Consistent detection of Trypanosoma brucei but not T. congolense DNA in faeces of experimentally infected cattle.

Animal African trypanosomiasis (AAT) is a significant food security and economic burden in sub-Saharan Africa. Current AAT empirical and immunodiagnostic surveillance tools suffer from poor sensitivity and specificity, with blood sampling requiring animal restraint and trained personnel. Faecal sampling could increase sampling accessibility, scale, and species range. Therefore, this study assessed feasibility of detecting Trypanosoma DNA in the faeces of experimentally-infected cattle. Holstein-Friesian calves were inoculated with Trypanosoma brucei brucei AnTat 1.1 (n = 5) or T. congolense Savannah IL3000 (n = 6) in separate studies. Faecal and blood samples were collected concurrently over 10 weeks and screened using species-specific PCR and qPCR assays. T. brucei DNA was detected in 85% of post-inoculation (PI) faecal samples (n = 114/134) by qPCR and 50% by PCR between 4 and 66 days PI. However, T. congolense DNA was detected in just 3.4% (n = 5/145) of PI faecal samples by qPCR, and none by PCR. These results confirm the ability to consistently detect T. brucei DNA, but not T. congolense DNA, in infected cattle faeces. This disparity may derive from the differences in Trypanosoma species tissue distribution and/or extravasation. Therefore, whilst faeces are a promising substrate to screen for T. brucei infection, blood sampling is required to detect T. congolense in cattle.

Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment.

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep.

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1-/-) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1-/- mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy.

Precurved, Fiber-Reinforced Actuators Enable Pneumatically Efficient Replication of Complex Biological Motions.

Much of the research on bioinspired soft robotics has focused on capturing the interplay of biological form and function. However, existing soft robotic actuators are mostly made with linear or planar fabrication orientations that do not represent the resting geometry of complex biological systems, such as curved musculature. This work introduces the ability to create fiber-reinforced actuators with precurved configurations. By tuning variables such as dimensions and fiber angles, an optimization algorithm can prescribe the mechanical fabrication parameters to create a fiber-reinforced actuator that can generate controlled motion to follow a desired input trajectory. Precurved configurations introduce an additional optimization parameter, the initial bend angle, allowing for a more accurate and robust algorithm and generating a median percent error of <1%. With a customized software tool, we can take existing motion data from biological systems-such as medical imaging-and build soft robotic actuators optimized to replicate these trajectories. We can predict the motion of precurved actuators both analytically and numerically and replicate the motion experimentally, with excellent trajectory matching between the three. In constructing actuators that better match the native forms found within biological systems, we find that precurved actuators are more efficient than their initially straight counterparts. This pneumatic efficiency allows for the use of control systems with lower power and precision, lowering the economic cost of the associated control hardware, while more accurately replicating the biological motion. Taking two examples from biology, that of the human diaphragm during respiration and that of a jellyfish bell during locomotion, we design and generate fiber reinforced actuators to mimic these motions.

Thinking Slow More Quickly: Development of Integrated Illness Scripts to Support Cognitively Integrated Learning and Improve Clinical Decision-Making.

Illness scripts describe the mental model used by experienced clinicians to store and recall condition-specific knowledge when making clinical decisions. Studies demonstrate that novice clinicians struggle to develop and apply strong illness scripts. We developed the Integrated Illness Script and Mechanism of Disease (IIS-MOD) map framework to address this challenge.

Hypothesis-driven physical examination curriculum.

BACKGROUND: Medical students traditionally learn physical examination skills as a rote list of manoeuvres. Alternatives like hypothesis-driven physical examination (HDPE) may promote students' understanding of the contribution of physical examination to diagnostic reasoning. We sought to determine whether first-year medical students can effectively learn to perform a physical examination using an HDPE approach, and then tailor the examination to specific clinical scenarios. Medical students traditionally learn physical examination skills as a rote list of manoeuvres CONTEXT: First-year medical students at the University of Minnesota were taught both traditional and HDPE approaches during a required 17-week clinical skills course in their first semester. The end-of-course evaluation assessed HDPE skills: students were assigned one of two cardiopulmonary cases. Each case included two diagnostic hypotheses. During an interaction with a standardised patient, students were asked to select physical examination manoeuvres in order to make a final diagnosis. Items were weighted and selection order was recorded. INNOVATION: First-year students with minimal pathophysiology performed well. All students selected the correct diagnosis. Importantly, students varied the order when selecting examination manoeuvres depending on the diagnoses under consideration, demonstrating early clinical decision-making skills. IMPLICATIONS: An early introduction to HDPE may reinforce physical examination skills for hypothesis generation and testing, and can foster early clinical decision-making skills. This has important implications for further research in physical examination instruction.

How Residents Develop Trust in Interns: A Multi-Institutional Mixed-Methods Study.

PURPOSE: Although residents trust interns to provide patient care, little is known about how trust forms. METHOD: Using a multi-institutional mixed-methods study design, the authors interviewed (March-September 2014) internal medicine (IM) residents in their second or third postgraduate year at a single institution to address how they develop trust in interns. Transcript analysis using grounded theory yielded a model for resident trust. Authors tested (January-March 2015) the model with residents from five IM programs using a two-section quantitative survey (38 items; 31 rated 0 = not at all to 100 = very much; 7 rated 0 = strongly disagree to 100 = strongly agree) to identify influences on how residents form trust. RESULTS: Qualitative analysis of 29 interviews yielded 14 themes within five previously identified factors of trust (resident, intern, relationship, task, and context). Of 478 residents, 376 (78.7%) completed the survey. Factor analysis yielded 11 factors that influence trust. Respondents rated interns' characteristics (reliability, competence, and propensity to make errors) highest when indicating importance to trust (respective means 86.3 [standard deviation = 9.7], 76.4 [12.9], and 75.8 [20.0]). They also rated contextual factors highly as influencing trust (access to an electronic medical record, duty hours, and patient characteristics; respective means 79.8 [15.3], 73.1 [14.4], and 71.9 [20.0]). CONCLUSIONS: Residents form trust based on primarily intern- and context-specific factors. Residents appear to consider trust in a way that prioritizes interns' execution of essential patient care tasks safely within the complexities and constraints of the hospital environment.

Where children and adolescents drown in Queensland: a population-based study.

OBJECTIVE: This retrospective population-based study examined drowning location by the site of immersion for both fatal and non-fatal drowning events in Queensland. Drowning location is not routinely collected, and this study used data linkage to identify drowning sites. The resulting enhanced quality data quantify drowning incidence for specific locations by geographic region, age group and by severity for the first time. DESIGN: Linked data were accessed from the continuum of care (prehospital, emergency, hospital admission and death data) on fatal and non-fatal drowning episodes in children aged 0-19 years in Queensland for the years 2002-2008 inclusive. RESULTS: Drowning locations ranked in order of overall incidence were pools, inland water, coastal water, baths and other man-made water hazards. Swimming pools produced the highest incidence rates (7.31/100,000) for overall drowning events and were more often privately owned pools and in affluent neighbourhoods. Toddlers 0-4 years were most at risk around pools (23.94/100,000), and static water bodies such as dams and buckets-the fatality ratios were highest at these 2 locations for this age group. Children 5-14 years incurred the lowest incidence rates regardless of drowning location. Adolescents 15-19 years were more frequently involved in a drowning incident on the coast shoreline, followed by inland dynamic water bodies. CONCLUSIONS: Linked data have resulted in the most comprehensive data collection on drowning location and severity to date for children in the state of Queensland. Most mortality and morbidity could have been prevented by improving water safety through engaged supervision around pools and bath time, and a heightened awareness of buckets and man-made water hazards around the farm home for young children. These data provide a different approach to inform prevention strategies.

Drowning mortality and morbidity rates in children and adolescents 0-19 yrs: a population-based study in Queensland, Australia.

OBJECTIVE: To redress the lack of Queensland population incidence mortality and morbidity data associated with drowning in those aged 0-19 yrs, and to understand survival and patient care. DESIGN, SETTING AND PARTICIPANTS: Retrospective population-based study used data linkage to capture both fatal and non-fatal drowning cases (N = 1299) among children aged 0-19 years in Queensland, from 2002-2008 inclusive. Patient data were accessed from pre-hospital, emergency department, hospital admission and death data, and linked manually to collate data across the continuum of care. MAIN OUTCOME MEASURES: Incidence rates were calculated separately by age group and gender for events resulting in death, hospital admission, and non-admission. Trends over time were analysed. RESULTS: Drowning death to survival ratio was 1:10, and two out of three of those who survived were admitted to hospital. Incidence rates for fatal and non-fatal drowning increased over time, primarily due to an increase in non-fatal drowning. There were non-significant reductions in fatal and admission rates. Rates for non-fatal drowning that did not result in hospitalisation more than doubled over the seven years. Children aged 5-9 yrs and 10-14 yrs incurred the lowest incidence rates 6.38 and 4.62 (expressed as per 100,000), and the highest rates were among children aged 0-4 yrs (all drowning events 43.90; fatal 4.04; non-fatal 39.85-comprising admission 26.69 and non-admission 13.16). Males were over-represented in all age groups except 10-14 yrs. Total male drowning events increased 44% over the seven years (P<0.001). CONCLUSION: This state-wide data collection has revealed previously unknown incidence and survival ratios. Increased trends in drowning survival rates may be viewed as both positive and challenging for drowning prevention and the health system. Males are over-represented, and although infants and toddlers did not have increased fatality rates, they had the greatest drowning burden demonstrating the need for continued drowning prevention efforts.

Maximizing teaching on the wards: review and application of the One-Minute Preceptor and SNAPPS models.

Hospitalist educators face a number of challenges in teaching clinical reasoning to residents and medical students. Helping to develop trainees' clinical acumen is an essential and highly nuanced process, yet complex patients, documentation requirements, and productivity goals compete with teaching time. Workplace-based assessment is particularly important for residents with the institution of the developmental milestones for meeting Accreditation Council for Graduate Medical Education competencies. Two frameworks for facilitating the clinical reasoning discussion-the One-Minute Preceptor preceptor and SNAPPS-have been well studied in the outpatient setting with positive results. Both models show promise for use in the inpatient teaching environment with little modification. This narrative review compares and contrasts these 2 teaching frameworks and discusses their application to the inpatient teaching environment. These models can provide opportunities for hospitalist educators to better assess trainees, integrate regular feedback, and encourage self-directed learning. These teaching frameworks can also allow hospitalists to provide more focused education to trainees without taking additional valuable time.

Interventions associated with drowning prevention in children and adolescents: systematic literature review.

INTRODUCTION: Drowning remains a leading cause of preventable death in children across the world. This systematic review identifies and critically analyses studies of interventions designed to reduce fatal and non-fatal drowning events among children and adolescents or reduce the injury severity incurred by such incidents. METHODS: A systematic search was undertaken on literature published between 1980 and 2010 relating to interventions around fatal and non-fatal drowning prevention in children and adolescents 0-19 years of age. Search methods and protocols developed and used by the WHO Global Burden of Disease Injury Expert Group were applied. RESULTS: Seven studies fulfilled the inclusion criteria. Interventions were categorised into three themes of Education, Swimming Lessons and Water Safety, and Pool Fencing. All are possible effective strategies to prevent children from drowning, particularly young children aged 2-4 years, but very little evidence exists for interventions to reduce drowning in older children and adolescents. There were methodological limitations associated with all studies, so results need to be interpreted in the context of these. CONCLUSIONS: Relatively few studies employ rigorous methods and high levels of evidence to assess the impact of interventions designed to reduce drowning. Studies are also limited by lack of consistency in measured outcomes and drowning terminology. Further work is required to establish efficacy of interventions for older children and adolescents. There is a need for rigorous, well-designed studies that use consistent terminology to demonstrate effective prevention solutions.

SNAPPS-Plus: an educational prescription for students to facilitate formulating and answering clinical questions.

PURPOSE: To analyze the content and quality of PICO-formatted questions (Patient-Intervention-Comparison-Outcome), and subsequent answers, from students' educational prescriptions added to the final SNAPPS Select step (SNAPPS-Plus). METHOD: Internal medicine clerkship students at the University of Minnesota Medical Center were instructed to use educational prescriptions to complement their bedside SNAPPS case presentations from 2006 to 2010. Educational prescriptions were collected from all eligible students and coded for topic of uncertainty, PICO conformity score, presence of answer, and quality of answer. Spearman rank-order correlation coefficient was used to compare ordinal variables, Kruskal-Wallis test to compare distribution of PICO scores between groups, and McNemar exact test to test for association between higher PICO scores and presence of an answer. RESULTS: A total of 191 education prescriptions were coded from 191 eligible students, of which 190 (99%) included a question and 176 (93%, 176/190) an answer. Therapy questions constituted 59% (112/190) of the student-generated questions; 19% (37/190) were related to making a diagnosis. Three-fifths of the questions (61%, 116/190) were scored either 7 or 8 on the 8-point PICO conformity scale. The quality of answers varied, with 37% (71/190) meeting all criteria for high quality. There was a positive correlation between the PICO conformity score and the quality of the answers (Spearman rank-order correlation coefficient = 0.726; P < .001). CONCLUSIONS: The SNAPPS-Plus technique was easily integrated into the inpatient clerkship structure and guaranteed that virtually every case presentation following this model had a well-formulated question and answer.

An entrustable professional activity (EPA) for handoffs as a model for EPA assessment development.

Medical education is moving toward assessment of educational outcomes rather than educational processes. The American Board of Internal Medicine and American Board of Pediatrics milestones and the concept of entrustable professional activities (EPA)--skills essential to the practice of medicine that educators progressively entrust learners to perform--provide new approaches to assessing outcomes. Although some defined EPAs exist for internal medicine and pediatrics, the continued development and implementation of EPAs remains challenging. As residency programs are expected to begin reporting milestone-based performance, however, they will need examples of how to overcome these challenges. The authors describe a model for the development and implementation of an EPA using the resident handoff as an example. The model includes nine steps: selecting the EPA, determining where skills are practiced and assessed, addressing barriers to assessment, determining components of the EPA, determining needed assessment tools, developing new assessments if needed, determining criteria for advancement through entrustment levels, mapping milestones to the EPA, and faculty development. Following implementation, 78% of interns at the University of Minnesota Medical School were observed giving handoffs and provided feedback. The authors suggest that this model of EPA development--which includes engaging stakeholders, an iterative process to describing the behavioral characteristics of each domain at each level of entrustment, and the development of specific assessment tools that support both formative feedback and summative decisions about entrustment--can serve as a model for EPA development for other clinical skills and specialty areas.

Socio-economic distribution of environmental risk factors for childhood injury.

OBJECTIVE: Childhood injury remains the single most important cause of mortality in children aged between 1-14 years in many countries. It has been proposed that lower socio-economic status (SES) and poorer housing contribute to potential hazards in the home environment. This study sought to establish whether the prevalence of observed hazards in and around the home was differentially distributed by SES, in order to identify opportunities for injury prevention. METHODS: This study was a cross-sectional, random sample survey of primary school children from 32 schools in Brisbane. Interviews and house audits were conducted between July 2000 and April 2003 to collect information on SES (income, employment and education) and previously identified household hazards. RESULTS: There was evidence of a relationship between prevalence of household environmental hazards and household SES; however, the magnitude and direction of this relationship appeared to be hazard-specific. Household income was related to play equipment characteristics, with higher SES groups being more likely to be exposed to risk. All three SES indicators were associated with differences in the home safety characteristics, with the lower SES groups more likely to be exposed to risk. CONCLUSION: The differential distribution of environmental risk factors by SES of household may help explain the SES differential in the burden of injury and provides opportunities for focusing efforts to address the problem.

Lack of support for the presence of an osteoarthritis susceptibility locus on chromosome 6p.

OBJECTIVE: To replicate, in a Northern Irish population, the previously reported association between a locus on chromosome 6 and hip osteoarthritis (OA). METHODS: Patients with hip OA were identified from a registry of patients who had undergone total hip replacement surgery over an 8-year period at a single large orthopedic unit in Northern Ireland. Patients identified as index cases were contacted by mail and asked to reply only if another family member also had undergone total hip replacement surgery. Using this approach, we identified 288 sibling pairs concordant for primary hip OA. DNA was extracted from peripheral blood, and microsatellite markers were amplified by polymerase chain reaction and subsequently genotyped. RESULTS: No evidence of linkage to this region was demonstrated by either 2-point analysis or multipoint analysis of 17 microsatellites. CONCLUSION: The reported association between a locus on chromosome 6 and hip OA could not be confirmed in this population. Different methods of ascertainment and phenotyping of OA may contribute to the current inability to replicate genetic associations for hip OA.

The effect of patient gait on the material properties of UHMWPE in hip replacements.

The wear of ultra-high molecular weight polyethylene (UHMWPE) acetabular components in total hip replacements (THRs) has been shown to be highly dependent on the direction of shear. Greatly reduced wear rates have been reported for unidirectional, compared to multidirectional, articulation in vitro. This work for the first time enables investigation of a relationship between clinical wear conditions, as determined by patient gait path, and the mechanical and structural changes that occur within the UHMWPE acetabular component. Individual patients' wear paths were determined prior to revision operation from hip joint kinematics measured by clinical gait analysis. The material properties of the acetabular components removed during the revision operation were subsequently analysed. A technique using Fourier transform infra- red analysis (FTIR) was developed to quantify the orientation of the individual UHMWPE lamellae. This study shows that there is a direct relationship between a patient's clinical gait path and the molecular properties of their UHMWPE acetabular socket. Patient kinematics are an important factor affecting the wear and long-term biocompatibility of UHMWPE used as a bearing surface in THR.

Preventing injuries on horizontal ladders and track rides.

OBJECTIVES: This study examined the type of injury, fall heights and measures of impact attenuation of surfaces on which children fell from horizontal ladders and track rides. METHOD: All injured children who presented to two children's hospitals and received medical attention following a fall from a horizontal ladder or track ride in a public school or park during 1996--1997 were interviewed and the playground visited. RESULTS: The number of children who fell from horizontal ladders and track rides and presented to hospitals with injury was 118. Of those children, 105 were injured when they hit the ground and data were available on 102 of those playground undersurfaces. Fractures to the arm or wrist were the most common injury. The median height fallen by children was 1930 mm, 73% of injuries were from falls greater than 1800mm. In 41% of sites, the surface was deficient in impact absorbing properties for the height of the equipment. Fractures were no more likely on loose surfaces than other surfaces, such as rubber matting (p = 0.556) but more prevalent on compliant than non-compliant surfaces. Relative to falls occurring on noncompliant surfaces, the odds of a fracture occurring on a compliant surface was 2.67 (95% CI 0.88-8.14). CONCLUSIONS: Modification of the height of horizontal ladders and track rides to 1800mm is preferable to removal of such equipment. The prevalence of fractures on compliant surfaces suggests that the threshold of 200g or 1000 head injury criteria (HIC) needs to be revisited, or additional test criteria added to take account of change in momentum that is not presently accounted for with either g-max on HIC calculations.