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OBJECTIVES/SPECIFIC AIMS: To introduce CCTS to the clinical and translational research community. METHODS/STUDY POPULATION: Established in the summer of 2017, the Center for Clinical and Translational Science (CCTS) fosters cooperative clinical and translational sciences between the University of Mississippi School of Pharmacy (UMSOP) and the University of Mississippi Medical Center (UMMC). CCTS facilitates the translation of basic research discoveries into clinically validated therapies to improve the health of populations in Mississippi and beyond. Priority areas of investigation in CCTS include Cardiometabolic disorders, Cancer, Neuroscience, Infectious diseases, Precision Medicine, and Community-Based Research. To accomplish CCTS mission three overarching goals have been defined: I) Develop progressive and sustainable capacity for clinical and translational research in Mississippi; II) Promote interprofessional engagement in clinical and translational science; and III) Foster research collaboration among stakeholders in and outside of Mississippi. RESULTS/ANTICIPATED RESULTS: To carry its CCTS’s mission three research units have been established: 1) The Pre-clinical Research Unit: Develops processes to move basic science discoveries towards translation into research in humans. This unit provides guidance in the development of Investigational New Drug (IND) applications; and identifies and pursues opportunities to develop progressive capacities for in vitro, ex vivo, in vivo, and in silico approaches for evaluating new pharmaceutical and therapeutic agents. 2) The Clinical Research Unit: Transitions projects that have received IND approval into the first phase of clinical trials. It also transitions clinical trials from Phase I to Phase II and to Phase III; develops standard operating procedures (SOPs), personnel training plans, and policies to guide clinical research; works with industry sponsors and governmental funding agencies; and assures compliance with regulatory requirements. 3) Community/population Research Unit: Develops, coordinates, and facilitates research activities and translation between clinical and community/population research stages. To do so, this unit works closely with community partners and Population Health programs on the Oxford and Jackson campuses. DISCUSSION/SIGNIFICANCE OF IMPACT: Since its inception, the CCTS has surpassed 1.5 million dollars in competitive funding. This early success positions the CCTS well to promote research collaboration between UMSOP and UMMC and to progress in becoming a national leader in clinical and translational investigation.
Introduction: Social desirability bias is a systematic error in self-report measures resulting from the desire of respondents to avoid embarrassment and project a favourable image of themselves to others. This bias may decrease the accuracy of self-reported health outcomes collected in health research compromise the validity of research findings. This study compared outcomes obtained by patient self-report vs. the same outcomes after undergoing verification and external adjudication, in trial involving patients with acute asthma. Methods: Cross-sectional analysis of outcome data obtained in a randomized controlled trial conducted in 6 Canadian emergency departments (ED). Adult patients were allocated to receive usual care (UC), opinion leader [OL] guidance to their primary care provider (PCP), or OL guidance+nurse case-management [OL+CM] for patients (NCT01079000). Asthma relapses and PCP follow-up visits were blindly assessed through patient self-report 30 and 90 days after their ED presentation for acute asthma. Each reported event was verified through the provincial electronic medical record, the ED Information Systems, and by calling the PCPs’ offices. Two study investigators, blinded to the study interventions, independently reviewed and adjudicated the verified outcomes. Disagreements were resolved by consensus prior to un-blinding. Results: Overall, 367 patients were enrolled; more were female (64%) and the median age was 28 years. Overall, patient follow-up was obtained in 85% of cases. The proportion of asthma relapses occurring within the first 90 days were lower when considering patient self-report than when considering the adjudicated outcomes (17%[39/227] vs. 19%[70/367]). The proportion of PCP follow-up visits occurring within the first 30 days were higher when considering patient self-report than when considering the adjudicated outcomes (47%[139/290] vs. 40%[146/367]). The pattern was similar, regardless of the arm of the study (UC vs. OL vs. OL+CM arms); outcome disagreement did not influence the direction of magnitude of the treatment effect. Conclusion: Social desirability bias could have influenced the outcomes obtained by patient self-report in this ED-based study. The direction of the bias was the same for both outcomes; however, the variation did not change the study results. This bias may play a role in studies with smaller sample sizes.
Introduction: Many patients presenting to Emergency Departments (EDs) with acute asthma have limited or no access to health care providers, medications and preventive resources. This study explored outpatient care gaps among subjects presenting to the ED for acute asthma, before being discharged. Methods: Cross-sectional analysis of data obtained in a comparative effectiveness trial conducted in six EDs in Alberta (NCT01079000). Data were collected through patient interviews and chart reviews at ED presentation. Two clinician-investigators independently reviewed and adjudicated the following preventive actions: use of spacer devices, written asthma action plans (AAPs) and asthma medication; influenza immunization, cigarette smoking, and referral to asthma education. Agreement between adjudicators was calculated based on kappa (k) statistics. Results: The median age of the study population (n=367) was 28 years and 64% were women. Overall, 26% of patients reported not having a regular family physician. Agreement between reviewers was excellent (k=0.96). More than half (59%) reported not using spacer devices despite being indicated and 3% reported having a written AAP. Following the recommendations of the current asthma guidelines, 38% of the patients required the initiation of inhaled corticosteroids (ICS), 11% required the addition of ICS/long-acting β-agonists combination agents and 39% required reinforcement of adherence with preventer medications. Finally, 37% reported receiving influenza vaccination in the past year, 7% had been referred to asthma education in the last 10 years, and 31% were still smoking, suggesting that cessation counselling was indicated. Conclusion: The ED encounter for patients with acute asthma represents a unique opportunity to establish important partnerships across the continuum of asthma care (e.g., link them with a family doctor). This study provided a robust assessment of the outpatient care gaps in this patient population, which identified many areas for targeted interventions. The method of delivery and type of messaging needs further study.
Introduction: Approximately 20% of Canadians who present to emergency departments (EDs) with acute asthma relapse within 4 weeks of discharge. The reasons are likely multi-factorial; however, the lack of timely primary care provider (PCP) follow-up and inadequate patient self-management are thought to be important variables. Therefore, we tested the effectiveness of ED-directed multifaceted interventions that targeted PCPs and enhanced patient self-management to reduce asthma relapse following ED discharge. Methods: Adults with acute asthma discharged from 6 Alberta EDs were randomly allocated, in a centralized and concealed manner, to receive usual care (UC), opinion leader [OL] guidance to their PCPs, or OL guidance + nurse case-management [OL+CM] for patients (NCT01079000). The main outcome was asthma relapse within 90-days of ED discharge. Secondary outcomes included PCP visits, time to relapse, hospitalizations and asthma-related quality of life (QoL). Outcomes were collected independently and assessors were masked to intervention assignment. Results: From 943 screened patients, 367 patients were allocated to the study arms (UC=146; OL=110; OL+CM=111). Median age was 28 years, 64% were women, median peak flow at discharge was 350 L/min; 77% were discharged home on prednisone and 85% on either inhaled corticosteroids (ICS) or ICS/long-acting β2-agonists. Compared with UC, both interventions significantly increased rates of relapse at 90-days: UC=12%, OL=28%, OL+CM=19%; p=0.006. Based on an absolute increased risk of 0.16 (95% CI: 0.05, 0.25), the number needed to treat for harm was 6 (95% CI: 3.9, 19.0) for the OL arm. Across study differences in PCP follow-up visits, time to relapse, hospitalizations or asthma-related QoL were not identified. Conclusion: Two different theory-informed and evidenced-based interventions intended to decrease asthma relapse robustly and significantly increased rates of relapse compared with UC. While the reasons for these unintended consequences require further study, we caution against the adoption of similar interventions by other EDs.
Neighboring tidewater glaciers often exhibit asynchronous dynamic behavior, despite relatively uniform regional atmospheric and oceanic forcings. This variability may be controlled by a combination of local factors, including glacier and fjord geometry, fjord heat content and circulation, and glacier surface melt. In order to characterize and understand contrasts in adjacent tidewater glacier and fjord dynamics, we made coincident ice-ocean-atmosphere observations at high temporal resolution (minutes to weeks) within a 10 000 km2 area near Uummannaq, Greenland. Water column velocity, temperature and salinity measurements reveal systematic differences in neighboring fjords that imply contrasting circulation patterns. The observed ocean velocity and hydrography, combined with numerical modeling, suggest that subglacial discharge plays a major role in setting fjord conditions. In addition, satellite remote sensing of seasonal ice flow speed and terminus position reveal both speedup and slow-down in response to melt, as well as differences in calving style among the neighboring glaciers. Glacier force budgets and modeling also point toward subglacial discharge as a key factor in glacier behavior. For the studied region, individual glacier and fjord geometry modulate subglacial discharge, which leads to contrasts in both fjord and glacier dynamics.
We will discuss the evolution of star clusters with a large initial binary fraction, up to 95%. The initial binary population is chosen to follow the invariant orbital-parameter distributions suggested by Kroupa (1995). The Monte Carlo MOCCA simulations of star cluster evolution are compared to the observations of Milone et al. (2012) for photometric binaries. It is demonstrated that the observed dependence on cluster mass of both the binary fraction and the ratio of the binary fractions inside and outside of the half mass radius are well recovered by the MOCCA simulations. This is due to a rapid decrease in the initial binary fraction due to the strong density-dependent destruction of wide binaries described by Marks, Kroupa & Oh (2011). We also discuss a new scenario for the formation of intermediate mass black holes in dense star clusters. In this scenario, intermediate mass black holes are formed as a result of dynamical interactions of hard binaries containing a stellar mass black hole, with other stars and binaries. We will discuss the necessary conditions to initiate the process of intermediate mass black hole formation and the dependence of its mass accretion rate on the global cluster properties.
Primary ciliary dyskinesia and heterotaxy are rare but not mutually exclusive disorders, which result from cilia dysfunction. Heterotaxy occurs in at least 12.1% of primary ciliary dyskinesia patients, but the prevalence of primary ciliary dyskinesia within the heterotaxy population is unknown. We designed and distributed a web-based survey to members of an international heterotaxy organisation to determine the prevalence of respiratory features that are common in primary ciliary dyskinesia and that might suggest the possibility of primary ciliary dyskinesia. A total of 49 members (25%) responded, and 37% of the respondents have features suggesting the possibility of primary ciliary dyskinesia, defined as (1) the presence of at least two chronic respiratory symptoms, or (2) bronchiectasis or history of respiratory pathogens suggesting primary ciliary dyskinesia. Of the respondents, four completed comprehensive, in-person evaluations, with definitive primary ciliary dyskinesia confirmed in one individual, and probable primary ciliary dyskinesia identified in two others. The high prevalence of respiratory features compatible with primary ciliary dyskinesia in this heterotaxy population suggests that a subset of heterotaxy patients have dysfunction of respiratory, as well as embryonic nodal cilia. To better assess the possibility of primary ciliary dyskinesia, heterotaxy patients with chronic oto-sino-respiratory symptoms should be referred for a primary ciliary dyskinesia evaluation.
This paper examines how the relationships between the factors (predisposing, enabling and illness) of the 1973 Andersen framework and service use are influenced by changes in the caring role in older women of the 1921–26 cohort of the Australian Longitudinal Study on Women's Health. Outcome variables were the use of three formal community support services: (a) nursing or community health services, (b) home-making services and (c) home maintenance services. Predictor variables were survey wave and the following carer characteristics: level of education, country of birth, age, area of residence, ability to manage on income, need for care, sleep difficulty and changes in caring role. Carer changes were a significant predictor of formal service use. Their inclusion did not attenuate the relationship between the Andersen framework factors and service use, but instead provided a more complete representation of carers' situations. Women were more likely to have used support services if they had changed into or out of co-resident caring or continued to provide co-resident care for a frail, ill or disabled person, needed care themselves, and reported sleep difficulties compared with women who did not provide care. These findings are important because they indicate that support services are particularly relevant to women who are changing their caring role and who are themselves in need of care.
Feeding stimulates robust increases in muscle protein synthesis (MPS); however, ageing may alter the anabolic response to protein ingestion and the subsequent aminoacidaemia. With this as background, we aimed to determine in the present study the dose–response of MPS with the ingestion of isolated whey protein, with and without prior resistance exercise, in the elderly. For the purpose of this study, thirty-seven elderly men (age 71 (sd 4) years) completed a bout of unilateral leg-based resistance exercise before ingesting 0, 10, 20 or 40 g of whey protein isolate (W0–W40, respectively). Infusion of l-[1-13C]leucine and l-[ring-13C6]phenylalanine with bilateral vastus lateralis muscle biopsies were used to ascertain whole-body leucine oxidation and 4 h post-protein consumption of MPS in the fed-state of non-exercised and exercised leg muscles. It was determined that whole-body leucine oxidation increased in a stepwise, dose-dependent manner. MPS increased above basal, fasting values by approximately 65 and 90 % for W20 and W40, respectively (P < 0·05), but not with lower doses of whey. While resistance exercise was generally effective at stimulating MPS, W20 and W40 ingestion post-exercise increased MPS above W0 and W10 exercised values (P < 0·05) and W40 was greater than W20 (P < 0·05). Based on the study, the following conclusions were drawn. At rest, the optimal whey protein dose for non-frail older adults to consume, to increase myofibrillar MPS above fasting rates, was 20 g. Resistance exercise increases MPS in the elderly at all protein doses, but to a greater extent with 40 g of whey ingestion. These data suggest that, in contrast to younger adults, in whom post-exercise rates of MPS are saturated with 20 g of protein, exercised muscles of older adults respond to higher protein doses.
Batch adsorption/dissolution experiments were conducted to examine the interactions between 233U(VI) and a synthetic aluminum oxyhydroxide (boehmite, γ-AlOOH) in 1.0M NaCl suspensions containing 1-hydroxyethane-1,1-diphosphonic acid (HEDPA). In the pH range 4 to 9, complexation of Al(III) by HEDPA significantly enhanced dissolution of boehmite. This phenomenon was especially pronounced in the neutral pH region where the solubility of aluminum, in the absence of complexants, is limited by the formation of sparsely soluble aluminum hydroxides. At high pH levels, dissolution of synthetic boehmite was inhibited by HEDPA, likely due to sorption of Al(III)/HEDPA complexes. Addition of HEDPA to equilibrated U(VI)-synthetic boehmite suspensions yielded an increase in the aqueous phase uranium concentration. The concentration of uranium continually increased over 59 days. Partitioning of uranium between the solid and aqueous phase was found to correlate well with HEDPA partitioning.
We have analyzed the redistribution parameters for InP grown by organometallic vapor phase epitaxy (OMVPE) on GaAs substrates. The layers, grown using (trimethyl Indium) TMIn at atmospheric pressure, have been characterized for epitaxial quality using photoluminescence, energy dispersed x-ray analysis, and optical microscopy. In order to better understand the effects of inter-diffusion and inter-mixing for the GaAs into the InP epitaxial layer, the layer-substrate interface was first probed by growing consecutive samples of InP for increasingly longer growth times, and thus characterizing the layers as one moves away from the interface. For more detailed analysis, cross-sections of the InP/GaAs interface were prepared for scanning transmission electron microscopy (STEM). Energy dispersed x-ray analysis has shown that all elements In, Ga, As, and P, are present on the epitaxial side of the interface, while only Ga and As are present on the substrate side. A combination of electron diffraction and luminescence measurements show the epitaxy is at least 80% InP at the interface and essentially 100% InP at a distance of 6000Å into the epilayer. Electron diffraction and bright field investigation at the interface show the existence of a second phase, existing in a mostly InP matrix. The effects of redistribution in heteroepitaxial InP/GaAs will be discussed.
We report on the defects present in doped InP and GaInAs grown by organometallic vapor phase epitaxy (OMVPE). The material was grown in an atmospheric pressure system using group III trimethyl sources, arsine and phosphine. Bis(cyclopentadienyl) magnesium (Cp2Mg) was present as a p-type source of magnesium. Defects in as-grown material were characterized using photoluminescence (PL), Hall-effect, and deep level transient spectroscopy (DLTS). Various levels of Mg doping were investigated, ranging from 5 × 1015 to 1 × 1019 cm−3. Radiative defects were observed at 77 K corresponding to PL emission from conduction band/shallow donor to acceptor levels including emission at 1.37 eV identified as the shallow hydrogenic acceptor, and emission lines at 1.3 eV and 1.0 eV in heavily doped material. Corresponding hole traps in InP:Mg were observed by DLTS having thermal activation energies of 0.20 and 0.40 eV, the 0.40 eV trap being the dominant defect in p-type InP. In GaInAs grown near lattice-matched to InP, radiative emission is also observed from deep centers 100 meV from band edge emission. This emission is observed to be related to lattice-mismatch of the ternary with the InP, and is found to be accentuated and broadened in GaInAs doped with Mg.