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Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response.
In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise.
Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times.
Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.
OBJECTIVES/GOALS: Innovations with positive health impact are a high priority for NCATS and CTSAs. Program design that uses the Causal Pathway approach incorporates performance indicators that assess impact. We applied Causal Pathway thinking to an ongoing national program to enhance the evaluation of program impact. We report Lessons Learned. METHODS/STUDY POPULATION: We conducted a day-long onsite workshop to introduce the model to the project team, build capacity, and map the existing program elements to Logic Models representing program Specific Aims. A local Causal Pathway (CP) champion was identified. Alignment of the Logic Models with the CP approach (input→activities→ outputs→effects/impact) developed iteratively through biweekly, then monthly conferral among stakeholders. Key tasks included distinguishing among activities, outputs, and effects (impacts), and identification of performance indicators for each stage of the Causal Pathway. Visualization tools and an additional late stage half-day workshop were used to foster consensus. Implementation of the CP model tested the feasibility of collecting specific indicators and prompted model revisions. RESULTS/ANTICIPATED RESULTS: Program leadership and team members (n = 30) participated in the kick-off workshop. Four Specific Aims were mapped to Logic Models. Multiple Causal Pathway (CP) diagrams, one for each project in the program, were developed and mapped to Aims. Alignment of CP threads to Aims and identification of performance indicators required iteration. CP threads converged onto common final Impacts, sometimes crossing to another Aim. Performance indicators for operations were readily accessible to team members, and less so for impacts. Assumptions about program effects were subjected to specific indicators. Over time, Leadership noticed more expression of CP thinking in daily activities. New projects developed during this period incorporated the CP approach. Teams were able to streamline and simplify Logic/CP models. DISCUSSION/SIGNIFICANCE OF IMPACT: Through capacity-building and mentored exercises, an innovation team was able to infuse CP thinking into the evaluation of their ongoing program. The CP approach to design and evaluation maps progress and indicators across the life of a program from initial activities to its ultimate impact.
Previous literature supports exercise as a preventative agent for prenatal depression; however, treatment effects for women at risk for prenatal depression remain unexplored. The purpose of the study was to examine whether exercise can lower depressive symptoms among women who began pregnancy at risk for depression using both a statistical significance and reliable and clinically significant change criteria.
This study is a secondary analysis of two randomized controlled trials that followed the same exercise protocol. Pregnant women were allocated to an exercise intervention group (IG) or control group (CG). All participants completed the Center for Epidemiological Depression (CES-D) scale at gestational week 9–16 and 36–38. Women with a baseline score ⩾16 were included. A clinically reliable cut-off was calculated as a 7-point change in scores from pre- to post-intervention.
Thirty-six women in the IG and 25 women in the CG scored ⩾16 on the CES-D at baseline. At week 36–38 the IG had a statistically significant lower CES-D score (14.4 ± 8.6) than the CG (19.4 ± 11.1; p < 0.05). Twenty-two women in the IG (61%) had a clinically reliable decrease in their post-intervention score compared to eight women in the CG (32%; p < 0.05). Among the women who met the reliable change criteria, 18 (81%) in the IG and 7 (88%) in the CG had a score <16 post-intervention, with no difference between groups (p > 0.05).
A structured exercise program might be a useful treatment option for women at risk for prenatal depression.
To investigate the potential dietary impact of the opening of new retailers of healthy foods.
Systematic review of the peer-reviewed research literature.
References published before November 2015 were retrieved from MEDLINE, EMBASE and Web of Science databases using keyword searches.
The outcome of the review was change in fruit and vegetable consumption among adults.
Of 3514 references retrieved, ninety-two articles were reviewed in full text, and twenty-three articles representing fifteen studies were included. Studies used post-test only (n 4), repeated cross-sectional (n 4) and repeated measures designs (n 7) to evaluate the dietary impact of supermarket (n 7), farmers’ market (n 4), produce stand (n 2) or mobile market (n 2) openings. Evidence of increased fruit and vegetable consumption was most consistent among adults who began shopping at the new retailer. Three of four repeated measures studies found modest, albeit not always statistically significant, increases in fruit and vegetable consumption (range 0·23–0·54 servings/d) at 6–12 months after baseline. Dietary change among residents of the broader community where the new retailer opened was less consistent.
The methodological quality of studies, including research designs, sampling methods, follow-up intervals and outcome measures, ranged widely. Future research should align methodologically with previous work to facilitate meta-analytic synthesis of results. Opening a new retailer may result in modest short-term increases in fruit and vegetable consumption among adults who choose to shop there, but the potential longer-term dietary impact on customers and its impact on the broader community remain unclear.
OBJECTIVES/SPECIFIC AIMS: Upper-extremity (UE) impairment affects 88% of stroke survivors due to dysfunctional shoulder-hand coordination. Patients may be able to grasp with the arm at rest, but unable to grasp in a functional context (eg, from a high shelf) because shoulder use elicits involuntary hand muscle activity. Further, much rehabilitation research is directed at unsuccessful stroke recovery (patients with persistent UE impairment) but very little towards patients who show successful clinical recovery (such as those with mild UE impairment) even though these patients have attained the desired rehabilitation outcome. We examined the neurophysiological trajectory of successful compared to unsuccessful post-stroke recovery in the context of functional UE movements to clearly identify what factors are necessary for successful recovery of functional UE movements after stroke. METHODS/STUDY POPULATION: We studied 3 populations: (1) mildly-impaired patients, early (at <17 d, 30 d, 90 d, and 180 d) after stroke as a model of successful post-stroke recovery, (2) moderately-impaired, chronic patients (>6-months post stroke) with persistent hand function impairment, as a model of incomplete post-stroke recovery (unsuccessful recovery), and (3) Healthy age-range matched controls. We used transcranial magnetic stimulation (TMS) in all 3 groups at the given time points to measure corticomotor excitability (motor evoked potentials, recruitment curve), corticomotor inhibition (short-interval intracortical inhibition, long-interval intracortical inhibition), and intracortical facilitation of hand muscles with the shoulder positioned in different degrees of flexion or abduction (these shoulder positions are known to elicit involuntary, undesired hand muscle activation, which leads to UE dysfunction and impairment in individuals with stroke). RESULTS/ANTICIPATED RESULTS: Data collection are in process and will be presented. Preliminary data from controls shows that corticomotor excitability of selected hand muscles is affected by changes in shoulder position. Preliminary findings in controls are consistent with clinical findings in stroke that certain shoulder positions elicit involuntary and undesired hand muscle activation, leading to UE dysfunction and disability. Findings from the stroke groups will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: We hypothesize that this centrally-facilitated coupling between shoulder and hand muscles is disrupted after stroke, which may play a central role in the inability of patients to perform functional UE movements. By comparing the TMS metrics in mildly-impaired Versus moderately-impaired chronic patients, we will be able to identify the longitudinal change in neurophysiology underlying shoulder-hand coordination that is associated with successful or unsuccessful clinical recovery of UE function after stroke. Thus, these findings will help us distinguish between the neurophysiology underlying successful from unsuccessful UE recovery leading to more mechanism-based interventions for UE dysfunction post stroke in the future.
Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.
Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.
Forty-eight competency statements in 8 domains were developed.
Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.
The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.
In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.
This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.
We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.
Promoting dignity is at the heart of the human capability approach to development. We introduce the concept of stakeholder capability enhancement, beginning with a discussion of the capability approach to development proposed by Sen (1985) and further advanced by Nussbaum (1990) to incorporate notions of dignity. Thereafter follows a review of the literature on value creation stakeholder management and convergent stakeholder theory (Freeman, 1984; Freeman, Harrison, Wicks, Palmer, & DeColle, 2010; Harrison & Wicks, 2013; Jones & Wicks, 1999), as the foundation for our concept of stakeholder capability enhancement. The remainder of this article develops a model that integrates stakeholder management with the human capability approach to detail the cooperative advantage that accrues to business and its stakeholders, as well as the gains in social wellbeing and dignity, when stakeholder capability enhancement becomes a common enterprise strategy. The model also explores the risks and boundary conditions firms face when seeking to profit from stakeholder capability tradeoffs. In explaining the model, we explore normative responsibilities and consequences with regard to human capabilities and dignity. We conclude with implications for future research.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
To determine the prevalence of Pseudomonas aeruginosa colonization on intensive care unit (ICU) admission, risk factors for P. aeruginosa colonization, and the incidence of subsequent clinical culture with P. aeruginosa among those colonized and not colonized.
We conducted a cohort study of patients admitted to a medical or surgical intensive care unit of a tertiary care hospital. Patients had admission perirectal surveillance cultures performed. Risk factors analyzed included comorbidities at admission, age, sex, antibiotics received during current hospitalization before ICU admission, and type of ICU.
Of 1,840 patients, 213 (11.6%) were colonized with P. aeruginosa on ICU admission. Significant risk factors in the multivariable analysis for colonization were age (odds ratio, 1.02 [95% CI, 1.01–1.03]), anemia (1.90 [1.05–3.42]), and neurologic disorder (1.80 [1.27–2.54]). Of the 213 patients colonized with P. aeruginosa on admission, 41 (19.2%) had a subsequent clinical culture positive for P. aeruginosa on ICU admission and 60 (28.2%) had a subsequent clinical culture positive for P. aeruginosa in the current hospitalization (ICU period and post-ICU period). Of these 60 patients, 49 (81.7%) had clinical infections. Of the 1,627 patients not colonized on admission, only 68 (4.2%) had a subsequent clinical culture positive for P. aeruginosa in the current hospitalization. Patients colonized with P. aeruginosa were more likely to have a subsequent positive clinical culture than patients not colonized (incidence rate ratio, 6.74 [95% CI, 4.91–9.25]).
Prediction rules or rapid diagnostic testing will help clinicians more appropriately choose empirical antibiotic therapy for subsequent infections.
Indigenous Studies is a rapidly growing field of enquiry both nationally and internationally. The internationalisation of the discipline is dependent on its interdiciplinarity and on the collaborative efforts of interdisciplinary scholars. Colonised Indigenous people globally share similar experiences despite differences in histories and contexts. In collaborative situations, dedicated scholarship brings together Indigenous people and allies who are committed to the global expansion of Indigenous knowledge through shared understandings of experiences and histories. Collective efforts can improve curriculum development, enhance opportunities for publication, bring scholars together in conferences and symposia and provide opportunities for new research networks for Indigenous scholarship. This paper addresses spheres of collaborative and collective endeavours that continue to reap benefits nationally and internationally in the field of international Indigenous Studies.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Deflection missions to near-Earth asteroids will encounter non-negligible uncertainties in the physical and orbital parameters of the target object. In order to reliably assess future impact threat mitigation operations such uncertainties have to be quantified and incorporated into the mission design. The implementation of deflection demonstration missions offers the great opportunity to test our current understanding of deflection relevant uncertainties and their consequences, e.g., regarding kinetic impacts on asteroid surfaces. In this contribution, we discuss the role of uncertainties in the NEOTωIST asteroid deflection demonstration concept, a low-cost kinetic impactor design elaborated in the framework of the NEOShield project. The aim of NEOTωIST is to change the spin state of a known and well characterized near-Earth object, in this case the asteroid (25143) Itokawa. Fast events such as the production of the impact crater and ejecta are studied via cube-sat chasers and a flyby vehicle. Long term changes, for instance, in the asteroid's spin and orbit, can be assessed using ground based observations. We find that such a mission can indeed provide valuable constraints on mitigation relevant parameters. Furthermore, the here proposed kinetic impact scenarios can be implemented within the next two decades without threatening Earth's safety.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
We report the results of a subgroup analysis of the Benefits of Universal Glove and Gown trial. In 20 intensive care units, the reduction in acquisition of methicillin-resistant Staphylococcus aureus observed in this trial was observed in units also using chlorhexidine bathing and in those that previously performed active surveillance.
To identify factors associated with the development of surgical site infection (SSI) among adult patients undergoing renal transplantation
A retrospective cohort study
An urban tertiary care center in Baltimore, Maryland, with a well-established renal transplantation program that performs ~200–250renal transplant procedures annually
At total of 441 adult patients underwent renal transplantation between January 1, 2010, and December 31, 2011. Of these 441patients, 66 (15%) developed an SSI; of these 66, 31 (47%) were superficial incisional infections and 35 (53%) were deep-incisional or organ-space infections. The average body mass index (BMI) among this patient cohort was 29.7; 84 (42%) were obese (BMI >30). Patients who developed an SSI had a greater mean BMI (31.7 vs 29.4; P=.004) and were more likely to have a history of peripheral vascular disease, rheumatologic disease, and narcotic abuse. History of cerebral vascular disease was protective. Multivariate analysis showed BMI (odds ratio [OR] 1.06; 95% confidence interval [CI], 1.02–1.11) and past history of narcotic use/abuse (OR, 4.86; 95% CI, 1.24–19.12) to be significantly associated with development of SSI after controlling for National Healthcare Surveillance Network (NHSN) score and presence of cerebrovascular, peripheral vascular, and rheumatologic disease.
We identified higher BMI as a risk factor for the development of SSI following renal transplantation. Notably, neither aggregate comorbidity scores nor NHSN risk index were associated with SSI in this population. Additional risk adjustment measures and research in this area are needed to compare SSIs across transplant centers.
In no other society in the world have urbanisation and industrialization been as comprehensively based on migrant labour as in South Africa. Rather than focusing on the well-documented narrative of displacement and oppression, A Long Way Home captures the humanity, agency and creative modes of self-expression of the millions of workers who helped to build and shape modern South Africa. The book spans a three-hundred-year history beginning with the exportation of slave labour from Mozambique in the eighteenth century and ending with the strikes and tensions on the platinum belt in recent years. It shows not only the age-old mobility of African migrants across the continent but also, with the growing demand for labour in the mining industry, the importation of Chinese indentured migrant workers. Contributions include 18 essays and over 90 artworks and photographs that traverse homesteads, chiefdoms and mining hostels, taking readers into the materiality of migrant life and its customs and traditions, including the rituals practiced by migrants in an effort to preserve connections to “home” and create a sense of “belonging”. The essays and visual materials provide multiple perspectives on the lived experience of migrant labourers and celebrate their extraordinary journeys. A Long Way Home was conceived during the planning of an art exhibition entitled ‘Ngezinyawo: Migrant Journeys’ at Wits Art Museum. The interdisciplinary nature of the contributions and the extraordinary collection of images selected to complement and expand on the text make this a unique collection.