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MD-PhD training programs train physician-scientists to pursue careers involving both clinical care and research, but decreasing numbers of physician-scientists stay engaged in clinical research. We sought to identify current clinical research training methods utilized by MD-PhD programs, and to assess how effective they are in promoting self-efficacy for clinical research.
U.S. MD-PhD students were surveyed in April-May 2018. Students identified the clinical research training methods they participated in, and self-efficacy in clinical research was determined using a modified 12-item Clinical Research Appraisal Inventory.
Responses were received from 61 of 108 MD-PhD institutions. Responses were obtained from 647 MD-PhD students in all years of training. The primary methods of clinical research training included no clinical research training, and various combinations of didactics, mentored clinical research, and a clinical research practicum. Students with didactics plus mentored clinical research had similar self-efficacy as those with didactics plus clinical research practicum. Training activities that differentiated students who did and did not have the clinical research practicum experience and were associated with higher self-efficacy included exposure to Institutional Review Boards and participation in human subject recruitment.
A clinical research practicum was found to be an effective option for MD-PhD students conducting basic science research to gain experience in clinical research skills. Clinical research self-efficacy was correlated with the amount of clinical research training and specific clinical research tasks, which may inform curriculum development for a variety of clinical & translational research training programs, e.g., MD-PhD, TL1, and KL2.
In vivo positron emission tomography (PET) using [C11]-labeled Pittsburgh Compound B ([C11]PiB) has previously been shown to detect amyloid-β (Aβ) in late-onset Alzheimer disease (LOAD) brain; however, the sensitivity of this technique for detecting β-amyloidosis in autosomal dominant Alzheimer disease (ADAD) has not been systematically investigated. To validate [C11]PiB PET as a useful biomarker of β-amyloidosis, we measured the cortical and regional standardized uptake value ratios (SUVRs) in 16 ADAD and 15 LOAD cases and compared them with histopathologic measures of β-amyloidosis in postmortem brain. The PiB-PET data were obtained between 40–70 min after bolus injection of ∼15 mCi of [11C]PiB. MRI and PiB-PET images were co-registered and SUVRs were generated for several brain regions. Using Aβ immunohistochemistry (10D5, Eli Lilly), the burden of Aβ plaques was quantified in 16 regions of interest using an area fraction fractionator probe (Stereo Investigator, MicroBrightfield, VT). There were regional variations in Aβ plaque burden with highest densities observed in the neocortical areas and the striatum. On spearman correlations, in vivo PiB-PET correlated with postmortem Aβ plaque burden in both LOAD and ADAD, with strongest correlations seen in neocortical areas. In summary, [C11]PiB-PET has utility as a biomarker in both ADAD and LOAD.
This presentation will enable the learner to:
1.Discuss how PET-PiB beta-amyloid imaging is used as a potential biomarker of Alzheimer disease (AD)
2.Correlate postmortem neuropathologic evidence of beta-amyloidosis with PET-PiB data, and learn that PET-PiB is a potentially useful tool to detect beta-amyloidosis in presymptomatic and symptomatic individuals
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
There are limited outcome data in adults with tetralogy of Fallot and pulmonary atresia. The purpose of this study was to describe re-operations and all-cause mortality in adults with tetralogy of Fallot and pulmonary atresia.
Retrospective review of adults with repaired tetralogy of Fallot and pulmonary atresia who received care at the Mayo Adult Congenital Heart Disease Clinic, 1990–2016. All-cause mortality was calculated as events per 100 patient-years from the time of first presentation to the Adult Congenital Heart Disease Clinic.
Of the 221 patients, the age at initial tetralogy of Fallot repair was 6 (5–13) years, and the age at first presentation to the clinic was 27 – 8 years. All patients had at least one right ventricular to pulmonary artery conduit re-operation. There were 31 deaths (14%) at mean age of 41 – 14 years. The causes of death were end-stage heart failure (n = 17), sudden cardiac death (n=9), post-operative death after cardiac surgery (n = 2), sepsis with multi-system organ failure (n = 2), and unknown (n = 1). All-cause mortality rate was 1.7 per 100 patient-years. The risk factors for all-cause mortality were older age (>12 years) at the time of repair (hazard ratio 1.41, 95 confidence interval 1.06–2.02, p = 0.033), non-sustained ventricular tachycardia (hazard ratio 1.36, 95 confidence interval 1.17–2.47, p = 0.015), and left ventricular ejection fraction <50% (hazard ratio 1.39, 95 confidence interval 1.08–2.31, p = 0.031).
Based on a review of 221 adults with repaired tetralogy of Fallot and pulmonary atresia, all patients had re-operations and all-cause mortality rate was 1.7 events per 100 patient-years. The current study provides important outcomes data for risk stratification in adults with tetralogy of Fallot and pulmonary atresia.
The South China Sea (SCS) is a biodiversity hotspot, however, most biodiversity surveys in the region are confined to shallow water reefs. Here, we studied the benthic habitat and fish assemblages in the upper mesophotic coral ecosystems (MCEs; 30–40 m) and SWRs (8–22 m) at three geographic locations (Luzon Strait; Palawan; and the Kalayaan Group of Islands) in the eastern SCS (also called the West Philippine Sea) using diver-based survey methods. Mean coral genera and fish species richness ranged from 17–25 (per 25 m2) and 11–17 (per 250 m2) in MCEs, respectively; although none of these were novel genera/species. Coral and fish assemblages were structured more strongly by location than by depth. Location differences were associated with the variability in benthic composition, wherein locations with higher hard coral cover had higher coral genera richness and abundance. Locations with higher algae and sand cover had higher diversity and density of fish herbivores and benthic invertivores. Fishing efforts may also have contributed to among-location differences as the highly exploited location had the lowest fish biomass. The low variation between depths may be attributed to the similar benthic composition at each location, the interconnectivity between depths due to hydrological conditions, fish motility, and the common fishing gears used in the Philippines that can likely extend beyond SWRs. Results imply that local-scale factors and anthropogenic disturbances probably dampen across-depth structuring in coral genera and fish species assemblages.
Incorporation of metallic nanoparticles (NPs) in polymer matrix has been used to enhance and control dissolution and release of drugs, for targeted drug delivery, as antimicrobial agents, localized heat sources, and for unique optoelectronic applications. Gold NPs in particular exhibit a plasmonic response that has been utilized for photothermal energy conversion. Because plasmonic nanoparticles typically exhibit a plasmon resonance frequency similar to the visible light spectrum, they present as good candidates for direct photothermal conversion with enhanced solar thermal efficiency in these wavelengths. In our work, we have incorporated ∼3-nm-diameter colloidal gold (Auc) NPs into electrospun polyethylene glycol (PEG) fibers to utilize the nanoparticle plasmonic response for localized heating and melting of the polymer to release medical treatment. Auc and Auc in PEG (PEG+Auc) both exhibited a minimum reflectivity at 522 nm or approximately green wavelengths of light under ultraviolet-visible (UV-Vis) spectroscopy. PEG+Auc ES fibers revealed a blue shift in minimum reflectivity at 504 nm. UV-Vis spectra were used to calculate the theoretical efficiency enhancement of PEG+Auc versus PEG alone, finding an approximate increase of 10 % under broad spectrum white light interrogation, and ∼14 % when illuminated with green light. Auc enhanced polymers were ES directly onto resistance temperature detectors and interrogated with green laser light so that temperature change could be recorded. Results showed a maximum increase of 8.9 °C. To further understand how gold nanomaterials effect the complex optical properties of our materials, spectroscopic ellipsometry was used. Using spectroscopic ellipsometry and modeling with CompleteEASE® software, the complex optical constants of our materials were determined. The complex optical constant n (index of refraction) provided us with optical density properties related to light wavelength divided by velocity, and k (extinction coefficient) was used to show the absorptive properties of the materials.
In 2010, South Africa (SA) hosted the Fédération Internationale de Football Association (FIFA) World Cup (soccer). Emergency Medical Services (EMS) used the SA mass gathering medicine (MGM) resource model to predict resource allocation. This study analyzed data from the World Cup and compared them with the resource allocation predicted by the SA mass gathering model.
Prospectively, data were collected from patient contacts at 9 venues across the Western Cape province of South Africa. Required resources were based on the number of patients seeking basic life support (BLS), intermediate life support (ILS), and advanced life support (ALS). Overall patient presentation rates (PPRs) and transport to hospital rates (TTHRs) were also calculated.
BLS services were required for 78.4% (n = 1279) of patients and were consistently overestimated using the SA mass gathering model. ILS services were required for 14.0% (n = 228), and ALS services were required for 3.1% (n = 51) of patients. Both ILS and ALS services, and TTHR were underestimated at smaller venues.
The MGM predictive model overestimated BLS requirements and inconsistently predicted ILS and ALS requirements. MGM resource models, which are heavily based on predicted attendance levels, have inherent limitations, which may be improved by using research-based outcomes.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Experimental and numerical investigations into the linear and nonlinear aeroelastic behaviour of very flexible High Altitude Long Endurance (HALE) wings are conducted to assess the effect of geometrical nonlinearities on wings displaying moderate-to-large displacement. The study shows that the dynamic behaviour of wings under large deflection, and specifically the edgewise and torsion natural frequencies and modal characteristics, are largely affected by the presence of geometrical nonlinearities. A modular wing structure has been manufactured by rapid prototyping and it has been tested to characterise its dynamic and aeroelastic behaviour. At first, several simple isotropic cantilever beams with selected crosssections are numerically investigated to extract their modal characteristics. Experiments are subsequently conducted to validate the geometrically nonlinear dynamics behaviour due to high tip displacement and to understand the influence of the beam cross-section geometry. The structural dynamics and aeroelastic analysis of a very flexible modular selected wing is then investigated. Clean-wing wind-tunnel tests are carried out to assess flutter and dynamic response. The wind-tunnel model display interesting aeroelastic features including the substantial influence of the wing large deformation on its natural frequencies and modal characteristics.
Maternal pre-pregnancy weight has been related with young singletons’ cognitive and behavioral development, but it is not clear if it has an effect on temperament. We used a twin cohort to evaluate the association between maternal pre-pregnancy body mass index (BMI) and infants’ temperament. The mothers of 834 twins answered questions regarding their pre-pregnancy BMI and their 0- to 18-month-old children’s temperament using the Revised Infant Behavior Questionnaire. Three temperamental dimensions were examined: activity level, distress to limitation and duration of orienting. The relationship between maternal pre-pregnancy BMI and each temperamental component was investigated by means of multilevel mixed-effects linear regression analysis. We found no clear evidence of an association of maternal pre-pregnancy BMI with twins’ temperament. The development of temperament is influenced by a large number of factors, probably different from those influencing children’s emotional and behavioral development.
The Foothills Erratics Train consists of large quartzite blocks of Rocky Mountains origin deposited on the eastern slopes of the Rocky Mountain Foothills in Alberta between ~53.5°N and 49°N. The blocks were deposited in their present locations when the western margin of the Laurentide Ice Sheet (LIS) detached from the local ice masses of the Rocky Mountains, which initiated the opening of the southern end of the ice-free corridor between the Cordilleran Ice Sheet and the LIS. We use 10Be exposure dating to constrain the beginning of this decoupling. Based on a group of 12 samples well-clustered in time, we date the detachment of the western LIS margin from the Rocky Mountain front to ~14.9 ± 0.9 ka. This is ~1000 years later than previously assumed, but a lack of a latitudinal trend in the ages over a distance of ~500 km is consistent with the rapid opening of a long wedge of unglaciated terrain portrayed in existing ice-retreat reconstructions. A later separation of the western LIS margin from the mountain front implies higher ice margin–retreat rates in order to meet the Younger Dryas ice margin position near the boundary of the Canadian Shield ~2000 years later.
Water exposures in healthcare settings and during healthcare delivery can place patients at risk for infection with water-related organisms and can potentially lead to outbreaks. We aimed to describe Centers for Disease Control and Prevention (CDC) consultations involving water-related organisms leading to healthcare-associated infections (HAIs).
Retrospective observational study.
We reviewed internal CDC records from January 1, 2014, through December 31, 2017, using water-related terms and organisms, excluding Legionella, to identify consultations that involved potential or confirmed transmission of water-related organisms in healthcare. We determined plausible exposure pathways and routes of transmission when possible.
Of 620 consultations during the study period, we identified 134 consultations (21.6%), with 1,380 patients, that involved the investigation of potential water-related HAIs or infection control lapses with the potential for water-related HAIs. Nontuberculous mycobacteria were involved in the greatest number of investigations (n = 40, 29.9%). Most frequently, investigations involved medical products (n = 48, 35.8%), and most of these products were medical devices (n = 40, 83.3%). We identified a variety of plausible water-exposure pathways, including medication preparation near water splash zones and water contamination at the manufacturing sites of medications and medical devices.
Water-related investigations represent a substantial proportion of CDC HAI consultations and likely represent only a fraction of all water-related HAI investigations and outbreaks occurring in US healthcare facilities. Water-related HAI investigations should consider all potential pathways of water exposure. Finally, healthcare facilities should develop and implement water management programs to limit the growth and spread of water-related organisms.
The transient force exerted by a low-speed liquid droplet impinging onto a flat rigid surface is investigated experimentally. The measurements employ a high-sensitivity piezo-electric sensor, along with a high-speed camera, and cover four decades in droplet Reynolds number and greater than two decades in Weber number. Across these ranges, the peak of individual force profiles span from 3 mN to over 1300 mN. Once normalised, the force–time profiles support the existence of an inertially dominated self-similar regime. Within this regime, previous numerical and theoretical studies predict a
dependence of impact normal force during the initial pre-peak rise. While our measurements confirm this finding, they also indicate that, after the peak force the profiles exhibit an exponential decay. This long-time decay law suggests treatment of the momentum transport from the droplet using a lumped model. An observed linear dependence between the force and force decay rate supports this approach. The reason for the efficacy of treating this system via a lumped model apparently connects to the physics right at the surface that limit the rate of momentum transport from the droplet to the surface. This is explored by estimating the momentum transfer by solely using the deforming droplet shape, but under the condition of negligible momentum gradients within the droplet. The short- and long-time solutions are combined and the resulting model equation is shown to accurately cover the entire force–time profile.
On 28 September 1990, the city of Qufu, Confucius' home town in northeastern China, celebrated the philosopher's 2541st birthday with the performance of a reconstructed ceremony of ritual offerings, music, and dance. Presented on the terrace of the Hall of Great Achievements (Dacheng dian) of the Confucian Temple in Qufu, the performance was propitious but controversial. While most of the participants and audience appeared to have approved the ceremony as efficacious, some critics contested that it was inappropriately ‘touristy’ and included many inauthentic details. A few even condemned the performance as a misrepresentation of historical sacrifices to Confucius. As a music scholar invited to attend the performance, I found the contrasting reactions and criticisms enlightening because they represent a characteristically vigorous Chinese tradition of pursuing historical truth with its proliferation of written documents about the Chinese past. Above all, the reactions and criticisms highlighted, for me, the roles music performances played in historical understanding of the musical past.