525 research outputs found
How Competent Are Emergency Medicine Interns for Level 1 Milestones: Who Is Responsible?
Objectives The Next Accreditation System ( NAS ) of the Accreditation Council for Graduate Medical Education ( ACGME ) includes the implementation of developmental milestones for each specialty. The milestones include five progressively advancing skill levels, with Level 1 defining the skill level of a medical student graduate, and Level 5, that of an attending physician. The goal of this study was to query interns on how well they thought their medical school had prepared them to meet the proposed emergency medicine ( EM ) Level 1 milestones. Methods In July 2012, an electronic survey was distributed to the interns of 13 EM residency programs, asking interns whether they were taught and assessed on the proposed Level 1 milestones. Results Of possible participants, 113 of 161 interns responded (70% response rate). The interns represented all four regions of the country. The interns responded that the rates of Level 1 milestones they had been taught ranged from 61% for ultrasound to 98% for performance of focused history and physical examination. A substantial number of interns (up to 39%) reported no instruction on milestones such as patient disposition, pain management, and vascular access. Graduating medical students were less commonly assessed than taught the milestones. Skills with technology, including “explain the role of the electronic health record and computerized physician order entry,” were assessed for only 39% of interns, and knowledge ( USMLE ) and history and physical were assessed in nearly all interns. Disposition, ultrasound, multitasking, and wound management were assessed less than half of the time. Conclusions Many entering EM interns may not have had either teaching or assessment on the knowledge, skills, and behaviors making up the Level 1 milestones expected for graduating medical students. Thus, there is a potential gap in the teaching and assessment of EM interns. Based on these findings, it is unclear who will be responsible (medical schools, EM clerkships, or residency programs) for ensuring that medical students entering residency have achieved Level 1 milestones. Resumen Competencia de los Residentes de Medicina de Urgencias y Emergencias para el Nivel 1: ¿Quién es el Responsable? El próximo sistema de acreditación ( NAS , Next Accreditation System ) del Accreditation Council for Graduate Medical Education ( ACGME ) incluye la implementación de objetivos por área de desarrollo para cada especialidad. Los objetivos por área incluyen cinco niveles de habilidades progresivamente avanzadas, con un nivel 1 definido por el nivel de habilidad de un estudiante licenciado de medicina, y un nivel definido por el nivel, de un médico adjunto. El objetivo de este estudio fue preguntar a los residentes cómo pensaban que sus universidades les habían preparado para alcanzar los objetivos por área de nivel 1 propuestos en medicina de urgencias y emergencias ( MUE ). Metodología En julio de 2012, se distribuyó una encuesta electrónica a los residentes de 13 programas de residencia de MUE , preguntándoles si estaban formados y evaluados en los objetivos por área de nivel 1 propuestos. Resultados De los posibles participantes, 113 de 161 residentes (70%) respondieron. Los residentes representaban las cuatro regiones del país. Los residentes respondieron que los porcentajes de objetivos por área de nivel 1 en los que se habían formado variaron del 61% para la ecografía al 98% para la realización de la historia clínica y la exploración física. Un número importante de residentes (hasta un 39%) respondieron no formarse en objetivos por áreas tales como la ubicación del paciente, el manejo del dolor y el acceso vascular. Los estudiantes licenciados de medicina fueron menos frecuentemente evaluados que formados en los objetivos por área. Las habilidades con la tecnología, incluyendo la explicación del rol de la historia clínica electrónica y la solicitud de órdenes médicas computarizadas, se evaluaron sólo en el 39% de los residentes y el conocimiento ( USMLE , United States Medical Licensing Examination ) y la historia clínica y exploración física se evaluaron en casi todos los residentes. Es más, la ubicación, la ecografía, la multitarea y el manejo de heridas se evaluaron en menos de la mitad de las ocasiones. Conclusiones Muchos de los residentes que se inician en MUE pueden no haber tenido formación o evaluación en el conocimiento, las habilidades y los comportamientos preparatorios para los objetivos por área de nivel 1 esperados para los estudiantes licenciados de medicina. Además, hay una brecha potencial en la formación y la evaluación de los residentes de MUE . En base a estos hallazgos, no está claro quién será el responsable, las facultades de medicina, la administración de la MUE o los programas de residencia, para asegurar que los estudiantes de medicina que entren en la residencia hayan alcanzado los objetivos por área de nivel 1.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99036/1/acem12162.pd
Expanding the toolbox of metabolically stable lipid prodrug strategies
Nucleoside- and nucleotide-based therapeutics are indispensable treatment options for patients suffering from malignant and viral diseases. These agents are most commonly administered to patients as prodrugs to maximize bioavailability and efficacy. While the literature provides a practical prodrug playbook to facilitate the delivery of nucleoside and nucleotide therapeutics, small context-dependent amendments to these popular prodrug strategies can drive dramatic improvements in pharmacokinetic (PK) profiles. Herein we offer a brief overview of current prodrug strategies, as well as a case study involving the fine-tuning of lipid prodrugs of acyclic nucleoside phosphonate tenofovir (TFV), an approved nucleotide HIV reverse transcriptase inhibitor (NtRTI) and the cornerstone of combination antiretroviral therapy (cART). Installation of novel lipid terminal motifs significantly reduced fatty acid hepatic ω-oxidation while maintaining potent antiviral activity. This work contributes important insights to the expanding repertoire of lipid prodrug strategies in general, but particularly for the delivery and distribution of acyclic nucleoside phosphonates
VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120
Multiple antibody effector functions arise in HIV-1 infection that could be harnessed to protect against infection or clear the persistent reservoir. Here, we have investigated the genetic and functional memory B cell and antibody landscape present during early infection in six individuals infected with either subtype A, C, or an A/C recombinant HIV-1. These individuals demonstrated varying levels of plasma autologous neutralization (nAb) against the transmitted/founder envelope (T/F Env) pseudovirus and non-neutralizing Fc-mediated effector function (nnFc) antibody-dependent cell-mediated cytotoxicity (ADCC) against the T/F Env gp120 protein at ~7 months after infection. Genetic analysis of the immunoglobulin heavy (VH) and light (VL) chain variable domain gene segments from 352 autologous T/F Env gp120-specific single B cells recovered at this same 7-month time-point revealed an over-representation of the VH1-69 germline in five of six individuals. A defining feature of the VH1-69 utilizing gp120-specific antibodies was their significantly more hydrophobic complementarity-determining region-2 (CDRH2) regions compared to other VH CDRH2 sequences from each individual. While none of the VH1-69 antibodies possessed strong neutralizing activity against virions pseudotyped with the autologous T/F Env, almost a third were capable of mediating high ADCC activity, as assayed by intracellular granzyme B activity in CEM.NKr.CCR5 target cells coated with autologous T/F Env gp120. High ADCC mediating VH1-69 antibodies exhibited shorter complementarity-determining region-3 (CDRH3) lengths and a more neutral isoelectric point than antibodies lacking this function. In the individual that developed the highest autologous ADCC responses, the high granzyme B producing antibodies bound to surface expressed envelope in the absence of CD4 and were not enhanced by the addition of soluble CD4. Overall, VH1-69 utilizing antibodies are commonly induced against gp120 in diverse HIV-1 infections and a subset of these antibodies can mediate ADCC functions, serving as a bridge between the innate and adaptive immune response to HIV-1
Morphological and compositional changes in the skeletons of new coral recruits reared in acidified seawater : insights into the biomineralization response to ocean acidification
Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 19 (2009): Q07005, doi:10.1029/2009GC002411.We reared primary polyps (new recruits) of the common Atlantic golf ball coral Favia fragum for 8 days at 25°C in seawater with aragonite saturation states ranging from ambient (Ω = 3.71) to strongly undersaturated (Ω = 0.22). Aragonite was accreted by all corals, even those reared in strongly undersaturated seawater. However, significant delays, in both the initiation of calcification and subsequent growth of the primary corallite, occurred in corals reared in treatment tanks relative to those grown at ambient conditions. In addition, we observed progressive changes in the size, shape, orientation, and composition of the aragonite crystals used to build the skeleton. With increasing acidification, densely packed bundles of fine aragonite needles gave way to a disordered aggregate of highly faceted rhombs. The Sr/Ca ratios of the crystals, measured by SIMS ion microprobe, increased by 13%, and Mg/Ca ratios decreased by 45%. By comparing these variations in elemental ratios with results from Rayleigh fractionation calculations, we show that the observed changes in crystal morphology and composition are consistent with a >80% decrease in the amount of aragonite precipitated by the corals from each “batch” of calcifying fluid. This suggests that the saturation state of fluid within the isolated calcifying compartment, while maintained by the coral at levels well above that of the external seawater, decreased systematically and significantly as the saturation state of the external seawater decreased. The inability of the corals in acidified treatments to achieve the levels of calcifying fluid supersaturation that drive rapid crystal growth could reflect a limit in the amount of energy available for the proton pumping required for calcification. If so, then the future impact of ocean acidification on tropical coral ecosystems may depend on the ability of individuals or species to overcome this limitation and achieve the levels of calcifying fluid supersaturation required to ensure rapid growth.This study
was supported by NSF OCE-0648157 and NSF OCE-0823527
and the Bermuda Institute for Ocean Sciences
Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design
Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability
Exercise for people living with frailty and receiving haemodialysis:a mixed-methods randomised controlled feasibility study
Objectives Frailty is highly prevalent in haemodialysis (HD) patients, leading to poor outcomes. This study aimed to determine whether a randomised controlled trial (RCT) of intradialytic exercise is feasible for frail HD patients, and explore how the intervention may be tailored to their needs.Design Mixed-methods feasibility.Setting and participants Prevalent adult HD patients of the CYCLE-HD trial with a Clinical Frailty Scale Score of 4–7 (vulnerable to severely frail) were eligible for the feasibility study.Interventions Participants in the exercise group undertook 6 months of three times per week, progressive, moderate intensity intradialytic cycling (IDC).Outcomes Primary outcomes were related to feasibility. Secondary outcomes were falls incidence measured from baseline to 1 year following intervention completion, and exercise capacity, physical function, physical activity and patient-reported outcomes measured at baseline and 6 months. Acceptability of trial procedures and the intervention were explored via diaries and interviews with n=25 frail HD patients who both participated in (n=13, 52%), and declined (n=12, 48%), the trial.Results 124 (30%) patients were eligible, and of these 64 (52%) consented with 51 (80%) subsequently completing a baseline assessment. n=24 (71% male; 59±13 years) dialysed during shifts randomly assigned to exercise and n=27 (81% male; 65±11 years) shifts assigned to usual care. n=6 (12%) were lost to follow-up. The exercise group completed 74% of sessions. 27%–89% of secondary outcome data were missing. Frail HD patients outlined several ways to enhance trial procedures. Maintaining ability to undertake activities of daily living and social participation were outcomes of primary importance. Participants desired a varied exercise programme.Conclusions A definitive RCT is feasible, however a comprehensive exercise programme may be more efficacious than IDC in this population.</div
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The Impact of Falls: A Qualitative Study of the Experiences of People Receiving Haemodialysis
The prevalence of falls is high in people receiving haemodialysis (HD). This study aimed to explore the experiences of people receiving HD who had fallen in the last six months. A qualitative study, informed by constructivist grounded theory, used semi-structured interviews in combination with falls diaries. Twenty-five adults (mean age of 69 ± 10 years, 13 female, 13 White British) receiving HD with a history of at least one fall in the last six months (median 3, IQR 2−4) participated. Data were organised within three themes: (a) participants’ perceptions of the cause of their fall(s): poor balance, weakness, and dizziness, exacerbated by environmental causes, (b) the consequences of the fall: injuries were disproportionate to the severity of the fall leading to loss of confidence, function and disruptions to HD, (c) reporting and coping with falls: most did not receive any specific care regarding falls. Those who attended falls services reported access barriers. In response, personal coping strategies included avoidance, vigilance, and resignation. These findings indicate that a greater focus on proactively identifying falls, comprehensive assessment, and timely access to appropriate falls prevention programmes is required to improve care and outcomes
Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding
Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.
Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity.
Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients.
Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour
Has land use pushed terrestrial biodiversity beyond the planetary boundary? A global assessment
Land use and related pressures have reduced local terrestrial biodiversity, but it is unclear how the magnitude of change relates to the recently proposed planetary boundary (“safe limit”). We estimate that land use and related pressures have already reduced local biodiversity intactness—the average proportion of natural biodiversity remaining in local ecosystems—beyond its recently proposed planetary boundary across 58.1% of the world’s land surface, where 71.4% of the human population live. Biodiversity intactness within most biomes (especially grassland biomes), most biodiversity hotspots, and even some wilderness areas is inferred to be beyond the boundary. Such widespread transgression of safe limits suggests that biodiversity loss, if unchecked, will undermine efforts toward long-term sustainable development
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