Echocardiographic and radiographic aortic remodeling in cats with confirmed systemic hypertension.

Systemic hypertension (SH) in cats may occur secondary to renal disease, hyperthyroidism, or idiopathic causes. Asymmetric dilation of the sinuses of Valsalva has been recognized in people with systemic hypertension as target organ damage (TOD). Aortic knob formation (lateral bowing of the aortic arch to proximal descending aorta on the posteroanterior/anteroposterior radiographic projection) is recognized as TOD in people due to SH. None of these changes have been reported in feline patients. The first objective of this retrospective case-controlled study was to compare echocardiographic changes in the aorta of 76 cats with systemic hypertension (SH) to those seen in 76 cats with normal blood pressure (NBP). Our second objective was to have blinded reviewers assess heart size and aortic shape and size from available thoracic radiographs of 49/76 cats with SH and 46/76 cats with NBP. A two-way unpaired t-test with significance set at alpha = 0.01 was used to evaluate aortic echocardiographic parameters. The mean of the aortic diameter and length of each aortic cusp was significantly larger in cats with SH than in cats with NBP. The aortic cusps were considered altered in size in 62 of 76 cats with SH, 12/62 ≥ with 0.5 mm, and 50/62 ≥ 1.0 mm. No significant difference in the vertebral heart score (VHS) was noted between groups. The aortic knob to lateral margin of the trachea in cats with SH had an area under the curve (AUC) of 0.74 (95% CI:0.61-0.87) with best cutoff of 1.12 cm with sensitivity of 81% and specificity of 69%.

Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) mimicking idiopathic inflammatory myopathy: key points to prevent misdiagnosis.

OBJECTIVES: Diagnosing the idiopathic inflammatory myopathies (IIMs) can be challenging as several conditions, including genetic myopathies such as limb girdle muscular dystrophy type R12 (LGMD 2 l, anoctaminopathy) mimic the presentation. Here we describe learning points identified from review of four patients with LGMD 2 l who were initially incorrectly diagnosed with IIM. Our aim is to provide clinicians working in adult rheumatology services with a toolkit to help identify non-inflammatory presentations of myopathy. METHODS: We performed retrospective review of medical notes, laboratory results, muscle imaging and histological findings of four patients with LGMD 2 l who were previously misdiagnosed with IIM. We focussed on clinical presentation and progression, therapeutic agents used and events leading to revision of the diagnosis. RESULTS: Three male patients and one female patient with a mean age of 51 years at presentation were reviewed. In each case, treatment with immunosuppressants, in one case for >15 years, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and available myositis-associated/specific autoantibodies and associated connective tissue disease features were absent. Prominent fatty infiltration and selective muscle involvement on thigh MRI was found in common. CONCLUSIONS: Adult-onset genetic myopathies, particularly LGMD R12, can mimic IIM. Accurate diagnosis is crucial to avoid the use of potentially harmful immunosuppressive therapies, to allow appropriate genetic counselling and to facilitate involvement in research studies.

An observational thoracic radiographic study of aortic remodeling in dogs with confirmed systemic hypertension.

Sustained systemic hypertension (SH) has been shown to cause target organ damage to various tissues in dogs and cats, including the aorta. Aortic dilatation occurs most commonly secondary to SH in people and develops prior to an aortic aneurysm. Our hypothesis was that blinded reviewers could be trained to recognize variable alterations of aortic shape and size on thoracic radiographs of canine patients with SH. A retrospective, observational, cross-sectional study was performed with three blinded reviewers evaluating thoracic radiographic images of 21 dogs with normal blood pressure compared to 145 dogs with system hypertension. Lateral radiographs showed variable aortic undulation and disproportionate enlargement of a portion of the aorta between the ascending and proximal descending aorta compared to the descending aorta just cranial to the diaphragm. On orthogonal projections, the aortic arch to proximal descending aorta bowed laterally similar to changes reported in people with the formation of an aortic "knob." After completing a training module, reviewers of the thoracic images had a 74% agreement with Fleiss' Kappa of 0.50 indicating moderate agreement recognizing SH changes to the thoracic aorta. The more experienced blinded reviewers had accuracies of 85% and 80% for identifying systemic hypertension, slightly better than the less experienced reviewer at 76%. The ratio of thoracic cavity width to aortic knob width was significantly different between the groups (median ratio 3.4 SH vs 4.1 normal). Evidence of target organ damage (TOD) to the thoracic aorta may prompt earlier recognition and treatment for systemic hypertension.

Echocardiographic changes in the shape and size of the aortic cusps in dogs with confirmed systemic hypertension.

Systemic hypertension (SH) in dogs typically occurs secondary to renal disease, diabetes mellitus, hyperadrenocorticism, malignant adrenal tumors, or various medications. Echocardiography performed on people with SH has shown asymmetric dilation of the sinuses at the level of the aortic valves, previously undescribed in canine patients. The objective of this retrospective case-control study was to determine if there was a difference in size and shape of the aortic cusps at the level of the sinus of Valsalva in dogs with SH compared to dogs with normal blood pressure. We reviewed echocardiographic findings in 74 dogs with SH and 37 dogs with normal blood pressure (NBP), defined as less than 150 mmHg. Systemic hypertension was classified as mild (150-159 mm Hg), moderate (160-179 mm Hg), or severe (greater than 180 mm Hg). There was a significant difference (P < .001) in the mean size of the aorta cusps at the level of the sinuses in 67 of 74 dogs with SH and none of 37 dogs with NBP. Of the 74 dogs with SH, 70 had left ventricular hypertrophy (18 asymmetric, 15 concentric, and 37 eccentric). Additionally, there was aortic root dilatation in 15 dogs, aortic insufficiency in 21, mitral regurgitation in 50, and left atrial enlargement in 71. The standard deviation of the three cusp measurements between the dogs with SH and dogs with NBP had a sensitivity of 92% and specificity of 97% for diagnosis of SH. Asymmetric size of the aortic cusps on echocardiography is therefore a reliable indicator of SH in dogs.

The role of governance in Indigenous medical education research.

CONTEXT: This article considers the role of governance in Indigenous medical education research through the lens of an Australian Aboriginal research project titled Healing Conversations. The Healing Conversations project is developing and testing a targeted educational framework for improved clinical communication between healthcare practitioners and Australian Aboriginal peoples in regional and urban locations. It is proposed that an effective governance approach can support Indigenous and non-Indigenous stakeholders to work together in decision-making structures to enable outcomes that promote and prioritise Indigenous worldviews and values in medical education research. ISSUE: The case study explored here puts forth the notion of effective governance as one practical way to decolonise medical education research structures in both the urban and regional setting. The importance of relationships between Indigenous and non-Indigenous stakeholders is supported in tailored governance structures, as knowledge translation efforts are situated in mainstream tertiary education structures that hold collective responsibility and accountability for change in this space. LESSONS LEARNT: Reflections from the Healing Conversations research case study are outlined for future consideration regarding sustainable and effective Indigenous governance initiatives in medical education and research structures. This includes the importance of an Indigenous governance structure within the research team and a strong understanding of the roles and contributions of each research team member, along with the required humanistic qualities to action effective governance in Indigenous medical education research. Collaborative governance structures are fundamental as the inclusion and prioritisation of Indigenous worldviews and values is a key step in redressing Indigenous healthcare disparities and providing culturally safe healthcare institutions.

Two-eyed seeing: A useful gaze in Indigenous medical education research.

CONTEXT: Medical education has a role in preparing future health care practitioners to have the skills to meaningfully address health disparities while providing effective clinical care considerate of diversity in our societies. This calls for medical education researchers to approach their craft in ways that prioritise and value inputs from a broader range of perspectives and worldviews in an effort to redress the negative impacts of social, political and structural forces on health outcomes. METHODS: Given the entrenched health inequities experienced by Indigenous populations across the globe, this paper details an approach to medical education research put forward by Canadian Mi'kmaw Elders Murdena and Albert Marshall and named 'two-eyed seeing'. This approach provides the opportunity for medical education researchers to address the ongoing impacts of colonisation, racism and marginalisation on health outcomes by prioritising Indigenous worldviews in medical curricula. The need for researchers and medical academies to critically consider Indigenous governance and processes of respectful knowledge sharing within the wider institutional and societal contexts is addressed. CONCLUSIONS: The benefits of two-eyed seeing in the context of better preparing the future workforce to effectively meet the needs of those most vulnerable, and to action change against health inequities, situate it as a promising research approach in medical education.

Aortic to caudal vena cava ratio measurements using abdominal ultrasound are increased in dogs with confirmed systemic hypertension.

Chronically sustained systemic hypertension in dogs can damage the kidneys, eye, brain, heart, and vessels. In human medicine, systemic hypertension has been implicated as the most common risk factor for aorta dilation, which can progress to an aneurysm. Abdominal ultrasound has been commonly used to monitor the size of the abdominal aorta in people with systemic hypertension. In this retrospective cross-sectional abdominal ultrasound study, evaluation of the size of the abdominal aorta relative to the caudal vena cava was performed in 18 control dogs and 128 dogs with confirmed systemic hypertension. Preexisting conditions contributing to systemic hypertension in these dogs were renal disease, hyperadrenocorticism, diabetes mellitus, adrenal tumors, and previous administration of phenylpropanolamine or palladia. The abdominal aorta and caudal vena cava were assessed from longitudinal images cranial to the trifurcation with measurements made from outer border to outer border of the walls, being careful not to compress the caudal vena cava that would alter its size. Our hypothesis was the ratio of the diameter of the abdominal aorta to caudal vena cava would be higher in dogs with systemic hypertension compared to dogs with normal blood pressure. The mean abdominal aorta-caudal vena cava ratio was 1.028 in control dogs with a normal blood pressure and 1.515 in dogs with systemic hypertension. In dogs with confirmed systemic hypertension, the abdominal aorta was dilated compared to the caudal vena cava in the caudal abdomen. An increase in the abdominal aorta-caudal vena cava ratio in a dog should raise suspicion for the presence of systemic hypertension and prompt evaluation of blood pressure.

Past is prologue: The role of memory retrieval in young children's episodic prospection.

Prior research has revealed a strong link between the ability to remember one's past (i.e., episodic memory) and the ability to envision one's future (i.e., episodic prospection). Indeed, the past holds valuable learning experiences that can inform future choices and plans. Although these abilities both emerge during preschool years, there exist few theoretical accounts of how memory processes might support developmental improvements in prospection abilities. We developed a novel paradigm to determine whether young children (3 and 4 years of age) use past knowledge to inform future choices. Experiment 1 revealed that children find it more difficult to retrieve relevant information from their past when they envision the future versus reflect on the past. Experiment 2 facilitated children's access to past event components and, thereby, eased retrieval of relevant components from memory for future event construction. We discuss results in light of recent proposals on the development of episodic prospection.

Medical student wellbeing - a consensus statement from Australia and New Zealand.

BACKGROUND: Medical student wellbeing - a consensus statement from Australia and New Zealand outlines recommendations for optimising medical student wellbeing within medical schools in our region. Worldwide, medical schools have responsibilities to respond to concerns about student psychological, social and physical wellbeing, but guidance for medical schools is limited. To address this gap, this statement clarifies key concepts and issues related to wellbeing and provides recommendations for educational program design to promote both learning and student wellbeing. The recommendations focus on student selection; learning, teaching and assessment; learning environment; and staff development. Examples of educational initiatives from the evidence-base are provided, emphasising proactive and preventive approaches to student wellbeing. MAIN RECOMMENDATIONS: The consensus statement provides specific recommendations for medical schools to consider at all stages of program design and implementation. These are: Design curricula that promote peer support and progressive levels of challenge to students. Employ strategies to promote positive outcomes from stress and to help others in need. Design assessment tasks to foster wellbeing as well as learning. Provide mental health promotion and suicide prevention initiatives. Provide physical health promotion initiatives. Ensure safe and health-promoting cultures for learning in on-campus and clinical settings. Train staff on student wellbeing and how to manage wellbeing concerns. CONCLUSION: A broad integrated approach to improving student wellbeing within medical school programs is recommended. Medical schools should work cooperatively with student and trainee groups, and partner with clinical services and other training bodies to foster safe practices and cultures. Initiatives should aim to assist students to develop adaptive responses to stressful situations so that graduates are prepared for the realities of the workplace. Multi-institutional, longitudinal collaborative research in Australia and New Zealand is needed to close critical gaps in the evidence needed by medical schools in our region.

From temporal updating to temporal reasoning: Developments in young children's temporal representations.

Evidence from our research on young children's temporal understanding supports Hoerl & McCormack's view that young children rely on a temporal updating system to change representations over time. We propose that the shift from temporal updating to temporal reasoning is enabled by children's expanding representations of event sequences, along with developments in language, memory, and other cognitive competencies.

Educating for collaborative practice: an interpretation of current achievements and thoughts for future directions.

CONTEXT: The Edinburgh Declaration, developed in 1998 as a pledge to alter the character of medical education to more effectively meet the needs of society, included a recommendation to increase the opportunity for joint learning between health and health-related professions, as part of the training for teamwork. This article acknowledges achievements since the Declaration in relation to this recommendation, using an umbrella term for the phenomenon, 'educating for collaborative practice', and presents a perspective framed as a series of questions to encourage reflection on future directions. METHODS: A literature interpretation, informed by philosophical hermeneutics, was conducted using text sets comprising reports and reviews from a section of the international literature since 1988. The interpretation involved: engaging with meanings as presented in the chosen texts; making iterative returns to the texts to explore emerging understanding; and ensuring parts of our understanding from particular texts were fused with complete understanding of the texts as a whole. A lens of appreciative inquiry facilitated acknowledgement of what has been achieved, while being curious about how it could be. RESULTS: Interpretation of the selected literature revealed notable achievements. Areas for further consideration were identified in relation to three themes: establishing shared understanding AND purpose behind use of terminology; being a conduit AND sharing responsibility for change; exploring ways of doing things AND ensuring ongoing inclusivity. CONCLUSIONS: Interpreting the current literature on 'educating for collaborative practice' has generated questions for reflection on how it may be otherwise. Readers are encouraged to embrace the tensions inherent in unanswered questions, providing space for communication, initiative and diversity of thought. An ongoing dialogue with the literature is proposed, asking whether educating students for a collective identity in settings where they are learning for and with patients is likely to advance educating for patient-centred collaborative practice.

Improving the validity of script concordance testing by optimising and balancing items.

BACKGROUND: A script concordance test (SCT) is a modality for assessing clinical reasoning. Concerns had been raised about the plausible validity threat to SCT scores if students deliberately avoided the extreme answer options to obtain higher scores. The aims of the study were firstly to investigate whether students' avoidance of the extreme answer options could result in higher scores, and secondly to determine whether a 'balanced approach' by careful construction of SCT items (to include extreme as well as median options as model responses) would improve the validity of an SCT. METHODS: Using the paired sample t-test, the actual average student scores for 10 SCT papers from 2012-2016 were compared with simulated scores. The latter were generated by recoding all '-2' responses to '-1' and '+2' responses to '+1' for the whole and bottom 10% of the cohort (simulation 1), and scoring as if all students had chosen '0' for their responses (simulation 2). The actual average and simulated average scores in 2012 (before the 'balanced approach') were compared with those from 2013-2016, when papers had a good balance of modal responses from the expert reference panel. RESULTS: In 2012, a score increase was seen in simulation 1 in the third-year cohort, from 50.2 to 55.6% (t [10] = 4.818; p = 0.001). Since 2013, with the 'balanced approach', the actual SCT scores (57.4%) were significantly higher than scores in both simulation 1 and simulation 2 (46.7% and 23.9% respectively). CONCLUSIONS: When constructing SCT examinations, apart from the rigorous pre-examination optimisation, it is desirable to achieve a balance between items that attract extreme responses and those that attract median response options. This could mitigate the validity threat to SCT scores, especially for the low-performing students who have previously been shown to only select median responses and avoid the extreme responses.

Children's understanding of yesterday and tomorrow.

A picture-sentence matching task was used to investigate children's understanding of yesterday and tomorrow. In Experiment 1, 3- to 5-year-olds viewed two pictures of an object with a visible change of state (e.g., a carved pumpkin and an intact pumpkin) while listening to sentences referring to past or future actions ("I carved the pumpkin yesterday" or "I'm gonna carve the pumpkin tomorrow") and selected the matching picture. Children performed better with past tense sentences than with future tense sentences, and including tomorrow in future tense sentences increased accuracy. In the next two experiments, 4- and 5-year-olds (Experiment 2) and adults (Experiment 3) completed the same task but with sentences containing conflicting temporal information ("I carved the pumpkin tomorrow"). Children tended to select pictures depicting the outcome of actions regardless of tense or temporal adverb, whereas adults' judgments were based on temporal adverbs. In Experiment 4, 3- to 5-year-olds completed tasks requiring either forward or backward temporal reasoning about sentences referring to before, after, yesterday, today, and tomorrow. Across sentence types, forward temporal reasoning was easier for children than backward temporal reasoning. Altogether, results indicated that children understand yesterday better than tomorrow due to the increased cognitive demands involved in reasoning about future events.

The Human 343delT HSPB5 Chaperone Associated with Early-onset Skeletal Myopathy Causes Defects in Protein Solubility.

Mutations of HSPB5 (also known as CRYAB or αB-crystallin), a bona fide heat shock protein and molecular chaperone encoded by the HSPB5 (crystallin, alpha B) gene, are linked to multisystem disorders featuring variable combinations of cataracts, cardiomyopathy, and skeletal myopathy. This study aimed to investigate the pathological mechanisms involved in an early-onset myofibrillar myopathy manifesting in a child harboring a homozygous recessive mutation in HSPB5, 343delT. To study HSPB5 343delT protein dynamics, we utilize model cell culture systems including induced pluripotent stem cells derived from the 343delT patient (343delT/343delT) along with isogenic, heterozygous, gene-corrected control cells (WT KI/343delT) and BHK21 cells, a cell line lacking endogenous HSPB5 expression. 343delT/343delT and WT KI/343delT-induced pluripotent stem cell-derived skeletal myotubes and cardiomyocytes did not express detectable levels of 343delT protein, contributable to the extreme insolubility of the mutant protein. Overexpression of HSPB5 343delT resulted in insoluble mutant protein aggregates and induction of a cellular stress response. Co-expression of 343delT with WT prevented visible aggregation of 343delT and improved its solubility. Additionally, in vitro refolding of 343delT in the presence of WT rescued its solubility. We demonstrate an interaction between WT and 343delT both in vitro and within cells. These data support a loss-of-function model for the myopathy observed in the patient because the insoluble mutant would be unavailable to perform normal functions of HSPB5, although additional gain-of-function effects of the mutant protein cannot be excluded. Additionally, our data highlight the solubilization of 343delT by WT, concordant with the recessive inheritance of the disease and absence of symptoms in carrier individuals.

A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings in 10 families, our study indicates that a dominantly inherited pattern of calpainopathy exists, and should be considered in the diagnostic work-up and genetic counselling of patients with calpainopathy and single-allele aberrations in CAPN3.

Longitudinal integrated clerkships.

There is increased interest in longitudinal integrated clerkships (LICs) due to mounting evidence of positive outcomes for students, patients and supervising clinicians. Emphasizing continuity as the organizing principle of an LIC, this article reviews evidence and presents perspectives of LIC participants concerning continuity of care, supervision and curriculum, and continuity with peers and systems of care. It also offers advice on implementing or evaluating existing LIC programs.

Rural multidisciplinary training: opportunity to focus on interprofessional rapport-building.

In 2016, the Australian Government committed further funds in support of quality rural health education to improve the health and wellbeing of rural and remote communities. The stated funding requirement for longer rural placements in all disciplines is an exciting opportunity for greater investment in interprofessional education to foster collaborative practice, a global system imperative for health care. This commentary explores how findings from earlier research, which investigated how students in a co-located area learn to work with other health professions, can be translated into practice. While recognising the importance of an individual's interpersonal capabilities, this commentary focuses on how the core contextual conditions for interprofessional-rapport-building opportunities (shared space, adequate time and balance of disciplines) were considered in one rural centre. Educational leaders and academics globally should recognise that offering health professional students opportunity to live and work together in extended placements in rural settings has potential benefits for interprofessional education. Understanding the contextual conditions for building rapport between health professional learners, and reflecting on these, potentially will lay the foundation for collaborative practice when these learners become health professionals. Through the reflective questions we pose, policy-makers, health managers and clinical leaders from all health disciplines can build on this foundation by considering the interpersonal capability and contextual conditions for rapport-building in the health workforce to foster a collaborative practice environment for graduates to embrace when they enter the health workplace.

Decline in medical students' attitudes to interprofessional learning and patient-centredness.

CONTEXT: Interprofessional learning (IPL) is valuable in preparing health care students to work collaboratively in teams, with patients' needs at the core. Patient-centredness is the impetus for communication and collaboration in health care. Debate continues on when it is best to develop positive student attitudes towards these aspects of care. Should IPL commence early before attitudes to patients, professional stereotypes and identity are formed, or later for advanced learners with greater experience of their roles and responsibility in health care? This study explores graduate-entry medical students' attitudes to IPL and patient-centred care, on programme entry and after an early interdisciplinary clinical experience (ICE). METHODS: An extended version of the Readiness for Interprofessional Learning Scale (RIPLS) was administered to four cohorts of medical students (n = 279) on entry and after the 3-week placement. This 26-item RIPLS comprised four subscales: team work and collaboration; professional identity; roles and responsibilities; and patient-centredness. The impact of the placement on students' attitudes was assessed by using repeated measures analysis of variance to compare pre- and post-ICE subscale scores. RESULTS: There were significant main effects of time (pre- versus post-ICE) for the subscales of teamwork and collaboration, professional identity and patient-centredness, but not for roles and responsibilities. Scores for teamwork and collaboration, professional identity and patient-centredness were all lower post-ICE. CONCLUSIONS: The students' less positive attitudes to teamwork and collaboration and professional identity may be due to the experience itself, or because it reinforced negative beliefs about the value of learning from non-medical health professionals. Perhaps the students' idealised view of their future role as a doctor was challenged by the experience, or they had an underdeveloped professional identity. Limited student experience of patients having an active role in their own health care may explain the decrease in attitudes to patient-centredness. A longitudinal qualitative study will explore these results.

Improving assessment practice through cross-institutional collaboration: An exercise on the use of OSCEs.

BACKGROUND: This study was undertaken to improve assessment practice on OSCEs through collaboration across geographically dispersed medical schools in Australia. METHODS: A total of eleven OSCE stations were co-developed by four medical schools and used in summative 2011 and 2012 examinations for the assessment of clinical performance in the early clinical and exit OSCEs in each school's medical course. Partial Credit Rasch Model was used to evaluate the psychometric properties of the shared OSCE data. Evaluation of the quality assurance reports was used to determine the beneficial impact of the collaborative benchmarking exercise on learning and teaching outcomes. RESULTS: The data for each examination demonstrated sufficient fit to the Rasch model with infit mean square values ranging from 0.88 to 0.99. Person separation (1.25-1.63) indices indicated good reliability. Evaluation of perceived benefits showed that the benchmarking process was successful as it highlighted common curriculum areas requiring specific focus and provided comparable data on the quality of teaching at the participating medical schools. CONCLUSION: This research demonstrates the validity of the psychometric data and benefits of evaluating clinical competence across medical schools without the enforcement of a prescriptive national curriculum or assessment.

Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy.

Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme ß-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease.