Paul B; Salem, Aliasger K; Sanyal, Arun J; Sarkar, Devanand

2017-08-01

Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease in the Western world. However, an optimum therapy for NASH is yet to be established, mandating more in-depth investigation into the molecular pathogenesis of NASH to identify novel regulatory molecules and develop targeted therapies. Here, we unravel a unique function of astrocyte elevated gene-1(AEG-1)/metadherin in NASH using a transgenic mouse with hepatocyte-specific overexpression of AEG-1 (Alb/AEG-1) and a conditional hepatocyte-specific AEG-1 knockout mouse (AEG-1 ΔHEP ). Alb/AEG-1 mice developed spontaneous NASH whereas AEG-1 ΔHEP mice were protected from high-fat diet (HFD)-induced NASH. Intriguingly, AEG-1 overexpression was observed in livers of NASH patients and wild-type (WT) mice that developed steatosis upon feeding HFD. In-depth molecular analysis unraveled that inhibition of peroxisome proliferator-activated receptor alpha activity resulting in decreased fatty acid β-oxidation, augmentation of translation of fatty acid synthase resulting in de novo lipogenesis, and increased nuclear factor kappa B-mediated inflammation act in concert to mediate AEG-1-induced NASH. Therapeutically, hepatocyte-specific nanoparticle-delivered AEG-1 small interfering RNA provided marked protection from HFD-induced NASH in WT mice. AEG-1 might be a key molecule regulating initiation and progression of NASH. AEG-1 inhibitory strategies might be developed as a potential therapeutic intervention in NASH patients. (Hepatology 2017;66:466-480). © 2017 by the American Association for the Study of Liver Diseases.

Uniqueness of Nash equilibrium in vaccination games.

PubMed

Bai, Fan

2016-12-01

One crucial condition for the uniqueness of Nash equilibrium set in vaccination games is that the attack ratio monotonically decreases as the vaccine coverage level increasing. We consider several deterministic vaccination models in homogeneous mixing population and in heterogeneous mixing population. Based on the final size relations obtained from the deterministic epidemic models, we prove that the attack ratios can be expressed in terms of the vaccine coverage levels, and also prove that the attack ratios are decreasing functions of vaccine coverage levels. Some thresholds are presented, which depend on the vaccine efficacy. It is proved that for vaccination games in homogeneous mixing population, there is a unique Nash equilibrium for each game.

Induction of steatohepatitis (NASH) with insulin resistance in wildtype B6 mice by a western-type diet containing soybean oil and cholesterol.

PubMed

Henkel, Janin; Coleman, Charles Dominic; Schraplau, Anne; Jӧhrens, Korinna; Weber, Daniela; Castro, José Pedro; Hugo, Martin; Schulz, Tim Julius; Krämer, Stephanie; Schürmann, Annette; Püschel, Gerhard Paul

2017-03-21

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g. high-fat diets) or overweight and insulin resistance (e.g. methionine-choline-deficient diets) or they are based on monogenetic defects (e.g. ob/ob mice). In the current study, a western-type diet containing soybean oil with high n 6-PUFA and 0.75% cholesterol (SOD+Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast a soybean oil-containing western-type diet without cholesterol (SOD) induced only mild steatosis but neither hepatic inflammation nor fibrosis, weight gain or insulin resistance. Another high-fat diet mainly consisting of lard and supplemented with fructose in drinking water (LAD+Fru) resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD+Cho but livers were devoid of inflammation and fibrosis. Although both LAD+Fru- and SOD+Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD+Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. Summarizing, dietary cholesterol in SOD+Cho diet may trigger hepatic inflammation and fibrosis. SOD+Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.

A Tribute to Gary Nash

ERIC Educational Resources Information Center

Jason-Fives, Alli

2009-01-01

In this article, the author gives tribute to Gary Nash, a brilliant scholar, an award-winning professor, a prolific writer, a true humanitarian, and a revered historian. She honors him for his work with public school teachers. He has provided the educational support, encouragement, and motivation behind the importance of teaching history. Here,…

NASH is an Inflammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications

PubMed Central

van Rooyen, Derrick; Gan, Lay; Chitturi, Shivrakumar

2012-01-01

While non-alcoholic fatty liver disease (NAFLD) is highly prevalent (15% to 45%) in modern societies, only 10% to 25% of cases develop hepatic fibrosis leading to cirrhosis, end-stage liver disease or hepatocellular carcinoma. Apart from pre-existing fibrosis, the strongest predictor of fibrotic progression in NAFLD is steatohepatitis or non-alcoholic steatohepatitis (NASH). The critical features other than steatosis are hepatocellular degeneration (ballooning, Mallory hyaline) and mixed inflammatory cell infiltration. While much is understood about the relationship of steatosis to metabolic factors (over-nutrition, insulin resistance, hyperglycemia, metabolic syndrome, hypoadiponectinemia), less is known about inflammatory recruitment, despite its importance for the perpetuation of liver injury and fibrogenesis. In this review, we present evidence that liver inflammation has prognostic significance in NAFLD. We then consider the origins and components of liver inflammation in NASH. Hepatocytes injured by toxic lipid molecules (lipotoxicity) play a central role in the recruitment of innate immunity involving Toll-like receptors (TLRs), Kupffer cells (KCs), lymphocytes and neutrophils and possibly inflammasome. The key pro-inflammatory signaling pathways in NASH are nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK). The downstream effectors include adhesion molecules, chemokines, cytokines and the activation of cell death pathways leading to apoptosis. The upstream activators of NF-κB and JNK are more contentious and may depend on the experimental model used. TLRs are strong contenders. It remains possible that inflammation in NASH originates outside the liver and in the gut microbiota that prime KC/TLR responses, inflamed adipose tissue and circulating inflammatory cells. We briefly review these mechanistic considerations and project their implications for the effective treatment of NASH. PMID:22570745

NASH resolution is associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels.

PubMed

Corey, K E; Vuppalanchi, R; Wilson, L A; Cummings, O W; Chalasani, N

2015-02-01

Nonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD). To determine the relationship between resolution of NASH and dyslipidemia. Individuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N = 222). In the PIVENS trial individuals were randomised to pioglitazone 30 mg, vitamin E 800 IU or placebo for 96 weeks. Change in lipid levels at 96 weeks was compared between those with and without NASH resolution. Dyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40 mg/dL in men or <50 mg/dL in women) in 63%, hypertriglyceridaemia (≥150 mg/dL) in 46%, hypercholesterolaemia (≥200 mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) ≥160 mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (≥130 mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9 mg/dL vs. -2.5 mg/dL, P < 0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3 mg/dL, P = 0.03 and TG/HDL: -0.7 vs. 0.1, P = 0.003). Non-HDL-C, LDL and cholesterol decreased over 96 weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids. NASH resolution is associated with improvements in TG and HDL but not in other cardiovascular disease risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of cardiovascular disease. ClinicalTrials.gov identifier: NCT00063622. © 2014 John Wiley & Sons Ltd.

Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1

PubMed Central

Matsushita, Noriko; Hassanein, Mohamed T.; Martinez-Clemente, Marcos; Lazaro, Raul; French, Samuel W.; Xie, Wen; Lai, Keane; Karin, Michael; Tsukamoto, Hidekazu

2017-01-01

Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients. PMID:28797077

On Nash-Equilibria of Approximation-Stable Games

NASA Astrophysics Data System (ADS)

Awasthi, Pranjal; Balcan, Maria-Florina; Blum, Avrim; Sheffet, Or; Vempala, Santosh

One reason for wanting to compute an (approximate) Nash equilibrium of a game is to predict how players will play. However, if the game has multiple equilibria that are far apart, or ɛ-equilibria that are far in variation distance from the true Nash equilibrium strategies, then this prediction may not be possible even in principle. Motivated by this consideration, in this paper we define the notion of games that are approximation stable, meaning that all ɛ-approximate equilibria are contained inside a small ball of radius Δ around a true equilibrium, and investigate a number of their properties. Many natural small games such as matching pennies and rock-paper-scissors are indeed approximation stable. We show furthermore there exist 2-player n-by-n approximation-stable games in which the Nash equilibrium and all approximate equilibria have support Ω(log n). On the other hand, we show all (ɛ,Δ) approximation-stable games must have an ɛ-equilibrium of support O(Δ^{2-o(1)}/ɛ2{log n}), yielding an immediate n^{O(Δ^{2-o(1)}/ɛ^2log n)}-time algorithm, improving over the bound of [11] for games satisfying this condition. We in addition give a polynomial-time algorithm for the case that Δ and ɛ are sufficiently close together. We also consider an inverse property, namely that all non-approximate equilibria are far from some true equilibrium, and give an efficient algorithm for games satisfying that condition.

TLR9 is up-regulated in human and murine NASH: pivotal role in inflammatory recruitment and cell survival.

PubMed

Mridha, Auvro R; Haczeyni, Fahrettin; Yeh, Matthew M; Haigh, W Geoffrey; Ioannou, George N; Barn, Vanessa; Ajamieh, Hussam; Adams, Leon; Hamdorf, Jeffrey M; Teoh, Narci C; Farrell, Geoffrey C

2017-08-15

Background and aims : TLR9 deletion protects against steatohepatitis due to choline-amino acid depletion and high-fat diet. We measured TLR9 in human non-alcoholic steatohepatitis (NASH) livers, and tested whether TLR9 mediates inflammatory recruitment in three murine models of non-alcoholic fatty liver disease (NAFLD). Methods : We assayed TLR mRNA in liver biopsies from bariatric surgery patients. Wild-type ( Wt ), appetite-dysregulated Alms1 mutant (foz/foz), Tlr9 -/- , and Tlr9 -/- foz/foz C57BL6/J mice and bone marrow (BM) chimeras were fed 0.2% cholesterol, high-fat, high sucrose (atherogenic[Ath]) diet or chow, and NAFLD activity score (NAS)/NASH pathology, macrophage/neutrophil infiltration, cytokines/chemokines, and cell death markers measured in livers. Results : Hepatic TLR9 and TLR4 mRNA were increased in human NASH but not simple steatosis, and in Ath-fed foz/foz mice with metabolic syndrome-related NASH. Ath-fed Tlr9 -/- mice showed simple steatosis and less Th1 cytokines than Wt. Tlr9 -/- foz/foz mice were obese and diabetic, but necroinflammatory changes were less severe than Tlr9 +/+ .foz/foz mice. TLR9-expressing myeloid cells were critical for Th1 cytokine production in BM chimeras. BM macrophages from Tlr9 -/- mice showed M2 polarization, were resistant to M1 activation by necrotic hepatocytes/other pro-inflammatory triggers, and provoked less neutrophil chemotaxis than Wt Livers from Ath-fed Tlr9 -/- mice appeared to exhibit more markers of necroptosis [receptor interacting protein kinase (RIP)-1, RIP-3, and mixed lineage kinase domain-like protein (MLKL)] than Wt , and ∼25% showed portal foci of mononuclear cells unrelated to NASH pathology. Our novel clinical data and studies in overnutrition models, including those with diabetes and metabolic syndrome, clarify TLR9 as a pro-inflammatory trigger in NASH. This response is mediated via M1-macrophages and neutrophil chemotaxis. © 2017 The Author(s). Published by Portland Press Limited on

Water extract of Vitis coignetiae Pulliat leaves attenuates oxidative stress and inflammation in progressive NASH rats.

PubMed

Pak, Wing; Takayama, Fusako; Hasegawa, Azusa; Mankura, Mitsumasa; Egashira, Toru; Ueki, Keiji; Nakamoto, Kazuo; Kawasaki, Hiromu; Mori, Akitane

2012-01-01

This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300 mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation.

Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH.

PubMed

Caballero, Francisco; Fernández, Anna; De Lacy, Antonio M; Fernández-Checa, Jose C; Caballería, Juan; García-Ruiz, Carmen

2009-04-01

Non-alcoholic fatty liver disease (NAFLD) pathogenesis remains unknown. Due to the emerging role of free cholesterol (FC) in NAFLD, our aim was to examine the correlation between FC accumulation in patients with NAFLD and the expression of enzymes that regulate cholesterol homeostasis. Filipin staining, indicative of FC accumulation, and real-time PCR analyses were performed in 31 NAFLD patients and in seven controls. All NASH patients (n=14) and 4 out of 17 patients with steatosis exhibited filipin staining compared to controls (0 out of 7 subjects with normal liver histology and BMI). Sterol regulatory element-binding protein-2 (SREBP-2) mRNA levels were 7- and 3-fold higher in NASH and steatosis patients, respectively, compared to controls. Since hydroxymethylglutaryl-CoA (HMG-CoA) reductase is the key enzyme in cholesterol synthesis and transcriptionally controlled by SREBP-2 we measured its mRNA levels, being 3- to 4-fold higher in NAFLD compared to controls, without any difference between NASH and steatosis patients. Fatty acid synthase (FAS) and SREBP-1c expression were not significantly induced in NAFLD, while ATP-binding cassette sub-family G member 1 (ABCG1), a transporter involved in cholesterol egress, and acyl-CoA-cholesterol acyltransferase mRNA levels were modestly increased (1.5- to 2.5-fold, p<0.05), regardless of fibrosis. Interestingly, mRNA levels of steroidogenic acute regulatory protein (StAR), a mitochondrial-cholesterol transporting polypeptide, increased 7- and 15-fold in steatosis and NASH patients, respectively, compared to controls. FC increases in NASH and correlates with SREBP-2 induction. Moreover, StAR overexpression in NASH suggests that mitochondrial FC may be a player in disease progression and a novel target for intervention.

Hepatic FTO expression is increased in NASH and its silencing attenuates palmitic acid-induced lipotoxicity.

PubMed

Lim, Andrea; Zhou, Jin; Sinha, Rohit A; Singh, Brijesh K; Ghosh, Sujoy; Lim, Kiat-Hon; Chow, Pierce Kah-Hoe; Woon, Esther C Y; Yen, Paul M

2016-10-21

Non-alcoholic steatohepatitis (NASH) is one of the most common causes of liver failure worldwide. It is characterized by excess fat accumulation, inflammation, and increased lipotoxicity in hepatocytes. Currently, there are limited treatment options for NASH due to lack of understanding of its molecular etiology. In the present study, we demonstrate that the expression of fat mass and obesity associated gene (FTO) is significantly increased in the livers of NASH patients and in a rodent model of NASH. Furthermore, using human hepatic cells, we show that genetic silencing of FTO protects against palmitate-induced oxidative stress, mitochondrial dysfunction, ER stress, and apoptosis in vitro. Taken together, our results show that FTO may have a deleterious role in hepatic cells during lipotoxic conditions, and strongly suggest that up-regulation of FTO may contribute to the increased liver damage in NASH. Copyright © 2016 Elsevier Inc. All rights reserved.

Overexpression of the Vitronectin V10 Subunit in Patients with Nonalcoholic Steatohepatitis: Implications for Noninvasive Diagnosis of NASH.

PubMed

Del Ben, Maria; Overi, Diletta; Polimeni, Licia; Carpino, Guido; Labbadia, Giancarlo; Baratta, Francesco; Pastori, Daniele; Noce, Valeria; Gaudio, Eugenio; Angelico, Francesco; Mancone, Carmine

2018-02-18

Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients. On the basis of the assumption that steatohepatitis leads to the remodelling of the liver extracellular matrix (ECM), NASH-specific fragments were in silico analysed for their involvement in the ECM molecular composition. The 10 kDa C-terminal fragment of the ECM protein vitronectin (VTN) was then selected as a promising circulating biomarker in discriminating NASH. The analysis of sera of patients provided these major findings: the circulating VTN fragment (i) is overexpressed in NASH patients and positively correlates with the NASH activity score (NAS); (ii) originates from the disulfide bond reduction between the V10 and the V65 subunits. In conclusion, V10 determination in the serum could represent a reliable tool for the noninvasive discrimination of NASH from simple steatosis.

Nash equilibrium and multi criterion aerodynamic optimization

NASA Astrophysics Data System (ADS)

Tang, Zhili; Zhang, Lianhe

2016-06-01

Game theory and its particular Nash Equilibrium (NE) are gaining importance in solving Multi Criterion Optimization (MCO) in engineering problems over the past decade. The solution of a MCO problem can be viewed as a NE under the concept of competitive games. This paper surveyed/proposed four efficient algorithms for calculating a NE of a MCO problem. Existence and equivalence of the solution are analyzed and proved in the paper based on fixed point theorem. Specific virtual symmetric Nash game is also presented to set up an optimization strategy for single objective optimization problems. Two numerical examples are presented to verify proposed algorithms. One is mathematical functions' optimization to illustrate detailed numerical procedures of algorithms, the other is aerodynamic drag reduction of civil transport wing fuselage configuration by using virtual game. The successful application validates efficiency of algorithms in solving complex aerodynamic optimization problem.

Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation

PubMed Central

Peverill, William; Powell, Lawrie W.; Skoien, Richard

2014-01-01

Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future. PMID:24830559

Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

PubMed Central

Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M.; Coelho, A.M.M.; Xerfan, M.P.; Cogliati, B.; Barbeiro, D.F.; Mazo, D.F.C.; Kubrusly, M.S.; D'Albuquerque, L.A.C.; Souza, H.P.; Carrilho, F.J.; Oliveira, C.P.

2015-01-01

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH. PMID:25714891

Gary Nash: Repairing a Necessary Connection

ERIC Educational Resources Information Center

Bender, Thomas

2009-01-01

In this essay, the author comments on the life and the contributions of author Gary Nash. Everyone is thanking him for his remarkable engagement with the schools, as a writer of outstanding textbooks and materials for teachers developed through his work as director of the Center for Teaching History in the Schools, and, of course, the National…

A clinical scoring system for predicting nonalcoholic steatohepatitis in morbidly obese patients.

PubMed

Campos, Guilherme M; Bambha, Kiran; Vittinghoff, Eric; Rabl, Charlotte; Posselt, Andrew M; Ciovica, Ruxandra; Tiwari, Umesh; Ferrel, Linda; Pabst, Mark; Bass, Nathan M; Merriman, Raphael B

2008-06-01

Nonalcoholic steatohepatitis (NASH) is common in morbidly obese persons. Liver biopsy is diagnostic but technically challenging in such individuals. This study was undertaken to develop a clinically useful scoring system to predict the probability of NASH in morbidly obese persons, thus assisting in the decision to perform liver biopsy. Consecutive subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. The outcome was pathologic diagnosis of NASH. Predictors evaluated were demographic, clinical, and laboratory variables. A clinical scoring system was constructed by rounding the estimated regression coefficients for the independent predictors in a multivariate logistic model for the diagnosis of NASH. Of 200 subjects studied, 64 (32%) had NASH. Median body mass index was 48 kg/m(2) (interquartile range, 43-55). Multivariate analysis identified six predictive factors for NASH: the diagnosis of hypertension (odds ratio [OR], 2.4; 95% confidence interval [CI], 1-5.6), type 2 diabetes (OR, 2.6; 95% CI, 1.1-6.3), sleep apnea (OR, 4.0; 95% CI, 1.3-12.2), AST > 27 IU/L (OR, 2.9; 95% CI, 1.2-7.0), alanine aminotransferase (ALT) > 27 IU/L (OR, 3.3; 95% CI, 1.4-8.0), and non-Black race (OR, 8.4; 95% CI, 1.9-37.1). A NASH Clinical Scoring System for Morbid Obesity was derived to predict the probability of NASH in four categories (low, intermediate, high, and very high). The proposed clinical scoring can predict NASH in morbidly obese persons with sufficient accuracy to be considered for clinical use, identifying a very high-risk group in whom liver biopsy would be very likely to detect NASH, as well as a low-risk group in whom biopsy can be safely delayed or avoided.

NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice.

PubMed

Mridha, Auvro R; Wree, Alexander; Robertson, Avril A B; Yeh, Matthew M; Johnson, Casey D; Van Rooyen, Derrick M; Haczeyni, Fahrettin; Teoh, Narci C-H; Savard, Christopher; Ioannou, George N; Masters, Seth L; Schroder, Kate; Cooper, Matthew A; Feldstein, Ariel E; Farrell, Geoffrey C

2017-05-01

NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in Non-alcoholic fatty liver disease (NAFLD). We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. We fed foz/foz and wild-type mice an atherogenic diet for 16weeks, gavaged MCC950 or vehicle until 24weeks, then determined NAFLD phenotype. In mice fed an methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle for 6weeks and determined the effects on liver fibrosis. In vehicle-treated foz/foz mice, hepatic expression of NLRP3, pro-IL-1β, active caspase-1 and IL-1β increased at 24weeks, in association with cholesterol crystal formation and NASH pathology; plasma IL-1β, IL-6, MCP-1, ALT/AST all increased. MCC950 treatment normalized hepatic caspase 1 and IL-1β expression, plasma IL-1β, MCP-1 and IL-6, lowered ALT/AST, and reduced the severity of liver inflammation including designation as NASH pathology, and liver fibrosis. In vitro, cholesterol crystals activated Kupffer cells and macrophages to release IL-1β; MCC950 abolished this, and the associated neutrophil migration. MCD diet-fed mice developed fibrotic steatohepatitis; MCC950 suppressed the increase in hepatic caspase 1 and IL-1β, lowered numbers of macrophages and neutrophils in the liver, and improved liver fibrosis. MCC950, an NLRP3 selective inhibitor, improved NAFLD pathology and fibrosis in obese diabetic mice. This is potentially attributable to the blockade of cholesterol crystal-mediated NLRP3 activation in myeloid cells. MCC950 reduced liver fibrosis in MCD-fed mice. Targeting NLRP3 is a logical direction in pharmacotherapy of NASH. Fatty liver disease caused by being overweight with diabetes and a high risk of heart attack, termed non-alcoholic steatohepatitis (NASH), is the most common serious liver disease with no current treatment. There could be several causes of inflammation

HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients.

PubMed

Martini, A; Fattovich, G; Guido, M; Bugianesi, E; Biasiolo, A; Ieluzzi, D; Gallotta, A; Fassina, G; Merkel, C; Gatta, A; Negro, F; Pontisso, P

2015-10-01

Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH. © 2015 John Wiley & Sons Ltd.

Grace Nash: Nine Decades of Graceful Teaching.

ERIC Educational Resources Information Center

Cole, Judith

2000-01-01

Provides information on the life of Grace Nash, an influential educator and pioneer of Orff Schulwerk in the United States, focusing on issues such as her young life, experience as a prisoner-of-war, development of her interest in the Orff, Kodaly, and Laban methods, and her own work. Offers selected resources. (CMK)

Memories of Gary Nash over Five Decades

ERIC Educational Resources Information Center

Mellor, Ronald

2009-01-01

It is as a longtime client, softball teammate, colleague, traveling companion, and friend that the author writes this article to honor Gary Nash. He has known him in varied guises in five different decades, and on five continents, with Africa coming in 2009. In this article, the author recalls some of his memories of Gary over five decades.

Pharmacological cholesterol lowering reverses fibrotic NASH in obese, diabetic mice with metabolic syndrome.

PubMed

Van Rooyen, Derrick M; Gan, Lay T; Yeh, Matthew M; Haigh, W Geoffrey; Larter, Claire Z; Ioannou, George; Teoh, Narci C; Farrell, Geoffrey C

2013-07-01

We have recently showed that hyperinsulinemia promotes hepatic free cholesterol (FC) accumulation in obese, insulin-resistant Alms1 mutant (foz/foz) mice with NASH. Here we tested whether cholesterol-lowering drugs reduce stress-activated c-Jun N-terminal kinase (JNK) activation, hepatocyte injury/apoptosis, inflammation, and fibrosis in this metabolic syndrome NASH model. Female foz/foz and WT mice were fed HF (0.2% cholesterol) 16 weeks, before adding ezetimibe (5 mg/kg), atorvastatin (20 mg/kg), or both to diet, another 8 weeks. Hepatic lipidomic analysis, ALT, liver histology, Sirius Red morphometry, hepatic mRNA and protein expression and immunohistochemistry (IHC) for apoptosis (M30), macrophages (F4/80), and polymorphs (myeloperoxidase) were determined. In mice with NASH, ezetimibe/atorvastatin combination normalized hepatic FC but did not alter saturated free fatty acids (FFA) and had minimal effects on other lipids; ezetimibe and atorvastatin had similar but less profound effects. Pharmacological lowering of FC abolished JNK activation, improved serum ALT, apoptosis, liver inflammation/NAFLD activity score, designation as "NASH", macrophage chemotactic protein-1 expression, reduced macrophage and polymorph populations, and liver fibrosis. Cholesterol lowering with ezetimibe/atorvastatin combination reverses hepatic FC but not saturated FFA accumulation. This dampens JNK activation, ALT release, hepatocyte apoptosis, and inflammatory recruitment, with reversal of steatohepatitis pathology and liver fibrosis. Ezetimibe/statin combination is a potent, mechanism-based treatment that could reverse NASH and liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Beyond Reasonable Doubt: Who Is the Culprit in Lipotoxicity in NAFLD/NASH?

PubMed Central

Arteel, Gavin E.

2016-01-01

BACKGROUND & AIMS Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. METHODS Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. RESULTS Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. CONCLUSIONS In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. PMID:22422583

Congestion schemes and Nash equilibrium in complex networks

NASA Astrophysics Data System (ADS)

Almendral, Juan A.; López, Luis; Cholvi, Vicent; Sanjuán, Miguel A. F.

2005-09-01

Whenever a common resource is scarce, a set of rules are needed to share it in a fairly way. However, most control schemes assume that users will behave in a cooperative way, without taking care of guaranteeing that they will not act in a selfish manner. Then, a fundamental issue is to evaluate the impact of cheating. From the point of view of game theory, a Nash equilibrium implies that nobody can take advantage by unilaterally deviating from this stable state, even in the presence of selfish users. In this paper we prove that any efficient Nash equilibrium strongly depends on the number of users, if the control scheme policy does not record their previous behavior. Since this is a common pattern in real situations, this implies that the system would be always out of equilibrium. Consequently, this result proves that, in practice, oblivious control schemes must be improved to cope with selfish users.

Distributed Nash Equilibrium Seeking for Generalized Convex Games with Shared Constraints

NASA Astrophysics Data System (ADS)

Sun, Chao; Hu, Guoqiang

2018-05-01

In this paper, we deal with the problem of finding a Nash equilibrium for a generalized convex game. Each player is associated with a convex cost function and multiple shared constraints. Supposing that each player can exchange information with its neighbors via a connected undirected graph, the objective of this paper is to design a Nash equilibrium seeking law such that each agent minimizes its objective function in a distributed way. Consensus and singular perturbation theories are used to prove the stability of the system. A numerical example is given to show the effectiveness of the proposed algorithms.

Long term highly saturated fat diet does not induce NASH in Wistar rats

PubMed Central

Romestaing, Caroline; Piquet, Marie-Astrid; Bedu, Elodie; Rouleau, Vincent; Dautresme, Marianne; Hourmand-Ollivier, Isabelle; Filippi, Céline; Duchamp, Claude; Sibille, Brigitte

2007-01-01

Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard). Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH. PMID:17313679

Gary Nash: Preeminent Scholar and Committed Educator

ERIC Educational Resources Information Center

Symcox, Linda

2009-01-01

The author has known Gary Nash as a friend since 1969, but she only began to work with him as a colleague in 1989, when he invited her to join the National Center for History in the Schools (NCHS) as it was just forming. During the seven years she spent as Assistant and then Associate Director of the NCHS, they shared the extraordinary experience…

Nash Equilibria in Noncooperative Predator-Prey Games

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramos, Angel Manuel; Roubicek, Tomas

2007-09-15

A noncooperative game governed by a distributed-parameter predator-prey system is considered, assuming that two players control initial conditions for predator and prey, respectively. Existence of a Nash equilibrium is shown under the condition that the desired population profiles and the environmental carrying capacity for the prey are sufficiently small. A conceptual approximation algorithm is proposed and analyzed. Finally, numerical simulations are performed, too.

Approximation of Nash equilibria and the network community structure detection problem

PubMed Central

2017-01-01

Game theory based methods designed to solve the problem of community structure detection in complex networks have emerged in recent years as an alternative to classical and optimization based approaches. The Mixed Nash Extremal Optimization uses a generative relation for the characterization of Nash equilibria to identify the community structure of a network by converting the problem into a non-cooperative game. This paper proposes a method to enhance this algorithm by reducing the number of payoff function evaluations. Numerical experiments performed on synthetic and real-world networks show that this approach is efficient, with results better or just as good as other state-of-the-art methods. PMID:28467496

Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy.

PubMed

Ding, Zhi-Ming; Xiao, Yue; Wu, Xikun; Zou, Haixia; Yang, Shurong; Shen, Yiyun; Xu, Juehua; Workman, Heather C; Usborne, Amy L; Hua, Haiqing

2018-01-01

Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods. Male C57BL/6 mice fed Western diet developed progressive hepatic steatosis/macrovesicular vacuolation, inflammation, and hepatocyte degeneration, as well as perisinusoidal fibrosis and occasionally portal fibrosis as early as 2 months after initiation of the Western diet. In the same period, the mice exhibited elevated ALT (alanine aminotransferase) and AST (aspartate aminotransferase) enzyme activities, CK18 (cytokeratin-18), PIIINP (N-terminal propeptide of type III collagen), and TIMP-1 (tissue inhibitor of metalloproteinase-1). Hepatic steatosis diminished rapidly when the Western diet was replaced by normal rodent chow diet and hepatic inflammation and hepatocyte degeneration were also reduced. Interestingly, perisinusoidal fibrosis and portal fibrosis regressed 8 months after chow diet replacement. To understand pharmacotherapy for NASH, mice with established NASH hepatic lesions were treated with either FXR agonist obeticholic acid (Ocaliva), or CCR2/5 antagonist Cenicriviroc. Similar to the diet replacement, metabolic modulator Ocaliva markedly reduced steatosis/macrovesicular vacuolation, hepatic inflammation, and hepatocyte degeneration effectively, but exhibited no significant effect on liver fibrosis. Anti-inflammation drug Cenicriviroc, on the other hand, markedly decreased inflammation and hepatocyte degeneration, and

Nash equilibrium in differential games and the construction of the programmed iteration method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Averboukh, Yurii V

This work is devoted to the study of nonzero-sum differential games. The set of payoffs in a situation of Nash equilibrium is examined. It is shown that the set of payoffs in a situation of Nash equilibrium coincides with the set of values of consistent functions which are fixed points of the program absorption operator. A condition for functions to be consistent is given in terms of the weak invariance of the graph of the functions under a certain differential inclusion. Bibliography: 18 titles.

Surviving History: Gary Nash and the National Standards

ERIC Educational Resources Information Center

Bingham, Marjorie

2009-01-01

In this article, the author recalls the first time she met Gary Nash. He came to speak at a Bradley Commission meeting and she was rather surprised to see him appear and to find out that he, along with Charlotte Crabtree, was involved in a National Center for History. She gives three reasons for her surprise which she thinks may tell aspects of…

A Graphical Analysis of the Cournot-Nash and Stackelberg Models.

ERIC Educational Resources Information Center

Fulton, Murray

1997-01-01

Shows how the Cournot-Nash and Stackelberg equilibria can be represented in the familiar supply-demand graphical framework, allowing a direct comparison with the monopoly, competitive, and industrial organization models. This graphical analysis is represented throughout the article. (MJP)

Factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD).

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan; Majid, Zain

2018-04-01

Introduction To determine the factors predicting non-alcoholic steatohepatitis (NASH) and advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Methodology All patients aged >18 years and having a fatty liver on abdominal ultrasound (US), presenting from January 2011 to January 2017, were included. A liver biopsy was performed on all the patients. Results Of 96 patients undergoing liver biopsy for non-alcoholic fatty liver disease (NAFLD), 76 (79.2%) were men. On liver US, diffuse fatty liver (DFL) was noted in 68 (70.8%) patients. Liver biopsy showed non-alcoholic steatohepatitis (NASH) in 78 (81.3%) patients. Factors associated with NASH were male gender, body mass index (BMI) > 27 kg/m 2 , DFL and raised alanine aminotransferase (ALT). A GULAB score (based on gender, US liver findings, lipid (fasting) levels, ALT level and BMI) of ≥5 predicted NASH with 82.05% sensitivity. Factors associated with advanced fibrosis in NAFLD were age >40 years, diabetes mellitus, AST/ALT ratio > 1 and raised GGT. Conclusion NASH is common in patients with male gender, high BMI, DFL on liver US, raised ALT and GULAB score ≥5.

Genetic Predisposition in NAFLD and NASH: Impact on Severity of Liver Disease and Response to Treatment

PubMed Central

Dongiovanni, Paola; Anstee, Quentin M; Valenti, Luca

2013-01-01

Liver fat deposition related to systemic insulin resistance defines non-alcoholic fatty liver disease (NAFLD) which, when associated with oxidative hepatocellular damage, inflammation, and activation of fibrogenesis, i.e. non-alcoholic steatohepatitis (NASH), can progress towards cirrhosis and hepatocellular carcinoma. Due to the epidemic of obesity, NAFLD is now the most frequent liver disease and the leading cause of altered liver enzymes in Western countries. Epidemiological, familial, and twin studies provide evidence for an element of heritability of NAFLD. Genetic modifiers of disease severity and progression have been identified through genome-wide association studies. These include the Patatin-like phosholipase domain-containing 3 (PNPLA3) gene variant I148M as a major determinant of inter-individual and ethnicity-related differences in hepatic fat content independent of insulin resistance and serum lipid concentration. Association studies confirm that the I148M polymorphism is also a strong modifier of NASH and progressive hepatic injury. Furthermore, a few large multicentre case-control studies have demonstrated a role for genetic variants implicated in insulin signalling, oxidative stress, and fibrogenesis in the progression of NAFLD towards fibrosing NASH, and confirm that hepatocellular fat accumulation and insulin resistance are key operative mechanisms closely involved in the progression of liver damage. It is now important to explore the molecular mechanisms underlying these associations between gene variants and progressive liver disease, and to evaluate their impact on the response to available therapies. It is hoped that this knowledge will offer further insights into pathogenesis, suggest novel therapeutic targets, and could help guide physicians towards individualised therapy that improves clinical outcome. PMID:23394097

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

PubMed

Argo, Curtis K; Patrie, James T; Lackner, Carolin; Henry, Thomas D; de Lange, Eduard E; Weltman, Arthur L; Shah, Neeral L; Al-Osaimi, Abdullah M; Pramoonjago, Patcharin; Jayakumar, Saumya; Binder, Lukas P; Simmons-Egolf, Winsor D; Burks, Sandra G; Bao, Yongde; Taylor, Ann Gill; Rodriguez, Jessica; Caldwell, Stephen H

2015-01-01

This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Critical Realism and Statistical Methods--A Response to Nash

ERIC Educational Resources Information Center

Scott, David

2007-01-01

This article offers a defence of critical realism in the face of objections Nash (2005) makes to it in a recent edition of this journal. It is argued that critical and scientific realisms are closely related and that both are opposed to statistical positivism. However, the suggestion is made that scientific realism retains (from statistical…

Follow-up CT findings of tamoxifen-induced non-alcoholic steatohepatitis (NASH) of breast cancer patients treated with bezafibrate.

PubMed

Ogawa, Yasuhiro; Murata, Yoriko; Saibara, Toshiji; Nishioka, Akihito; Kariya, Shinji; Yoshida, Shoji

2003-01-01

One-third of the breast cancer patients who underwent tamoxifen intake showed less than 0.9 of their liver/spleen CT (computed tomography) ratio on their annual CT study, and were diagnosed as having fatty liver (hepatic steatosis). Among them, patients who showed a lower liver/spleen CT ratio of less than 0.5 were recommended to undergo needle biopsy of the liver in order to obtain histopathological confirmation of non-alcoholic steatohepatitis (NASH), with 15 patients undergoing needle biopsy of the liver. As a result, 14 out of the 15 patients were diagnosed as having NASH, and these patients were additionally administered bezafibrate in order to prevent possible progressive changes of NASH into liver cirrhosis. In this study, we show the changes of follow-up CT findings of 6 patients with histopathologically-proven NASH who continued to undergo bezafibrate intake after the diagnosis of NASH. Two patients showed almost complete improvement as indicated by the liver/spleen CT ratio several months after completion of a tamoxifen intake of 5 years, and another 3 showed partial improvement on their liver/spleen CT ratio by bezafibrate intake in spite of continuing tamoxifen intake. Another patient with diabetes mellitus (type II) showed a continually decreasing liver/spleen CT ratio during adjuvant tamoxifen in spite of bezafibrate intake. Therefore, we concluded that the progression of NASH could be prevented by bezafibrate without any interruption of adjuvant tamoxifen treatment. For patients with diabetes mellitus, critical follow-up using CT study and laboratory tests is considered essential.

Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma

PubMed Central

Vongsuvanh, Roslyn; van der Poorten, David; Iseli, Tristan; Strasser, Simone I.; McCaughan, Geoffrey W.; George, Jacob

2016-01-01

Robust biomarkers for population-level hepatocellular carcinoma (HCC) surveillance are lacking. We compared serum midkine (MDK), dickkopf-1 (DKK1), osteopontin (OPN) and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD) and 86 healthy controls (HC). Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49) had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86) of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54%) of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior. Conclusion: AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC. PMID:27219517

Kupffer Cells Undergo Fundamental Changes during the Development of Experimental NASH and Are Critical in Initiating Liver Damage and Inflammation

PubMed Central

Reid, D. T.; Reyes, J. L.; McDonald, B. A.; Vo, T.; Reimer, R. A.; Eksteen, B.

2016-01-01

Non-alcoholic fatty liver disease has become the leading liver disease in North America and is associated with the progressive inflammatory liver disease non-alcoholic steatohepatitis (NASH). Considerable effort has been made to understand the role of resident and recruited macrophage populations in NASH however numerous questions remain. Our goal was to characterize the dynamic changes in liver macrophages during the initiation of NASH in a murine model. Using the methionine-choline deficient diet we found that liver-resident macrophages, Kupffer cells were lost early in disease onset followed by a robust infiltration of Ly-6C+ monocyte-derived macrophages that retained a dynamic phenotype. Genetic profiling revealed distinct patterns of inflammatory gene expression between macrophage subsets. Only early depletion of liver macrophages using liposomal clodronate prevented the development of NASH in mice suggesting that Kupffer cells are critical for the orchestration of inflammation during experimental NASH. Increased understanding of these dynamics may allow us to target potentially harmful populations whilst promoting anti-inflammatory or restorative populations to ultimately guide the development of effective treatment strategies. PMID:27454866

Information Structures in Nash and Leader-Follower Strategies.

DTIC Science & Technology

1981-01-01

OICkASSIPICATION/ OOWNGRAOING IS. OISTNIIIUTION STATEMINT (ao tD. esPort ) * Approved for public release; distribution unlimited. 17. DISTRIBUTION STATEMENT...problems and two market models of duopoly ith this type of information structure are extensively analyzed and examined. DO jAN7, 1473 EDIION OF NV SS IS...information 3 structure is employed in both Nash games and optimal coordination problems and two market models of duopoly with this type of information

On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised by the Folk Theorem

PubMed Central

Li, Jiawei; Kendall, Graham

2015-01-01

In evolutionary game theory, evolutionarily stable states are characterised by the folk theorem because exact solutions to the replicator equation are difficult to obtain. It is generally assumed that the folk theorem, which is the fundamental theory for non-cooperative games, defines all Nash equilibria in infinitely repeated games. Here, we prove that Nash equilibria that are not characterised by the folk theorem do exist. By adopting specific reactive strategies, a group of players can be better off by coordinating their actions in repeated games. We call it a type-k equilibrium when a group of k players coordinate their actions and they have no incentive to deviate from their strategies simultaneously. The existence and stability of the type-k equilibrium in general games is discussed. This study shows that the sets of Nash equilibria and evolutionarily stable states have greater cardinality than classic game theory has predicted in many repeated games. PMID:26288088

Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients.

PubMed

Noureddin, Mazen; Yates, Katherine P; Vaughn, Ivana A; Neuschwander-Tetri, Brent A; Sanyal, Arun J; McCullough, Arthur; Merriman, Raphael; Hameed, Bilal; Doo, Edward; Kleiner, David E; Behling, Cynthia; Loomba, Rohit

2013-11-01

The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age ≥65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P = 0.02), and advanced fibrosis (25% versus 44%, P = 0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P = 0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤ 0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR] = 1.12, P = 0.007) and lower platelets (OR = 0.98, P = 0.02); and independent determinants of advanced fibrosis included higher AST (OR = 1.08, P = 0.007), lower alanine aminotransferase value (OR = 0.91, P = 0.002), and an increased odds of having low high-density lipoprotein (OR = 8.35, P = 0.02). Elderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis. �

Remediating Language Deficient/Dyslexic College Students: An Interview with Robert Nash.

ERIC Educational Resources Information Center

Lundquist, Arlene J.; Nash, Robert

1988-01-01

Robert Nash responds to questions concerning his personal and professional background, the Simultaneous Multisensory Instructional Procedure for Teaching the Complete Sound Structure of the Language, problems associated with dyslexia, the social/emotional impact of learning disabilities, and the University of Wisconsin's Project Success for…

77 FR 10553 - Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-Amendment to Liquor Beverage...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-- Amendment to Liquor Beverage Control Ordinance AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice SUMMARY: This notice publishes the amendments to the Match-E-Be-Nash- She-Wish...

Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH.

PubMed

Ioannou, George N; Van Rooyen, Derrick M; Savard, Christopher; Haigh, W Geoffrey; Yeh, Matthew M; Teoh, Narci C; Farrell, Geoffrey C

2015-02-01

Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥ 3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation.

Optimization, Monotonicity and the Determination of Nash Equilibria — An Algorithmic Analysis

NASA Astrophysics Data System (ADS)

Lozovanu, D.; Pickl, S. W.; Weber, G.-W.

2004-08-01

This paper is concerned with the optimization of a nonlinear time-discrete model exploiting the special structure of the underlying cost game and the property of inverse matrices. The costs are interlinked by a system of linear inequalities. It is shown that, if the players cooperate, i.e., minimize the sum of all the costs, they achieve a Nash equilibrium. In order to determine Nash equilibria, the simplex method can be applied with respect to the dual problem. An introduction into the TEM model and its relationship to an economic Joint Implementation program is given. The equivalence problem is presented. The construction of the emission cost game and the allocation problem is explained. The assumption of inverse monotony for the matrices leads to a new result in the area of such allocation problems. A generalization of such problems is presented.

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α.

PubMed

Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang

2017-02-27

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets ( p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models ( p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) ( p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3

Multifunctional Effects of a Small-Molecule STAT3 Inhibitor on NASH and Hepatocellular Carcinoma in Mice.

PubMed

Jung, Kwang Hwa; Yoo, Wonbeak; Stevenson, Heather L; Deshpande, Dipti; Shen, Hong; Gagea, Mihai; Yoo, Suk-Young; Wang, Jing; Eckols, T Kris; Bharadwaj, Uddalak; Tweardy, David J; Beretta, Laura

2017-09-15

Purpose: The incidence of hepatocellular carcinoma is increasing in the United States, and liver cancer is the second leading cause of cancer-related mortality worldwide. Nonalcoholic steatohepatitis (NASH) is becoming an important risk for hepatocellular carcinoma, and most patients with hepatocellular carcinoma have underlying liver cirrhosis and compromised liver function, which limit treatment options. Thus, novel therapeutic strategies to prevent or treat hepatocellular carcinoma in the context of NASH and cirrhosis are urgently needed. Experimental Design: Constitutive activation of STAT3 is frequently detected in hepatocellular carcinoma tumors. STAT3 signaling plays a pivotal role in hepatocellular carcinoma survival, growth, angiogenesis, and metastasis. We identified C188-9, a novel small-molecule STAT3 inhibitor using computer-aided rational drug design. In this study, we evaluated the therapeutic potential of C188-9 for hepatocellular carcinoma treatment and prevention. Results: C188-9 showed antitumor activity in vitro in three hepatocellular carcinoma cell lines. In mice with hepatocyte-specific deletion of Pten (Hep Pten - mice), C188-9 treatment blocked hepatocellular carcinoma tumor growth, reduced tumor development, and reduced liver steatosis, inflammation, and bile ductular reactions, resulting in improvement of the pathological lesions of NASH. Remarkably, C188-9 also greatly reduced liver injury in these mice as measured by serum aspartate aminotransferase and alanine transaminase levels. Analysis of gene expression showed that C188-9 treatment of Hep Pten - mice resulted in inhibition of signaling pathways downstream of STAT3, STAT1, TREM-1, and Toll-like receptors. In contrast, C188-9 treatment increased liver specification and differentiation gene pathways. Conclusions: Our results suggest that C188-9 should be evaluated further for the treatment and/or prevention of hepatocellular carcinoma. Clin Cancer Res; 23(18); 5537-46. ©2017 AACR

Nash equilibrium strategy in the deregulated power industry and comparing its lost welfare with Iran wholesale electricity market

NASA Astrophysics Data System (ADS)

Mousavi, Seyed Hosein; Nazemi, Ali; Hafezalkotob, Ashkan

2016-09-01

With the increasing use of different types of auctions in market designing, modeling of participants' behaviors to evaluate the market structure is one of the main discussions in the studies related to the deregulated power industries. In this article, we apply an approach of the optimal bidding behavior to the Iran wholesale electricity market as a restructured electric power industry and model how the participants of the market bid in the spot electricity market. The problem is formulated analytically using the Nash equilibrium concept composed of large numbers of players having discrete and very large strategy spaces. Then, we compute and draw supply curve of the competitive market in which all generators' proposed prices are equal to their marginal costs and supply curve of the real market in which the pricing mechanism is pay-as-bid. We finally calculate the lost welfare or inefficiency of the Nash equilibrium and the real market by comparing their supply curves with the competitive curve. We examine 3 cases on November 24 (2 cases) and July 24 (1 case), 2012. It is observed that in the Nash equilibrium on November 24 and demand of 23,487 MW, there are 212 allowed plants for the first case (plants are allowed to choose any quantity of generation except one of them that should be equal to maximum Power) and the economic efficiency or social welfare of Nash equilibrium is 2.77 times as much as the real market. In addition, there are 184 allowed plants for the second case (plants should offer their maximum power with different prices) and the efficiency or social welfare of Nash equilibrium is 3.6 times as much as the real market. On July 24 and demand of 42,421 MW, all 370 plants should generate maximum energy due to the high electricity demand that the economic efficiency or social welfare of the Nash equilibrium is about 2 times as much as the real market.

Geometry of Cournot-Nash Equilibrium with Application to Commons and Anticommons

ERIC Educational Resources Information Center

D'Agata, Antonio

2010-01-01

The author develops a simple geometric analysis of Cournot-Nash equilibrium in the price-quantity space by exploiting the economic content of the first-order condition. The approach makes it clear that strategic interdependency in oligopoly originates from externalities among producers. This explains why cartels are unstable and casts oligopoly…

Challenges and Management of Liver Cirrhosis: Practical Issues in the Therapy of Patients with Cirrhosis due to NAFLD and NASH.

PubMed

Traussnigg, Stefan; Kienbacher, Christian; Halilbasic, Emina; Rechling, Christian; Kazemi-Shirazi, Lili; Hofer, Harald; Munda, Petra; Trauner, Michael

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC. The therapeutic options in NAFLD/NASH include lifestyle modification, pharmacological treatment, bariatric surgery for patients with morbid obesity and treatment of complications of liver cirrhosis and HCC, including liver transplantation. Insulin sensitizers and antioxidative treatment strategies with vitamin E are among the best-established pharmacological approaches, but both drugs have long-term safety issues and there is limited evidence in cirrhotic patients. Treatment of concomitant/underlying metabolic conditions with statins or metformin may also have beneficial effects on portal hypertension, complications of liver cirrhosis and HCC prevention. The bile acid receptor FXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies. Morbidly obese NASH patients can benefit from bariatric surgery which may reduce liver fibrosis but carries a risk of decompensation in patients with advanced liver cirrhosis. When carefully selected, patients with NASH cirrhosis undergoing liver transplantation have a good outcome. This review summarizes recent progress in the management of patients with liver cirrhosis due to NASH. © 2015 S. Karger AG, Basel.

Cholesterol-lowering drugs cause dissolution of cholesterol crystals and disperse Kupffer cell crown-like structures during resolution of NASH

PubMed Central

Ioannou, George N.; Van Rooyen, Derrick M.; Savard, Christopher; Haigh, W. Geoffrey; Yeh, Matthew M.; Teoh, Narci C.; Farrell, Geoffrey C.

2015-01-01

Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation. PMID:25520429

Characterizing the Nash equilibria of three-player Bayesian quantum games

NASA Astrophysics Data System (ADS)

Solmeyer, Neal; Balu, Radhakrishnan

2017-05-01

Quantum games with incomplete information can be studied within a Bayesian framework. We analyze games quantized within the EWL framework [Eisert, Wilkens, and Lewenstein, Phys Rev. Lett. 83, 3077 (1999)]. We solve for the Nash equilibria of a variety of two-player quantum games and compare the results to the solutions of the corresponding classical games. We then analyze Bayesian games where there is uncertainty about the player types in two-player conflicting interest games. The solutions to the Bayesian games are found to have a phase diagram-like structure where different equilibria exist in different parameter regions, depending both on the amount of uncertainty and the degree of entanglement. We find that in games where a Pareto-optimal solution is not a Nash equilibrium, it is possible for the quantized game to have an advantage over the classical version. In addition, we analyze the behavior of the solutions as the strategy choices approach an unrestricted operation. We find that some games have a continuum of solutions, bounded by the solutions of a simpler restricted game. A deeper understanding of Bayesian quantum game theory could lead to novel quantum applications in a multi-agent setting.

Role of white adipose lipolysis in the development of NASH induced by methionine-and choline-deficient diet

PubMed Central

Tanaka, Naoki; Takahashi, Shogo; Fang, Zhong-Ze; Matsubara, Tsutomu; Krausz, Kristopher W.; Qu, Aijuan; Gonzalez, Frank J.

2014-01-01

Methionine- and choline-deficient diet (MCD) is a model for nonalcoholic steatohepatitis (NASH) in rodents. However, the mechanism of NASH development by dietary methionine/choline deficiency remains undetermined. To elucidate the early metabolic changes associated with MCD-NASH, serum metabolomic analysis was performed using mice treated with MCD and control diet for three days and one week, revealing significant increases in oleic and linoleic acids after MCD treatment. These increases were correlated with reduced body weight and white adipose tissue (WAT) mass, increased phosphorylation of hormone-sensitive lipase, and up-regulation of genes encoding carboxylesterase 3 and β2-adrenergic receptor in WAT, indicating accelerated lipolysis in adipocytes. The changes in serum fatty acids and WAT by MCD treatment were reversed by methionine supplementation, and similar alterations were detected in mice fed a methionine-deficient diet (MD), thus demonstrating that dietary methionine deficiency enhances lipolysis in WAT. MD treatment decreased glucose and increased fibroblast growth factor 21 in serum, thus exhibiting a similar metabolic phenotype as the fasting response. Comparison between MCD and choline-deficient diet (CD) treatments suggested that the addition of MD-induced metabolic alterations, such as WAT lipolysis, to CD-induced hepatic steatosis promotes liver injury. Collectively, these results demonstrate an important role for dietary methionine deficiency and WAT lipolysis in the development of MCD-NASH. PMID:25178843

The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

PubMed Central

Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang

2017-01-01

Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway

A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

PubMed

Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

2017-06-01

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of

CHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications

PubMed Central

Kim, Sung-Mi; Grenert, James P.; Patterson, Cam; Correia, Maria Almira

2016-01-01

Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP−/−-mice over the first 8–9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5′-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP−/−-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models. PMID:27406999

A long-acting FGF21 alleviates hepatic steatosis and inflammation in NASH mice partly through an FGF21- adiponectin- IL17A axis.

PubMed

Bao, Lichen; Yin, Jun; Gao, Wen; Wang, Qun; Yao, Wenbing; Gao, Xiangdong

2018-06-02

NASH is the most severe form of NAFLD and is a serious public health problem around the world. There are currently no approved treatments for NASH. FGF21 has recently emerged as a promising drug candidate for metabolic diseases. However, the challenges in developing FGF21 as a novel medicine include its short plasma half-life and poor drug-like properties. Here, we explored the therapeutic effects of PsTag600-FGF21, an engineered long-acting FGF21 fusion protein, in NASH mice and revealed some of the mechanisms responsible for this activity. A long-acting FGF21 was prepared by genetic fusion with a 600 residues polypeptide (PsTag600). We conducted our studies using a choline-deficient high-fat diet (CD-HFD) induced NASH mouse model. In NASH mice, the effects on body weight, insulin sensitivity, inflammation and levels of hormones and metabolites were studied first. We further investigated whether PsTag600-FGF21 attenuated inflammation through the Th17-IL17A axis and the associated mechanisms. PsTag600-FGF21 dose-dependently reduced body weight, blood glucose, insulin and lipid levels and reversed hepatic steatosis. PsTag600-FGF21 enhanced fatty acid activation and mitochondrial β-oxidation in the liver. The profound reduction in hepatic inflammation in NASH mice was associated with PsTag600-FGF21 inhibition of IL17A expression in Th17 cells. Furthermore, PsTag600-FGF21 depended on adiponectin to exert its suppression effects on Th17 cell differentiation and IL17A expression. Our data begin to uncover the indirect mechanism by which PsTag600-FGF21 suppresses hepatic inflammation and further suggest that PsTag600-FGF21 could be an effective approach in NASH treatment. This article is protected by copyright. All rights reserved.

Nash Equilibria in Theory of Reasoned Action

NASA Astrophysics Data System (ADS)

Almeida, Leando; Cruz, José; Ferreira, Helena; Pinto, Alberto Adrego

2009-08-01

Game theory and Decision Theory have been applied to many different areas such as Physics, Economics, Biology, etc. In its application to Psychology, we introduce, in the literature, a Game Theoretical Model of Planned Behavior or Reasoned Action by establishing an analogy between two specific theories. In this study we take in account that individual decision-making is an outcome of a process where group decisions can determine individual probabilistic behavior. Using Game Theory concepts, we describe how intentions can be transformed in behavior and according to the Nash Equilibrium, this process will correspond to the best individual decision/response taking in account the collective response. This analysis can be extended to several examples based in the Game Theoretical Model of Planned Behavior or Reasoned Action.

Nash Equilibrium of Social-Learning Agents in a Restless Multiarmed Bandit Game.

PubMed

Nakayama, Kazuaki; Hisakado, Masato; Mori, Shintaro

2017-05-16

We study a simple model for social-learning agents in a restless multiarmed bandit (rMAB). The bandit has one good arm that changes to a bad one with a certain probability. Each agent stochastically selects one of the two methods, random search (individual learning) or copying information from other agents (social learning), using which he/she seeks the good arm. Fitness of an agent is the probability to know the good arm in the steady state of the agent system. In this model, we explicitly construct the unique Nash equilibrium state and show that the corresponding strategy for each agent is an evolutionarily stable strategy (ESS) in the sense of Thomas. It is shown that the fitness of an agent with ESS is superior to that of an asocial learner when the success probability of social learning is greater than a threshold determined from the probability of success of individual learning, the probability of change of state of the rMAB, and the number of agents. The ESS Nash equilibrium is a solution to Rogers' paradox.

From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov strategies in the iterated Prisoner's Dilemma.

PubMed

Menshikov, Ivan S; Shklover, Alexsandr V; Babkina, Tatiana S; Myagkov, Mikhail G

2017-01-01

In this research, the social behavior of the participants in a Prisoner's Dilemma laboratory game is explained on the basis of the quantal response equilibrium concept and the representation of the game in Markov strategies. In previous research, we demonstrated that social interaction during the experiment has a positive influence on cooperation, trust, and gratefulness. This research shows that the quantal response equilibrium concept agrees only with the results of experiments on cooperation in Prisoner's Dilemma prior to social interaction. However, quantal response equilibrium does not explain of participants' behavior after social interaction. As an alternative theoretical approach, an examination was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built a totally mixed Nash equilibrium in this game; the equilibrium agrees with the results of the experiments both before and after social interaction.

Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model.

PubMed

Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry

2018-01-05

The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P < 0.05). Hamsters treated with OCA showed a trend towards higher scavenger receptor Class B type I (SR-BI) and lower LDL-receptor hepatic protein expression. OCA reduced NAS score for inflammation (P < 0.01) and total NAS score, although not significantly. Compared to mouse and rat models, the DIN hamster replicates benefits and side effects of OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

High-fat, high-fructose, high-cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine.

PubMed

Panasevich, M R; Meers, G M; Linden, M A; Booth, F W; Perfield, J W; Fritsche, K L; Wankhade, Umesh D; Chintapalli, Sree V; Shankar, K; Ibdah, J A; Rector, R S

2018-01-01

Pediatric obesity and nonalcoholic steatohepatitis (NASH) are on the rise in industrialized countries, yet our ability to mechanistically examine this relationship is limited by the lack of a suitable higher animal models. Here, we examined the effects of high-fat, high-fructose corn syrup, high-cholesterol Western-style diet (WD)-induced obesity on NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine. Juvenile female Ossabaw swine (5 wk old) were fed WD (43.0% fat; 17.8% high-fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wk ( n = 6 each) or 36 wk ( n = 4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In addition, obese WD-fed pigs developed severe NASH, with hepatic steatosis, hepatocyte ballooning, inflammatory cell infiltration, and fibrosis after 16 wk, with further exacerbation of histological inflammation and fibrosis after 36 wk of WD feeding. WD feeding also resulted in robust cecal microbiota changes including increased relative abundances of families and genera in Proteobacteria ( P < 0.05) (i.e., Enterobacteriaceae, Succinivibrionaceae, and Succinivibrio) and LPS-containing Desulfovibrionaceae and Desulfovibrio and a greater ( P < 0.05) predicted microbial metabolic function for LPS biosynthesis, LPS biosynthesis proteins, and peptidoglycan synthesis compared with CON-fed pigs. Overall, juvenile Ossabaw swine fed a high-fat, high-fructose, high-cholesterol diet develop obesity and severe microbiota dysbiosis with a proinflammatory signature and a NASH phenotype directly relevant to the pediatric/adolescent and young adult population.

Foraging swarms as Nash equilibria of dynamic games.

PubMed

Özgüler, Arif Bülent; Yildiz, Aykut

2014-06-01

The question of whether foraging swarms can form as a result of a noncooperative game played by individuals is shown here to have an affirmative answer. A dynamic game played by N agents in 1-D motion is introduced and models, for instance, a foraging ant colony. Each agent controls its velocity to minimize its total work done in a finite time interval. The game is shown to have a unique Nash equilibrium under two different foraging location specifications, and both equilibria display many features of a foraging swarm behavior observed in biological swarms. Explicit expressions are derived for pairwise distances between individuals of the swarm, swarm size, and swarm center location during foraging.

Transforming the Ordinary into Extraordinary: Gary Nash and the Visions of History

ERIC Educational Resources Information Center

Vigilante, David

2009-01-01

Through his long career, Gary Nash has been a pioneer in opening the often-stuffy chambers of academia. He has shown a devotion to K-12 teachers throughout the nation and has ventured into their classrooms to observe, to teach, and, yes, to learn. It is all too rare for a noted historian, famous for his many seminal works, to roll up his sleeves…

A Differential Evolution Algorithm Based on Nikaido-Isoda Function for Solving Nash Equilibrium in Nonlinear Continuous Games

PubMed Central

He, Feng; Zhang, Wei; Zhang, Guoqiang

2016-01-01

A differential evolution algorithm for solving Nash equilibrium in nonlinear continuous games is presented in this paper, called NIDE (Nikaido-Isoda differential evolution). At each generation, parent and child strategy profiles are compared one by one pairwisely, adapting Nikaido-Isoda function as fitness function. In practice, the NE of nonlinear game model with cubic cost function and quadratic demand function is solved, and this method could also be applied to non-concave payoff functions. Moreover, the NIDE is compared with the existing Nash Domination Evolutionary Multiplayer Optimization (NDEMO), the result showed that NIDE was significantly better than NDEMO with less iterations and shorter running time. These numerical examples suggested that the NIDE method is potentially useful. PMID:27589229

Keeping Clinicians in Clinical Research: The Clinical Research/Reproductive Scientist Training Program

PubMed Central

Armstrong, Alicia Y.; DeCherney, Alan; Leppert, Phyllis; Rebar, Robert; Maddox, Yvonne T.

2009-01-01

In recent years the need for translational and clinical research has increased while the number of physicians involved in clinical research has diminished. There is clearly a need for formalized academic training in the quantitative and methodological principles of clinical research in reproductive medicine. The Clinical Research/Reproductive Scientist Training Program (CREST), a program supported by the National Institute of Child Health and Human Development, the Clinical Research Training Program (CRTP) at Duke University, and the American Society for Reproductive Medicine,(ASRM) meets this existing need. In addition, this program is specifically designed for physicians in private or academic clinical practice in reproductive medicine. Innovative programs such as CREST encourage the practicing physician to engage in clinical research while maintaining an active role in clinical practice. Participants in the program receive didactic on-line training from the CRTP, attend intensive weekend seminars at the National Institutes of Health (NIH) and CREST seminars at the annual meeting of ASRM. Successful participants in the program receive a Certificate in Clinical Research from the CRTP. The program’s goal is to provide practicing physicians with the tools and research credentials that will facilitate collaborations with investigators involved in large clinical trials. PMID:19144332

High prevalence of normal serum albumin in NASH patients with ascites: a retrospective analysis.

PubMed

Sourianarayanane, Achuthan; O'Shea, Robert S; Barnes, David S; McCullough, Arthur J

2013-06-01

Ascites usually occurs in the setting of end-stage liver disease and low serum albumin and is associated with increased mortality. However, some patients develop ascites despite normal serum albumin (NSA), when a higher portal pressure and/or enhanced renal sodium retention would be expected. This study investigated the relationship between the hepatic venous pressure gradient (HVPG) and serum albumin in ascitic patients with different etiologies of cirrhosis and mortality. Records of all patients with non-malignant ascites who underwent HVPG measurement from 2005 to 2009 were reviewed. One hundred and thirty-eight 138 patients met inclusion criteria; 18.8% had NSA. No difference in sodium excretion or diuretic use was noted in patients with and without NSA. NASH patients were more likely to have a NSA (34.2% vs 12.4%; P=0.001) as well as lower HVPG (15 vs 17.9 mmHg; P=0.009) compared to other etiologies. MELD and HVPG predicted overall survival. However, mortality did not differ by disease etiology, though NASH patients had lower CTP (7.6 vs 8.5; P<0.001) and MELD (15.6 vs 18.1; P=0.09) scores, particularly among patients who died. In patients with ascites and NSA, there were no increase in HVPG or urinary sodium retention. NASH patients with ascites had lower HVPG and a higher prevalence of NSA. They also had a higher mortality relative to MELD and CTP scores in other patients. In these patients, mechanisms other than portal and oncotic pressures and sodium retention play a role in ascites development, and increase mortality rate when complicated by low albumin. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).

PubMed

Jha, Pooja; Knopf, Astrid; Koefeler, Harald; Mueller, Michaela; Lackner, Carolin; Hoefler, Gerald; Claudel, Thierry; Trauner, Michael

2014-07-01

Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation. This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury. Copyright © 2014. Published by Elsevier B.V.

From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov strategies in the iterated Prisoner’s Dilemma

PubMed Central

Myagkov, Mikhail G.

2017-01-01

In this research, the social behavior of the participants in a Prisoner's Dilemma laboratory game is explained on the basis of the quantal response equilibrium concept and the representation of the game in Markov strategies. In previous research, we demonstrated that social interaction during the experiment has a positive influence on cooperation, trust, and gratefulness. This research shows that the quantal response equilibrium concept agrees only with the results of experiments on cooperation in Prisoner’s Dilemma prior to social interaction. However, quantal response equilibrium does not explain of participants’ behavior after social interaction. As an alternative theoretical approach, an examination was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built a totally mixed Nash equilibrium in this game; the equilibrium agrees with the results of the experiments both before and after social interaction. PMID:29190280

Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPAR{alpha} with clofibrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.

2008-08-01

The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPAR{alpha} via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. {sup 14}C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAPmore » hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by {sup 3}H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPAR{alpha} was tested. PPAR{alpha} was downregulated in NASH. To investigate whether downregulation of PPAR{alpha} in NASH is the critical mechanism of compromised liver tissue repair, PPAR{alpha} was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPAR{alpha} expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity.« less

Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

PubMed

Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

2017-04-01

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (P<0.05). Moreover, hepatic total and free cholesterol of CDHF-BCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

Case-control and cohort studies are invaluable research tools and provide the strongest feasible research designs for addressing some questions. Case-control studies usually involve retrospective data collection. Cohort studies can involve retrospective, ambidirectional, or prospective data collection. Observational studies are subject to errors attributable to selection bias, confounding, measurement bias, and reverse causation-in addition to errors of chance. Confounding can be statistically controlled to the extent that potential factors are known and accurately measured, but, in practice, bias and unknown confounders usually remain additional potential sources of error, often of unknown magnitude and clinical impact. Causality-the most clinically useful relation between exposure and outcome-can rarely be definitively determined from observational studies because intentional, controlled manipulations of exposures are not involved. In this article, we review several types of observational clinical research: case series, comparative case-control and cohort studies, and hybrid designs in which case-control analyses are performed on selected members of cohorts. We also discuss the analytic issues that arise when groups to be compared in an observational study, such as patients receiving different therapies, are not comparable in other respects.

Cardiovascular risk across the histological spectrum and the clinical manifestations of non-alcoholic fatty liver disease: An update

PubMed Central

Athyros, Vasilios G; Tziomalos, Konstantinos; Katsiki, Niki; Doumas, Michael; Karagiannis, Asterios; Mikhailidis, Dimitri P

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is considered to be an independent cardiovascular disease (CVD) risk factor. However, simple steatosis has a benign clinical course without excess mortality. In contrast, the advanced form of NAFLD, non-alcoholic steatohepatitis (NASH) with liver fibrosis increases mortality by approximately 70%, due to an increase in CVD mortality by approximately 300%. Chronic kidney disease (CKD) may be caused by NAFLD/NASH and it substantially increases CVD risk, especially in the presence of type 2 diabetes mellitus. Moreover, CKD may trigger NAFLD/NASH deterioration in a vicious cycle. NAFLD/NASH is also related to increased arterial stiffness (AS), an independent CVD risk factor that further raises CVD risk. Diagnosis of advanced liver fibrosis (mainly by simple non-invasive tests), CKD, and increased AS should be made early in the course of NAFLD and treated appropriately. Lifestyle measures and statin treatment may help resolve NAFLD/NASH and beneficially affect the CVD risk factors mentioned above. PMID:26078558

Research leadership: should clinical directors be distinguished researchers?

PubMed

Allison, Stephen; Goodall, Amanda H; Bastiampillai, Tarun

2016-06-01

Clinical directors established research-led healthcare by combining research, teaching and clinical excellence within the teaching hospitals. This research culture created high clinical standards, which benefited patients, the workforce and healthcare organisations. The current paper explores this research leadership role for clinical directors. It reviews studies arising from the theory of expert leadership, which focuses on the relationship between a leader's core knowledge and organisational performance. More specifically, we examine the expert leader's research track record, the associations with their organisation's performance, and the influence of research activity on clinical excellence. Distinguished researchers still lead the most prestigious teaching hospitals and the most trusted departments of psychiatry in the United States where the clinical directorate structure originated. It is also known that good scholars can improve research output when appointed to leadership positions. This suggests that the clinical director's research track record should be a consideration at a time when research is being embedded in Australia's local health networks. A clinical director's leadership may influence the research performance of their department and contribute to the quality of mental healthcare. © The Royal Australian and New Zealand College of Psychiatrists 2015.

75 FR 41518 - Match-E-Be-Nash-She-Wish (Gun Lake) Tribe Liquor Control Ordinance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... ethyl alcohol, hydrated oxide of ethyl, or spirit of wine, commonly produced by the fermentation or... benefit of the Tribe. (j) ``Tribe'' means the Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians of... and wine shall be purchased from distributors licensed by the Michigan Liquor Control Commission. (f...

Navigable networks as Nash equilibria of navigation games.

PubMed

Gulyás, András; Bíró, József J; Kőrösi, Attila; Rétvári, Gábor; Krioukov, Dmitri

2015-07-03

Common sense suggests that networks are not random mazes of purposeless connections, but that these connections are organized so that networks can perform their functions well. One function common to many networks is targeted transport or navigation. Here, using game theory, we show that minimalistic networks designed to maximize the navigation efficiency at minimal cost share basic structural properties with real networks. These idealistic networks are Nash equilibria of a network construction game whose purpose is to find an optimal trade-off between the network cost and navigability. We show that these skeletons are present in the Internet, metabolic, English word, US airport, Hungarian road networks, and in a structural network of the human brain. The knowledge of these skeletons allows one to identify the minimal number of edges, by altering which one can efficiently improve or paralyse navigation in the network.

Reorganizing the General Clinical Research Center to improve the clinical and translational research enterprise.

PubMed

Allen, David; Ripley, Elizabeth; Coe, Antoinette; Clore, John

2013-12-01

In 2010, Virginia Commonwealth University (VCU) was granted a Clinical and Translational Science Award which prompted reorganization and expansion of their clinical research infrastructure. A case study approach is used to describe the implementation of a business and cost recovery model for clinical and translational research and the transformation of VCU's General Clinical Research Center and Clinical Trials Office to a combined Clinical Research Services entity. We outline the use of a Plan, Do, Study, Act cycle that facilitated a thoughtful transition process, which included the identification of required changes and cost recovery processes for implementation. Through this process, the VCU Center for Clinical and Translational Research improved efficiency, increased revenue recovered, reduced costs, and brought a high level of fiscal responsibility through financial reporting.

Navigable networks as Nash equilibria of navigation games

PubMed Central

Gulyás, András; Bíró, József J.; Kőrösi, Attila; Rétvári, Gábor; Krioukov, Dmitri

2015-01-01

Common sense suggests that networks are not random mazes of purposeless connections, but that these connections are organized so that networks can perform their functions well. One function common to many networks is targeted transport or navigation. Here, using game theory, we show that minimalistic networks designed to maximize the navigation efficiency at minimal cost share basic structural properties with real networks. These idealistic networks are Nash equilibria of a network construction game whose purpose is to find an optimal trade-off between the network cost and navigability. We show that these skeletons are present in the Internet, metabolic, English word, US airport, Hungarian road networks, and in a structural network of the human brain. The knowledge of these skeletons allows one to identify the minimal number of edges, by altering which one can efficiently improve or paralyse navigation in the network. PMID:26138277

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

PubMed

Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

Clinical Research: A Globalized Network

PubMed Central

Richter, Trevor A.

2014-01-01

Clinical research has become increasingly globalized, but the extent of globalization has not been assessed. To describe the globalization of clinical research, we used all (n = 13,208) multinational trials registered at ClinicalTrials.gov to analyzed geographic connections among individual countries. Our findings indicate that 95% (n = 185) of all countries worldwide have participated in multinational clinical research. Growth in the globalization of clinical research peaked in 2009, suggesting that the global infrastructure that supports clinical research might have reached its maximum capacity. Growth in the globalization of clinical research is attributable to increased involvement of non-traditional markets, particularly in South America and Asia. Nevertheless, Europe is the most highly interconnected geographic region (60.64% of global connections), and collectively, Europe, North America, and Asia comprise more than 85% of all global connections. Therefore, while the expansion of clinical trials into non-traditional markets has increased over the last 20 years and connects countries across the globe, traditional markets still dominate multinational clinical research, which appears to have reached a maximum global capacity. PMID:25517976

Iterative algorithms for computing the feedback Nash equilibrium point for positive systems

NASA Astrophysics Data System (ADS)

Ivanov, I.; Imsland, Lars; Bogdanova, B.

2017-03-01

The paper studies N-player linear quadratic differential games on an infinite time horizon with deterministic feedback information structure. It introduces two iterative methods (the Newton method as well as its accelerated modification) in order to compute the stabilising solution of a set of generalised algebraic Riccati equations. The latter is related to the Nash equilibrium point of the considered game model. Moreover, we derive the sufficient conditions for convergence of the proposed methods. Finally, we discuss two numerical examples so as to illustrate the performance of both of the algorithms.

Strain dependence of diet-induced NASH and liver fibrosis in obese mice is linked to diabetes and inflammatory phenotype.

PubMed

Farrell, Geoffrey C; Mridha, Auvro R; Yeh, Matthew M; Arsov, Todor; Van Rooyen, Derrick M; Brooling, John; Nguyen, Tori; Heydet, Deborah; Delghingaro-Augusto, Viviane; Nolan, Christopher J; Shackel, Nicholas A; McLennan, Susan V; Teoh, Narci C; Larter, Claire Z

2014-08-01

Obese Alms1 mutant (foz/foz) NOD.B10 mice develop diabetes and fibrotic NASH when fed high-fat(HF) diet. To establish whether diabetes or obesity is more closely associated with NASH fibrosis, we compared diabetic foz/foz C57BL6/J with non-diabetic foz/foz BALB/c mice. We also determined hepatic cytokines, growth factors and related profibrotic pathways. Male and female foz/foz BALB/c and C57BL6/J mice were fed HF or chow for 24 weeks before determining metabolic indices, liver injury, cytokines, growth factors, pathology/fibrosis and matrix deposition pathways. All foz/foz mice were obese. Hepatomegaly, hyperinsulinemia, hyperglycaemia and hypoadiponectinaemia occurred only in foz/foz C57BL6/J mice, whereas foz/foz BALB/c formed more adipose. Serum ALT, steatosis, ballooning, liver inflammation and NAFLD activity score were worse in C57BL6/J mice. In HF-fed mice, fibrosis was severe in foz/foz C57BL6/J, appreciable in WT C57BL6/J, but absent in foz/foz BALB/c mice. Hepatic mRNA expression of TNF-α, IL-12, IL-4, IL-10 was increased (but not IFN-γ, IL-1β, IL-17A), and IL-4:IFN-γ ratio (indicating Th-2 predominance) was higher in HF-fed foz/foz C57BL6/J than BALB/c mice. In livers of HF-fed foz/foz C57BL6/J mice, TGF-β was unaltered but PDGFα and CTGF were increased in association with enhanced α-SMA, CD147and MMP activity. In mice with equivalent genetic/dietary obesity, NASH development is linked to strain differences in hyperinsulinaemia and hyperglycaemia inversely related to lipid partitioning between adipose and liver. Diabetes-mediated CTGF-regulation of MMPs as well as cytokines/growth factors (Th-2 cytokine predominant, PDGFα, not TGF-β) mobilized in the resultant hepatic necroinflammatory change may contribute to strain differences in NASH fibrosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease.

PubMed

Dietrich, Christoph G; Rau, Monika; Jahn, Daniel; Geier, Andreas

2017-06-01

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications. Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD. Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.

59th Clinical Research Division Research Day Briefing

DTIC Science & Technology

2016-10-27

59th Medical Wing a ’r’. ’ ( ~ ~ ’ ""· ~... ’ .,,,. lS! lflof!’~l. 59th Clinical Research Division Research Day Briefing Colonel Linda Steel...oversight and guidance to researchers in the development, performance, and dissemination of clinical investigations. CRD directly supports wing...Clinical Investigation Support 2. Training 3. Support of RDT&E protocols 4. Research Subject Protection • Human Subjects: IRS - Institutional

Evaluation of Clinical Research Training Programs Using the Clinical Research Appraisal Inventory

PubMed Central

Lipira, Lauren; Jeffe, Donna B.; Krauss, Melissa; Garbutt, Jane; Piccirillo, Jay; Evanoff, Bradley; Fraser, Victoria

2010-01-01

Abstract The purpose of this study was to measure change in clinical research self‐efficacy after participating in KL2, postdoctoral and predoctoral clinical research training programs at Washington University School of Medicine. We surveyed program participants using a 76‐item version of the Clinical Research Appraisal Inventory (CRAI). Principal components analysis (PCA) examined the CRAI’s underlying factor structure; Cronbach alpha measured the internal consistency of items on each subscale and the overall CRAI. CRAI score changes from baseline to 1‐year follow‐up were assessed using repeated‐measures analysis of variance. All 29 KL2, 47 postdoctoral, and 31 TL1 scholars enrolled 2006–2009 (mean age 31.6 years, range 22–44; 59.6% female; 65.4% white) completed baseline surveys. Of these participants, 22 KL2, 17 postdoctoral, and 21 TL1 scholars completed the 1‐year follow‐up assessment. PCA resulted in a seven‐factor solution with 69 items (alphas > 0.849 for each subscale and 69‐item CRAI). Significant improvements at 1‐year follow‐up were observed across all programs for Study Design/Data Analysis (p= .016), Interpreting/Reporting/Presenting (p= .034), and overall CRAI (p= .050). Differences between programs were observed for all but one subscale (each p < .05). Clinical research self‐efficacy increased 1 year after clinical research training. Whether this short‐term outcome correlates with long‐term clinical research productivity, requires further study. Clin Trans Sci 2010; Volume 3: 243–248. PMID:21442017

Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for...AND SUBTITLE Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

PubMed Central

Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

2013-01-01

Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

High-fat, high-fructose, high-cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine

USDA-ARS?s Scientific Manuscript database

Pediatric obesity and nonalcoholic steatohepatitis (NASH) are on the rise in industrialized countries, yet our ability to mechanistically examine this relationship is limited by the lack of a suitable higher animal models. Here, we examined the effects of high-fat, high-fructose corn syrup, high-cho...

Spontaneous Time Symmetry Breaking in System with Mixed Strategy Nash Equilibrium: Evidences in Experimental Economics Data

NASA Astrophysics Data System (ADS)

Wang, Zhijian; Xu, Bin; Zhejiang Collaboration

2011-03-01

In social science, laboratory experiment with human subjects' interaction is a standard test-bed for studying social processes in micro level. Usually, as in physics, the processes near equilibrium are suggested as stochastic processes with time-reversal symmetry (TRS). To the best of our knowledge, near equilibrium, the breaking time symmetry, as well as the existence of robust time anti-symmetry processes, has not been reported clearly in experimental economics till now. By employing Markov transition method to analysis the data from human subject 2x2 Games with wide parameters and mixed Nash equilibrium, we study the time symmetry of the social interaction process near Nash equilibrium. We find that, the time symmetry is broken, and there exists a robust time anti-symmetry processes. We also report the weight of the time anti-symmetry processes in the total processes of each the games. Evidences in laboratory marketing experiments, at the same time, are provided as one-dimension cases. In these cases, time anti-symmetry cycles can also be captured. The proposition of time anti-symmetry processes is small, but the cycles are distinguishable.

Danish research-active clinical nurses overcome barriers in research utilization.

PubMed

Adamsen, Lis; Larsen, Kristian; Bjerregaard, Lene; Madsen, Jan K

2003-03-01

The aim of this study was to examine whether there was a difference between clinical nurses who were research-active, and clinical nurses who were nonresearch-active in utilization of research. A further aim was to identify the most significant barriers faced by a group of Danish clinical nurses in their use of research. Discrepancy between the improved quality of research results and the lack of implementing them was the starting point for a series of studies which showed the types of barriers clinical nurses found especially cumbersome when applying the research results of other researchers. This study investigates whether the clinical nurses' own engagement in research had any impact on their perception of research utilization. The study had an exploratory and descriptive design. Seventy-nine Danish clinical nurses participated and semi-structured interviewing was used as the research method. There was a statistically significant difference between the research-active and nonresearch-active nurses on various variables. The study showed that, to a larger extent, research-active nurses used evidence-based knowledge and were generally more internationally orientated. Furthermore, two important barriers for research utilization were identified by all 79 clinical nurses included in the study, i.e. 90% of the nurses explained that the quantity of research results was overwhelming, and 75% of them found that they were unable to evaluate the quality of the research. Clinical nurses, who were research-active themselves, experienced more success in overcoming some of the barriers, which existed in applying research to practice. The research potential found amongst clinical nurses in Denmark needed to be further supported through training and guidance in research methodology, establishing introductory stipends and part-time research positions. By doing so, some of the barriers affecting research utilization and the so-called theory-practice gap might be reduced. Further

Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science.

PubMed

Siddiqui, Mohammad Shadab; Harrison, Stephen A; Abdelmalek, Manal F; Anstee, Quentin M; Bedossa, Pierre; Castera, Laurent; Dimick-Santos, Lara; Friedman, Scott L; Greene, Katherine; Kleiner, David E; Megnien, Sophie; Neuschwander-Tetri, Brent A; Ratziu, Vlad; Schabel, Elmer; Miller, Veronica; Sanyal, Arun J

2018-05-01

Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001-2012). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

Quantitative imaging of fibrotic and morphological changes in liver of non-alcoholic steatohepatitis (NASH) model mice by second harmonic generation (SHG) and auto-fluorescence (AF) imaging using two-photon excitation microscopy (TPEM).

PubMed

Yamamoto, Shin; Oshima, Yusuke; Saitou, Takashi; Watanabe, Takao; Miyake, Teruki; Yoshida, Osamu; Tokumoto, Yoshio; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Imamura, Takeshi

2016-12-01

Non-alcoholic steatohepatitis (NASH) is a common liver disorder caused by fatty liver. Because NASH is associated with fibrotic and morphological changes in liver tissue, a direct imaging technique is required for accurate staging of liver tissue. For this purpose, in this study we took advantage of two label-free optical imaging techniques, second harmonic generation (SHG) and auto-fluorescence (AF), using two-photon excitation microscopy (TPEM). Three-dimensional ex vivo imaging of tissues from NASH model mice, followed by image processing, revealed that SHG and AF are sufficient to quantitatively characterize the hepatic capsule at an early stage and parenchymal morphologies associated with liver disease progression, respectively.

Overview of clinical research design.

PubMed

Hartung, Daniel M; Touchette, Daniel

2009-02-15

Basic concepts and terminology of clinical research design are presented for new clinical investigators. Clinical research, research involving human subjects, can be described as either observational or experimental. The findings of all clinical research can be threatened by issues of bias and confounding. Biases are systematic errors in how study subjects are selected or measured, which result in false inferences. Confounding is a distortion in findings that is attributable to mixing variable effects. Uncontrolled observation research is generally more prone to bias and confounding than experimental research. Observational research includes designs such as the cohort study, case-control study, and cross-sectional study, while experimental research typically involves a randomized controlled trial (RCT). The cohort study, which includes the RCT, defines subject allocation on the basis of exposure interest (e.g., drug, disease-management program) and follows the patients to assess the outcomes. The case-control study uses the primary outcome of interest (e.g., adverse event) to define subject allocation, and different exposures are assessed in a retrospective manner. Cross-sectional research evaluates both exposure and outcome concurrently. Each of these design methods possesses different strengths and weaknesses in answering research questions, as well as underlying many study subtypes. While experimental research is the strongest method for establishing causality, it can be difficult to accomplish under many scenarios. Observational clinical research offers many design alternatives that may be appropriate if planned and executed carefully.

Prostate Cancer Clinical Consortium Clinical Research Site:Targeted Therapies

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-2-0159 TITLE: Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies PRINCIPAL INVESTIGATOR...Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies 5b. GRANT NUMBER... therapy resistance/sensitivity, identification of new therapeutic targets through high quality genomic analyses, providing access to the highest quality

NIH Clinical Research Trials and You

MedlinePlus

... Record Research & Training Medical Research Initiatives Science Highlights Science Education Research in NIH Labs & Clinics Training Opportunities Library Resources Research Resources Clinical Research Resources Safety, Regulation ...

The Ontology of Clinical Research (OCRe): An Informatics Foundation for the Science of Clinical Research

PubMed Central

Sim, Ida; Tu, Samson W.; Carini, Simona; Lehmann, Harold P.; Pollock, Brad H.; Peleg, Mor; Wittkowski, Knut M.

2013-01-01

To date, the scientific process for generating, interpreting, and applying knowledge has received less informatics attention than operational processes for conducting clinical studies. The activities of these scientific processes — the science of clinical research — are centered on the study protocol, which is the abstract representation of the scientific design of a clinical study. The Ontology of Clinical Research (OCRe) is an OWL 2 model of the entities and relationships of study design protocols for the purpose of computationally supporting the design and analysis of human studies. OCRe’s modeling is independent of any specific study design or clinical domain. It includes a study design typology and a specialized module called ERGO Annotation for capturing the meaning of eligibility criteria. In this paper, we describe the key informatics use cases of each phase of a study’s scientific lifecycle, present OCRe and the principles behind its modeling, and describe applications of OCRe and associated technologies to a range of clinical research use cases. OCRe captures the central semantics that underlies the scientific processes of clinical research and can serve as an informatics foundation for supporting the entire range of knowledge activities that constitute the science of clinical research. PMID:24239612

Critical issues in clinical periodontal research.

PubMed

Preshaw, Philip M

2012-06-01

As periodontal researchers and clinicians, we are challenged every day to make decisions relating to the clinical management of our patients and about how best to conduct clinical periodontal research. This volume of Periodontology 2000 addresses some of the critical issues in contemporary clinical periodontics and periodontal research that are of direct relevance to clinicians, researchers, teachers and students. The 11 review articles in this volume of Periodontology 2000 focus on aspects of periodontal research methodology and clinical periodontology. In terms of research methodology, the articles aim to inform the reader on topics relating to randomized controlled trials in periodontal research, evidence-based dentistry, calibration of clinical examiners and statistics relevant to periodontal research. The clinical periodontology articles address issues relating to decisions on retaining periodontally compromised teeth or replacing them with implants, periodontal management in the patient with osteoporosis, surgical approaches for root coverage and the emerging science of advanced regenerative technologies, including the use of stem cells, for periodontal regeneration. It is hoped that these critical reviews will address many of the dilemmas that confront us on a regular basis and provide practical guidance to those engaged in both clinical periodontology and clinical periodontal research. © 2012 John Wiley & Sons A/S.

[Support Team for Investigator-Initiated Clinical Research].

PubMed

Fujii, Hisako

2017-07-01

Investigator-initiated clinical research is that in which investigators plan and carry out their own clinical research in academia. For large-scale clinical research, a team should be organized and implemented. This team should include investigators and supporting staff, who will promote smooth research performance by fulfilling their respective roles. The supporting staff should include project managers, administrative personnel, billing personnel, data managers, and clinical research coordinators. In this article, I will present the current status of clinical research support and introduce the research organization of the Dominantly Inherited Alzheimer Network (DIAN) study, an investigator-initiated international clinical research study, with particular emphasis on the role of the project management staff and clinical research coordinators.

[ECRIN (European clinical research infrastructures network), a pan-European infrastructure for clinical research].

PubMed

Demotes-Mainard, Jacques

2010-12-01

Clinical research plays a key role both in the development of innovative health products and in the optimisation of medical strategies, leading to evidence-based practice and healthcare cost containment. ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific providing services to multinational. Servicing of multinational trials started during the preparatory phase, and ECRIN has applied for ERIC status in 2011. In parallel, ECRIN has also proposed an FP7 integrating activity project to further develop, upgrade and expand the ECRIN infrastructure built up during the past FP6 and FP7 projects, facilitating an efficient organization of clinical research in Europe, with ECRIN developing generic tools and providing generic services for multinational studies, and supporting the construction of pan-European disease-oriented networks that will in turn act as ECRIN users. This organization will improve Europe's attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens. The three medical areas supported in this project (rare diseases, medical devices, and nutrition) will serve as pilots for other biomedical research fields. By creating a single area for clinical research in Europe, this structure will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of research and educational capacities, tackling the major societal challenges (starting with healthy aging), and removing barriers to bringing ideas to the market.

Research Areas - Clinical Trials

Cancer.gov

Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

Mixed-strategy Nash equilibrium for a discontinuous symmetric N-player game

NASA Astrophysics Data System (ADS)

Hilhorst, H. J.; Appert-Rolland, C.

2018-03-01

We consider a game in which each player must find a compromise between more daring strategies that carry a high risk for him to be eliminated, and more cautious ones that, however, reduce his final score. For two symmetric players this game was originally formulated in 1961 by Dresher, who modeled a duel between two opponents. The game has also been of interest in the description of athletic competitions. We extend here the two-player game to an arbitrary number N of symmetric players. We show that there is a mixed-strategy Nash equilibrium and find its exact analytic expression, which we analyze in particular in the limit of large N, where mean-field behavior occurs. The original game with N  =  2 arises as a singular limit of the general case.

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study

PubMed Central

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-01-01

Objectives Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. Setting The setting for this research was a major academic institution in Beijing, China. Participants The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Methods Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Results Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. Conclusion These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate

Clinical Research Nurse | Center for Cancer Research

Cancer.gov

We are looking for a Research Nurse to join our women’s malignancies clinical team to help us manage the care of patients participating in clinical trials. Duties include, but are not limited to, collection and reporting of clinical data; reporting adverse events; filing amendments and regulatory documents; consenting, screening and collecting samples from patients and

Ethical aspects of clinical research with minors.

PubMed

Bos, Wendy; Tromp, Krista; Tibboel, Dick; Pinxten, Wim

2013-07-01

Over the past decades, clinical research has increasingly been subjected to ethical requirements and legal regulation. The specific focus of ethical and legal frameworks on competent adults (which serve as the paradigmatic research subject), however, has created an ambivalent attitude towards pediatric clinical research. On one hand, minors are regarded as a vulnerable population that deserves additional protection against the risks and burdens involved in clinical research. On the other hand, the population of minors should not be denied (or not get timely) access to the benefits of clinical research. In this paper, we will explore the legal regulation and ethical guidance that currently governs pediatric clinical research in the European Union and discuss the future challenges in this field. In addition, we will discuss major ethical concerns in pediatric clinical research, with a focus on the acceptability of research risks and the informed consent process. In the discussion, we will address key concerns in both regulating pediatric clinical research and implementing ethical and legal requirement in the actual pediatric research conduct.

How novice, skilled and advanced clinical researchers include variables in a case report form for clinical research: a qualitative study.

PubMed

Chu, Hongling; Zeng, Lin; Fetters, Micheal D; Li, Nan; Tao, Liyuan; Shi, Yanyan; Zhang, Hua; Wang, Xiaoxiao; Li, Fengwei; Zhao, Yiming

2017-09-18

Despite varying degrees in research training, most academic clinicians are expected to conduct clinical research. The objective of this research was to understand how clinical researchers of different skill levels include variables in a case report form for their clinical research. The setting for this research was a major academic institution in Beijing, China. The target population was clinical researchers with three levels of experience, namely, limited clinical research experience, clinicians with rich clinical research experience and clinical research experts. Using a qualitative approach, we conducted 13 individual interviews (face to face) and one group interview (n=4) with clinical researchers from June to September 2016. Based on maximum variation sampling to identify researchers with three levels of research experience: eight clinicians with limited clinical research experience, five clinicians with rich clinical research experience and four clinical research experts. These 17 researchers had diverse hospital-based medical specialties and or specialisation in clinical research. Our analysis yields a typology of three processes developing a case report form that varies according to research experience level. Novice clinician researchers often have an incomplete protocol or none at all, and conduct data collection and publication based on a general framework. Experienced clinician researchers include variables in the case report form based on previous experience with attention to including domains or items at risk for omission and by eliminating unnecessary variables. Expert researchers consider comprehensively in advance data collection and implementation needs and plan accordingly. These results illustrate increasing levels of sophistication in research planning that increase sophistication in selection for variables in the case report form. These findings suggest that novice and intermediate-level researchers could benefit by emulating the comprehensive

The Mathematics of Aggregation, Interdependence, Organizations and Systems of Nash Equilibria (NE): A Replacement for Game Theory

DTIC Science & Technology

2011-06-01

there a free-market economist in the House?, American Journal of Economics and Sociology, 66(2): 309-334. Jasny, B. R., Zahn, L.M., & Marshall, E...1   The Mathematics of Aggregation, Interdependence, Organizations and Systems of Nash equilibria (NE): A replacement for Game Theory...level data to group, organization and systems levels, making it one of social science’s biggest challenges, if not the most important (Giles, 2011). For

Clinical Research Nursing: A Critical Resource in the National Research Enterprise

PubMed Central

Hastings, Clare E.; Fisher, Cheryl A.; McCabe, Margaret A.

2012-01-01

Translational clinical research has emerged as an important priority for the national research enterprise, with a clearly stated mandate to deliver prevention strategies, treatments and cures based on scientific innovations faster to the public. Within this national effort, a lack of consensus persists concerning the need for clinical nurses with expertise and specialized training in study implementation and the delivery of care to research participants. This paper reviews efforts to define and document the role of practicing nurses in implementing studies and coordinating clinical research in a variety of clinical settings and differentiates this clinical role from the role of nurses as scientists and principal investigators. We propose an agenda for building evidence that having nurses provide and coordinate study treatments and procedures can potentially improve research efficiency, participant safety, and the quality of research data. We also provide recommendations for the development of the emerging specialty of clinical research nursing. PMID:22172370

Individual researcher liability for clinical research on humans.

PubMed

Miller, Ruth K

2003-01-01

Despite international guidelines and federal regulations, a recent rash of problems in clinical trials have highlighted weaknesses in the oversight process. The federal regulatory system depends on self-policing by researchers and institutions. Because the existing system is overworked, applying common law forms of liability to clinical researchers may encourage improvements in this self-regulation. While research necessarily involves uncertainties, researchers have the greatest direct control over the implementation of the research protocol and the most extensive direct contact with subjects, and must bear corresponding responsibility for acts which fall below the standard of care. This paper argues that the existing FDA patient protections should be adopted as the standards of care for researchers. It examines the possible application of negligence, negligence per se, and fraud and misrepresentation claims against researchers.

Decline of clinical research in academic medical centers.

PubMed

Meador, Kimford J

2015-09-29

Marked changes in US medical school funding began in the 1960s with progressively increasing revenues from clinical services. The growth of clinical revenues slowed in the mid-1990s, creating a funding crisis for US academic health care centers, who responded by having their faculty increase their clinical duties at the expense of research activities. Surveys document the resultant stresses on the academic clinician researcher. The NIH provides greater funding for basic and translational research than for clinical research, and the new Patient-Centered Outcomes Research Institute is inadequately funded to address the scope of needed clinical research. An increasing portion of clinical research is funded by industry, which leaves many important clinical issues unaddressed. There is an inadequate supply of skilled clinical researchers and a lack of external support for clinical research. The impact on the academic environment in university medical centers is especially severe on young faculty, who have a shrinking potential to achieve successful academic careers. National health care research funding policies should encourage the right balance of life-science investigations. Medical universities need to improve and highlight education on clinical research for students, residents, fellows, and young faculty. Medical universities also need to provide appropriate incentives for clinical research. Without training to ensure an adequate supply of skilled clinical researchers and a method to adequately fund clinical research, discoveries from basic and translational research cannot be clinically tested and affect patient care. Thus, many clinical problems will continue to be evaluated and treated with inadequate or even absent evidence-based knowledge. © 2015 American Academy of Neurology.

Decline of clinical research in academic medical centers

PubMed Central

2015-01-01

Marked changes in US medical school funding began in the 1960s with progressively increasing revenues from clinical services. The growth of clinical revenues slowed in the mid-1990s, creating a funding crisis for US academic health care centers, who responded by having their faculty increase their clinical duties at the expense of research activities. Surveys document the resultant stresses on the academic clinician researcher. The NIH provides greater funding for basic and translational research than for clinical research, and the new Patient-Centered Outcomes Research Institute is inadequately funded to address the scope of needed clinical research. An increasing portion of clinical research is funded by industry, which leaves many important clinical issues unaddressed. There is an inadequate supply of skilled clinical researchers and a lack of external support for clinical research. The impact on the academic environment in university medical centers is especially severe on young faculty, who have a shrinking potential to achieve successful academic careers. National health care research funding policies should encourage the right balance of life-science investigations. Medical universities need to improve and highlight education on clinical research for students, residents, fellows, and young faculty. Medical universities also need to provide appropriate incentives for clinical research. Without training to ensure an adequate supply of skilled clinical researchers and a method to adequately fund clinical research, discoveries from basic and translational research cannot be clinically tested and affect patient care. Thus, many clinical problems will continue to be evaluated and treated with inadequate or even absent evidence-based knowledge. PMID:26156509

Research-active clinical nurses: against all odds.

PubMed

Siedlecki, Sandra L; Albert, Nancy M

2017-03-01

To develop a theoretical understanding of factors that impact decisions of clinical nurses to conduct a research study. Only a small percentage of all nurses are research-active and even fewer clinical nurses are research-active. Several researchers have explored barriers to research activity by clinical nurses, but few have examined why, in spite of all odds, some clinical nurses are research-active. As the purpose of this study was to develop a theoretical understanding of the research-active nurse, a grounded theory approach was used. The sample interviewed for this study consisted of registered nurses (n = 26) who worked in a hospital or ambulatory setting, had daily direct patient contact and had participated as principal investigator on at least one completed clinical nursing research study that was not in fulfilment of an educational requirement. The interviews were digitally recorded and analysed by two researchers using the constant comparative method. The findings from this study suggest that the conduct of research by clinical nurses was the direct result of a clinical trigger, characteristics and beliefs of the nurse about research and their role in generating knowledge, and the presence of support conditions, such as a research mentor. Clinical nurses can and do conduct research, in spite of constraints due to a lack of time, money and/or knowledge, if they have access to research mentors and are practising in a research-supportive environment. Nurses at the bedside are in a unique position to identify problems most in need of solutions. Findings from this study provide a foundation upon which to develop and test various programmes that seek to increase the number of clinical nurses who are research-active. © 2016 John Wiley & Sons Ltd.

American Society of Clinical Oncology policy statement: oversight of clinical research.

PubMed

2003-06-15

Well-publicized lapses in the review or implementation of clinical research studies have raised public questions about the integrity of the clinical research process. Public trust in the integrity of research is critical not only for funding and participation in clinical trials but also for confidence in the treatments that result from the trials. The questions raised by these unfortunate cases pose an important opportunity to reassess the clinical trials oversight system to ensure the integrity of clinical research and the safety of those who enroll in clinical trials. Since its inception, the American Society of Clinical Oncology (ASCO) has worked for the advancement of cancer treatments through clinical research and to help patients gain prompt access to scientifically excellent and ethically unimpeachable clinical trials. As an extension of its mission, ASCO is affirming with this policy statement the critical importance of a robust review and oversight system to ensure that clinical trials participants give fully informed consent and that their safety is a top priority. Ensuring the integrity of research cannot be stressed enough because of its seminal connection to the advancement of clinical cancer treatment. The overall goal of this policy is to enhance public trust in the cancer clinical trials process. To achieve this, the following elements are essential: 1. Ensure safety precautions for clinical trial participants and their fully informed consent. 2. Ensure the validity and integrity of scientific research. 3. Enhance the educational training of clinical scientists and research staff to ensure the highest standards of research conduct. 4. Promote accountability and responsibility among all those involved in clinical research (not just those serving on institutional review boards [IRBs], but also institutional officials, researchers, sponsors, and participants) and ensure support for an effective oversight process. 5. Enhance the professional and public

Improvement of Clinical Skills through Pharmaceutical Education and Clinical Research.

PubMed

Ishizaki, Junko

2017-01-01

Professors and teaching staff in the field of pharmaceutical sciences should devote themselves to staying abreast of relevant education and research. Similarly those in clinical pharmacies should contribute to the advancement of pharmaceutical research and the development of next generation pharmacists and pharmaceuticals. It is thought that those who work in clinical pharmacies should improve their own skills and expertise in problem-finding and -solving, i.e., "clinical skills". They should be keen to learn new standard treatments based on the latest drug information, and should try to be in a position where collecting clinical information is readily possible. In the case of pharmacists in hospitals and pharmacies, they are able to aim at improving their clinical skills simply through performing their pharmaceutical duties. On the other hand, when a pharmaceutical educator aims to improve clinical skills at a level comparable to those of clinical pharmacists, it is necessary to devote or set aside considerable time for pharmacist duties, in addition to teaching, which may result in a shortage of time for hands-on clinical practice and/or in a decline in the quality of education and research. This could be a nightmare for teaching staff in clinical pharmacy who aim to take part in such activities. Nonetheless, I believe that teaching staff in the clinical pharmacy area could improve his/her clinical skills through actively engaging in education and research. In this review, I would like to introduce topics on such possibilities from my own experiences.

Qualitative analysis of clinical research coordinators' role in phase I cancer clinical trials.

PubMed

Fujiwara, Noriko; Ochiai, Ryota; Shirai, Yuki; Saito, Yuko; Nagamura, Fumitaka; Iwase, Satoru; Kazuma, Keiko

2017-12-01

Clinical research coordinators play a pivotal role in phase I cancer clinical trials. We clarified the care coordination and practice for patients provided by clinical research coordinators in phase I cancer clinical trials in Japan and elucidated clinical research coordinators' perspective on patients' expectations and understanding of these trials. Fifteen clinical research coordinators participated in semi-structured interviews regarding clinical practices; perceptions of patients' expectations; and the challenges that occur before, during, and after phase I cancer clinical trials. Qualitative content analysis showed that most clinical research coordinators observed that patients have high expectations from the trials. Most listened to patients to confirm patients' understanding and reflected on responses to maintain hope, but to avoid excessive expectations; clinical research coordinators considered avoiding unplanned endings; and they aimed to establish good relationships between patients, medical staff, and among the professional team. Clinical research coordinators were insightful about the needs of patients and took a meticulous approach to the phase I cancer clinical trial process, allowing time to connect with patients and to coordinate the inter-professional research team. Additionally, education in advanced oncology care was valuable for comforting participants in cancer clinical trials.

Challenges in Measuring Benefit of Clinical Research Training Programs--the ASH Clinical Research Training Institute Example.

PubMed

Sung, Lillian; Crowther, Mark; Byrd, John; Gitlin, Scott D; Basso, Joe; Burns, Linda

2015-12-01

The American Society of Hematology developed the Clinical Research Training Institute (CRTI) to address the lack of training in patient-oriented research among hematologists. As the program continues, we need to consider metrics for measuring the benefits of such a training program. This article addresses the benefits of clinical research training programs. The fundamental and key components are education and mentorship. However, there are several other benefits including promotion of collaboration, job and advancement opportunities, and promotion of work-life balance. The benefits of clinical research training programs need to be measured so that funders and society can judge if they are worth the investment in time and resources. Identification of elements that are important to program benefit is essential to measuring the benefit of the program as well as program planning. Future work should focus on the constructs which contribute to benefits of clinical research training programs such as CRTI.

Justice in international clinical research.

PubMed

Pratt, Bridget; Loff, Bebe

2011-08-01

Debates about justice in international clinical research problematically conflate two quite different forms of obligation. International research ethics guidelines were intended to describe how to conduct biomedical research in a just manner at the micro or clinical level (within the researcher-participant interaction) but have come to include requirements that are clearly intended to promote justice at the global level. Ethicists have also made a variety of claims regarding what international research should contribute to global justice. This paper argues that the conflation of debates about justice at the micro and macro-levels has not only resulted in the placement of obligations upon the wrong actors but has also served to exclude relevant actors from the ethical picture. Suggestions for who should properly bear macro-level obligations of justice in international clinical research are offered. The paper further contends that, unlike researchers who violate informed consent requirements, no similar type of accountability exists for obligations of global justice, even for those obligation-bearers (incorrectly) identified by current ethics guidelines. © 2010 Blackwell Publishing Ltd.

Clinical research for neuropathies.

PubMed

Kaufmann, Petra

2012-05-01

The National Institutes of Health (NIH) has a long-standing commitment to neuropathy research. From 2005-2009, the NIH has committed US $115 million each year. A collaborative effort between researchers and patients can accelerate the translation of pre-clinical discoveries into better treatments for neuropathy patients. Clinical trials are needed to test these new treatments, but they can only be implemented in a timely fashion if patients with neuropathies are willing to participate. This perspective focuses on the value of having various outlets for informing both the patients and the physicians about existing clinical research opportunities and on the potential benefit of establishing patient registries to help with trial recruitment. Once data have been collected, there is a need to broadly share the data in order to inform future trials, and a first step would be to harmonize data collection by using Common Data Elements (CDEs). Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

PROFESSIONAL INTEGRATION AND CLINICAL RESEARCH.

ERIC Educational Resources Information Center

WARD, TED W.

THE RATIONALE OF A CLINICAL APPROACH TO RESEARCH ON TEACHER BEHAVIOR IS SET FORTH TOGETHER WITH INDICATION OF DIFFICULTIES. IN ONE CLINICAL STUDY, RECORDS OF FOCUSED OBSERVATIONS OF TEACHER BEHAVIOR WERE REVIEWED BY A SPECIALIST IN LEARNING AND A SPECIALIST IN SOCIAL PSYCHOLOGY IN RELATION TO RESEARCH FROM THESE FIELDS. TEACHER DECISIONS PROVED…

Visual research in clinical education.

PubMed

Bezemer, Jeff

2017-01-01

The aim of this paper is to explore what might be gained from collecting and analysing visual data, such as photographs, scans, drawings, video and screen recordings, in clinical educational research. Its focus is on visual research that looks at teaching and learning 'as it naturally occurs' in the work place, in simulation centres and other sites, and also involves the collection and analysis of visual learning materials circulating in these sites. With the ubiquity of digital recording devices, video data and visual learning materials are now relatively cheap to collect. Compared to other domains of education research visual materials are not widely used in clinical education research. The paper sets out to identify and reflect on the possibilities for visual research using examples from an ethnographic study on surgical and inter-professional learning in the operating theatres of a London hospital. The paper shows how visual research enables recognition, analysis and critical evaluation of (1) the hidden curriculum, such as the meanings implied by embodied, visible actions of clinicians; (2) the ways in which clinical teachers design multimodal learning environments using a range of modes of communication available to them, combining, for instance, gesture and speech; (3) the informal assessment of clinical skills, and the intricate relation between trainee performance and supervisor feedback; (4) the potentialities and limitations of different visual learning materials, such as textbooks and videos, for representing medical knowledge. The paper concludes with theoretical and methodological reflections on what can be made visible, and therefore available for analysis, explanation and evaluation if visual materials are used for clinical education research, and what remains unaccounted for if written language remains the dominant mode in the research cycle. Opportunities for quantitative analysis and ethical implications are also discussed. © 2016 John Wiley

How can we improve clinical research in pneumonia?

PubMed

Ramirez, Julio A

2018-05-01

The primary challenges in the field of clinical research include a lack of support within existing infrastructure, insufficient number of clinical research training programs and a paucity of qualified mentors. Most medical centers offer infrastructure support for investigators working with industry sponsors or government-funded clinical trials, yet there are a significant amount of clinical studies performed in the field of pneumonia which are observational studies. For this type of research, which is frequently unfunded, support is usually lacking. In an attempt to optimize clinical research in pneumonia, at the University of Louisville, we developed a clinical research coordinating center (CRCC). The center manages clinical studies in the field of respiratory infections, with the primary focus being pneumonia. Other activities of the CRCC include the organization of an annual clinical research training course for physicians and other healthcare workers, and the facilitation of international research mentoring by a process of connecting new pneumonia investigators with established clinical investigators. To improve clinical research in pneumonia, institutions need to have the appropriate infrastructure in place to support investigators in all aspects of the clinical research process.

Establishing a successful clinical research program.

PubMed

Scoglio, Daniele; Fichera, Alessandro

2014-06-01

Clinical research (CR) is a natural corollary to clinical surgery. It gives an investigator the opportunity to critically review their results and develop new strategies. This article covers the critical factors and the important components of a successful CR program. The first and most important step is to build a dedicated research team to overcome time constraints and enable a surgical practice to make CR a priority. With the research team in place, the next step is to create a program on the basis of an original idea and new clinical hypotheses. This often comes from personal experience supported by a review of the available evidence. Randomized controlled (clinical) trials are the most stringent way of determining whether a cause-effect relationship exists between the intervention and the outcome. In the proper setting, translational research may offer additional avenues allowing clinical application of basic science discoveries.

Database on veterinary clinical research in homeopathy.

PubMed

Clausen, Jürgen; Albrecht, Henning

2010-07-01

The aim of the present report is to provide an overview of the first database on clinical research in veterinary homeopathy. Detailed searches in the database 'Veterinary Clinical Research-Database in Homeopathy' (http://www.carstens-stiftung.de/clinresvet/index.php). The database contains about 200 entries of randomised clinical trials, non-randomised clinical trials, observational studies, drug provings, case reports and case series. Twenty-two clinical fields are covered and eight different groups of species are included. The database is free of charge and open to all interested veterinarians and researchers. The database enables researchers and veterinarians, sceptics and supporters to get a quick overview of the status of veterinary clinical research in homeopathy and alleviates the preparation of systematical reviews or may stimulate reproductions or even new studies. 2010 Elsevier Ltd. All rights reserved.

Maintenance of Clinical Expertise and Clinical Research by the Clinical Professors at Gifu Pharmaceutical University.

PubMed

Tachi, Tomoya; Noguchi, Yoshihiro; Teramachi, Hitomi

2017-01-01

The clinical professors at Gifu Pharmaceutical University (GPU) provide pharmaceutical services at GPU Pharmacy, Gifu University Hospital, and Gifu Municipal Hospital to keep their clinical skills up-to-date; they also perform clinical research in collaboration with many clinical institutes. The Laboratory of Clinical Pharmacy is part of the Department of Pharmacy Practice and Science, to which the clinical professors belong, and is composed of three clinical professors (a professor, an associate professor, and an assistant professor). The professor administers the GPU Pharmacy as its director, while the associate professor and assistant professor provide pharmaceutical services to patients at Gifu Municipal Hospital, and also provide practical training for students in the GPU Pharmacy. Collectively, they have performed research on such topics as medication education for students, clinical communication education, and analysis of clinical big data. They have also conducted research in collaboration with clinical institutes, hospitals, and pharmacies. Here, we introduce the collaborative research between the Laboratory of Clinical Pharmacy and Gifu Municipal Hospital. These studies include "Risk factors contributing to urinary protein expression resulting from bevacizumab combination chemotherapy", "Hyponatremia and hypokalemia as risk factors for falls", "Economic evaluation of adjustments of levofloxacin dosage by dispensing pharmacists for patients with renal dysfunction", and "Effect of patient education upon discharge for use of a medication notebook on purchasing over-the-counter drugs and health foods". In this symposium, we would like to demonstrate one model of the association and collaborative research between these clinical professors and clinical institutes.

Development of a Research Participants’ Perception Survey to Improve Clinical Research

PubMed Central

Yessis, Jennifer L.; Kost, Rhonda G.; Lee, Laura M.; Coller, Barry S.; Henderson, David K.

2012-01-01

Abstract Introduction: Clinical research participants’ perceptions regarding their experiences during research protocols provide outcome‐based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants’ clinical research experiences. Use of validated surveys measuring patient‐centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes. Methods: We derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion‐related validity, and item usefulness. Responses were tested for fit into existing patient‐centered dimensions of care and new clinical research dimensions using Cronbach's alpha coefficient. Results: Surveys were mailed to 18,890 individuals; 4,961 were returned (29%). Survey completion was 89% overall; completion rates exceeded 90% for 88 of 93 evaluable items. Questions fit into three dimensions of patient‐centered care and two novel clinical research dimensions (Cronbach's alpha for dimensions: 0.69–0.85). Conclusions: The validated survey offers a new method for assessing and improving outcomes of clinical research processes. Clin Trans Sci 2012; Volume 5: 452–460 PMID:23253666

Dissemination of research into clinical nursing literature.

PubMed

Oermann, Marilyn H; Shaw-Kokot, Julia; Knafl, George J; Dowell, Jo

2010-12-01

The purpose of our study was to describe the dissemination of research into the clinical nursing literature. The literature provides a means of transferring knowledge from a research study through citations of the work by other authors. This was a citation analysis study to explore the dissemination of research into the clinical nursing literature, beginning with the publication of an original research study and including all of the citations to that article through 2009. The authors searched five academic nursing research journal titles, using CINAHL, for original research reports that had clinical relevance and were published between 1990-1999. The search process yielded a final data set of 28 research articles. For each of the articles, the authors searched three databases, CINAHL, Web of Science(®) and Google Scholar, to determine the citation patterns from the date of publication to August 2009. All of the research studies were cited in articles published in clinical journals although there was a wide range in the number of citations, from 3-80. The 28 research articles had a total of 759 citations; 717 (94.5%) of those citations were in articles published in clinical nursing journals. The median length of time between publication of the original study and the first citation was 1.5 years. Some of the studies were still being cited for 18 years after publication of the original work. All of the original research reports examined in this study were cited in articles in clinical journals, disseminating the research beyond the original work to reach clinicians. Clinical nursing journals keep readers up-to-date and informed about new practices in nursing and serve another important role: they disseminate research that is clinically relevant by publishing original studies and papers that cite research reports. © 2010 Blackwell Publishing Ltd.

Best practice & research in anaesthesiology issue on new approaches in clinical research ethics in clinical research.

PubMed

Schwenzer, Karen J

2011-12-01

The history of ethics in clinical research parallels the history of abuse of human beings. The Nuremberg Code, Declaration of Helsinki, and the Belmont Report laid the foundations for modern research ethics. In the United States, the OHRP and the FDA provide guidelines for the ethical conduct of research. Investigators should be familiar with regulations concerning informed consent, doing research in vulnerable populations, and protection of privacy. Copyright © 2011 Elsevier Ltd. All rights reserved.

An Opportunity to Bridge the Gap Between Clinical Research and Clinical Practice: Implications for Clinical Training

PubMed Central

Hershenberg, Rachel; Drabick, Deborah A. G.; Vivian, Dina

2013-01-01

Clinical researchers and clinical practitioners share a goal of increasing the integration of research and clinical practice, which is reflected in an evidence-based practice (EBP) approach to psychology. The EBP framework involves the integration of research findings with clinical expertise and client characteristics, values, and preferences, and consequently provides an important foundation for conducting clinically relevant research, as well as empirically based and clinically sensitive practice. Given the critical role that early training can play in the integration of science and practice and in promoting the future of the field, the present article addresses predoctoral training programs as a context for adopting an EBP approach to clinical work. We address training in the three components of EBP and provide suggestions for curriculum development and practicum training that we hope will contribute to bridging the gap between research and practice. PMID:22642520

Be a Partner in Clinical Research

MedlinePlus

... Print this issue Be a Partner in Clinical Research Help Others, Help Yourself En español Send us ... you know that you can participate in clinical research? Whether you’re healthy or sick, young or ...

The Weiland Medal: Clinical Research in Hand Surgery

PubMed Central

Chung, Kevin C.

2015-01-01

Clinical research designed to enhance the quality of healthcare has always received a great deal of national attention. Outcomes studies, clinical trials, and evidence-based research are key components of clinical research that have advanced the field of hand surgery. The purpose of the Weiland Award is to encourage innovations and progress in clinical research in hand surgery for the betterment of patients and to promote hand surgery’s visibility in American medicine. This article will highlight my efforts in clinical research through three specific research themes: (1) outcomes research, (2) economic analysis, and (3) evidence-based research and quality assessment in healthcare. PMID:20117312

Clinical outcomes research in gynecologic oncology.

PubMed

Melamed, Alexander; Rauh-Hain, J Alejandro; Schorge, John O

2017-09-01

Clinical outcomes research seeks to understand the real-world manifestations of clinical care. In particular, outcomes research seeks to reveal the effects of pharmaceutical, procedural, and structural aspects of healthcare on patient outcomes, including mortality, disease control, toxicity, cost, and quality of life. Although outcomes research can utilize interventional study designs, insightful use of observational data is a defining feature of this field. Many questions in gynecologic oncology are not amenable to investigation in randomized clinical trials due to cost, feasibility, or ethical concerns. When a randomized trial is not practical or has not yet been conducted, well-designed observational studies have the potential to provide the best available evidence about the effects of clinical care. Such studies may use surveys, medical records, disease registries, and a variety of administrative data sources. Even when a randomized trial has been conducted, observational studies can be used to estimate the real-world effect of an intervention, which may differ from the results obtained in the controlled setting of a clinical trial. This article reviews the goals, methodologies, data sources, and limitations of clinical outcomes research, with a focus on gynecologic oncology. Copyright © 2017. Published by Elsevier Inc.

Evaluating Various Areas of Process Improvement in an Effort to Improve Clinical Research: Discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management Workshop

PubMed Central

Cola, Philip A.; Rosenblum, Daniel

2013-01-01

Abstract Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to “improve human health.” Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled “Learning by doing; applying evidence‐based tools to re‐engineer clinical research management” took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants. PMID:23919369

Evaluating various areas of process improvement in an effort to improve clinical research: discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management workshop.

PubMed

Strasser, Jane E; Cola, Philip A; Rosenblum, Daniel

2013-08-01

Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to "improve human health." Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled "Learning by doing; applying evidence-based tools to re-engineer clinical research management" took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants. © 2013 Wiley Periodicals, Inc.

Clinical Research Nursing: Development of a Residency Program
.

PubMed

Showalter, Brandi L; Cline, Debbie; Yungclas, Jan; Frentz, Kelly; Stafford, Susan R; Maresh, Kelly J

2017-10-01

Clinical research nurses are essential in the coordination of clinical trials and the management of research participants. Without a stable, knowledgeable research nurse workforce, the conduct of research is affected. A research nurse residency is a novel approach to preparing new graduate nurses for the oncology research nurse role. This article will describe the development and content of the research nurse residency and how this approach is being used to address a need for clinical research nurses to support burgeoning clinical trials at a National Cancer Institute-designated comprehensive cancer center.
.

Research nurse manager perceptions about research activities performed by non-nurse clinical research coordinators.

PubMed

Jones, Carolynn Thomas; Hastings, Clare; Wilson, Lynda Law

2015-01-01

There has been limited research to document differences in roles between nurses and non-nurses who assume clinical research coordination and management roles. Several authors have suggested that there is no acknowledged guidance for the licensure requirements for research study coordinators and that some non-nurse research coordinators may be assuming roles that are outside of their legal scopes of practice. There is a need for further research on issues related to the delegation of clinical research activities to non-nurses. This study used nominal group process focus groups to identify perceptions of experienced research nurse managers at an academic health science center in the Southern United States about the clinical research activities that are being performed by non-nurse clinical research coordinators without supervision that they believed should only be performed by a nurse or under the supervision of a nurse. A total of 13 research nurse managers volunteered to be contacted about the study. Of those, 8 participated in two separate nominal group process focus group sessions. The group members initially identified 22 activities that they felt should only be performed by a nurse or under the direct supervision of a nurse. After discussion and clarification of results, activities were combined into 12 categories of clinical research activities that participants believed should only be performed by a nurse or under the direct supervision of a nurse. Copyright © 2015 Elsevier Inc. All rights reserved.

Key factors of clinical research network capacity building.

PubMed

Li, Guowei; Wu, Qianyu; Jin, Yanling; Vanniyasingam, Thuva; Thabane, Lehana

2018-01-01

In general, clinical research network capacity building refers to programs aimed at enhancing networks of researchers to conduct clinical research. Although in the literature there is a large body of research on how to develop and build capacity in clinical research networks, the conceptualizations and implementations remain controversial and challenging. Moreover, the experiences learnt from the past accomplishments and failures can assist in the future capacity building efforts to be more practical, effective and efficient. In this paper, we aim to provide an overview of capacity building in clinical research network by (1) identifying the key barriers to clinical research network capacity building, (2) providing insights into how to overcome those obstacles, and (3) sharing our experiences in collaborating with national and international partners to build capacity in clinical research networks. In conclusion, we have provided some insight into how to address the key factors of clinical research network capacity building and shared some empirical experiences. A successful capacity building practice requires a joint endeavor to procure sufficient resources and support from the relevant stakeholders, to ensure its efficiency, cost-effectiveness, and sustainability.

Leveraging electronic health records for clinical research.

PubMed

Raman, Sudha R; Curtis, Lesley H; Temple, Robert; Andersson, Tomas; Ezekowitz, Justin; Ford, Ian; James, Stefan; Marsolo, Keith; Mirhaji, Parsa; Rocca, Mitra; Rothman, Russell L; Sethuraman, Barathi; Stockbridge, Norman; Terry, Sharon; Wasserman, Scott M; Peterson, Eric D; Hernandez, Adrian F

2018-04-30

Electronic health records (EHRs) can be a major tool in the quest to decrease costs and timelines of clinical trial research, generate better evidence for clinical decision making, and advance health care. Over the past decade, EHRs have increasingly offered opportunities to speed up, streamline, and enhance clinical research. EHRs offer a wide range of possible uses in clinical trials, including assisting with prestudy feasibility assessment, patient recruitment, and data capture in care delivery. To fully appreciate these opportunities, health care stakeholders must come together to face critical challenges in leveraging EHR data, including data quality/completeness, information security, stakeholder engagement, and increasing the scale of research infrastructure and related governance. Leaders from academia, government, industry, and professional societies representing patient, provider, researcher, industry, and regulator perspectives convened the Leveraging EHR for Clinical Research Now! Think Tank in Washington, DC (February 18-19, 2016), to identify barriers to using EHRs in clinical research and to generate potential solutions. Think tank members identified a broad range of issues surrounding the use of EHRs in research and proposed a variety of solutions. Recognizing the challenges, the participants identified the urgent need to look more deeply at previous efforts to use these data, share lessons learned, and develop a multidisciplinary agenda for best practices for using EHRs in clinical research. We report the proceedings from this think tank meeting in the following paper. Copyright © 2018 Elsevier, Inc. All rights reserved.

Alcoholic and non-alcoholic steatohepatitis

PubMed Central

Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

2015-01-01

This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

Translating research findings to clinical nursing practice.

PubMed

Curtis, Kate; Fry, Margaret; Shaban, Ramon Z; Considine, Julie

2017-03-01

To describe the importance of, and methods for, successfully conducting and translating research into clinical practice. There is universal acknowledgement that the clinical care provided to individuals should be informed on the best available evidence. Knowledge and evidence derived from robust scholarly methods should drive our clinical practice, decisions and change to improve the way we deliver care. Translating research evidence to clinical practice is essential to safe, transparent, effective and efficient healthcare provision and meeting the expectations of patients, families and society. Despite its importance, translating research into clinical practice is challenging. There are more nurses in the frontline of health care than any other healthcare profession. As such, nurse-led research is increasingly recognised as a critical pathway to practical and effective ways of improving patient outcomes. However, there are well-established barriers to the conduct and translation of research evidence into practice. This clinical practice discussion paper interprets the knowledge translation literature for clinicians interested in translating research into practice. This paper is informed by the scientific literature around knowledge translation, implementation science and clinician behaviour change, and presented from the nurse clinician perspective. We provide practical, evidence-informed suggestions to overcome the barriers and facilitate enablers of knowledge translation. Examples of nurse-led research incorporating the principles of knowledge translation in their study design that have resulted in improvements in patient outcomes are presented in conjunction with supporting evidence. Translation should be considered in research design, including the end users and an evaluation of the research implementation. The success of research implementation in health care is dependent on clinician/consumer behaviour change and it is critical that implementation strategy

Quality Assurance in Biobanking for Pre-Clinical Research

PubMed Central

Simeon-Dubach, Daniel; Zeisberger, Steffen M.; Hoerstrup, Simon P.

2016-01-01

It is estimated that not less than USD 28 billion are spent each year in the USA alone on irreproducible pre-clinical research, which is not only a fundamental loss of investment and resources but also a strong inhibitor of efficiency for upstream processes regarding the translation towards clinical applications and therapies. The issues and cost of irreproducibility has mainly been published on pre-clinical research. In contrast to pre-clinical research, test material is often being transferred into humans in clinical research. To protect treated human subjects and guarantee a defined quality standard in the field of clinical research, the manufacturing and processing infrastructures have to strictly follow and adhere to certain (inter-)national quality standards. It is assumed and suggested by the authors that by an implementation of certain quality standards within the area of pre-clinical research, billions of USD might be saved and the translation phase of promising pre-clinical results towards clinical applications may substantially be improved. In this review, we discuss how an implementation of a quality assurance (QA) management system might positively improve sample quality and sustainability within pre-clinically focused biobank infrastructures. Biobanks are frequently positioned at the very beginning of the biomedical research value chain, and, since almost every research material has been stored in a biobank during the investigated life cycle, biobanking seems to be of substantial importance from this perspective. The role model of a QA-regulated biobank structure can be found in biobanks within the context of clinical research organizations such as in regenerative medicine clusters. PMID:27781023

Retooling Institutional Support Infrastructure for Clinical Research

PubMed Central

Snyder, Denise C.; Brouwer, Rebecca N.; Ennis, Cory L.; Spangler, Lindsey L.; Ainsworth, Terry L.; Budinger, Susan; Mullen, Catherine; Hawley, Jeffrey; Uhlenbrauck, Gina; Stacy, Mark

2016-01-01

Clinical research activities at academic medical centers are challenging to oversee. Without effective research administration, a continually evolving set of regulatory and institutional requirements can detract investigator and study team attention away from a focus on scientific gain, study conduct, and patient safety. However, even when the need for research administration is recognized, there can be struggles over what form it should take. Central research administration may be viewed negatively, with individual groups preferring to maintain autonomy over processes. Conversely, a proliferation of individualized approaches across an institution can create inefficiencies or invite risk. This article describes experiences establishing a unified research support office at the Duke University School of Medicine based on a framework of customer support. The Duke Office of Clinical Research was formed in 2012 with a vision that research administration at academic medical centers should help clinical investigators navigate the complex research environment and operationalize research ideas. The office provides an array of services that have received high satisfaction ratings. The authors describe the ongoing culture change necessary for success of the unified research support office. Lessons learned from implementation of the Duke Office of Clinical Research may serve as a model for other institutions undergoing a transition to unified research support. PMID:27125563

Clinical Research Informatics Contributions from 2015.

PubMed

Daniel, C; Choquet, R

2016-11-10

To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select best papers published in 2015. A bibliographic search using a combination of MeSH and free terms search over PubMed on Clinical Research Informatics (CRI) was performed followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. A consensus meeting between the two section editors and the editorial team was finally organized to conclude on the selection of best papers. Among the 579 returned papers published in the past year in the various areas of Clinical Research Informatics (CRI) - i) methods supporting clinical research, ii) data sharing and interoperability, iii) re-use of healthcare data for research, iv) patient recruitment and engagement, v) data privacy, security and regulatory issues and vi) policy and perspectives - the full review process selected four best papers. The first selected paper evaluates the capability of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM) to support the representation of case report forms (in both the design stage and with patient level data) during a complete clinical study lifecycle. The second selected paper describes a prototype for secondary use of electronic health records data captured in non-standardized text. The third selected paper presents a privacy preserving electronic health record linkage tool and the last selected paper describes how big data use in US relies on access to health information governed by varying and often misunderstood legal requirements and ethical considerations. A major trend in the 2015 publications is the analysis of observational, "nonexperimental" information and the potential biases and confounding factors hidden in the data that will have to be carefully taken into account to validate new predictive models. In addiction, researchers have to understand

A plea for pragmatism in clinical research ethics.

PubMed

Brendel, David H; Miller, Franklin G

2008-04-01

Pragmatism is a distinctive approach to clinical research ethics that can guide bioethicists and members of institutional review boards (IRBs) as they struggle to balance the competing values of promoting medical research and protecting human subjects participating in it. After defining our understanding of pragmatism in the setting of clinical research ethics, we show how a pragmatic approach can provide guidance not only for the day-to-day functioning of the IRB, but also for evaluation of policy standards, such as the one that addresses acceptable risks for healthy children in clinical research trials. We also show how pragmatic considerations might influence the debate about the use of deception in clinical research. Finally, we show how a pragmatic approach, by regarding the promotion of human research and the protection of human subjects as equally important values, helps to break down the false dichotomy between science and ethics in clinical research.

Participants' responsibilities in clinical research.

PubMed

Resnik, David B; Ness, Elizabeth

2012-12-01

Discussions on the ethics and regulation of clinical research have a great deal to say about the responsibilities of investigators, sponsors, research institutions and institutional review boards, but very little about the responsibilities of research participants. In this article, we discuss the responsibilities of participants in clinical research. We argue that competent adult participants are responsible for complying with study requirements and fulfilling other obligations they undertake when they make an informed choice to enroll in a study. These responsibilities are based on duties related to promise-keeping, avoiding harm to one's self or others, beneficence and reciprocity. Investigators and research staff should inform participants about their responsibilities during the consent process, and should stress the importance of fulfilling study requirements. They should address any impediments to compliance, and they may provide participants with financial incentives for meeting study requirements. In very rare cases, coercive measures may be justified to prevent immanent harm to others resulting from non-compliance with study requirements.

E-recruitment based clinical research: notes for Research Ethics Committees/Institutional Review Boards.

PubMed

Refolo, P; Sacchini, D; Minacori, R; Daloiso, V; Spagnolo, A G

2015-01-01

Patient recruitment is a critical point of today's clinical research. Several proposals have been made for improving it, but the effectiveness of these measures is actually uncertain. The use of Internet (e-recruitment) could represent a great chance to improve patient enrolment, even though the effectiveness of this implementation is not so evident. E-recruitment could bring some advantages, such as better interaction between clinical research demand and clinical research supply, time and resources optimization, and reduction of data entry errors. It raises some issues too, such as sampling errors, validity of informed consent, and protection of privacy. Research Ethics Committees/Institutional Review Boards should consider these critical points. The paper deals with Internet recruitment for clinical research. It also attempts to provide Research Ethics Committees/Institutional Review Boards with notes for assessing e-recruitment based clinical protocols.

Statistical reporting of clinical pharmacology research.

PubMed

Ring, Arne; Schall, Robert; Loke, Yoon K; Day, Simon

2017-06-01

Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta-analyses of drug usage after market approval, the investigation of pharmacokinetic-pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research. © 2017 The British Pharmacological Society.

[Conflict of interests in clinical research].

PubMed

Alves, Elaine Maria de Oliveira; Tubino, Paulo

2007-01-01

In clinical research there is a real possibility to have some conflict of interests. Even for the researcher, the identification of these conflicts cannot be clear. There are many aspects to be considered, involving all participants of the process: the research subject, the researcher, the institution where the research is carried through, the sponsor, the ethics committees, the regulating agencies, the scientific community and the society. The conclusion is that conflicts of interests are common and inevitable in the academic field. The challenge is not to eradicate them, but to recognize them and to manage them properly. The only acceptable way to do this is to expose clearly the conflicts of interests and always to submit the clinical research projects to the ethics committees.

Enrolling Minority and Underserved Populations in Cancer Clinical Research

PubMed Central

Wallington, Sherrie Flynt; Dash, Chiranjeev; Sheppard, Vanessa B.; Goode, Tawara D.; Oppong, Bridget A.; Dodson, Everett E.; Hamilton, Rhonda N.; Adams-Campbell, Lucile L.

2015-01-01

Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials—a “gold standard.” Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six non-therapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients—their physical locales, cultural values, and environments in which they live—is essential to recruiting culturally and ethnically diverse population samples. PMID:26470805

Enrolling Minority and Underserved Populations in Cancer Clinical Research.

PubMed

Wallington, Sherrie F; Dash, Chiranjeev; Sheppard, Vanessa B; Goode, Tawara D; Oppong, Bridget A; Dodson, Everett E; Hamilton, Rhonda N; Adams-Campbell, Lucile L

2016-01-01

Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six nontherapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients-their physical locales, cultural values, and environments in which they live-is essential to recruiting culturally and ethnically diverse population samples. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Clinical research with economically disadvantaged populations

PubMed Central

Denny, Colleen C; Grady, Christine

2007-01-01

Concerns about exploiting the poor or economically disadvantaged in clinical research are widespread in the bioethics community. For some, any research that involves economically disadvantaged individuals is de facto ethically problematic. The economically disadvantaged are thought of as “venerable” to exploitation, impaired decision making, or both, thus requiring either special protections or complete exclusion from research. A closer examination of the worries about vulnerabilities among the economically disadvantaged reveals that some of these worries are empirically or logically untenable, while others can be better resolved by improved study designs than by blanket exclusion of poorer individuals from research participation. The scientific objective to generate generalisable results and the ethical objective to fairly distribute both the risks and benefits of research oblige researchers not to unnecessarily bar economically disadvantaged subjects from clinical research participation. PMID:17601862

The Clinical Research Landscape in Rhode Island.

PubMed

Mao, George; Ramratnam, Bharat

2017-01-06

To present an overview of clinical research activity and the state of medical research funding in Rhode Island. We utilized clinicaltrials.gov registry to profile clinical studies between 2011 to 2016. NIH RePORT and other federal databases were used to extract information on levels of federal funding. Previously published hospital financial reports were reviewed for data on hospital-specific total external research funding. During 2011-2016, 1651 clinical studies were registered in clinicaltrials.gov. Nearly a third of all clinical studies were in oncology (21%) and cardiovascular diseases (10%). Alzheimer's dementia, breast cancer, HIV, and hepatitis C accounted for nearly 17% of all clinical trials. Seventy-five percent (75%) of clinical trials in RI were conducted in hospitals affiliated with Lifespan or Care New England. Financial support for clinical trials largely came from industry (60%) with 23% being supported by the National Institutes of Health (NIH). The rest are funded by nonprofit organizations, charitable foundations, educational institutions, and unlisted concerns. [Full article available at http://rimed.org/rimedicaljournal-2017-01.asp].

A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge.

PubMed

Steck, R; Epari, D R; Schuetz, M A

2010-07-01

The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Clinical Research Informatics: Supporting the Research Study Lifecycle.

PubMed

Johnson, S B

2017-08-01

Objectives: The primary goal of this review is to summarize significant developments in the field of Clinical Research Informatics (CRI) over the years 2015-2016. The secondary goal is to contribute to a deeper understanding of CRI as a field, through the development of a strategy for searching and classifying CRI publications. Methods: A search strategy was developed to query the PubMed database, using medical subject headings to both select and exclude articles, and filtering publications by date and other characteristics. A manual review classified publications using stages in the "research study lifecycle", with key stages that include study definition, participant enrollment, data management, data analysis, and results dissemination. Results: The search strategy generated 510 publications. The manual classification identified 125 publications as relevant to CRI, which were classified into seven different stages of the research lifecycle, and one additional class that pertained to multiple stages, referring to general infrastructure or standards. Important cross-cutting themes included new applications of electronic media (Internet, social media, mobile devices), standardization of data and procedures, and increased automation through the use of data mining and big data methods. Conclusions: The review revealed increased interest and support for CRI in large-scale projects across institutions, regionally, nationally, and internationally. A search strategy based on medical subject headings can find many relevant papers, but a large number of non-relevant papers need to be detected using text words which pertain to closely related fields such as computational statistics and clinical informatics. The research lifecycle was useful as a classification scheme by highlighting the relevance to the users of clinical research informatics solutions. Georg Thieme Verlag KG Stuttgart.

Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis.

PubMed

Hameed, B; Terrault, N A; Gill, R M; Loomba, R; Chalasani, N; Hoofnagle, J H; Van Natta, M L

2018-03-01

In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight. Because weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH. The analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end. Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo-treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost weight, OCA was associated with opposite effects from placebo on changes in alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P = 0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%, P = 0.01). OCA leads to weight loss in up to 44% of patients with NASH, and OCA therapy and weight loss have additive benefits on serum aminotransferases and histology. However, favourable effects of weight loss on alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients were absent or reversed on OCA treatment. These findings stress the importance of assessing concomitant metabolic effects of new therapies of NASH. Clinical trial number: NCT01265498. © 2018 John Wiley & Sons Ltd.

Preparing clinical pharmacy scientists for careers in clinical/translational research: can we meet the challenge?: ACCP Research Affairs Committee Commentary.

PubMed

Parker, Robert B; Ellingrod, Vicki; DiPiro, Joseph T; Bauman, Jerry L; Blouin, Robert A; Welage, Lynda S

2013-12-01

Developing clinical pharmacists' research skills and their ability to compete for extramural funding is an important component of the American College of Clinical Pharmacy's (ACCP) vision for pharmacists to play a prominent role in generating the new knowledge used to guide patient pharmacotherapy. Given the recent emphasis on clinical/translational research at the National Institutes of Health (NIH) and the key role of drug therapy in the management of many diseases, there is an unprecedented opportunity for the profession to contribute to this enterprise. A crucial question facing the profession is whether we can generate enough appropriately trained scientists to take advantage of these opportunities to generate the new knowledge to advance drug therapy. Since the 2009 publication of the ACCP Research Affairs Committee editorial recommending the Ph.D. degree (as opposed to fellowship training) as the optimal method for preparing pharmacists as clinical/translational scientists, significant changes have occurred in the economic, professional, political, and research environments. As a result, the 2012 ACCP Research Affairs Committee was charged with reexamining the college's position on training clinical pharmacy scientists in the context of these substantial environmental changes. In this commentary, the potential impact of these changes on opportunities for pharmacists in clinical/translational research are discussed as are strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. Failure of our profession to take advantage of these opportunities risks our ability to contribute substantively to the biomedical research enterprise and ultimately improve the pharmacotherapy of our patients. © 2013 Pharmacotherapy Publications, Inc.

Clinical Research Informatics and Electronic Health Record Data

PubMed Central

Horvath, M. M.; Rusincovitch, S. A.

2014-01-01

Summary Objectives The goal of this survey is to discuss the impact of the growing availability of electronic health record (EHR) data on the evolving field of Clinical Research Informatics (CRI), which is the union of biomedical research and informatics. Results Major challenges for the use of EHR-derived data for research include the lack of standard methods for ensuring that data quality, completeness, and provenance are sufficient to assess the appropriateness of its use for research. Areas that need continued emphasis include methods for integrating data from heterogeneous sources, guidelines (including explicit phenotype definitions) for using these data in both pragmatic clinical trials and observational investigations, strong data governance to better understand and control quality of enterprise data, and promotion of national standards for representing and using clinical data. Conclusions The use of EHR data has become a priority in CRI. Awareness of underlying clinical data collection processes will be essential in order to leverage these data for clinical research and patient care, and will require multi-disciplinary teams representing clinical research, informatics, and healthcare operations. Considerations for the use of EHR data provide a starting point for practical applications and a CRI research agenda, which will be facilitated by CRI’s key role in the infrastructure of a learning healthcare system. PMID:25123746

Clinical research informatics and electronic health record data.

PubMed

Richesson, R L; Horvath, M M; Rusincovitch, S A

2014-08-15

The goal of this survey is to discuss the impact of the growing availability of electronic health record (EHR) data on the evolving field of Clinical Research Informatics (CRI), which is the union of biomedical research and informatics. Major challenges for the use of EHR-derived data for research include the lack of standard methods for ensuring that data quality, completeness, and provenance are sufficient to assess the appropriateness of its use for research. Areas that need continued emphasis include methods for integrating data from heterogeneous sources, guidelines (including explicit phenotype definitions) for using these data in both pragmatic clinical trials and observational investigations, strong data governance to better understand and control quality of enterprise data, and promotion of national standards for representing and using clinical data. The use of EHR data has become a priority in CRI. Awareness of underlying clinical data collection processes will be essential in order to leverage these data for clinical research and patient care, and will require multi-disciplinary teams representing clinical research, informatics, and healthcare operations. Considerations for the use of EHR data provide a starting point for practical applications and a CRI research agenda, which will be facilitated by CRI's key role in the infrastructure of a learning healthcare system.

CLARA: an integrated clinical research administration system.

PubMed

Bian, Jiang; Xie, Mengjun; Hogan, William; Hutchins, Laura; Topaloglu, Umit; Lane, Cheryl; Holland, Jennifer; Wells, Thomas

2014-10-01

Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Completed | Office of Cancer Clinical Proteomics Research

Cancer.gov

Prior to the current Clinical Proteomic Tumor Analysis Consortium (CPTAC), previously funded initiatives associated with clinical proteomics research included: Clinical Proteomic Tumor Analysis Consortium (CPTAC 2.0) Clinical Proteomic Technologies for Cancer Initiative (CPTC) Mouse Proteomic Technologies Initiative

Prevalence of Prediabetes and Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease.

PubMed

Newton, Kimberly P; Hou, Jiayi; Crimmins, Nancy A; Lavine, Joel E; Barlow, Sarah E; Xanthakos, Stavra A; Africa, Jonathan; Behling, Cynthia; Donithan, Michele; Clark, Jeanne M; Schwimmer, Jeffrey B

2016-10-03

Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease in children in the United States and is associated with insulin resistance. In adults, NAFLD is also associated with type 2 diabetes. To our knowledge, the prevalence of type 2 diabetes in children with NAFLD is unknown. To determine the prevalence of type 2 diabetes and prediabetes in children with NAFLD and assess type 2 diabetes and prediabetes as risk factors for nonalcoholic steatohepatitis (NASH). This was a multicenter, cross-sectional study at 12 pediatric clinical centers across the United States participating in the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network. Children younger than 18 years with biopsy-confirmed NAFLD enrolled in the NASH Clinical Research Network. The presence of type 2 diabetes and prediabetes as determined by American Diabetes Association screening criteria using clinical history and fasting laboratory values. There were 675 children with NAFLD included in the study with a mean age of 12.6 years and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 32.5. Most of the children were boys (480 of 675) and Hispanic (445 of 675).The estimated prevalence of prediabetes was 23.4% (95% CI, 20.2%-26.6%), and the estimated prevalence of type 2 diabetes was 6.5% (95% CI, 4.6%-8.4%). Girls with NAFLD had 1.6 (95% CI, 1.04-2.40) times greater odds of having prediabetes and 5.0 (95% CI, 2.49-9.98) times greater odds of having type 2 diabetes than boys with NAFLD. The prevalence of NASH was higher in those with type 2 diabetes (43.2%) compared with prediabetes (34.2%) or normal glucose (22%) (P < .001). The odds of having NASH were significantly higher in those with prediabetes (OR, 1.9; 95% CI, 1.21-2.9) or type 2 diabetes (OR, 3.1; 95% CI, 1.5-6.2) compared with those with normal glucose. In this study, nearly 30% of children with NAFLD also had type 2 diabetes or prediabetes

Electronic health records to facilitate clinical research.

PubMed

Cowie, Martin R; Blomster, Juuso I; Curtis, Lesley H; Duclaux, Sylvie; Ford, Ian; Fritz, Fleur; Goldman, Samantha; Janmohamed, Salim; Kreuzer, Jörg; Leenay, Mark; Michel, Alexander; Ong, Seleen; Pell, Jill P; Southworth, Mary Ross; Stough, Wendy Gattis; Thoenes, Martin; Zannad, Faiez; Zalewski, Andrew

2017-01-01

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

Guidance for Researchers Developing and Conducting Clinical Trials in Practice-based Research Networks (PBRNs)

PubMed Central

Dolor, Rowena J.; Schmit, Kristine M.; Graham, Deborah G.; Fox, Chester H.; Baldwin, Laura Mae

2015-01-01

Background There is increased interest nationally in multicenter clinical trials to answer questions about clinical effectiveness, comparative effectiveness, and safety in real-world community settings. Primary care practice-based research networks (PBRNs), comprising community- and/or academically affiliated practices committed to improving medical care for a range of health problems, offer ideal settings for these trials, especially pragmatic clinical trials. However, many researchers are not familiar with working with PBRNs. Methods Experts in practice-based research identified solutions to challenges that researchers and PBRN personnel experience when collaborating on clinical trials in PBRNs. These were organized as frequently asked questions in a draft document presented at a 2013 Agency for Health care Research and Quality PBRN conference workshop, revised based on participant feedback, then shared with additional experts from the DARTNet Institute, Clinical Translational Science Award PBRN, and North American Primary Care Research Group PBRN workgroups for further input and modification. Results The “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice-Based Research Networks” offers guidance in the areas of recruiting and engaging practices, budgeting, project management, and communication, as well as templates and examples of tools important in developing and conducting clinical trials. Conclusion Ensuring the successful development and conduct of clinical trials in PBRNs requires a highly collaborative approach between academic research and PBRN teams. PMID:25381071

The value of formal clinical research training in initiating a career as a clinical investigator.

PubMed

Kapoor, Karan; Wu, Bechien U; Banks, Peter A

2011-12-01

The aim of this study was to determine whether formal clinical research training is of value in the initiation of a successful career as a clinical investigator. We conducted a retrospective review of the career choices of all 25 fellows who entered the Academic Clinical Research Track at Brigham and Women's Hospital since its inception in 1995 and examined the impact of formal clinical research training during their fellowship on their career choice. The primary measure of a successful career as a clinical investigator was the obtainment of external funding for clinical research within 3 years of completion of fellowship. Thirteen of the 25 fellows (52%) received a Master of Public Health (MPH) degree at the Harvard School of Public Health during their fellowship. Ten of these 13 fellows (77%) obtained external funding for clinical research within 3 years of completion of their fellowship. None of the 5 fellows who had already obtained an MPH degree prior to their fellowship and none of the 7 fellows who completed a 7-week summer Program in Clinical Effectiveness but did not complete an MPH degree attempted to receive external funding for clinical research within 3 years of completion of their fellowship. We conclude that formal clinical research training culminating in an MPH degree was extremely valuable in the initiation of a successful career as a clinical investigator.

Conducting Clinical Research Using Crowdsourced Convenience Samples.

PubMed

Chandler, Jesse; Shapiro, Danielle

2016-01-01

Crowdsourcing has had a dramatic impact on the speed and scale at which scientific research can be conducted. Clinical scientists have particularly benefited from readily available research study participants and streamlined recruiting and payment systems afforded by Amazon Mechanical Turk (MTurk), a popular labor market for crowdsourcing workers. MTurk has been used in this capacity for more than five years. The popularity and novelty of the platform have spurred numerous methodological investigations, making it the most studied nonprobability sample available to researchers. This article summarizes what is known about MTurk sample composition and data quality with an emphasis on findings relevant to clinical psychological research. It then addresses methodological issues with using MTurk--many of which are common to other nonprobability samples but unfamiliar to clinical science researchers--and suggests concrete steps to avoid these issues or minimize their impact.

Highly effective cystic fibrosis clinical research teams: critical success factors.

PubMed

Retsch-Bogart, George Z; Van Dalfsen, Jill M; Marshall, Bruce C; George, Cynthia; Pilewski, Joseph M; Nelson, Eugene C; Goss, Christopher H; Ramsey, Bonnie W

2014-08-01

Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study. To use clinical trial performance metrics data analysis to select high-performing cystic fibrosis (CF) clinical research teams and then identify factors contributing to their success. Mixed-methods research, including semi-structured qualitative interviews of high-performing research teams. CF research teams at nine clinical centers from the CF Foundation Therapeutics Development Network. Survey of site characteristics, direct observation of team meetings and facilities, and semi-structured interviews with clinical research team members and institutional program managers and leaders in clinical research. Critical success factors noted at all nine high-performing centers were: 1) strong leadership, 2) established and effective communication within the research team and with the clinical care team, and 3) adequate staff. Other frequent characteristics included a mature culture of research, customer service orientation in interactions with study participants, shared efficient processes, continuous process improvement activities, and a businesslike approach to clinical research. Clinical research metrics allowed identification of high-performing clinical research teams. Site visits identified several critical factors leading to highly successful teams that may help other clinical research teams improve clinical trial performance.

[Research activity in clinical biochemistry].

PubMed

Jørgensen, Henrik L; Larsen, Birger; Ingwersen, Peter; Rehfeld, Jens F

2008-09-01

Quantitative bibliometric measurements of research activity are frequently used, e.g. for evaluating applicants for academic positions. The purpose of this investigation is to assess research activity within the medical speciality of Clinical Biochemistry by comparing it with a matched control group from other medical specialities in Denmark. A list of all physicians registered in Denmark (23,127 persons) was drawn from the database "Laeger.dk". Of these, 5,202 were generalists (not included) while 11,691 were from other specialities. Of the 126 specialists from Clinical Biochemistry, 57 fulfilled the inclusion criteria. Each of these 57 was matched according to medical title with two randomly chosen specialists from other specialities, totaling 114. Using Medline and the Web of Science, the number of publications and the number of citations were then ascertained. 25% of the 11,691 specialists held a PhD degree or doctoral degree, DMSci, (Clinical Biochemistry: 61%). The 171 specialists included in the study had 9,823 papers in Medline and 10,140 papers in the Web of Science. The number of Medline papers per specialist was 71 for Clinical Biochemistry compared to 51 for the control group. The number of citations per specialist was 1,844 for Clinical Biochemistry compared to 816 for the control group. The top ten H-indices (of which 8 were in Clinical Biochemistry) ranged from 30 to 69. Both the number of papers and the number of citations were higher for Clinical Biochemistry than for the control group. The difference was most pronounced among professors.

Total body weight loss of ≥ 10 % is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis.

PubMed

Glass, Lisa M; Dickson, Rolland C; Anderson, Joseph C; Suriawinata, Arief A; Putra, Juan; Berk, Brian S; Toor, Arifa

2015-04-01

Given the rising epidemics of obesity and metabolic syndrome, nonalcoholic steatohepatitis (NASH) is now the most common cause of liver disease in the developed world. Effective treatment for NASH, either to reverse or prevent the progression of hepatic fibrosis, is currently lacking. To define the predictors associated with improved hepatic fibrosis in NASH patients undergoing serial liver biopsies at prolonged biopsy interval. This is a cohort study of 45 NASH patients undergoing serial liver biopsies for clinical monitoring in a tertiary care setting. Biopsies were scored using the NASH Clinical Research Network guidelines. Fibrosis regression was defined as improvement in fibrosis score ≥1 stage. Univariate analysis utilized Fisher's exact or Student's t test. Multivariate regression models determined independent predictors for regression of fibrosis. Forty-five NASH patients with biopsies collected at a mean interval of 4.6 years (±1.4) were included. The mean initial fibrosis stage was 1.96, two patients had cirrhosis and 12 patients (26.7 %) underwent bariatric surgery. There was a significantly higher rate of fibrosis regression among patients who lost ≥10 % total body weight (TBW) (63.2 vs. 9.1 %; p = 0.001) and who underwent bariatric surgery (47.4 vs. 4.5 %; p = 0.003). Factors such as age, gender, glucose intolerance, elevated ferritin, and A1AT heterozygosity did not influence fibrosis regression. On multivariate analysis, only weight loss of ≥10 % TBW predicted fibrosis regression [OR 8.14 (CI 1.08-61.17)]. Results indicate that regression of fibrosis in NASH is possible, even in advanced stages. Weight loss of ≥10 % TBW predicts fibrosis regression.

Interventions for improving research productivity in clinical radiology.

PubMed

Akhtar, Waseem; Arain, Mubashir Aslam; Ali, Arif; Sajjad, Zafar

2012-07-01

The purpose of this study was to evaluate the effects of research promotion activities on overall quality and quantity of research output in a clinical department of a teaching tertiary care hospital. Simple research enhancing strategies including regular journal club, research hour, basic research skills training, hiring of research faculty, research awards, and annual research retreat and research board to increase research production were implemented in the Department of Radiology of a teaching hospital in Pakistan. A total of 77 papers were produced by the Department of Radiology before the intervention, which increased to 92 after the introduction of research initiatives. There was a significant increase in the overall proportion of publications in the international journals after the intervention (p < 0.001) with an increasing trend towards indexed journals (p < 0.001). The research enhancing interventions had a positive effect on increasing clinical research output by the Department of Radiology. Such interventions can also be replicated in other clinical departments to increase their research productivity.

The role and potential contribution of clinical research nurses to clinical trials.

PubMed

Spilsbury, Karen; Petherick, Emily; Cullum, Nicky; Nelson, Andrea; Nixon, Jane; Mason, Su

2008-02-01

This study explores the scope and potential contribution of the Clinical Research Nurse (CRN) role to clinical trials of a nursing-specific topic. Over the past two decades, there have been increases in the numbers of nurses working as CRNs because of the increasing global demand for clinical trials. CRNs can influence the quality of clinical trials but the scope and contribution of the role to clinical trials is not known. Qualitative focus group study. A focus group interview was carried out with CRNs (n = 9) employed on a large, multi-centre (six NHS Trusts) randomized controlled trial of pressure area care. The focus group interview was recorded, alongside field notes of participant interactions and behaviours, and transcribed verbatim. Data were analysed for thematic content and process. CRNs described their transition to a clinical research role. They reported a lack of confidence, role conflict as researcher and nurse, the challenges of gaining cooperation of clinical nursing staff to comply with trial protocols and difficulties maintaining their own motivation. CRNs provided their perceptions and observations of pressure area care and prevention. They identified areas of inadequate treatment, management and care, influenced by organizational and clinical aspects of care delivery. The study reveals challenges associated with training and management of CRNs. CRNs are usually associated with trial recruitment and data collection. This study highlights the additional contributions of CRNs for the study of topics specific to nursing as the result of their unique placement in the research centres as informal 'participant observers.' Such observations enhance understanding of the contexts being studied. These findings are relevant to the design and conduct of research studies of nursing care and practice and present ways for investigators to optimize the skills and knowledge of nurses working as CRNs.

A European perspective--the European clinical research infrastructures network.

PubMed

Demotes-Mainard, J; Kubiak, C

2011-11-01

Evaluating research outcomes requires multinational cooperation in clinical research for optimization of treatment strategies and comparative effectiveness research, leading to evidence-based practice and healthcare cost containment. The European Clinical Research Infrastructures Network (ECRIN) is a distributed ESFRI (European Strategy Forum on Research Infrastructures) roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific potential. Servicing multinational trials started during its preparatory phase, and ECRIN will now apply for an ERIC (European Research Infrastructures Consortium) status by 2011. By creating a single area for clinical research in Europe, this achievement will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of the research and education capacity, tackling the major societal challenges starting with the area of healthy ageing, and removing barriers to bring ideas to the market.

Implementing Clinical Research Using Factorial Designs: A Primer.

PubMed

Baker, Timothy B; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Fiore, Michael C; Piper, Megan E; Collins, Linda M

2017-07-01

Factorial experiments have rarely been used in the development or evaluation of clinical interventions. However, factorial designs offer advantages over randomized controlled trial designs, the latter being much more frequently used in such research. Factorial designs are highly efficient (permitting evaluation of multiple intervention components with good statistical power) and present the opportunity to detect interactions amongst intervention components. Such advantages have led methodologists to advocate for the greater use of factorial designs in research on clinical interventions (Collins, Dziak, & Li, 2009). However, researchers considering the use of such designs in clinical research face a series of choices that have consequential implications for the interpretability and value of the experimental results. These choices include: whether to use a factorial design, selection of the number and type of factors to include, how to address the compatibility of the different factors included, whether and how to avoid confounds between the type and number of interventions a participant receives, and how to interpret interactions. The use of factorial designs in clinical intervention research poses choices that differ from those typically considered in randomized clinical trial designs. However, the great information yield of the former encourages clinical researchers' increased and careful execution of such designs. Copyright © 2017. Published by Elsevier Ltd.

Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.

PubMed

Du, Xianhong; Wu, Zhuanchang; Xu, Yong; Liu, Yuan; Liu, Wen; Wang, Tixiao; Li, Chunyang; Zhang, Cuijuan; Yi, Fan; Gao, Lifen; Liang, Xiaohong; Ma, Chunhong

2018-05-07

As an immune checkpoint, Tim-3 plays roles in the regulation of both adaptive and innate immune cells including macrophages and is greatly involved in chronic liver diseases. However, the precise roles of Tim-3 in nonalcoholic steatohepatitis (NASH) remain unstated. In the current study, we analyzed Tim-3 expression on different subpopulations of liver macrophages and further investigated the potential roles of Tim-3 on hepatic macrophages in methionine and choline-deficient diet (MCD)-induced NASH mice. The results of flow cytometry demonstrated the significantly increased expression of Tim-3 on all detected liver macrophage subsets in MCD mice, including F4/80 + CD11b + , F4/80 + CD68 + , and F4/80 + CD169 + macrophages. Remarkably, Tim-3 knockout (KO) significantly accelerated MCD-induced liver steatosis, displaying higher serum ALT, larger hepatic vacuolation, more liver lipid deposition, and more severe liver fibrosis. Moreover, compared with wild-type C57BL/6 mice, Tim-3 KO MCD mice demonstrated an enhanced expression of NOX2, NLRP3, and caspase-1 p20 together with increased generation of IL-1β and IL-18 in livers. In vitro studies demonstrated that Tim-3 negatively regulated the production of reactive oxygen species (ROS) and related downstream pro-inflammatory cytokine secretion of IL-1β and IL-18 in macrophages. Exogenous administration of N-Acetyl-L-cysteine (NAC), a small molecular inhibitor of ROS, remarkably suppressed caspase-1 p20 expression and IL-1β and IL-18 production in livers of Tim-3 KO mice, thus significantly reducing the severity of steatohepatitis induced by MCD. In conclusion, Tim-3 is a promising protector in MCD-induced steatohepatitis by controlling ROS and the associated pro-inflammatory cytokine production in macrophages.

A dietary restriction influences the progression but not the initiation of MSG-Induced nonalcoholic steatohepatitis.

PubMed

Fujimoto, Makoto; Tsuneyama, Koichi; Nakanishi, Yuko; Salunga, Thucydides L; Nomoto, Kazuhiro; Sasaki, Yoshiyuki; Iizuka, Seiichi; Nagata, Mitsunobu; Suzuki, Wataru; Shimada, Tsutomu; Aburada, Masaki; Shimada, Yutaka; Gershwin, M Eric; Selmi, Carlo

2014-03-01

The metabolic syndrome is a major worldwide health care issue and a dominant risk factor for cardiovascular disease. The liver manifestations of this syndrome include nonalcoholic fatty liver disease (NAFLD) and its progressive variant nonalcoholic steatohepatitis (NASH). Although significant research has been performed, the basic pathogenesis of NAFLD/NASH remains controversial and effective treatments are still unavailable. We have previously reported on a murine model of NASH induced by the neonatal injection of monosodium glutamate (MSG), which includes the clinical manifestations of central obesity, diabetes, hyperlipidemia, and ultimately liver inflammation, fibrosis, and cancer. Although MSG is considered a safe food additive, its administration to pregnant rats increases the voracity and growth hormone levels in the offspring. To further understand the biology of this model, we have investigated the influence of the calorie intake on these clinical manifestations by feeding animals a restrictive diet. MSG-treated animals fed a restrictive diet continue to manifest obesity and early stage NASH but have improvements in serum lipid profiles. At 12 months of age, mice had manifestations of obesity, whether animals were fed a restricted or control diet, but animals fed a restrictive diet had a reduction in the progression of NASH. In conclusion, MSG appears to be a critical factor in the initiation of obesity, whereas calorie intake may modulate the progression of disease.

Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery.

PubMed

Pirvulescu, I; Gheorghe, L; Csiki, I; Becheanu, G; Dumbravă, M; Fica, S; Martin, S; Sarbu, A; Gheorghe, C; Diculescu, M; Copăescu, C

2012-01-01

Liver biopsy, an invasive method, is the gold standard for differentiate nonalcoholic steatohepatitis (NASH) from other stages of fatty liver disease. A noninvasive test to diagnose NASH and disease severity before surgery and also for monitoring disease status after bariatric surgery (BS) will be an important medical challenge. To create a noninvasive biomarkers model for the diagnosis of NASH in overweight, obese and morbidly obese patients (MOP). Sixty patients (mean BMI= 47.81kg/m2) were admitted after exclusion of other causes of liver disease. Liver biopsies were obtained at the time of the bariatric surgery or by percutaneous liver biopsy and graded using Kleiner score. Continuous variables were compared using Wilcoxon rank sum test and for prediction of NASH we used logistic regression. Logistic regression analysis showed that BMI, ALT, AST, alkaline phosphatase (ALP), HOMA-R, hs-CRP, M30, M65, leptine and adiponectine levels remained independent predictors for NASH (p less than 0.02). Using AUC analysis, we established the following cutoff levels being indicative of NASH: BMI ė 47 kg/m2, ALT ė 32 IU/mL, AST ė 25 IU/mL, ALP ė 85 IU/mL, HOMA-IR ė 4, M65 ė 389 U/L. Adiponectine less than 13.5 mg/L. A NASH-score, calculated as the sum of these 7 parameters, at a cutoff level of 4 points, can accurately predict NASH (sensitivity of 90%, specificity of 93.94% and AUC of 0.9576). We propose a noninvasive model for NASH diagnosis in MOP that should be validated prospectively. Using this noninvasive score, NASH would be predicted without the risks of liver biopsy. Celsius.

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

PubMed Central

Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

Clinical approaches to non-alcoholic fatty liver disease

PubMed Central

Schwenger, Katherine JP; Allard, Johane P

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

Gender identity, research self-efficacy and research intention in trainee clinical psychologists in the UK.

PubMed

Wright, Anne B; Holttum, Sue

2012-01-01

This study tested, with a sample of United Kingdom (UK) trainee clinical psychologists, part of an existing model of factors that influence clinical psychologists' levels of research activity, in which gender identity is hypothesized to influence research self-efficacy and this in turn strength of intention to do research. A sample of 121 trainee clinical psychologists (56 men and 65 women) completed a measure of gender identity, research intention, and a research self-efficacy scale. Results indicated no differences in levels of research intention or research self-efficacy between the biological sexes or according to category-based gender identities (masculine and feminine). However, masculinity as a scale quantity was statistically significantly related to stronger research intention, preference for conducting quantitative research and research self-efficacy. Multiple regression analysis provided evidence that research self-efficacy may mediate between masculinity and strength of research intention. Research self-efficacy was the strongest predictor of intention to do research in the future. Findings have relevance for clinical psychology training as research activity directly impacts upon advances in the discipline of clinical psychology, implementation of research into practice, and evaluation of psychological therapies. Copyright © 2010 John Wiley & Sons, Ltd.

Integration of clinical research documentation in electronic health records.

PubMed

Broach, Debra

2015-04-01

Clinical trials of investigational drugs and devices are often conducted within healthcare facilities concurrently with clinical care. With implementation of electronic health records, new communication methods are required to notify nonresearch clinicians of research participation. This article reviews clinical research source documentation, the electronic health record and the medical record, areas in which the research record and electronic health record overlap, and implications for the research nurse coordinator in documentation of the care of the patient/subject. Incorporation of clinical research documentation in the electronic health record will lead to a more complete patient/subject medical record in compliance with both research and medical records regulations. A literature search provided little information about the inclusion of clinical research documentation within the electronic health record. Although regulations and guidelines define both source documentation and the medical record, integration of research documentation in the electronic health record is not clearly defined. At minimum, the signed informed consent(s), investigational drug or device usage, and research team contact information should be documented within the electronic health record. Institutional policies should define a standardized process for this integration in the absence federal guidance. Nurses coordinating clinical trials are in an ideal position to define this integration.

Clinical Investigator Development Program | Center for Cancer Research

Cancer.gov

Clinical Investigator Development Program Application Deadline:  September 30, 2018 Program Starts: July 1, 2019 The NCI Center for Cancer Research (CCR) is pleased to announce our annual call for applications for an exciting training opportunity intended for physicians interested in dedicating their careers to clinical research. Come join a vibrant, multidisciplinary research

The UK clinical research network--has it been a success for dermatology clinical trials?

PubMed

Thomas, Kim S; Koller, Karin; Foster, Katharine; Perdue, Jo; Charlesworth, Lisa; Chalmers, Joanne R

2011-06-16

Following the successful introduction of five topic-specific research networks in the UK, the Comprehensive Local Research Network (CLRN) was established in 2008 in order to provide a blanket level of support across the whole country regardless of the clinical discipline. The role of the CLRN was to facilitate recruitment into clinical trials, and to encourage greater engagement in research throughout the National Health Service (NHS). This report evaluates the impact of clinical research networks in supporting clinical trials in the UK, with particular reference to our experiences from two non-commercial dermatology trials. It covers our experience of engaging with the CLRN (and other research networks) using two non-commercial dermatology trials as case studies. We present the circumstances that led to our approach to the research networks for support, and the impact that this support had on the delivery of these trials. In both cases, recruitment was boosted considerably following the provision of additional support, although other factors such as the availability of experienced personnel, and the role of advertising and media coverage in promoting the trials were also important in translating this additional resource into increased recruitment. Recruitment into clinical trials is a complex task that can be influenced by many factors. A world-class clinical research infrastructure is now in place in England (with similar support available in Scotland and Wales), and it is the responsibility of the research community to ensure that this unique resource is used effectively and responsibly.

Conducting research in clinical psychology practice: Barriers, facilitators, and recommendations.

PubMed

Smith, Kirsten V; Thew, Graham R

2017-09-01

The combination of clinical psychologists' therapeutic expertise and research training means that they are in an ideal position to be conducting high-quality research projects. However, despite these skills and the documented benefits of research to services and service users, research activity in practice remains low. This article aims to give an overview of the advantages of, and difficulties in conducting research in clinical practice. We reviewed the relevant literature on barriers to research and reflected on our clinical and research experiences in a range of contexts to offer practical recommendations. We considered factors involved in the planning, sourcing support, implementation, and dissemination phases of research, and outline suggestions to improve the feasibility of research projects in post-qualification roles. We suggest that research leadership is particularly important within clinical psychology to ensure the profession's continued visibility and influence within health settings. Clinical implications Emerging evidence suggests that clinical settings that foster research are associated with better patient outcomes. Suggestions to increase the feasibility of research projects in clinical settings are detailed. Limitations The present recommendations are drawn from the authors' practical experience and may need adaptation to individual practitioners' settings. This study does not attempt to assess the efficacy of the strategies suggested. © 2017 The Authors. British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Clinical Research Informatics for Big Data and Precision Medicine.

PubMed

Weng, C; Kahn, M G

2016-11-10

To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors.

Clinical Epidemiology Unit - overview of research areas

Cancer.gov

Clinical Epidemiology Unit (CEU) conducts etiologic research with potential clinical and public health applications, and leads studies evaluating population-based early detection and cancer prevention strategies

Nature and governance of veterinary clinical research conducted in the UK.

PubMed

Fordyce, P; Mullan, S

2017-01-21

In order to quantify the amount of clinical research conducted on client-owned animals under the Veterinary Surgeons Act 1966, and the nature and extent of any ethical review of that research, a questionnaire was sent to 6 UK veterinary schools, 1 charity veterinary clinic and 12 private referral clinics. The questionnaire examined whether and how much clinical research respondents undertook, and the composition of any ethical review panels examining research proposals. The questionnaire revealed a substantial amount of clinical research was conducted in the UK, with over 200 veterinary surgeons involved in the year of the survey, with at least 170 academic papers involving clinical research published by respondents in the same year. However, it proved impossible to quantify the full extent of clinical research in the UK. All UK veterinary schools required ethical review of clinical research. The composition and working practices of their ethical review panels generally reflected skill sets in ethical review panels set-up under statute to consider the ethics of non-clinical biomedical research on animals and clinical research conducted on human patients. The process for review of clinical research in the private sector was less clear. British Veterinary Association.

Development, Testing, and Psychometric Qualities of the Nash Duty to Care Scale for Disaster Response.

PubMed

Nash, Tracy Jeanne

2017-08-01

Although nurses struggle with the decision to report for work during disaster events, there are no instruments to measure nurses' duty to care for disaster situations. The purpose of this study was to describe the development, testing, and psychometric qualities of the Nash Duty to Care Scale. A convenience sample of 409 registered nurses were recruited from 3 universities in the United States. Exploratory factor analysis resulted in a 19-item, 4-factor model explaining 67.34% of the variance. Internal consistency reliability was supported by Cronbach's alpha ranging from .81 to .91 for the 4-factor subscales and .92 for the total scale. The psychometrically sound instrument for measuring nurses' perceived duty to care for disasters is applicable to contemporary nursing practice, institutional disaster management plans, and patient health outcomes worldwide.

Construction of databases: advances and significance in clinical research.

PubMed

Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

2015-12-01

Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research.

ResearchMatch: A National Registry to Recruit Volunteers for Clinical Research

PubMed Central

Harris, Paul A.; Scott, Kirstin W; Lebo, Laurie; Hassan, NikNik; Lighter, Chad; Pulley, Jill

2013-01-01

The authors designed ResearchMatch, a disease-neutral, web-based recruitment registry to help match individuals who wish to participate in clinical research studies with researchers actively searching for volunteers throughout the United States. In this article, they describe ResearchMatch’s stakeholders, workflow model, technical infrastructure, and, for the registry’s first 19 months of operation, utilization metrics. Having launched volunteer registration tools in November 2009 and researcher registration tools in March 2010, ResearchMatch had, as of June 2011, registered 15,871 volunteer participants from all 50 states. The registry was created as a collaborative project for institutions in the Clinical and Translational Science Awards (CTSA) consortium. Also as of June 2011, a total of 751 researchers from 61 participating CTSA institutions had registered to use the tool to recruit participants into 540 active studies and trials. ResearchMatch has proven successful in connecting volunteers with researchers, and the authors are currently evaluating regulatory and workflow options to open access to researchers at non-CTSA institutions. PMID:22104055

A metadata schema for data objects in clinical research.

PubMed

Canham, Steve; Ohmann, Christian

2016-11-24

A large number of stakeholders have accepted the need for greater transparency in clinical research and, in the context of various initiatives and systems, have developed a diverse and expanding number of repositories for storing the data and documents created by clinical studies (collectively known as data objects). To make the best use of such resources, we assert that it is also necessary for stakeholders to agree and deploy a simple, consistent metadata scheme. The relevant data objects and their likely storage are described, and the requirements for metadata to support data sharing in clinical research are identified. Issues concerning persistent identifiers, for both studies and data objects, are explored. A scheme is proposed that is based on the DataCite standard, with extensions to cover the needs of clinical researchers, specifically to provide (a) study identification data, including links to clinical trial registries; (b) data object characteristics and identifiers; and (c) data covering location, ownership and access to the data object. The components of the metadata scheme are described. The metadata schema is proposed as a natural extension of a widely agreed standard to fill a gap not tackled by other standards related to clinical research (e.g., Clinical Data Interchange Standards Consortium, Biomedical Research Integrated Domain Group). The proposal could be integrated with, but is not dependent on, other moves to better structure data in clinical research.

Reflections on clinical research in sub-Saharan Africa.

PubMed

Kuepfer, Irene; Burri, Christian

2009-07-15

The urgent need for new, safe and sustainable interventions against diseases that disproportionally affect the poor is finally receiving global attention and the funding landscape for development projects has significantly improved during the past decade. For the development of new drug and vaccine candidates, clinical trials have become the most important tool to assess their safety and efficacy. Recently, there has been a seismic shift in the number of clinical trials conducted in resource-limited settings. We discuss the current framework of clinical research in sub-Saharan Africa, from building product pipelines to the capacities needed for the conduct of trials according the harmonised Good Clinical Practice (GCP) ICH E6 guideline. We place emphasis on clinical research in neglected tropical diseases which still frequently has to be conducted with limited financial, logistical and human resources. Given those short-comings we recommend minimum standards needed at the local, national and sponsor levels to provide GCP-compliant clinical research.

Strategies to successfully recruit and engage clinical nurses as participants in qualitative clinical research.

PubMed

Coyne, Elisabeth; Grafton, Eileen; Reid, Alayne

2016-12-01

Research conducted in the clinical area promotes the delivery of evidence-based patient care. Involving nurses as participants in research is considered essential to link patient care with evidence-based interventions. However recruitment is influenced by nurses' competing demands and understanding engagement strategies may assist future research. This reflective analysis aimed to understand influencing factors and strategies that support successful recruitment nurses in clinical research. A reflective analysis of research notes and focus group data from research with oncology nurses was completed. This research identified that gaining support from key staff, understanding work constraints and developing a rapport with nurses is important. Establishing clear relevance and benefits of the research and being flexible with research requirements enabled nurses to participate in the research. Clear information and a willingness to accommodate the demands and dynamic nature of the environment, ensures ongoing support and engagement of nurses in the clinical setting as participants in research.

Korea University Joins the International Efforts in Clinical Proteogenomics Cancer Research | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute's (NCI) Office of Cancer Clinical Proteomics Research, part of the National Institutes of Health, and Korea University (KU) located in The Republic of Korea have signed a Memorandum of Understanding (MOU) in clinical proteogenomics cancer research. The MOU between NCI and KU represents the twenty-ninth institution and eleventh country to join the continued effort of the International Cancer Proteogenome Consortium (ICPC), an effort catalyzed through the vision of the 47th Vice President of the United States Joseph R. Biden, Jr. and the Cancer Moonshot.

Clinical and translational research in global health and emergency care: a research agenda.

PubMed

Runyon, Michael S; Sawe, Hendry R; Levine, Adam C; Pousson, Amelia; House, Darlene R; Agrawal, Pooja; Osei-Ampofo, Maxwell; Weiner, Scott G; Douglass, Katherine

2013-12-01

As policy-makers increasingly recognize emergency care to be a global health priority, the need for high-quality clinical and translational research in this area continues to grow. As part of the proceedings of the 2013 Academic Emergency Medicine consensus conference, this article discusses the importance of: 1) including clinical and translational research in the initial emergency care development plan, 2) defining the burden of acute disease and the barriers to conducting research in resource-limited settings, 3) assessing the appropriateness and effectiveness of local and global acute care guidelines within the local context, 4) studying the local research infrastructure needs to understand the best methods to build a sustainable research infrastructure, and 5) studying the long-term effects of clinical research programs on health care systems. © 2013 by the Society for Academic Emergency Medicine.

Autoimmune Hepatitis

MedlinePlus

... Living with a Liver Transplant Clinical Trials Nonalcoholic Fatty Liver Disease & NASH Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Nonalcoholic Fatty Liver Disease & NASH in Children Definition & Facts Symptoms & Causes ...

The Ethics of Clinical Care and the Ethics of Clinical Research: Yin and Yang.

PubMed

Kowalski, Charles J; Hutchinson, Raymond J; Mrdjenovich, Adam J

2017-02-01

The Belmont Report's distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical Research Informatics for Big Data and Precision Medicine

PubMed Central

Kahn, M. G.

2016-01-01

Summary Objectives To reflect on the notable events and significant developments in Clinical Research Informatics (CRI) in the year of 2015 and discuss near-term trends impacting CRI. Methods We selected key publications that highlight not only important recent advances in CRI but also notable events likely to have significant impact on CRI activities over the next few years or longer, and consulted the discussions in relevant scientific communities and an online living textbook for modern clinical trials. We also related the new concepts with old problems to improve the continuity of CRI research. Results The highlights in CRI in 2015 include the growing adoption of electronic health records (EHR), the rapid development of regional, national, and global clinical data research networks for using EHR data to integrate scalable clinical research with clinical care and generate robust medical evidence. Data quality, integration, and fusion, data access by researchers, study transparency, results reproducibility, and infrastructure sustainability are persistent challenges. Conclusion The advances in Big Data Analytics and Internet technologies together with the engagement of citizens in sciences are shaping the global clinical research enterprise, which is getting more open and increasingly stakeholder-centered, where stakeholders include patients, clinicians, researchers, and sponsors. PMID:27830253

Untapped Potential of Observational Research to Inform Clinical Decision Making: American Society of Clinical Oncology Research Statement.

PubMed

Visvanathan, Kala; Levit, Laura A; Raghavan, Derek; Hudis, Clifford A; Wong, Sandra; Dueck, Amylou; Lyman, Gary H

2017-06-01

ASCO believes that high-quality observational studies can advance evidence-based practice for cancer care and are complementary to randomized controlled trials (RCTs). Observational studies can generate hypotheses by evaluating novel exposures or biomarkers and by revealing patterns of care and relationships that might not otherwise be discovered. Researchers can then test these hypotheses in RCTs. Observational studies can also answer or inform questions that either have not been or cannot be answered by RCTs. In addition, observational studies can be used for postmarketing surveillance of new cancer treatments, particularly in vulnerable populations. The incorporation of observational research as part of clinical decision making is consistent with the position of many leading institutions. ASCO identified five overarching recommendations to enhance the role of observational research in clinical decision making: (1) improve the quality of electronic health data available for research, (2) improve interoperability and the exchange of electronic health information, (3) ensure the use of rigorous observational research methodologies, (4) promote transparent reporting of observational research studies, and (5) protect patient privacy.

Asking good clinical research questions and choosing the right study design.

PubMed

Bragge, P

2010-07-01

Clinicians and researchers seek answers to clinical research questions, primarily by accessing the results of clinical research studies. This paper moves the focus of research enquiry from getting answers to developing good clinical research questions. Using worked examples, the steps involved in refining questions drawn from various sources to create 'answerable' clinical research questions using the 'PICO' principle are described. Issues to consider in prioritising clinical research questions are also identified. Theoretical and practical considerations involved in choosing the right study design for a clinical research question are then discussed using the worked examples. These include: Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Centralized Research Recruitment—Evolving a Local Clinical Research Recruitment Web Application to Better Meet User Needs

PubMed Central

Dwyer‐White, Molly; Doshi, Aalap; Hill, Mary; Pienta, Kenneth J.

2011-01-01

Abstract  Recruiting volunteers into clinical research remains a significant challenge for many clinical research study teams, thus the Michigan Institute for Clinical and Health Research (MICHR) at the University of Michigan developed UMClinicalStudies (http://www.UMClinicalStudies.org)—a Web application that links the community to a single gateway for clinical research. UMClinicalStudies (formerly named “Engage”) is an integral piece of MICHR’s efforts to increase clinical research participation in order to advance medical discoveries. Despite the initial success of the application, barriers to research participation remain, including the applications accessibility for potential research volunteers and study team members. In response, new initiatives were instigated to identify user needs, in order to broaden the ability to simultaneously assist researchers in recruitment activities, while also aiding potential volunteers in the exploration of and participation in clinical research opportunities. To do this, improvements to the interface and functionality were identified and implemented for both the public and the research audiences through extensive system analysis, and through the application of human computer interactivity processes, resulting in significant improvements in usability and ultimately research volunteerism, indicating that utilizing such technology is pivotal in reaching broader audiences for clinical trial participation. Clin Trans Sci 2011; Volume 4: 363–368 PMID:22029810

Perceptions and attitudes to clinical research participation in Qatar.

PubMed

Tohid, Hiba; Choudhury, Sopna M; Agouba, Sahar; Aden, Abdi; Ahmed, Lina H M; Omar, Omar; Chagoury, Odette; Taheri, Shahrad

2017-12-01

Recruitment into clinical research studies is a major challenge. This study was carried out to explore the perceptions and attitudes towards clinical research participation among the general public in Qatar. A population based questionnaire study was carried out at public events held in Qatar. Residents of Qatar, 18 years or above in age were surveyed, anonymously, following verbal consent. Descriptive and multivariate analyses were conducted. We administered 2517 questionnaires to examine clinical research participation, of which 2379 complete forms were analyzed. Those who had previously been approached to participate in research completed a more detailed assessment. Data showed that only 5.7% participants (n = 134) had previously been approached to participate in a clinical research study. Of these 63.4% (n = 85) had agreed to participate while 36.6% (n = 49) had declined. The main reasons for declining participation included: time constraint (47.8%, n = 11), 'fear' (13.0%, n = 3), lack of awareness about clinical research (8.7%, n = 2) and lack of interest (8.7%, n = 2). 'To help others' (31.8%, n = 27) and 'thought it might improve my access to health care' (24.7%, n = 21) were the prime motivators for participation. There was a general agreement among participants that their previous research experience was associated with positive outcomes for self and others, that the research conduct was ethical, and that opportunities for participation will be welcomed in future. More than ten years of stay within Qatar was a statistically significant determinant of willingness to participate, adjusted odds ratio 5.82 (95% CI 1.93-17.55), p = 0.002. Clinical research participation in Qatar needs improvement. Time constraints, lack of trust in and poor awareness about clinical research are main barriers to participation. Altruism, and improved health access are reported as prime motivators. Deeper insight in to the factors affecting clinical research

The distribution of outcomes research papers across clinical journals.

PubMed

Goldsack, Jennifer; McLaughlin, Chris; Bristol, Mirar N; Loeb, Alex; Bergey, Meredith; Sonnad, Seema S

2011-06-01

This study examines the distribution of health outcomes research (HOR) studies in the clinical literature by clinical areas and journal impact factor. The authors reviewed 535 journals and divided the sample into higher and lower impact journals across four clinical area. Mann-Whitney and Kruskal-Wallis tests were used to examine differences across four categories of outcomes research articles published, specifically the incidence of articles in higher versus lower impact journals and differences across clinical areas. All high-impact journals published more safety and quality articles than process assessment, quality of life, or cost analysis studies. The number of each type of outcomes research study published was highly variable across all clinical areas. Only arthritis and outcomes research journals showed statistically significant differences between higher versus lower impact journals. Authors may benefit from considering these differences in their clinical specialty area when deciding where to submit HOR studies.

Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries.

PubMed

Kagan, Jonathan; Giang, Dao Duc; Iademarco, Michael F; Phung, Van Tt; Lau, Chuen-Yen; Quang, Nguyen Ngo

2016-01-01

Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts.

Ethics in clinical research: the Indian perspective.

PubMed

Sanmukhani, J; Tripathi, C B

2011-03-01

Ethics in clinical research focuses largely on identifying and implementing the acceptable conditions for exposure of some individuals to risks and burdens for the benefit of society at large. Ethical guidelines for clinical research were formulated only after discovery of inhumane behaviour with participants during research experiments. The Nuremberg Code was the first international code laying ethical principles for clinical research. With increasing research all over, World Health Organization formulated guidelines in the form of Declaration of Helsinki in 1964. The US laid down its guidelines for ethical principles in the Belmont Report after discovery of the Tuskegee's Syphilis study. The Indian Council of Medical Research has laid down the 'Ethical Guidelines for Biomedical Research on Human Subjects' in the year 2000 which were revised in 2006. It gives twelve general principles to be followed by all biomedical researchers working in the country. The Ethics Committee stands as the bridge between the researcher and the ethical guidelines of the country. The basic responsibility of the Ethics Committee is to ensure an independent, competent and timely review of all ethical aspects of the project proposals received in order to safeguard the dignity, rights, safety and well-being of all actual or potential research participants. A well-documented informed consent process is the hallmark of any ethical research work. Informed consent respects individual's autonomy, to participate or not to participate in research. Concepts of vulnerable populations, therapeutic misconception and post trial access hold special importance in ethical conduct of research, especially in developing countries like India, where most of the research participants are uneducated and economically backward.

Five-year review of an international clinical research-training program

PubMed Central

Suemoto, Claudia Kimie; Ismail, Sherine; Corrêa, Paulo César Rodrigues Pinto; Khawaja, Faiza; Jerves, Teodoro; Pesantez, Laura; Germani, Ana Claudia Camargo Gonçalves; Zaina, Fabio; dos Santos, Augusto Cesar Soares; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomás, Rita; Illigens, Ben MW; Fregni, Felipe

2015-01-01

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008–2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background. PMID:25878518

Five-year review of an international clinical research-training program.

PubMed

Suemoto, Claudia Kimie; Ismail, Sherine; Corrêa, Paulo César Rodrigues Pinto; Khawaja, Faiza; Jerves, Teodoro; Pesantez, Laura; Germani, Ana Claudia Camargo Gonçalves; Zaina, Fabio; Dos Santos, Augusto Cesar Soares; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomás, Rita; Illigens, Ben Mw; Fregni, Felipe

2015-01-01

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background.

Nursing research. Components of a clinical research study.

PubMed

Bargagliotti, L A

1988-09-01

Nursing research is the systematic collection and analysis of data about clinically important phenomena. While there are norms for conducting research and rules for using certain research procedures, the reader must always filter the research report against his or her nursing knowledge. The most common questions a reader should ask are "Does it make sense? Can I think of any other reasonable explanation for the findings? Do the findings fit what I have observed?" If the answers are reasonable, research findings from carefully conducted studies can provide a basis for making nursing decisions. One of the earliest accounts of nursing research, which indicates the power of making systematic observations, was Florence Nightingale's study. It compared deaths among soldiers in the Crimean War with deaths of soldiers in the barracks of London. Her research demonstrated that soldiers in the barracks had a much higher death rate than did the soldiers at war. On the basis of the study, sanitary conditions in the barracks were changed substantially.

Clinical research: business opportunities for pharmacy-based investigational drug services.

PubMed

Marnocha, R M

1999-02-01

The application by an academic health center of business principles to the conduct of clinical research is described. Re-engineering of the infrastructure for clinical research at the University of Wisconsin and University of Wisconsin Hospital and Clinics began in 1990 with the creation of the Center for Clinical Trials (CCT) and the restructuring of the investigational drug services (IDS). Strategies to further improve the institution's clinical research activities have been continually assessed and most recently have centered on the adaptation of a business philosophy within the institution's multidisciplinary research infrastructure. Toward that end, the CCT and IDS have introduced basic business principles into operational activities. Four basic business concepts have been implemented: viewing the research protocol as a commodity, seeking payment for services rendered, tracking investments, and assessing performance. It is proposed that incorporation of these basic business concepts is not only compatible with the infrastructure for clinical research but beneficial to that infrastructure. The adaptation of a business mindset is likely to enable an academic health center to reach its clinical research goals.

An Integrative Review of Engaging Clinical Nurses in Nursing Research.

PubMed

Scala, Elizabeth; Price, Carrie; Day, Jennifer

2016-07-01

To review the literature for best practices for engaging clinical nurses in nursing research. Review of the research and nonresearch papers published between 2005 and 2015 that answered the evidence-based practice (EBP) question: what are the best practices for engaging clinical nursing staff in nursing research? PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Joanna Briggs Institute, and Cochrane were searched using a combination of controlled vocabulary and key words. Nineteen papers that answered the EBP question were selected for review. It can be difficult to involve clinical nurses in research. There are multiple factors to consider when nursing leadership looks to engage clinical nurses in nursing research. Nurse leaders can take many approaches to engage clinical nurses in research. Each organization must perform its own assessment to identify areas of opportunity. Nursing leadership can take these areas of opportunity to structure a multifaceted approach to support clinical staff in the conduct and dissemination of nursing research. The evidence from this review offers EBP recommendations as well as reports on the gaps in the literature related to best practices for engaging clinical nurses in nursing research. © 2016 Sigma Theta Tau International.

The Secure Medical Research Workspace: An IT Infrastructure to Enable Secure Research on Clinical Data

PubMed Central

Owen, Phillips; Mostafa, Javed; Lamm, Brent; Wang, Xiaoshu; Schmitt, Charles P.; Ahalt, Stanley C.

2013-01-01

Abstract Clinical data have tremendous value for translational research, but only if security and privacy concerns can be addressed satisfactorily. A collaboration of clinical and informatics teams, including RENCI, NC TraCS, UNC's School of Information and Library Science, Information Technology Service's Research Computing and other partners at the University of North Carolina at Chapel Hill have developed a system called the Secure Medical Research Workspace (SMRW) that enables researchers to use clinical data securely for research. SMRW significantly minimizes the risk presented when using identified clinical data, thereby protecting patients, researchers, and institutions associated with the data. The SMRW is built on a novel combination of virtualization and data leakage protection and can be combined with other protection methodologies and scaled to production levels. PMID:23751029

Vitamin B5 and N-acetylcysteine in nonalcoholic steatohepatitis: a pre-clinical study in a dietary mouse model

PubMed Central

Machado, Mariana Verdelho; Kruger, Leandi; Jewell, Mark L.; Michelotti, Gregory Alexander; de Almeida Pereira, Thiago; Xie, Guanhua; Moylan, Cynthia A.; Diehl, Anna Mae

2015-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for caspase-2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), the potentially progressive form of NAFLD. An imbalance between free Coenzyme A (CoA) and acyl-CoA ratio is known to induce caspase-2 activation. Objectives We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. Methods CoA metabolism was evaluated in methionine-choline deficient (MCD) and Western diet mouse models of NASH. MCD-diet fed mice were treated with pantothenate and N-acetylcysteine or placebo to determine effects on NASH. Results Liver free CoA content was reduced, pantothenate kinase (PANK), the rate-limiting enzyme in the CoA biosynthesis pathway, was down-regulated, and CoA degrading enzymes were increased in mice with NASH. Decreased hepatic free CoA content was associated with increased caspase-2 activity, and correlated with worse liver cell apoptosis, inflammation and fibrosis. Treatment with pantothenate and N-acetylcysteine did not inhibit caspase-2 activation, improve NASH, normalize PANK expression, or restore free CoA levels in MCD diet-fed mice. Conclusion In mice with NASH, hepatic CoA metabolism is impaired, leading to decreased free CoA content, activation of caspase-2, and increased liver cell apoptosis. Dietary supplementation with CoA precursors did not restore CoA levels or improve NASH, suggesting that alternative approaches are necessary to normalize free CoA during NASH. PMID:26403427

Run-Reversal Equilibrium for Clinical Trial Randomization

PubMed Central

Grant, William C.

2015-01-01

In this paper, we describe a new restricted randomization method called run-reversal equilibrium (RRE), which is a Nash equilibrium of a game where (1) the clinical trial statistician chooses a sequence of medical treatments, and (2) clinical investigators make treatment predictions. RRE randomization counteracts how each investigator could observe treatment histories in order to forecast upcoming treatments. Computation of a run-reversal equilibrium reflects how the treatment history at a particular site is imperfectly correlated with the treatment imbalance for the overall trial. An attractive feature of RRE randomization is that treatment imbalance follows a random walk at each site, while treatment balance is tightly constrained and regularly restored for the overall trial. Less predictable and therefore more scientifically valid experiments can be facilitated by run-reversal equilibrium for multi-site clinical trials. PMID:26079608

Is audit research? The relationships between clinical audit and social-research.

PubMed

Hughes, Rhidian

2005-01-01

Quality has an established history in health care. Audit, as a means of quality assessment, is well understood and the existing literature has identified links between audit and research processes. This paper reviews the relationships between audit and research processes, highlighting how audit can be improved through the principles and practice of social research. The review begins by defining the audit process. It goes on to explore salient relationships between clinical audit and research, grouped into the following broad themes: ethical considerations, highlighting responsibilities towards others and the need for ethical review for audit; asking questions and using appropriate methods, emphasising transparency in audit methods; conceptual issues, including identifying problematic concepts, such as "satisfaction", and the importance of reflexivity within audit; emphasising research in context, highlighting the benefits of vignettes and action research; complementary methods, demonstrating improvements for the quality of findings; and training and multidisciplinary working, suggesting the need for closer relationships between researchers and clinical practitioners. Audit processes cannot be considered research. Both audit and research processes serve distinct purposes. Attention to the principles of research when conducting audit are necessary to improve the quality of audit and, in turn, the quality of health care.

Encouraging primary care research: evaluation of a one-year, doctoral clinical epidemiology research course.

PubMed

Liira, Helena; Koskela, Tuomas; Thulesius, Hans; Pitkälä, Kaisu

2016-01-01

Research and PhDs are relatively rare in family medicine and primary care. To promote research, regular one-year research courses for primary care professionals with a focus on clinical epidemiology were started. This study explores the academic outcomes of the first four cohorts of research courses and surveys the participants' perspectives on the research course. An electronic survey was sent to the research course participants. All peer-reviewed scientific papers published by these students were retrieved by literature searches in PubMed. Primary care in Finland. A total of 46 research course participants who had finished the research courses between 2007 and 2012. Of the 46 participants 29 were physicians, eight nurses, three dentists, four physiotherapists, and two nutritionists. By the end of 2014, 28 of the 46 participants (61%) had published 79 papers indexed in PubMed and seven students (15%) had completed a PhD. The participants stated that the course taught them critical thinking, and provided basic research knowledge, inspiration, and fruitful networks for research. A one-year, multi-professional, clinical epidemiology based research course appeared to be successful in encouraging primary care research as measured by research publications and networking. Activating teaching methods, encouraging focus on own research planning, and support from peers and tutors helped the participants to embark on research projects that resulted in PhDs for 15% of the participants. Clinical research and PhDs are rare in primary care in Finland, which has consequences for the development of the discipline and for the availability of clinical lecturers at the universities. A clinical epidemiology oriented, one-year research course increased the activity in primary care research. Focus on own research planning and learning the challenges of research with peers appeared to enhance the success of a doctoral research course. A doctoral research course encouraged networking, and

Postdoctoral Clinical-Research Training in Psychiatry

PubMed Central

Reynolds, Charles F.; Martin, Christopher; Brent, David; Ryan, Neal; Dahl, Ronald E.; Pilkonis, Paul; Marcus, Marsha D.; Kupfer, David J.

2009-01-01

The authors describe a model for teaching grant writing and other research survival skills to postdoctoral clinical-research fellows in psychiatry and for improving research mentoring. Over the past 4 years, the authors have developed a course on writing grant applications for postdoctoral clinical-research fellows, using peer-review processes modeled after a National Institutes of Health study section. At the same time, the authors have clarified expectations of mentors in ways designed to help fellows prepare “K” (Research Career Development) applications and to receive mentored practice in skills being taught in the course. Sixteen of 30 fellows have succeeded in receiving their first extramural support by the end of their two-year fellowship tenure or during the succeeding year. The authors conclude that by teaching grant-writing skills in a supportive peer environment, providing peer review of proposals, and sharpening expectations of mentors, it may be possible to reduce the time between the end of fellowship and the receipt of the first extramural grant. PMID:19617924

Role of the clinical research nurse in tissue viability.

PubMed

Hemingway, Beverley; Storey, Carron

Opportunities for nurses to be involved in clinical research have increased with the growing emphasis on research in the NHS. This article examines the experiences of two registered nurses adapting to the role of clinical research nurse in a pressure ulcer programme of research. The challenges, rewards and strategies involved are discussed.

Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

PubMed

Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel

2010-06-04

The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.

[Cut a long story too short: Challenges in clinical research].

PubMed

Stallmach, A; Hagel, S; Bruns, T; Bauer, M

2012-03-01

Clinical research reflects a mandatory prerequisite to translate basic research into clinical practice. While a lack of available qualified doctors to fill positions in hospitals as well as in the ambulant sector has prompted political decisions to counteract, Germany has witnessed an insidious deterioration of clinical research over time and compared to other industrialized countries. Measures to prevent an increasing loss of academic profile have to tackle all aspects from undergraduate to postgraduate training to attract highly skilled doctors in sustainable structures to reflourish academic medicine. Cornerstones to achieve these goals involve establishing of structured graduate programs, acknowledgment of time spend in clinical research in residency programs, extra occupational opportunities to achieve dual qualification (e. g. Master programs in clinical research) as well as independent positions with inherent carrier perspectives in academic medicine for doctors interested in clinical and translational research. © Georg Thieme Verlag KG Stuttgart · New York.

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

PubMed

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these

Clinical trials: bringing research to the bedside.

PubMed

Arvay, C A

1991-02-01

Over the years, clinical trials with their structured treatment plans and multicenter involvement have been instrumental in developing new treatments and establishing standard of care therapy. While clinical trials strive to advance medical knowledge, they provide scientifically sound, state of the art care and their use should be increased. The Brain Tumor Cooperative Group, one such NCI-sponsored cooperative group, has been the primary group for the treatment of malignant gliomas. As the field of neuro-oncology expands, the neuroscience nurse needs to develop an understanding of clinical trials and their operation. The nurse is in an optimal position to support medical research and the research participant.

A proposed clinical research support career pathway for noninvestigators.

PubMed

Smith, Sheree; Gullick, Janice; Ballard, Jacqueline; Perry, Lin

2018-06-01

To discuss the international experience of clinical research support for noninvestigator roles and to propose a new pathway for Australia, to promote a sustainable research support workforce capable of delivering high-quality clinical research. Noninvestigator research support roles are currently characterized by an ad hoc approach to training, with limited role delineation and perceived professional isolation with implications for study completion rates and participant safety. A focused approach to developing and implementing research support pathways has improved patient recruitment, study completion, job satisfaction, and research governance. The Queensland and New South Wales state-based Nurses' Awards, the Australian Qualifications Framework, and a University Professional (Research) Staff Award. Research nurses in the clinical environment improve study coordination, adherence to study protocol, patient safety, and clinical care. A career pathway that guides education and outlines position descriptions and skill sets would enhance development of the research support workforce. This pathway could contribute to changing the patient outcomes through coordination and study completion of high-quality research. A wide consultative approach is required to determine a cost-effective and feasible approach to implementation and evaluation of the proposed pathway. © 2018 John Wiley & Sons Australia, Ltd.

Strategic trade between two regions with partial local consumer protection - General setup and nash equilibria

NASA Astrophysics Data System (ADS)

Iordanov, Iordan V.; Vassilev, Andrey A.

2017-12-01

We construct a model of the trade relations between two regions for the case when the trading entities (consumers) compete for a scarce good and there is an element of strategic interdependence in the trading process. Additionally, local consumers enjoy partial protection in the form of guaranteed access to a part of the locally-supplied quantity of the good. The model is formulated for the general asymmetric case, where the two regions differ in terms of parameters such as income, size of the local market supply, degree of protection and transportation costs. For this general model we establish the existence of Nash equilibria and obtain their form as a function of the model parameters, producing a typology of the equilibria. This is a required step in order to rigorously study various types of price dynamics for the model.

Needs assessment for collaborative network in pediatric clinical research and education.

PubMed

Ishiguro, Akira; Sasaki, Hatoko; Yahagi, Naohisa; Kato, Hitoshi; Kure, Shigeo; Mori, Rintaro

2017-01-01

A collaborative network for pediatric research has not been fully established in Japan. To identify the network infrastructure, we conducted a survey on the support and education for clinical research currently available in children's hospitals. In November 2014, a 27-question survey was distributed to 31 hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions (JACHRI) to assess clinical research support, research education, research achievements, and their expectations. All the hospitals responded to the survey. Overall, 74.2% of hospitals had clinical research support divisions. Although all hospitals had ethics committees, <30% of the hospitals had a data manager, intellectual property management unit, biostatistician, and English-language editor. Seven hospitals had education programs for clinical research. The number of seminars and workshops for clinical research had significant correlations with the number of physicians (r = 0.927), pediatricians (r = 0.922), and clinical trial management physicians (r = 0.962). There was a significant difference in the number of clinical trials initiated by physicians between hospitals with research education programs and those without (P < 0.01). The number of education programs was significantly correlated with the number of original articles and case reports in English (r = 0.788), and the number of publications in Japanese (r = 0.648). All hospitals recognized the need for a leader to establish a collaborative network for clinical research. Important factors for creating a collaborative system for pediatric research in Japan were identified. Human resources to support clinical research are a key factor to improve clinical research education and research achievements. © 2016 Japan Pediatric Society.

Physician to investigator: clinical practice to clinical research--ethical, operational, and financial considerations.

PubMed

Pierre, Christine

2008-01-01

Physicians who participate in clinical research studies gain benefits for themselves, their practice, and their patients. Historically, private practice physicians have chosen to defer to their counterparts in academic medicine when it comes to contributing to scientific advancement through clinical studies. A growing number of private practice physicians are now taking a serious second look and deciding that there are unique benefits for both the practice and the patient. Physicians who decide to participate in clinical research should give serious consideration to the time and resources that are required to meet both federal regulations and industry standards. In addition, ethical and scientific principles for assuring the protection of human research subjects must be a paramount commitment.

Nurse awareness of clinical research: a survey in a Japanese University Hospital

PubMed Central

2014-01-01

Background Clinical research plays an important role in establishing new treatments and improving the quality of medical practice. Since the introduction of the concept of clinical research coordinators (CRC) in Japan, investigators and CRC work as a clinical research team that coordinates with other professionals in clinical trials leading to drug approval (registration trials). Although clinical nurses collaborate with clinical research teams, extended clinical research teams that include clinical nurses may contribute to the ethical and scientific pursuit of clinical research. Methods As knowledge of clinical research is essential for establishing an extended clinical research team, we used questionnaires to survey the knowledge of clinical nurses at Tokushima University Hospital. Five-point and two-point scales were used. Questions as for various experiences were also included and the relationship between awareness and experiences were analyzed. Results Among the 597 nurses at Tokushima University Hospital, 453 (75.9%) responded to the questionnaires. In Japan, registration trials are regulated by pharmaceutical affairs laws, whereas other types of investigator-initiated research (clinical research) are conducted based on ethical guidelines outlined by the ministries of Japan. Approximately 90% of respondents were aware of registration trials and clinical research, but less than 40% of the nurses were aware of their difference. In clinical research terminology, most respondents were aware of informed consent and related issues, but ≤50% were aware of other things, such as the Declaration of Helsinki, ethical guidelines, Good Clinical Practice, institutional review boards, and ethics committees. We found no specific tendency in the relationship between awareness and past experiences, such as nursing patients who were participating in registration trials and/or clinical research or taking a part in research involving patients as a nursing student or a nurse

AIDS--Challenges to Basic and Clinical Biomedical Research.

ERIC Educational Resources Information Center

Fauci, Anthony S.

1989-01-01

Clinical trials and access to therapeutic drugs pose dilemmas for researchers, physicians, and AIDS patients. The National Institute of Allergy and Infectious Diseases, recognizing the need for greater access to drugs by a broader spectrum of the infected population, is establishing the Community Programs for Clinical Research on AIDS. (Author/MLW)

Creating a Research Agenda and Setting Research Priorities for Clinical Nurse Specialists.

PubMed

Foster, Jan; Bautista, Cynthia; Ellstrom, Kathleen; Kalowes, Peggy; Manning, Jennifer; Pasek, Tracy Ann

The purpose of this article is to describe the evolution and results of the process for establishing a research agenda and identification of research priorities for clinical nurse specialists, approved by the National Association of Clinical Nurse Specialists (NACNS) membership and sanctioned by the NACNS Board of Directors. Development of the research agenda and identification of the priorities were an iterative process and involved a review of the literature; input from multiple stakeholders, including individuals with expertise in conducting research serving as task force members, and NACNS members; and feedback from national board members. A research agenda, which is to provide an enduring research platform, was established and research priorities, which are to be applied in the immediate future, were identified as a result of this process. Development of a research agenda and identification of research priorities are a key method of fulfilling the mission and goals of NACNS. The process and outcomes are described in this article.

Framework conditions facilitating paediatric clinical research

PubMed Central

2011-01-01

The use of unlicensed and "off-label" medicines in children is widespread. Between 50-80% of the medicines currently administered to children have neither been tested nor authorized for their use in the paediatric population which represents approximately 25% of the whole European population. On 26 January 2007, entered into force the European Regulation of Paediatric Medicines. It aims at the quality of research into medicines for children but without subjecting the paediatric population to unnecessary clinical trial. This article addresses ethical and legal issues arising from the regulation and makes recommendations for the framework conditions facilitating the development of clinical research with children. PMID:21345195

Bioethical Issues in Conducting Pediatric Dentistry Clinical Research.

PubMed

Garrocho-Rangel, Arturo; Cerda-Cristerna, Bernardino; Pozos-Guillen, Amaury

Pediatric clinical research on new drugs and biomaterials involves children in order to create valid and generalizable knowledge. Research on vulnerable populations, such as children, is necessary but only admissible when researchers strictly follow methodological and ethical standards, together with the respect to human rights; and very especially when the investigation cannot be conducted with other population or when the potential benefits are specifically for that age group. Clinical research in Pediatric Dentistry is not an exception. The aim of the present article was to provide the bioethical principles (with respect to the child/parents' autonomy, benefit/risk analysis, and distributive justice), and recommendations, including informed consent, research ethics committees, conflict of interest, and the "equipoise" concept. Current and future worldwide oral health research in children and adolescents must be conducted incorporating their perspectives in the decision-making process as completely as possible. This concept must be carefully considered when a dental clinical study research is going to be planned and conducted, especially in the case of randomized controlled trials, in which children will be recruited as participants.

The influence of an elective introductory clinical research course on pharmacy student interest in pursuing research-based careers.

PubMed

Overholser, Brian R; Foster, David R; Henry, Joshua R; Plake, Kimberly S; Sowinski, Kevin M

2010-11-10

To assess the impact of an elective clinical research course on second- and third-year pharmacy students' knowledge of clinical research methods, training programs, career options, and interest in pursuing postgraduate training. A 2-credit hour elective course in clinical research was designed that included lectures, discussions, workshops, and in-class presentations related to study design and implementation, protocol synthesis, research evaluation, ethical and legal considerations, data analysis, and professional opportunities involving clinical research. Learner knowledge of these topics was assessed using several methods, including 3 assignments related to research protocol, ethical documentation, and presentation. A survey instrument designed to evaluate the effect the course had on pharmacy students' knowledge of clinical research methods and interest in pursuing postgraduate training in clinical research was administered. Students who completed the elective had a greater level of familiarity with research-related topics, training options, and career opportunities (p < 0.05) and a greater interest in pursuing a career in clinical research (p < 0.05) than did students in a matched control group. Taking a 2-credit hour elective course in clinical research increased pharmacy students' interest in pursuing a career in clinical research.

Comparative audit of clinical research in pediatric neurology.

PubMed

Al-Futaisi, Amna; Shevell, Michael

2004-11-01

Clinical research involves direct observation or data collection on human subjects. This study was conducted to evaluate the profile of pediatric neurology clinical research over a decade. Trends in pediatric neurology clinical research were documented through a systematic comparative review of articles published in selected journals. Eleven journals (five pediatric neurology, three general neurology, three general pediatrics) were systematically reviewed for articles involving a majority of human subjects less than 18 years of age for the years 1990 and 2000. Three hundred thirty-five clinical research articles in pediatric neurology were identified in the 11 journals for 1990 and 398 for 2000, a 19% increase. A statistically significant increase in analytic design (21.8% vs 39.5%; P = .01), statistical support (6% vs 16.6%; P < .0001), and multidisciplinary team (69.9% vs 87%; P = .003) was observed. In terms of specific study design, a significant decline in case reports (34.3% vs 10.3%; P < .0001) and an increase in case-control studies (11.3% vs 22.9%; P = .02) were evident over the 10-year interval. This comparative audit revealed that there has been a discernible change in the methodology profile of clinical research in child neurology over a decade. Trends apparently suggest a more rigorous approach to study design and investigation in this field.

Cannabis in Pain Treatment: Clinical and Research Considerations.

PubMed

Savage, Seddon R; Romero-Sandoval, Alfonso; Schatman, Michael; Wallace, Mark; Fanciullo, Gilbert; McCarberg, Bill; Ware, Mark

2016-06-01

Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse. Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts. Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care. Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications. This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids. Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

A research mentor training curriculum for clinical and translational researchers.

PubMed

Pfund, Christine; House, Stephanie; Spencer, Kimberly; Asquith, Pamela; Carney, Paula; Masters, Kristyn S; McGee, Richard; Shanedling, Janet; Vecchiarelli, Stephanie; Fleming, Michael

2013-02-01

To design and evaluate a research mentor training curriculum for clinical and translational researchers. The resulting 8-hour curriculum was implemented as part of a national mentor training trial. The mentor training curriculum was implemented with 144 mentors at 16 academic institutions. Facilitators of the curriculum participated in a train-the-trainer workshop to ensure uniform delivery. The data used for this report were collected from participants during the training sessions through reflective writing, and following the last training session via confidential survey with a 94% response rate. A total of 88% of respondents reported high levels of satisfaction with the training experience, and 90% noted they would recommend the training to a colleague. Participants also reported significant learning gains across six mentoring competencies as well as specific impacts of the training on their mentoring practice. The data suggest the described research mentor training curriculum is an effective means of engaging research mentors to reflect upon and improve their research mentoring practices. The training resulted in high satisfaction, self-reported skill gains as well as behavioral changes of clinical and translational research mentors. Given success across 16 diverse sites, this training may serve as a national model. © 2012 Wiley Periodicals, Inc.

A Research Mentor Training Curriculum for Clinical and Translational Researchers

PubMed Central

House, Stephanie; Spencer, Kimberly; Asquith, Pamela; Carney, Paula; Masters, Kristyn S.; McGee, Richard; Shanedling, Janet; Vecchiarelli, Stephanie; Fleming, Michael

2012-01-01

Abstract Purpose To design and evaluate a research mentor training curriculum for clinical and translational researchers. The resulting 8‐hour curriculum was implemented as part of a national mentor training trial. Method The mentor training curriculum was implemented with 144 mentors at 16 academic institutions. Facilitators of the curriculum participated in a train‐the‐trainer workshop to ensure uniform delivery. The data used for this report were collected from participants during the training sessions through reflective writing, and following the last training session via confidential survey with a 94% response rate. Results A total of 88% of respondents reported high levels of satisfaction with the training experience, and 90% noted they would recommend the training to a colleague. Participants also reported significant learning gains across six mentoring competencies as well as specific impacts of the training on their mentoring practice. Conclusions The data suggest the described research mentor training curriculum is an effective means of engaging research mentors to reflect upon and improve their research mentoring practices. The training resulted in high satisfaction, self‐reported skill gains as well as behavioral changes of clinical and translational research mentors. Given success across 16 diverse sites, this training may serve as a national model. Clin Trans Sci 2013; Volume 6: 26–33 PMID:23399086

Platelet Immunology in China: Research and Clinical Applications.

PubMed

Wu, Guoguang; Zhou, Yan; Li, Lilan; Zhong, Zhoulin; Li, Hengchong; Li, Haiyan; Yu, Mei; Shen, Weidong; Ni, Heyu

2017-04-01

Immunization against human platelet alloantigens (HPAs) is associated with a number of clinical complications. The detection and identification of clinically relevant platelet antibodies are important for the diagnosis and management of patients affected with immune-mediated thrombocytopenias. Human platelet alloantigen frequencies and the characteristics of antiplatelet antibodies vary widely between ethnic groups. Since 2008, the importance of platelet immunology in the field of transfusion medicine has gained greater recognition by clinical laboratories in China. Laboratories in China have established and improved methods for platelet antibody detection and HPA genotyping techniques, which are used for the diagnosis of alloimmune platelet disorders in clinic and research environments. Research has revealed the frequencies of HPA alleles in different Chinese ethnic groups and compared the differences in HPA gene frequencies between the Chinese Han and other ethnic groups of the world. Production of anti-CD36 isoantibodies is an important risk factor for immune-mediated thrombocytopenia in the Chinese population. Advances in research and clinical application of platelet immunology have significantly improved the clinical diagnosis, treatment including transfusion support, and prevention of alloimmune platelet disorders in the Chinese population. Copyright © 2017. Published by Elsevier Inc.

Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative.

PubMed

Pencina, Michael J; Louzao, Darcy M; McCourt, Brian J; Adams, Monique R; Tayyabkhan, Rehbar H; Ronco, Peter; Peterson, Eric D

2016-02-01

There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity. Copyright © 2015 Elsevier Inc. All rights reserved.

Media | Office of Cancer Clinical Proteomics Research

Cancer.gov

The Office of Cancer Clinical Proteomics Research (OCCPR) is committed to providing the media with timely and accurate information.  This section offers key resources for patients, cancer researchers, physicians, and media professionals.

Altruism in clinical research: coordinators' orientation to their professional roles.

PubMed

Fisher, Jill A; Kalbaugh, Corey A

2012-01-01

Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus reshaping their professional identities. The purpose of this study was to identify how research coordinators manage role and ethical conflicts within clinical research trials. A qualitative study combining observation and 63 semistructured interviews at 25 research organizations was used. Altruism is a recurring theme in how research coordinators define and view their work. Altruism is adopted by research coordinators to: (1) Teach patient-subjects the appropriate reasons to participate in clinical research, (2) minimize the conflict between research and care, and (3) contest the undervaluation of coordinating. Altruism is a strategy used to handle the various conflicts they experience in a difficult job, and it has become part of the professional identity of clinical research coordinators. Copyright © 2012 Elsevier Inc. All rights reserved.

Altruism in Clinical Research: Coordinators’ Orientation to their Professional Roles

PubMed Central

Fisher, Jill A.; Kalbaugh, Corey A.

2011-01-01

Background Research coordinators have significant responsibilities in clinical trials that often require them to find unique ways to manage their jobs, thus re-shaping their professional identities. Purpose The purpose of this study is to identify how research coordinators manage role and ethical conflicts within clinical research trials. Method A qualitative study combining observation and 63 semi-structured interviews at 25 research organizations was used. Discussion Altruism is a recurring theme in how research coordinators define and view their work. Conclusion Altruism is adopted by research coordinators: 1) to teach patient-subjects the appropriate reasons to participate in clinical research, 2) to minimize the conflict between research and care, and 3) to contest the undervaluation of coordinating. Altruism is a strategy employed to handle the various conflicts they experience in a difficult job, and it has become part of the professional identity of clinical research coordinators. PMID:22083045

Semantic processing of EHR data for clinical research.

PubMed

Sun, Hong; Depraetere, Kristof; De Roo, Jos; Mels, Giovanni; De Vloed, Boris; Twagirumukiza, Marc; Colaert, Dirk

2015-12-01

There is a growing need to semantically process and integrate clinical data from different sources for clinical research. This paper presents an approach to integrate EHRs from heterogeneous resources and generate integrated data in different data formats or semantics to support various clinical research applications. The proposed approach builds semantic data virtualization layers on top of data sources, which generate data in the requested semantics or formats on demand. This approach avoids upfront dumping to and synchronizing of the data with various representations. Data from different EHR systems are first mapped to RDF data with source semantics, and then converted to representations with harmonized domain semantics where domain ontologies and terminologies are used to improve reusability. It is also possible to further convert data to application semantics and store the converted results in clinical research databases, e.g. i2b2, OMOP, to support different clinical research settings. Semantic conversions between different representations are explicitly expressed using N3 rules and executed by an N3 Reasoner (EYE), which can also generate proofs of the conversion processes. The solution presented in this paper has been applied to real-world applications that process large scale EHR data. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Trials: A Crucial Key to Human Health Research

MedlinePlus

... Clinical Trials: A Crucial Key to Human Health Research Past Issues / Summer 2006 Table of Contents For ... Photo: PhotoDisc At the forefront of human health research today are clinical trials—studies that use human ...

Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

PubMed Central

Shapiro, Robyn S.; Layde, Peter M.

2008-01-01

Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

Report of the Task Force on Clinical Research in Dentistry.

ERIC Educational Resources Information Center

Journal of Dental Education, 1994

1994-01-01

A report on clinical dental research reviews current conditions and makes recommendations for increased funding, improved peer review for research proposals, establishment of a well-defined training track for clinical researchers, and better institutional integration of and support for research and teaching. Projected need for researchers is also…

How to emerge from the conservatism in clinical research methodology?

PubMed

Kotecki, Nuria; Penel, Nicolas; Awada, Ahmad

2017-09-01

Despite recent changes in clinical research methodology, many challenges remain in drug development methodology. Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed. Moreover, the classical frontier between phase I, phase II, and phase III has become unclear in particular for immunological approaches. So, investigators are facing major challenges in drug development methodology. We propose to individualize clinical research using innovative approaches to significantly improve patient outcomes and targeting what is considered unmet need. Integrating high level of translational research and performing well designed biomarker studies with great potential for clinical practice are of utmost importance. This could be performed within new models of clinical research networks and by building a strong collaboration between academic, cooperative groups, on-site investigators, and pharma.

Building research capacity: through a hospital-based clinical school of nursing.

PubMed

Lee, Geraldine; Metcalf, Suzanne

2009-04-01

For clinical nurses and nursing academics wishing to participate in research, there are several logistical issues such as high workloads, lack of time and poor research skills and knowledge that can impede research being undertaken. To address these issues, La Trobe University in partnership with one of Melbourne's acute care hospitals developed a clinical school with the aim of delivering postgraduate courses and undertaking collaborative clinically focused nursing research. Clinical issues were identified jointly between university academics and clinical nursing staff. Research questions were developed to examine these issues with the clinical school staff facilitating the research process. Research has been undertaken in many specialty areas including emergency, cardiac and intensive care nursing and diabetes. The success of this collaboration is evident with many studies being undertaken and consequently dissemination of research findings published (with clinicians being the primary author on many papers), presentations at national and international conferences by clinical staff as well as an increased enrollment into masters and doctoral programmes. The presence of the clinical school at the hospital has been beneficial both to clinicians and nurse academics and resulted in developing a positive research environment. More importantly, the research has led to changes in patient care and enabled clinicians to gain research experience and further academic qualifications. The other benefit is that nurse academics have strengthened their working relationship with clinicians and ensured visible research outputs were achieved.

The Effect of Metformin and Standard Therapy Versus Standard Therapy Alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial

DTIC Science & Technology

2009-01-01

histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA - IR scores, serum...BMI through diet and exercise significantly improved HOMA - IR scores, serum aminotransferases and liver histology. 15. SUBJECT TERMS 16. SECURITY...insulin resistance (or HOMA - IR ) score was calculated using the formula: fasting insulin (mIU/ml) fasting glu- cose (mg/dl)/405 [Matthews et al. 1985

Clinical Research Environment in India: Challenges and Proposed Solutions

PubMed Central

Burt, Tal; Sharma, Pooja; Dhillon, Savita; Manchanda, Mukul; Mittal, Sanjay; Trehan, Naresh

2015-01-01

India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005–2013, phase-2 trials grew by (+) 19.8% CAGR from 2005–2009 and contracted by (-) 12.6% CAGR from 2009–2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005–2010 and contracted by (-) 28.8% CAGR from 2010–2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India. PMID:25590017

Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

PubMed

Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

2013-05-01

Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

Interpretation of correlations in clinical research.

PubMed

Hung, Man; Bounsanga, Jerry; Voss, Maren Wright

2017-11-01

Critically analyzing research is a key skill in evidence-based practice and requires knowledge of research methods, results interpretation, and applications, all of which rely on a foundation based in statistics. Evidence-based practice makes high demands on trained medical professionals to interpret an ever-expanding array of research evidence. As clinical training emphasizes medical care rather than statistics, it is useful to review the basics of statistical methods and what they mean for interpreting clinical studies. We reviewed the basic concepts of correlational associations, violations of normality, unobserved variable bias, sample size, and alpha inflation. The foundations of causal inference were discussed and sound statistical analyses were examined. We discuss four ways in which correlational analysis is misused, including causal inference overreach, over-reliance on significance, alpha inflation, and sample size bias. Recent published studies in the medical field provide evidence of causal assertion overreach drawn from correlational findings. The findings present a primer on the assumptions and nature of correlational methods of analysis and urge clinicians to exercise appropriate caution as they critically analyze the evidence before them and evaluate evidence that supports practice. Critically analyzing new evidence requires statistical knowledge in addition to clinical knowledge. Studies can overstate relationships, expressing causal assertions when only correlational evidence is available. Failure to account for the effect of sample size in the analyses tends to overstate the importance of predictive variables. It is important not to overemphasize the statistical significance without consideration of effect size and whether differences could be considered clinically meaningful.

Epidemiology and Clinical Research Design, Part 2: Principles.

PubMed

Manja, Veena; Lakshminrusimha, Satyan

This is the third article covering core knowledge in scholarly activities for neonatal physicians. In this article, we discuss various principles of epidemiology and clinical research design. A basic knowledge of these principles is necessary for conducting clinical research and for proper interpretation of studies. This article reviews bias and confounding, causation, incidence and prevalence, decision analysis, cost-effectiveness, sensitivity analysis, and measurement.

Challenging Assumptions About Minority Participation in US Clinical Research

PubMed Central

Kalbaugh, Corey A.

2011-01-01

Although extensive research addresses minorities’ low participation in clinical research, most focuses almost exclusively on therapeutic trials. The existing literature might mask important issues concerning minorities’ participation in clinical trials, and minorities might actually be overrepresented in phase I safety studies that require the participation of healthy volunteers. It is critical to consider the entire spectrum of clinical research when discussing the participation of disenfranchised groups; the literature on minorities’ distrust, poor access, and other barriers to trial participation needs reexamination. Minority participation in clinical trials is an important topic in public health discussions because this representation touches on issues of equality and the elimination of disparities, which are core values of the field. PMID:22021285

Informatics Tools to Improve Clinical Research

PubMed Central

Argraves, S; Brandt, CA; Money, R; Nadkarni, P

2005-01-01

During the conduct of complex clinical trials, there are numerous sources and types of data collection and project coordination problems. Methods and approaches to address the conduct of a trial vary in both the cost and time to perform and the potential benefit. Informatics tools can help trial coordinators and investigators ensure the collection of high quality research data during all phases of a clinical trial. PMID:16779170

Clinical research in the United States at a crossroads: proposal for a novel public-private partnership to establish a national clinical research enterprise.

PubMed

Crowley, William F; Sherwood, Louis; Salber, Patricia; Scheinberg, David; Slavkin, Hal; Tilson, Hugh; Reece, E Albert; Catanese, Veronica; Johnson, Stephen B; Dobs, Adrian; Genel, Myron; Korn, Allan; Reame, Nancy; Bonow, Robert; Grebb, Jack; Rimoin, David

2004-03-03

The clinical research infrastructure of the United States is currently at a critical crossroads. To leverage the enormous biomedical research gains made in the past century efficiently, a drastic need exists to reengineer this system into a coordinated, safe, and more efficient and effective enterprise. To accomplish this task, clinical research must be transformed from its current state as a cottage industry to an enterprise-wide health care pipeline whose function is to bring the novel research from both government and private entities to the US public. We propose the establishment of a unique public-private partnership termed the National Clinical Research Enterprise (NCRE). Its agenda should consist of informed public participation, supportive information technologies, a skilled workforce, and adequate funding in clinical research. Devoting only 0.25% of the budgets from all health care stakeholders to support the NCRE would permit adequate funding to build the infrastructure required to address these problems in an enterprise fashion. All participants in the US health care delivery system must come together to focus on system-wide improvements that will benefit the public.

Clinical research in small genomically stratified patient populations.

PubMed

Martin-Liberal, J; Rodon, J

2017-07-01

The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Establishment of a research pharmacy to support Ebola clinical research in Liberia.

PubMed

Pierson, Jerome F; Kirchoff, Matthew Carl; Tyee, Rev Tijli; Montello, Michael J; Rhie, Julie K

This article describes the establishment of a research pharmacy to support the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) vaccine study for Ebola virus disease. This article describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia, in 2014 and 2015. The need for the rapid establishment of infrastructure to support the Liberia-United States joint clinical research partnership in response to the emerging Ebola virus disease provided the opportunity for collaboration among Liberian and U.S. pharmacists. Resource austere and research naïve. Research pharmacy prepared and randomized 1500 vaccinations in support of PREVAIL. Experiences of the Liberian and U.S. pharmacists involved in the program are described. The partnership was successful in the conduct of the study. More importantly, the capacity for Liberian pharmacists to support clinical research was established. In addition, the U.S. team learned several important lessons that will help prepare them for responding to research needs in future infectious disease outbreaks. Published by Elsevier Inc.

Epidemiology and Clinical Research Design, Part 2: Principles

PubMed Central

Manja, Veena; Lakshminrusimha, Satyan

2015-01-01

This is the third article covering core knowledge in scholarly activities for neonatal physicians. In this article, we discuss various principles of epidemiology and clinical research design. A basic knowledge of these principles is necessary for conducting clinical research and for proper interpretation of studies. This article reviews bias and confounding, causation, incidence and prevalence, decision analysis, cost-effectiveness, sensitivity analysis, and measurement. PMID:26236171

Pathology and biopsy assessment of non-alcoholic fatty liver disease.

PubMed

Straub, Beate Katharina; Schirmacher, Peter

2010-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases in Western industrialized countries with dramatically rising incidence. The diagnosis of NAFLD requires the existence of steatosis in the absence of significant alcohol consumption. In cases of relevant inflammation pathogenetically linked to steatosis, it is termed non-alcoholic steatohepatitis (NASH). While pure steatosis represents a relatively harmless and rapidly reversible condition without a significant tendency to progression, NASH carries a significant morbidity and progression risk. Noninvasive methods neither reliably establish the diagnosis nor define the extent of disease in NASH, making histopathology the diagnostic gold standard. Since current therapeutic options in NASH are limited, indication for biopsy is made in the clinical context, predominantly in unclear clinical constellations, prior to invasive measures, for follow-up purposes and in the context of clinical studies. Histological hallmarks of NASH are steatosis, hepatocellular ballooning (with and without Mallory-Denk bodies), necroinflammation, and progressing disease a characteristic with perisinusoidal fibrosis. For semiquantitative assessment of necroinflammation (grading) and fibrosis (staging), a score has recently been implemented. Although histology does not reliably distinguish alcoholic steatohepatitis/alcoholic fatty liver disease from NASH/NAFLD, it may give valuable hints. NASH has a tendency for more steatosis, the so-called glycogenated nuclei, and less necroinflammatory activity. Future development of biopsy diagnosis will be coupled to the development of differential systemic therapeutic approaches. Especially in the context of clinical studies, detailed histological evaluation should be considered for the detection of predictive parameters. Copyright 2010 S. Karger AG, Basel.

Comparative effectiveness research in clinical practice.

PubMed

Lawrence, William F; Chang, Stephanie; Kane, Robert L; Wilt, Timothy J

2014-08-01

The Agency for Healthcare Research and Quality (AHRQ) has funded systematic reviews of comparative effectiveness research in 17 areas over the last 10 years as part of a federal mandate. These reviews provide a reliable and unbiased source of comprehensive information about the effectiveness and risks of treatment alternatives for patients and clinicians. This article describes comparative effectiveness research, provides an overview of how physicians can use it in clinical practice, and references important contributions made by the Minnesota Evidence-based Practice Center.

Physician participation in clinical research and trials: issues and approaches

PubMed Central

Rahman, Sayeeda; Majumder, Md Anwarul Azim; Shaban, Sami F; Rahman, Nuzhat; Ahmed, Moslehuddin; Abdulrahman, Khalid Bin; D’Souza, Urban JA

2011-01-01

The rapid development of new drugs, therapies, and devices has created a dramatic increase in the number of clinical research studies that highlights the need for greater participation in research by physicians as well as patients. Furthermore, the potential of clinical research is unlikely to be reached without greater participation of physicians in research. Physicians face a variety of barriers with regard to participation in clinical research. These barriers are system-or organization-related as well as research-and physician-related. To encourage physician participation, appropriate organizational and operational infrastructures are needed in health care institutes to support research planning and management. All physicians should receive education and training in the fundamentals of research design and methodology, which need to be incorporated into undergraduate medical education and postgraduate training curricula and then reinforced through continuing medical education. Medical schools need to analyze current practices of teaching–learning and research, and reflect upon possible changes needed to develop a ‘student-focused teaching–learning and research culture’. This article examines the barriers to and benefits of physician participation in clinical research as well as interventions needed to increase their participation, including the specific role of undergraduate medical education. The main challenge is the unwillingness of many physicians and patients to participate in clinical trials. Barriers to participation include lack of time, lack of resources, trial-specific issues, communication difficulties, conflicts between the role of clinician and scientist, inadequate research experience and training for physicians, lack of rewards and recognition for physicians, and sometimes a scientifically uninteresting research question, among others. Strategies to encourage physician participation in clinical research include financial and nonfinancial

Establishment of a Research Pharmacy to Support Ebola Clinical Research in Liberia

PubMed Central

Pierson, Jerome F.; Kirchoff, Matthew Carl; Tyee, Rev Tegli; Rhie, Julie K.; Montello, Michael J

2017-01-01

Objective This paper describes the establishment of a research pharmacy to support the PREVAIL vaccine study for Ebola Virus Disease. Setting This paper describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia in 2014 and 2015. Practice Innovation The need to rapidly establish infrastructure to support the Liberian-US joint clinical research partnership in response to the emerging Ebola Virus Disease provided the opportunity for collaboration among Liberian and US pharmacists. Evaluation and Results Experiences of the Liberian and US pharmacists involved in the program are described. Conclusion The partnership was successful in the conduct of the study, but more importantly, capacity for Liberian pharmacists to support clinical research was established. Additionally, the US team learned several important lessons that will help prepare them for responding to research needs in future infectious disease outbreaks. PMID:28610940

[Alfredo Lanari, a clinical research style].

PubMed

Romero, Lucía

2012-01-01

The institutionalization of clinical research in Argentina reached its point of greatest maturity with the creation, in 1957, of the Institute of Medical Investigations (Instituto de Investigaciones Médicas) of the Faculty of Medicine of the Universidad de Buenos Aires, and the drive of the man who was its director for almost 20 years, Alfredo Lanari. In this paper I analyze the ways in which he generated a style of clinical research and a referential position in local medical field that allowed him to carry out said institutional realization. This achievement was the result of a personal enterprise and at the same time part of a larger context of transformations within the medical discipline world-wide and at the Universidad de Buenos Aires. This study was carried out combining oral and documentary sources, such as interviews with physicians at the Institute of Medical Investigations, members of the journal Medicina and of the Argentine Society of Clinical Investigation (Sociedad Argentina de Investigación Clínica), as well as academic files and scientific articles.

Using Computerized Clinical Nursing Data Bases for Nursing Research.

ERIC Educational Resources Information Center

Nail, Lillian M.; Lange, Linda L.

1996-01-01

Addresses the recognition of differences between clinical and research data in using computerized clinical nursing databases and the issues of privacy and confidentiality for patients whose records are involved. Describes procedures for assessing the quality and usability of these data for nursing research. (SK)

Clinical and translational research in Pneumocystis and Pneumocystis pneumonia*

PubMed Central

Huang, L.

2011-01-01

Pneumocystis pneumonia (PcP) remains a significant cause of morbidity and mortality in immunocompromised persons, especially those with human immunodeficiency virus (HIV) infection. Pneumocystis colonization is described increasingly in a wide range of immunocompromised and immunocompetent populations and associations between Pneumocystis colonization and significant pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have emerged. This mini-review summarizes recent advances in our clinical understanding of Pneumocystis and PcP, describes ongoing areas of clinical and translational research, and offers recommendations for future clinical research from researchers participating in the “First centenary of the Pneumocystis discovery”. PMID:21395200

[Assessment of innovations in clinical research: strengths and potentials for improvement of research in Germany].

PubMed

Vollmar, Horst Christian; Georgieff, Peter; Bührlen, Bernhard

2010-01-01

Clinical research is a central link in the development chain of new treatment methods; scientifically, it belongs between basic science and health services research. It spans from the first application of a new substance or device in humans to the main proofs of its efficacy and safety. Economically speaking, it absorbs almost half of the total expenditures for the research and development of a new drug and represents a significant factor in the labour market for researchers and study personnel. Also, through participation in clinical trials, patients gain early access to new treatment methods, while on the other hand they are placed at higher risk for undesired side effects. Politics have taken significant steps to strengthen clinical research, but the pharmaceutical industry continues to complain about competitive disadvantages. Despite internationally recognised and, to a large extent, legally codified guidelines there are still significant national differences in implementation. In addition, traditional practices in clinical research are challenged by novel, mainly biotechnological therapeutic methods for which our current knowledge base is rather limited and which therefore entail a higher risk for patients or trial participants. The following paper summarises a report for the Office of Technology Assessment at the German Federal Parliament (TAB). Based on current regulations, scientific literature and expert interviews, current challenges and solution strategies for clinical research will be analysed in terms of an international comparison.

Using connected objects in clinical research.

PubMed

Dhainaut, Jean-François; Huot, Laure; Pomar, Valérie Bouchara; Dubray, Claude

2018-02-01

Connected objects (CO), whether medical devices or not, are used in clinical research for data collection, a specific activity (communication, diagnosis, effector, etc.), or several functions combined. Their validation should be based on three approaches: technical and clinical reliability, data protection and cybersecurity. Consequently, the round table recommends that the typology of COs, their uses and limitations, be known and shared by all, particularly for implementing precise specifications. COs are used in clinical research during observational studies (assessment of the device itself or data collection), randomized studies, where only one group has a CO (assessment of its impact on patient follow-up or management), or randomized studies where both groups have a CO, which is then used as a tool to help with assessment. The benefits of using COs in clinical research includes: improved collection and quality of data, compliance of patients and pharmacovigilance, easier implementation of e-cohorts and a better representative balance of patients. The societal limits and risks identified relate to the sometimes intrusive nature of certain collected parameters and the possible misuse of data. The round table recommends the following on this last point: anticipation, by securing transmission methods, the qualification of data hosts, and assessment of the object's vulnerability. For this, a risk analysis appears necessary for each project. It is also necessary to accurately document the data flow, in order to inform both patients and healthcare professionals and to ensure adequate security. Anticipating regulatory changes and involving users starting from the study design stage are also recommended. Copyright © 2018 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Cancer Center Clinic and Research Team Perceptions of Identity and Interactions.

PubMed

Reimer, Torsten; Lee, Simon J Craddock; Garcia, Sandra; Gill, Mary; Duncan, Tobi; Williams, Erin L; Gerber, David E

2017-12-01

Conduct of cancer clinical trials requires coordination and cooperation among research and clinic teams. Diffusion of and confusion about responsibility may occur if team members' perceptions of roles and objectives do not align. These factors are critical to the success of cancer centers but are poorly studied. We developed a survey adapting components of the Adapted Team Climate Inventory, Measure of Team Identification, and Measure of In-Group Bias. Surveys were administered to research and clinic staff at a National Cancer Institute-designated comprehensive cancer center. Data were analyzed using descriptive statistics, t tests, and analyses of variance. Responses were received from 105 staff (clinic, n = 55; research, n = 50; 61% response rate). Compared with clinic staff, research staff identified more strongly with their own group ( P < .01) but less strongly with the overall cancer center ( P = .02). Both clinic staff and research staff viewed their own group's goals as clearer than those of the other group ( P < .01) and felt that members of their groups interacted and shared information within ( P < .01) and across ( P < .01) groups more than the other group did. Research staff perceived daily outcomes as more important than did clinic staff ( P = .05), specifically research-related outcomes ( P = .07). Although there are many similarities between clinic and research teams, we also identified key differences, including perceptions of goal clarity and sharing, understanding and alignment with cancer center goals, and importance of outcomes. Future studies should examine how variation in perceptions and group dynamics between clinic and research teams may impact function and processes of cancer care.

Considerations for planning and conducting clinic-based research in physical therapy.

PubMed

Fitzgerald, G K; Delitto, A

2001-08-01

There is growing demand to increase the volume of clinic-based research in physical therapy. Special considerations, unique to the planning and conduct of clinic-based research, need to be addressed to increase the likelihood that these studies will be completed successfully. The purposes of this perspective are to discuss factors affecting clinic-based research and to offer suggestions for addressing these problems when designing and conducting research studies in a clinical setting. This perspective discusses issues such as patient management, determining the availability of target patient populations, acquiring support from physical therapists and physicians, reporting and managing research-related injury or illness, and modifying or terminating projects. Some of the points made in this perspective are illustrated using examples from the authors' experiences in conducting clinical research.

Effects of disclosing financial interests on attitudes toward clinical research.

PubMed

Weinfurt, Kevin P; Hall, Mark A; Dinan, Michaela A; DePuy, Venita; Friedman, Joëlle Y; Allsbrook, Jennifer S; Sugarman, Jeremy

2008-06-01

The effects of disclosing financial interests to potential research participants are not well understood. To examine the effects of financial interest disclosures on potential research participants' attitudes toward clinical research. Computerized experiment conducted with 3,623 adults in the United States with either diabetes mellitus or asthma, grouped by lesser and greater severity. Respondents read a description of a hypothetical clinical trial relevant to their diagnosis that included a financial disclosure statement. Respondents received 1 of 5 disclosure statements. Willingness to participate in the hypothetical clinical trial, relative importance of information about the financial interest, change in trust after reading the disclosure statement, surprise regarding the financial interest, and perceived effect of the financial interest on the quality of the clinical trial. Willingness to participate in the hypothetical clinical trial did not differ substantially among the types of financial disclosures. Respondents viewed the disclosed information as less important than other factors in deciding to participate. Disclosures were associated with some respondents trusting the researchers less, although trust among some respondents increased. Most respondents were not surprised to learn of financial interests. Researchers owning equity were viewed as more troubling than researchers who were compensated for the costs of research through per capita payments. Aside from a researcher holding an equity interest, the disclosure to potential research participants of financial interests in research, as recommended in recent policies, is unlikely to affect willingness to participate in research.

Integrating Single-System Design Research into the Clinical Practice Class

ERIC Educational Resources Information Center

Cooper, Marlene G.

2006-01-01

Clinical practice and research are generally taught separately in Master of Social Work programs by faculty with distinct areas of expertise. This paper discusses the teaching of single-subject design research methodology by clinical faculty, in the clinical practice class. Examples from student papers demonstrate the effectiveness of integrating…

Heart Failure: From Research to Clinical Practice.

PubMed

Islam, Md Shahidul

2018-01-01

"Heart failure: from research to clinical practice", a collection of selected reviews, which comes out also as a book, covers essentially all important aspects of heart failure, including the pathogenesis, clinical features, biomarkers, imaging techniques, medical treatment and surgical treatments, use of pacemakers and implantable cardioverter defibrillators, and palliative care. The reviews include essential background information, state of the art, critical and in-depth analysis, and directions for future researches for elucidation of the unresolved issues. Everyone interested in heart failure is expected to find this compilation helpful for a deeper understanding of some of the complex issues.

Clinical Research Priorities in Adult Congenital Heart Disease

PubMed Central

Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.

2014-01-01

Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207

Clinical research priorities in adult congenital heart disease.

PubMed

Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R; John, Anitha S; Valente, Anne Marie; Zaidi, Ali N; Cook, Stephen C; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S

2014-02-15

Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Legitimating Clinical Research in the Study of Organizational Culture.

ERIC Educational Resources Information Center

Schein, Edgar H.

1993-01-01

Argues that traditional research model used in industrial-organizational psychology is not useful in understanding deeper dynamics of organizations, especially those phenomena labeled as "cultural." Contends that use of data obtained during clinical and consulting work should be legitimated as valid research data. Spells out clinical model and…

Feasibility of Conducting Autism Biomarker Research in the Clinical Setting.

PubMed

Sices, Laura; Pawlowski, Katherine; Farfel, Laura; Phillips, Deirdre; Howe, Yamini; Cochran, David M; Choueiri, Roula; Forbes, Peter W; Brewster, Stephanie J; Frazier, Jean A; Neumeyer, Ann; Bridgemohan, Carolyn

2017-09-01

Recruitment and completion of research activities during regular clinical care has the potential to increase research participation in complex neurodevelopmental disorders. We evaluated the feasibility, and effect on clinical care, of conducting biomarker research within a subspecialty clinical visit for autism spectrum disorder (ASD). Children, aged 5 to 10 years, were recruited by providers in ASD clinics at 5 institutions. Biomarkers collected were growth measurements, head circumference, neurologic and dysmorphology examinations, digit ratio (2D:4D) measurement, and platelet serotonin and urinary melatonin sulfate excretion levels. Parents completed the Aberrant Behavior Checklist-Community and a medical/demographic questionnaire. Cognitive level was abstracted from the medical record. Parents and clinicians completed surveys on the effect of the study on the clinical visit. Eighty-three children and their caregivers participated. Factors limiting participation included difficulty reaching families by phone and parent concern about the study blood draw requirement. All children completed at least 4 of 7 planned research activities. Demographic factors, educational placement, and child behavior were not associated with completion of study activities. Lower nonverbal cognitive function was weakly associated with fewer activities completed. Forty-four percent of clinicians reported an effect of the research study on the clinical visit. However, neither parent-reported nor clinician-reported effect was associated with the degree of study activity completion. Recruiting study participants in the context of scheduled ASD clinical visits required significant effort. However, once recruited, participants completed most study activities, regardless of behavioral symptom severity. Research activities did not adversely affect the clinical visit.

The Role of the Clinical and Translational Science Awards Program in Improving the Quality and Efficiency of Clinical Research

PubMed Central

Rosenblum, Daniel

2011-01-01

Recognizing the need to increase the efficiency and quality of translating basic discovery into treatment and prevention strategies for patients and the public, the National Institutes of Health (NIH) announced the Clinical and Translational Science Awards (CTSAs) in 2006. Academic health centers that competed successfully for these awards agreed to work as a consortium and in cooperation with the NIH to improve the translation process by training the next generation of investigators to work in interdisciplinary teams, developing public-private partnerships in the movement of basic discovery to preclinical and clinical studies and trials, improving clinical research management, and engaging with communities to ensure their involvement in shaping research questions and in implementing research results. The CTSAs have addressed the crucial need to improve the quality and efficiency of clinical research by (1) providing training for clinical investigators and for bench researchers to facilitate their participation in the clinical and translational research environment, (2) developing more systematic approaches to clinical research management, and (3) engaging communities as active participants in the design and conduct of clinical research studies and trials and as leaders in implementing health advances that are of high importance to them. We provide an overview of the CTSA activities with attention to these three areas, which are essential to developing efficient clinical research efforts and effective implementation of research results on a national level. PMID:21896519

Novel target for high-risk neuroblastoma identified in pre-clinical research | Center for Cancer Research

Cancer.gov

Pre-clinical research by investigators at the Center for Cancer Research and their colleagues have identified a number of novel epigenetic targets for high-risk neuroblastoma and validated a promising new targeted inhibitor in pre-clinical models.  Read more...

Ensuring rigour and trustworthiness of qualitative research in clinical pharmacy.

PubMed

Hadi, Muhammad Abdul; José Closs, S

2016-06-01

The use of qualitative research methodology is well established for data generation within healthcare research generally and clinical pharmacy research specifically. In the past, qualitative research methodology has been criticized for lacking rigour, transparency, justification of data collection and analysis methods being used, and hence the integrity of findings. Demonstrating rigour in qualitative studies is essential so that the research findings have the "integrity" to make an impact on practice, policy or both. Unlike other healthcare disciplines, the issue of "quality" of qualitative research has not been discussed much in the clinical pharmacy discipline. The aim of this paper is to highlight the importance of rigour in qualitative research, present different philosophical standpoints on the issue of quality in qualitative research and to discuss briefly strategies to ensure rigour in qualitative research. Finally, a mini review of recent research is presented to illustrate the strategies reported by clinical pharmacy researchers to ensure rigour in their qualitative research studies.

Blockchain technology for improving clinical research quality.

PubMed

Benchoufi, Mehdi; Ravaud, Philippe

2017-07-19

Reproducibility, data sharing, personal data privacy concerns and patient enrolment in clinical trials are huge medical challenges for contemporary clinical research. A new technology, Blockchain, may be a key to addressing these challenges and should draw the attention of the whole clinical research community.Blockchain brings the Internet to its definitive decentralisation goal. The core principle of Blockchain is that any service relying on trusted third parties can be built in a transparent, decentralised, secure "trustless" manner at the top of the Blockchain (in fact, there is trust, but it is hardcoded in the Blockchain protocol via a complex cryptographic algorithm). Therefore, users have a high degree of control over and autonomy and trust of the data and its integrity. Blockchain allows for reaching a substantial level of historicity and inviolability of data for the whole document flow in a clinical trial. Hence, it ensures traceability, prevents a posteriori reconstruction and allows for securely automating the clinical trial through what are called Smart Contracts. At the same time, the technology ensures fine-grained control of the data, its security and its shareable parameters, for a single patient or group of patients or clinical trial stakeholders.In this commentary article, we explore the core functionalities of Blockchain applied to clinical trials and we illustrate concretely its general principle in the context of consent to a trial protocol. Trying to figure out the potential impact of Blockchain implementations in the setting of clinical trials will shed new light on how modern clinical trial methods could evolve and benefit from Blockchain technologies in order to tackle the aforementioned challenges.

Data management by using R: big data clinical research series.

PubMed

Zhang, Zhongheng

2015-11-01

Electronic medical record (EMR) system has been widely used in clinical practice. Instead of traditional record system by hand writing and recording, the EMR makes big data clinical research feasible. The most important feature of big data research is its real-world setting. Furthermore, big data research can provide all aspects of information related to healthcare. However, big data research requires some skills on data management, which however, is always lacking in the curriculum of medical education. This greatly hinders doctors from testing their clinical hypothesis by using EMR. To make ends meet, a series of articles introducing data management techniques are put forward to guide clinicians to big data clinical research. The present educational article firstly introduces some basic knowledge on R language, followed by some data management skills on creating new variables, recoding variables and renaming variables. These are very basic skills and may be used in every project of big data research.

Clinical research in Finland in 2002 and 2007: quantity and type

PubMed Central

2013-01-01

Background Regardless of worries over clinical research and various initiatives to overcome problems, few quantitative data on the numbers and type of clinical research exist. This article aims to describe the volume and type of clinical research in 2002 and 2007 in Finland. Methods The research law in Finland requires all medical research to be submitted to regional ethics committees (RECs). Data from all new projects in 2002 and 2007 were collected from REC files and the characteristics of clinical projects (76% of all submissions) were analyzed. Results The number of clinical projects was large, but declining: 794 in 2002 and 762 in 2007. Drug research (mainly trials) represented 29% and 34% of the clinical projects; their total number had not declined, but those without a commercial sponsor had. The number of different principal investigators was large (630 and 581). Most projects were observational, while an experimental design was used in 43% of projects. Multi-center studies were common. In half of the projects, the main funder was health care or was done as unpaid work; 31% had industry funding as the main source. There was a clear difference in the type of research by sponsorship. Industry-funded research was largely drug research, international multi-center studies, with randomized controlled or other experimental design. The findings for the two years were similar, but a university hospital as the main research site became less common between 2002 and 2007. Conclusions Clinical research projects were common, but numbers are declining; research was largely funded by health care, with many physicians involved. Drug trials were a minority, even though most research promotion efforts and regulation concerns them. PMID:23680289

Clinical research in Finland in 2002 and 2007: quantity and type.

PubMed

Hemminki, Elina; Virtanen, Jorma; Veerus, Piret; Regushevskaya, Elena

2013-05-16

Regardless of worries over clinical research and various initiatives to overcome problems, few quantitative data on the numbers and type of clinical research exist. This article aims to describe the volume and type of clinical research in 2002 and 2007 in Finland. The research law in Finland requires all medical research to be submitted to regional ethics committees (RECs). Data from all new projects in 2002 and 2007 were collected from REC files and the characteristics of clinical projects (76% of all submissions) were analyzed. The number of clinical projects was large, but declining: 794 in 2002 and 762 in 2007. Drug research (mainly trials) represented 29% and 34% of the clinical projects; their total number had not declined, but those without a commercial sponsor had. The number of different principal investigators was large (630 and 581). Most projects were observational, while an experimental design was used in 43% of projects. Multi-center studies were common. In half of the projects, the main funder was health care or was done as unpaid work; 31% had industry funding as the main source. There was a clear difference in the type of research by sponsorship. Industry-funded research was largely drug research, international multi-center studies, with randomized controlled or other experimental design. The findings for the two years were similar, but a university hospital as the main research site became less common between 2002 and 2007. Clinical research projects were common, but numbers are declining; research was largely funded by health care, with many physicians involved. Drug trials were a minority, even though most research promotion efforts and regulation concerns them.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration.

PubMed

Chalmers, James D; Crichton, Megan; Goeminne, Pieter C; Loebinger, Michael R; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-09-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

PubMed Central

Crichton, Megan; Goeminne, Pieter C.; Loebinger, Michael R.; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja ; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-01-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. Educational aims To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areas To understand some of the key features of successful disease registries To review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 years To understand the key research priorities identified by EMBARC for the next 5 years PMID:28894479

In Defense of a Social Value Requirement for Clinical Research

PubMed Central

Wendler, David; Rid, Annette

2017-01-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present paper assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. PMID:28060427

Usability Evaluation of an Unstructured Clinical Document Query Tool for Researchers.

PubMed

Hultman, Gretchen; McEwan, Reed; Pakhomov, Serguei; Lindemann, Elizabeth; Skube, Steven; Melton, Genevieve B

2018-01-01

Natural Language Processing - Patient Information Extraction for Researchers (NLP-PIER) was developed for clinical researchers for self-service Natural Language Processing (NLP) queries with clinical notes. This study was to conduct a user-centered analysis with clinical researchers to gain insight into NLP-PIER's usability and to gain an understanding of the needs of clinical researchers when using an application for searching clinical notes. Clinical researcher participants (n=11) completed tasks using the system's two existing search interfaces and completed a set of surveys and an exit interview. Quantitative data including time on task, task completion rate, and survey responses were collected. Interviews were analyzed qualitatively. Survey scores, time on task and task completion proportions varied widely. Qualitative analysis indicated that participants found the system to be useful and usable in specific projects. This study identified several usability challenges and our findings will guide the improvement of NLP-PIER 's interfaces.

Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial.

PubMed

Bomhof, Marc R; Parnell, Jill A; Ramay, Hena R; Crotty, Pam; Rioux, Kevin P; Probert, Chris S; Jayakumar, Saumya; Raman, Maitreyi; Reimer, Raylene A

2018-05-19

In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. This trial was registered at Clinicaltrials.com as NCT03184376.

Systematic collection of patient reported outcome research data: A checklist for clinical research professionals.

PubMed

Wehrlen, Leslie; Krumlauf, Mike; Ness, Elizabeth; Maloof, Damiana; Bevans, Margaret

2016-05-01

Understanding the human experience is no longer an outcome explored strictly by social and behavioral researchers. Increasingly, biomedical researchers are also including patient reported outcomes (PROs) in their clinical research studies not only due to calls for increased patient engagement in research but also healthcare. Collecting PROs in clinical research studies offers a lens into the patient's unique perspective providing important information to industry sponsors and the FDA. Approximately 30% of trials include PROs as primary or secondary endpoints and a quarter of FDA new drug, device and biologic applications include PRO data to support labeling claims. In this paper PRO, represents any information obtained directly from the patient or their proxy, without interpretation by another individual to ascertain their health, evaluate symptoms or conditions and extends the reference of PRO, as defined by the FDA, to include other sources such as patient diaries. Consumers and clinicians consistently report that PRO data are valued, and can aide when deciding between treatment options; therefore an integral part of clinical research. However, little guidance exists for clinical research professionals (CRPs) responsible for collecting PRO data on the best practices to ensure quality data collection so that an accurate assessment of the patient's view is collected. Therefore the purpose of this work was to develop and validate a checklist to guide quality collection of PRO data. The checklist synthesizes best practices from published literature and expert opinions addressing practical and methodological challenges CRPs often encounter when collecting PRO data in research settings. Published by Elsevier Inc.

Clinical research in a hospital--from the lone rider to teamwork.

PubMed

Hannisdal, E

1996-01-01

Clinical research of high international standard is very demanding and requires clinical data of high quality, software, hardware and competence in research design and statistical treatment of data. Most busy clinicians have little time allocated for clinical research and this increases the need for a potent infrastructure. This paper describes how the Norwegian Radium Hospital, a specialized cancer hospital, has reorganized the clinical research process. This includes a new department, the Clinical Research Office, which serves the formal framework, a central Diagnosis Registry, clinical databases and multicentre studies. The department assists about 120 users, mainly clinicians. Installation of a network software package with over 10 programs has strongly provided an internal standardization, reduced the costs and saved clinicians a great deal of time. The hospital is building up about 40 diagnosis-specific clinical databases with up to 200 variables registered. These databases are shared by the treatment group and seem to be important tools for quality assurance. We conclude that the clinical research process benefits from a firm infrastructure facilitating teamwork through extensive use of modern information technology. We are now ready for the next phase, which is to work for a better external technical framework for cooperation with other institutions throughout the world.

Negotiation skills for clinical research professionals

PubMed Central

Hake, Sanjay; Shah, Tapankumar

2011-01-01

Negotiation as a skill is a key requirement for each and every job profile where dealing with multiple parties is involved. The important focus while negotiating should be on the interest then position. Key to every successful negotiation is advance planning, preparation, and patience as the objective is to create value and establish the terms on which parties with differing and often conflicting aims will co-operate. While preparing one should collect facts, know priorities, principles, identify common ground, decide on walk-away position, and try and identify the next best alternative. Negotiation is a set of skills that can be learned and practiced so that your ability to utilize relationship, knowledge, money, power, time, and personality to negotiate improves with each negotiation. In a successful negotiation, all parties win. Important thing to note is that not every negotiation involves money. Anytime you want something from someone else and anytime someone wants something from you, you are negotiating. Everything is negotiable and every day you negotiate with customers, suppliers, colleagues, your wife, and even your children. Negotiation is a game, and like any game it has its rules and tactics. Clinical Research professionals deal with various parties for different purposes at the same time; hence, they require excellent negotiation skills. Project Mangers and Clinical Research Associates are the two most important roles in clinical research industry who require negotiation skills as they deal with various internal and external customers and vendors. PMID:21897886

From Nonclinical Research to Clinical Trials and Patient-registries: Challenges and Opportunities in Biomedical Research

PubMed Central

de la Torre Hernández, José M.; Edelman, Elazer R.

2018-01-01

The most important challenge faced by human beings is health. The only way to provide better solutions for health care is innovation, true innovation. The only source of true innovation is research, good research indeed. The pathway from a basic science study to a randomized clinical trial is long and not free of bumps and even landmines. These are all the obstacles and barriers that limit the availability of resources, entangle administrative-regulatory processes, and restrain investigators’ initiatives. There is increasing demand for evidence to guide clinical practice but, paradoxically, biomedical research has become increasingly complex, expensive, and difficult to integrate into clinical care with increased barriers to performing the practical aspects of investigation. We face the challenge of increasing the volume of biomedical research and simultaneously improving the efficiency and output of this research. In this article, we review the main stages and methods of biomedical research, from nonclinical studies with animal and computational models to randomized trials and clinical registries, focusing on their limitations and challenges, but also providing alternative solutions to overcome them. Fortunately, challenges are always opportunities in disguise. PMID:28838647

The social value of clinical research.

PubMed

Habets, Michelle G J L; van Delden, Johannes J M; Bredenoord, Annelien L

2014-09-05

International documents on ethical conduct in clinical research have in common the principle that potential harms to research participants must be proportional to anticipated benefits. The anticipated benefits that can justify human research consist of direct benefits to the research participant, and societal benefits, also called social value. In first-in-human research, no direct benefits are expected and the benefit component of the risks-benefit assessment thus merely exists in social value. The concept social value is ambiguous by nature and is used in numerous ways in the research ethics literature. Because social value justifies involving human participants, especially in early human trials, this is problematic. Our analysis and interpretation of the concept social value has led to three proposals. First, as no direct benefits are expected for the research participants in first-in-human trials, we believe it is better to discuss a risk- value assessment instead of a risk - benefit assessment. This will also make explicit the necessity to have a clear and common use for the concept social value. Second, to avoid confusion we propose to limit the concept social value to the intervention tested. It is the expected improvement the intervention can bring to the wellbeing of (future) patients or society that is referred to when we speak about social value. For the sole purpose of gaining knowledge, we should not expose humans to potential harm; the ultimate justification of involving humans in research lies in the anticipated social value of the intervention. Third, at the moment only the validity of the clinical research proposal is a prerequisite for research to take place. We recommend making the anticipated social value a prerequisite as well. In this paper we analyze the use of the concept social value in research ethics. Despite its unavoidable ambiguity, we aim to find a best use of the concept, subject to its role in justifying involving humans in first

Clinical nursing and midwifery research: grey literature in African countries.

PubMed

Sun, C; Dohrn, J; Omoni, G; Malata, A; Klopper, H; Larson, E

2016-03-01

This study reviewed grey literature to assess clinical nursing and midwifery research conducted in southern and eastern African countries over the past decade. The shortage of published nursing research from African countries severely limits the ability of practicing nurses and midwives to base clinical decisions on solid evidence. However, little is known regarding unpublished or unindexed clinical research ('grey literature'), a potentially rich source of information. Identifying these sources may reveal resources to assist nurses in providing evidence-based care. This scoping review of grey literature on clinical nursing and midwifery research in southern and eastern African countries helped to identify gaps in research and assess whether these gaps differ from published research. Systematic searches of grey literature were performed. Research was included if it was conducted by nurses in 1 of 25 southern or eastern African countries, between 2004 and 2014 and included patient outcomes. Data were extracted on location, institution, research topic, institutional connections and author information. Chi-square tests were performed to compare differences between indexed and non-indexed literature. We found 262 studies by 287 authors from 17 southern and eastern African countries covering 13 topics. Although all topics were also found in indexed literature and there were statistically significant differences between the number of times, fewer topics were covered in grey literature vs. indexed. Patient satisfaction and experience and traditional health practices were more likely to be published, whereas chronic disease, assault and paediatric-related research were less often published. Generally, there is a paucity of clinical nursing research in this region. This could reflect the shortage of nurses prepared to conduct research in this region. Nurses may find additional resources for evidence in the grey literature. A complete understanding of the state of nursing

From Free to Free Market: Cost Recovery in Federally Funded Clinical Research

PubMed Central

McCammon, Margaret G.; Fogg, Thomas T.; Jacobsen, Lynda; Roache, John; Sampson, Royce; Bower, Cynthia L.

2012-01-01

In a climate of increased expectation for the translation of research, academic clinical research units are looking at new ways to streamline their operation and maintain effective translational support services. Clinical research, although undeniably expensive, is an essential step in the translation of any medical breakthrough, and as a result, many academic clinical research units are actively looking to expand their clinical services despite financial pressures. We examine some of the hybrid academic-business models in 19 clinical research centers within the Clinical and Translational Science Award consortium that are emerging to address the issue of cost recovery of clinical research that is supported by the United States federal government. We identify initiatives that have succeeded or failed, essential supporting and regulatory components, and lessons learned from experience to design an optimal cost recovery model and a timeline for its implementation. PMID:22764204

Characteristics Desired in Clinical Data Warehouse for Biomedical Research

PubMed Central

Shin, Soo-Yong; Kim, Woo Sung

2014-01-01

Objectives Due to the unique characteristics of clinical data, clinical data warehouses (CDWs) have not been successful so far. Specifically, the use of CDWs for biomedical research has been relatively unsuccessful thus far. The characteristics necessary for the successful implementation and operation of a CDW for biomedical research have not clearly defined yet. Methods Three examples of CDWs were reviewed: a multipurpose CDW in a hospital, a CDW for independent multi-institutional research, and a CDW for research use in an institution. After reviewing the three CDW examples, we propose some key characteristics needed in a CDW for biomedical research. Results A CDW for research should include an honest broker system and an Institutional Review Board approval interface to comply with governmental regulations. It should also include a simple query interface, an anonymized data review tool, and a data extraction tool. Also, it should be a biomedical research platform for data repository use as well as data analysis. Conclusions The proposed characteristics desired in a CDW may have limited transfer value to organizations in other countries. However, these analysis results are still valid in Korea, and we have developed clinical research data warehouse based on these desiderata. PMID:24872909

Exploitation of prisoners in clinical research: perceptions of study participants

PubMed Central

Christopher, Paul P.; Stein, Michael D.; Johnson, Jennifer E.; Rich, Josiah D.; Friedmann, Peter D.; Clarke, Jennifer G.; Lidz, Charles W.

2015-01-01

This paper discusses findings of a study examining whether prisoners view their participation in clinical research studies as exploitative. Perspectives of seventy prisoners who were enrolled in one of six different clinical studies were analyzed. A minority of participants agreed with statements suggestive of potential exploitation. All but one participant believed that prisoners should have greater access to research. On balance, these data provide reassurance that prisoners in this sample do not view their involvement in clinical research as inappropriately exploitative. PMID:26964404

Children's self reported discomforts as participants in clinical research.

PubMed

Staphorst, Mira S; Hunfeld, Joke A M; van de Vathorst, Suzanne; Passchier, Jan; van Goudoever, Johannes B

2015-10-01

There is little empirical evidence on children's subjective experiences of discomfort during clinical research procedures. Therefore, Institutional Review Boards have limited empirical information to guide their decision-making on discomforts for children in clinical research. To get more insight into what children's discomforts are during clinical research procedures, we interviewed a group of children on this topic and also asked for suggestions to reduce possible discomforts. Forty-six children (aged 6-18) participating in clinical research studies (including needle-related procedures, food provocation tests, MRI scans, pulmonary function tests, questionnaires) were interviewed about their experiences during the research procedures. Thematic analysis was used to analyze the interviews. The discomforts of the interviewed children could be divided into two main groups: physical and mental discomforts. The majority experienced physical discomforts during the research procedures: pain, shortness of breath, nausea, itchiness, and feeling hungry, which were often caused by needle procedures, some pulmonary procedures, and food provocation tests. Mental discomforts included anxiousness because of anticipated pain and not knowing what to expect from a research procedure, boredom and tiredness during lengthy research procedures and waiting, and embarrassment during Tanner staging. Children's suggestions to reduce the discomforts of the research procedures were providing distraction (e.g. watching a movie or listening to music), providing age-appropriate information and shortening the duration of lengthy procedures. Our study shows that children can experience various discomforts during research procedures, and it provides information about how these discomforts can be reduced according to them. Further research is needed with larger samples to study the number of children that experience these mentioned discomforts during research procedures in a quantitative way

Clinical-academic partnerships research: converting the rhetoric into reality.

PubMed

Happell, Brenda

2005-09-01

An increasing recognition of the importance of research-based practice to the nursing profession has led to a number of strategies designed to increase the utilization and conduct of nursing research. The transfer of nursing education from hospitals to universities occurred partly in response to the identified theory-practice gap. Subsequently, a significant investment in joint clinical-academic positions and clinical professorial positions has been made with the intention of bridging the gap between the tertiary sector and the clinical field. Anecdotal evidence suggests that neither strategy has achieved the desired degree of success. The available literature suggests that nurses do not tend to become involved in the conduct of research, nor do they readily utilise research findings in their practice. It is hypothesized in this paper that this reflects the strong cultural differences between the clinical and academic worlds in nursing. The aim of this paper is to discuss the impact of these cultural differences and describe specific principals that could contribute to significant cultural change and the bridging of the academic-clinician divide.

Financial conflict-of-interest policies in clinical research: issues for clinical investigators.

PubMed

Boyd, Elizabeth A; Cho, Mildred K; Bero, Lisa A

2003-08-01

As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.

Clinical diabetes research using data mining: a Canadian perspective.

PubMed

Shah, Baiju R; Lipscombe, Lorraine L

2015-06-01

With the advent of the digitization of large amounts of information and the computer power capable of analyzing this volume of information, data mining is increasingly being applied to medical research. Datasets created for administration of the healthcare system provide a wealth of information from different healthcare sectors, and Canadian provinces' single-payer universal healthcare systems mean that data are more comprehensive and complete in this country than in many other jurisdictions. The increasing ability to also link clinical information, such as electronic medical records, laboratory test results and disease registries, has broadened the types of data available for analysis. Data-mining methods have been used in many different areas of diabetes clinical research, including classic epidemiology, effectiveness research, population health and health services research. Although methodologic challenges and privacy concerns remain important barriers to using these techniques, data mining remains a powerful tool for clinical research. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Experimental and clinical psychopharmacology: National Institute on Drug Abuse's clinical research agenda.

PubMed

Leshner, Alan I

2002-08-01

Studies of drugs and behavior are a core component of virtually every portfolio within the broad purview of the National Institute on Drug Abuse (NIDA). Moreover, psychopharmacological research is an important vehicle for advancing understanding of how drugs of abuse produce their effects, particularly including addiction. However, as with all major public health issues, simply understanding the issue is not enough. NIDA's psychopharmacology projects, therefore, span basic, clinical, and applied (e.g., medication development) research activities. These include the establishment of a nationwide clinical trials network designed to provide an infrastructure to test both behavioral and psychopharmacological treatments in a real-life practice setting with diverse patients.

ClinicalCodes: an online clinical codes repository to improve the validity and reproducibility of research using electronic medical records.

PubMed

Springate, David A; Kontopantelis, Evangelos; Ashcroft, Darren M; Olier, Ivan; Parisi, Rosa; Chamapiwa, Edmore; Reeves, David

2014-01-01

Lists of clinical codes are the foundation for research undertaken using electronic medical records (EMRs). If clinical code lists are not available, reviewers are unable to determine the validity of research, full study replication is impossible, researchers are unable to make effective comparisons between studies, and the construction of new code lists is subject to much duplication of effort. Despite this, the publication of clinical codes is rarely if ever a requirement for obtaining grants, validating protocols, or publishing research. In a representative sample of 450 EMR primary research articles indexed on PubMed, we found that only 19 (5.1%) were accompanied by a full set of published clinical codes and 32 (8.6%) stated that code lists were available on request. To help address these problems, we have built an online repository where researchers using EMRs can upload and download lists of clinical codes. The repository will enable clinical researchers to better validate EMR studies, build on previous code lists and compare disease definitions across studies. It will also assist health informaticians in replicating database studies, tracking changes in disease definitions or clinical coding practice through time and sharing clinical code information across platforms and data sources as research objects.

ClinicalCodes: An Online Clinical Codes Repository to Improve the Validity and Reproducibility of Research Using Electronic Medical Records

PubMed Central

Springate, David A.; Kontopantelis, Evangelos; Ashcroft, Darren M.; Olier, Ivan; Parisi, Rosa; Chamapiwa, Edmore; Reeves, David

2014-01-01

Lists of clinical codes are the foundation for research undertaken using electronic medical records (EMRs). If clinical code lists are not available, reviewers are unable to determine the validity of research, full study replication is impossible, researchers are unable to make effective comparisons between studies, and the construction of new code lists is subject to much duplication of effort. Despite this, the publication of clinical codes is rarely if ever a requirement for obtaining grants, validating protocols, or publishing research. In a representative sample of 450 EMR primary research articles indexed on PubMed, we found that only 19 (5.1%) were accompanied by a full set of published clinical codes and 32 (8.6%) stated that code lists were available on request. To help address these problems, we have built an online repository where researchers using EMRs can upload and download lists of clinical codes. The repository will enable clinical researchers to better validate EMR studies, build on previous code lists and compare disease definitions across studies. It will also assist health informaticians in replicating database studies, tracking changes in disease definitions or clinical coding practice through time and sharing clinical code information across platforms and data sources as research objects. PMID:24941260

Reengineering Clinical Research Science: A Focus on Translational Research

ERIC Educational Resources Information Center

Ferrell, Courtney B.

2009-01-01

The burden of disease in the United States is high. Mental illness is currently the leading cause of disease burden among 15- to 44-year-olds. This phenomenon is occurring despite the many advances that have been made in clinical research. Several efficacious interventions are available to treat many of these disorders; however, they are greatly…

Team building: electronic management-clinical translational research (eM-CTR) systems.

PubMed

Cecchetti, Alfred A; Parmanto, Bambang; Vecchio, Marcella L; Ahmad, Sjarif; Buch, Shama; Zgheib, Nathalie K; Groark, Stephen J; Vemuganti, Anupama; Romkes, Marjorie; Sciurba, Frank; Donahoe, Michael P; Branch, Robert A

2009-12-01

Classical drug exposure: response studies in clinical pharmacology represent the quintessential prototype for Bench to Bedside-Clinical Translational Research. A fundamental premise of this approach is for a multidisciplinary team of researchers to design and execute complex, in-depth mechanistic studies conducted in relatively small groups of subjects. The infrastructure support for this genre of clinical research is not well-handled by scaling down of infrastructure used for large Phase III clinical trials. We describe a novel, integrated strategy, whose focus is to support and manage a study using an Information Hub, Communication Hub, and Data Hub design. This design is illustrated by an application to a series of varied projects sponsored by Special Clinical Centers of Research in chronic obstructive pulmonary disease at the University of Pittsburgh. In contrast to classical informatics support, it is readily scalable to large studies. Our experience suggests the culture consequences of research group self-empowerment is not only economically efficient but transformative to the research process.

In Defense of a Social Value Requirement for Clinical Research.

PubMed

Wendler, David; Rid, Annette

2017-02-01

Many guidelines and commentators endorse the view that clinical research is ethically acceptable only when it has social value, in the sense of collecting data which might be used to improve health. A version of this social value requirement is included in the Declaration of Helsinki and the Nuremberg Code, and is codified in many national research regulations. At the same time, there have been no systematic analyses of why social value is an ethical requirement for clinical research. Recognizing this gap in the literature, recent articles by Alan Wertheimer and David Resnik argue that the extant justifications for the social value requirement are unpersuasive. Both authors conclude, contrary to almost all current guidelines and regulations, that it can be acceptable across a broad range of cases to conduct clinical research which is known prospectively to have no social value. The present article assesses this conclusion by critically evaluating the ethical and policy considerations relevant to the claim that clinical research must have social value. This analysis supports the standard view that social value is an ethical requirement for the vast majority of clinical research studies and should be mandated by applicable guidelines and policies. © 2017 John Wiley & Sons Ltd.

Developing translational research infrastructure and capabilities associated with cancer clinical trials.

PubMed

Hall, Jacqueline A; Brown, Robert

2013-09-27

The integration of molecular information in clinical decision making is becoming a reality. These changes are shaping the way clinical research is conducted, and as reality sets in, the challenges in conducting, managing and organising multi-disciplinary research become apparent. Clinical trials provide a platform to conduct translational research (TR) within the context of high quality clinical data accrual. Integrating TR objectives in trials allows the execution of pivotal studies that provide clinical evidence for biomarker-driven treatment strategies, targeting early drug development trials to a homogeneous and well defined patient population, supports the development of companion diagnostics and provides an opportunity for deepening our understanding of cancer biology and mechanisms of drug action. To achieve these goals within a clinical trial, developing translational research infrastructure and capabilities (TRIC) plays a critical catalytic role for translating preclinical data into successful clinical research and development. TRIC represents a technical platform, dedicated resources and access to expertise promoting high quality standards, logistical and operational support and unified streamlined procedures under an appropriate governance framework. TRIC promotes integration of multiple disciplines including biobanking, laboratory analysis, molecular data, informatics, statistical analysis and dissemination of results which are all required for successful TR projects and scientific progress. Such a supporting infrastructure is absolutely essential in order to promote high quality robust research, avoid duplication and coordinate resources. Lack of such infrastructure, we would argue, is one reason for the limited effect of TR in clinical practice beyond clinical trials.

The clinical application of research utilization: amphotericin B.

PubMed

Reedy, A M; Shivnan, J C; Hanson, J L; Haisfield, M E; Gregory, R E

1994-05-01

To describe the first application of the research utilization process by clinical nurses using the Stetler-Marram Model of Research Utilization to the practice of amphotericin B administration; to share the findings; and to discuss issues encountered in the process and their solutions. Published articles identified through computerized literature searches, published abstracts and books, personal communication with one author, and an informal survey of other cancer centers' amphotericin B infusion practices; research articles were selected for review if studies included settings and patient populations similar to those of the authors and if they used experimental designs. Studies were reviewed for scientific merit and clinical applicability according to the Stetler-Marram model; findings were used to develop a specific nursing protocol for infusion times of amphotericin B based on clinical criteria. The Stetler-Marram model helped staff nurses decide how to apply research findings to practice, although using it was difficult and required mentorship. A research base exists for amphotericin B administration time but not for test doses or premedications to prevent or minimize side effects. Staff nurses can use the Stetler-Marram model but need resources and support from individuals, committees, and administration. A specific protocol representing a practice change was implemented and may be applicable to other settings.

CRC Clinical Trials Management System (CTMS): An Integrated Information Management Solution for Collaborative Clinical Research

PubMed Central

Payne, Philip R.O.; Greaves, Andrew W.; Kipps, Thomas J.

2003-01-01

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC’s clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment. PMID:14728471

The STAR Data Reporting Guidelines for Clinical High Altitude Research.

PubMed

Brodmann Maeder, Monika; Brugger, Hermann; Pun, Matiram; Strapazzon, Giacomo; Dal Cappello, Tomas; Maggiorini, Marco; Hackett, Peter; Bärtsch, Peter; Swenson, Erik R; Zafren, Ken

2018-03-01

Brodmann Maeder, Monika, Hermann Brugger, Matiram Pun, Giacomo Strapazzon, Tomas Dal Cappello, Marco Maggiorini, Peter Hackett, Peter Baärtsch, Erik R. Swenson, Ken Zafren (STAR Core Group), and the STAR Delphi Expert Group. The STARdata reporting guidelines for clinical high altitude research. High AltMedBiol. 19:7-14, 2018. The goal of the STAR (STrengthening Altitude Research) initiative was to produce a uniform set of key elements for research and reporting in clinical high-altitude (HA) medicine. The STAR initiative was inspired by research on treatment of cardiac arrest, in which the establishment of the Utstein Style, a uniform data reporting protocol, substantially contributed to improving data reporting and subsequently the quality of scientific evidence. The STAR core group used the Delphi method, in which a group of experts reaches a consensus over multiple rounds using a formal method. We selected experts in the field of clinical HA medicine based on their scientific credentials and identified an initial set of parameters for evaluation by the experts. Of 51 experts in HA research who were identified initially, 21 experts completed both rounds. The experts identified 42 key parameters in 5 categories (setting, individual factors, acute mountain sickness and HA cerebral edema, HA pulmonary edema, and treatment) that were considered essential for research and reporting in clinical HA research. An additional 47 supplemental parameters were identified that should be reported depending on the nature of the research. The STAR initiative, using the Delphi method, identified a set of key parameters essential for research and reporting in clinical HA medicine.

Developing a clinical trial unit to advance research in an academic institution.

PubMed

Croghan, Ivana T; Viker, Steven D; Limper, Andrew H; Evans, Tamara K; Cornell, Alissa R; Ebbert, Jon O; Gertz, Morie A

2015-11-01

Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit. Copyright © 2015 Mayo Clinic. Published by Elsevier Inc. All rights reserved.

Found in translation: Integrating laboratory and clinical oncology research

PubMed Central

Wagner, H

2008-01-01

Translational research in medicine aims to inform the clinic and the laboratory with the results of each other’s work, and to bring promising and validated new therapies into clinical application. While laudable in intent, this is complicated in practice and the current state of translational research in cancer shows both striking success stories and examples of the numerous potential obstacles as well as opportunities for delays and errors in translation. This paper reviews the premises, promises, and problems of translational research with a focus on radiation oncology and suggests opportunities for improvements in future research design. PMID:21611010

Global Health and Emergency Care: Defining Clinical Research Priorities.

PubMed

Hansoti, Bhakti; Aluisio, Adam R; Barry, Meagan A; Davey, Kevin; Lentz, Brian A; Modi, Payal; Newberry, Jennifer A; Patel, Melissa H; Smith, Tricia A; Vinograd, Alexandra M; Levine, Adam C

2017-06-01

Despite recent strides in the development of global emergency medicine (EM), the field continues to lag in applying a scientific approach to identifying critical knowledge gaps and advancing evidence-based solutions to clinical and public health problems seen in emergency departments (EDs) worldwide. Here, progress on the global EM research agenda created at the 2013 Academic Emergency Medicine Global Health and Emergency Care Consensus Conference is evaluated and critical areas for future development in emergency care research internationally are identified. A retrospective review of all studies compiled in the Global Emergency Medicine Literature Review (GEMLR) database from 2013 through 2015 was conducted. Articles were categorized and analyzed using descriptive quantitative measures and structured data matrices. The Global Emergency Medicine Think Tank Clinical Research Working Group at the Society for Academic Emergency Medicine 2016 Annual Meeting then further conceptualized and defined global EM research priorities utilizing consensus-based decision making. Research trends in global EM research published between 2013 and 2015 show a predominance of observational studies relative to interventional or descriptive studies, with the majority of research conducted in the inpatient setting in comparison to the ED or prehospital setting. Studies on communicable diseases and injury were the most prevalent, with a relative dearth of research on chronic noncommunicable diseases. The Global Emergency Medicine Think Tank Clinical Research Working Group identified conceptual frameworks to define high-impact research priorities, including the traditional approach of using global burden of disease to define priorities and the impact of EM on individual clinical care and public health opportunities. EM research is also described through a population lens approach, including gender, pediatrics, and migrant and refugee health. Despite recent strides in global EM research and

[Organization of clinical research: in general and visceral surgery].

PubMed

Schneider, M; Werner, J; Weitz, J; Büchler, M W

2010-04-01

The structural organization of research facilities within a surgical university center should aim at strengthening the department's research output and likewise provide opportunities for the scientific education of academic surgeons. We suggest a model in which several independent research groups within a surgical department engage in research projects covering various aspects of surgically relevant basic, translational or clinical research. In order to enhance the translational aspects of surgical research, a permanent link needs to be established between the department's scientific research projects and its chief interests in clinical patient care. Importantly, a focus needs to be placed on obtaining evidence-based data to judge the efficacy of novel diagnostic and treatment concepts. Integration of modern technologies from the fields of physics, computer science and molecular medicine into surgical research necessitates cooperation with external research facilities, which can be strengthened by coordinated support programs offered by research funding institutions.

[Application of Delphi method in traditional Chinese medicine clinical research].

PubMed

Bi, Ying-fei; Mao, Jing-yuan

2012-03-01

In recent years, Delphi method has been widely applied in traditional Chinese medicine (TCM) clinical research. This article analyzed the present application situation of Delphi method in TCM clinical research, and discussed some problems presented in the choice of evaluation method, classification of observation indexes and selection of survey items. On the basis of present application of Delphi method, the author analyzed the method on questionnaire making, selection of experts, evaluation of observation indexes and selection of survey items. Furthermore, the author summarized the steps of application of Delphi method in TCM clinical research.

Building an Ontology-driven Database for Clinical Immune Research

PubMed Central

Ma, Jingming

2006-01-01

The clinical researches of immune response usually generate a huge amount of biomedical testing data over a certain period of time. The user-friendly data management systems based on the relational database will help immunologists/clinicians to fully manage the data. On the other hand, the same biological assays such as ELISPOT and flow cytometric assays are involved in immunological experiments no matter of different study purposes. The reuse of biological knowledge is one of driving forces behind this ontology-driven data management. Therefore, an ontology-driven database will help to handle different clinical immune researches and help immunologists/clinicians easily understand the immunological data from each other. We will discuss some outlines for building an ontology-driven data management for clinical immune researches (ODMim). PMID:17238637

Electronic workflow for imaging in clinical research.

PubMed

Hedges, Rebecca A; Goodman, Danielle; Sachs, Peter B

2014-08-01

In the transition from paper to electronic workflow, the University of Colorado Health System's implementation of a new electronic health record system (EHR) forced all clinical groups to reevaluate their practices including the infrastructure surrounding clinical trials. Radiological imaging is an important piece of many clinical trials and requires a high level of consistency and standardization. With EHR implementation, paper orders were manually transcribed into the EHR, digitizing an inefficient work flow. A team of schedulers, radiologists, technologists, research personnel, and EHR analysts worked together to optimize the EHR to accommodate the needs of research imaging protocols. The transition to electronic workflow posed several problems: (1) there needed to be effective communication throughout the imaging process from scheduling to radiologist interpretation. (2) The exam ordering process needed to be automated to allow scheduling of specific research studies on specific equipment. (3) The billing process needed to be controlled to accommodate radiologists already supported by grants. (4) There needed to be functionality allowing exams to finalize automatically skipping the PACS and interpretation process. (5) There needed to be a way to alert radiologists that a specialized research interpretation was needed on a given exam. These issues were resolved through the optimization of the "visit type," allowing a high-level control of an exam at the time of scheduling. Additionally, we added columns and fields to work queues displaying grant identification numbers. The build solutions we implemented reduced the mistakes made and increased imaging quality and compliance.

Impact of the European Clinical Trials Directive on academic clinical research.

PubMed

Baeyens, A J

2004-01-01

With the adoption of the Clinical Trials Directive it was Europe's intention to make the performance of multi-national clinical trials in Europe easier through the harmonization of the regulatory procedures. As the Directive was mainly conceived to facilitate the performance of multi-national clinical trials to develop new drugs, it is to be determined to what extent academic clinical trials will be concerned by the Directive and more importantly what will be its impact on daily academic clinical research. Contrary to several national regulations the scope of the Directive is very large only excluding non-interventional trials. This implies that most of the academic clinical trials will be concerned by the Directive. Besides the handling of the regulatory procedures in the different countries, issues related to insurance, labeling requirements and provision of the investigational medical products will expose the academic sponsor to additional administrative and financial challenges that will have to be handled appropriately, as the academic sponsors will be controlled by Inspectors regarding their compliance with the new regulations to come.