From admissions to licensure: education data associations from a multi-centre undergraduate medical education collaboration.

This paper reports the findings of a Canada based multi-institutional study designed to investigate the relationships between admissions criteria, in-program assessments, and performance on licensing exams. The study's objective is to provide valuable insights for improving educational practices across different institutions. Data were gathered from six medical schools: McMaster University, the Northern Ontario School of Medicine University, Queen's University, University of Ottawa, University of Toronto, and Western University. The dataset includes graduates who undertook the Medical Council of Canada Qualifying Examination Part 1 (MCCQE1) between 2015 and 2017. The data were categorized into five distinct sections: demographic information as well as four matrices: admissions, course performance, objective structured clinical examination (OSCE), and clerkship performance. Common and unique variables were identified through an extensive consensus-building process. Hierarchical linear regression and a manual stepwise variable selection approach were used for analysis. Analyses were performed on data set encompassing graduates of all six medical schools as well as on individual data sets from each school. For the combined data set the final model estimated 32% of the variance in performance on licensing exams, highlighting variables such as Age at Admission, Sex, Biomedical Knowledge, the first post-clerkship OSCE, and a clerkship theta score. Individual school analysis explained 41-60% of the variance in MCCQE1 outcomes, with comparable variables to the analysis from of the combined data set identified as significant independent variables. Therefore, strongly emphasising the need for variety of high-quality assessment on the educational continuum. This study underscores the importance of sharing data to enable educational insights. This study also had its challenges when it came to the access and aggregation of data. As such we advocate for the establishment of a common framework for multi-institutional educational research, facilitating studies and evaluations across diverse institutions. This study demonstrates the scientific potential of collaborative data analysis in enhancing educational outcomes. It offers a deeper understanding of the factors influencing performance on licensure exams and emphasizes the need for addressing data gaps to advance multi-institutional research for educational improvements.

Quantifying the efficacy of an automated facial coding software using videos of parents.

Introduction: This work explores the use of an automated facial coding software - FaceReader - as an alternative and/or complementary method to manual coding. Methods: We used videos of parents (fathers, n = 36; mothers, n = 29) taken from the Avon Longitudinal Study of Parents and Children. The videos-obtained during real-life parent-infant interactions in the home-were coded both manually (using an existing coding scheme) and by FaceReader. We established a correspondence between the manual and automated coding categories - namely Positive, Neutral, Negative, and Surprise - before contingency tables were employed to examine the software's detection rate and quantify the agreement between manual and automated coding. By employing binary logistic regression, we examined the predictive potential of FaceReader outputs in determining manually classified facial expressions. An interaction term was used to investigate the impact of gender on our models, seeking to estimate its influence on the predictive accuracy. Results: We found that the automated facial detection rate was low (25.2% for fathers, 24.6% for mothers) compared to manual coding, and discuss some potential explanations for this (e.g., poor lighting and facial occlusion). Our logistic regression analyses found that Surprise and Positive expressions had strong predictive capabilities, whilst Negative expressions performed poorly. Mothers' faces were more important for predicting Positive and Neutral expressions, whilst fathers' faces were more important in predicting Negative and Surprise expressions. Discussion: We discuss the implications of our findings in the context of future automated facial coding studies, and we emphasise the need to consider gender-specific influences in automated facial coding research.

Acrylic-based culture plate format perfusion device to establish liver endothelial-epithelial interface.

Microphysiological Systems (MPSs) or organs-on-chips, are microfluidic devices used to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to its established fabrication methods and biocompatibility properties. However, non-specific binding of small molecules limits PDMS for drug screening applications. Here, we designed a novel acrylic-based MPS to capture the physiological architecture that is observed universally in tissues across the body: the endothelial-epithelial interface (EEI). To reconstruct the EEI biology, we designed a membrane-based chip that features endothelial cells on the underside of the membrane exposed to mechanical shear from the path of media flow, and epithelial cells on the opposite side of the membrane protected from flow, as they are in vivo. We used a liver model with a hepatic progenitor cell line and human umbilical vein endothelial cells to assess the biological efficacy of the MPS. We computationally modeled the physics that govern the function of perfusion through the MPS. Empirically, efficacy was measured by comparing differentiation of the hepatic progenitor cells between the MPS and 2D culture conditions. We demonstrated that the MPS significantly improved hepatocyte differentiation, increased extracellular protein transport, and raised hepatocyte sensitivity to drug treatment. Our results strongly suggest that physiological perfusion has a profound effect on proper hepatocyte function, and the modular chip design motivates opportunities for future study of multi-organ interactions.

Mouse models of NADK2 deficiency analyzed for metabolic and gene expression changes to elucidate pathophysiology.

NADK2 encodes the mitochondrial form of nicotinamide adenine dinucleotide (NAD) kinase, which phosphorylates NAD. Rare recessive mutations in human NADK2 are associated with a syndromic neurological mitochondrial disease that includes metabolic changes, such as hyperlysinemia and 2,4 dienoyl CoA reductase (DECR) deficiency. However, the full pathophysiology resulting from NADK2 deficiency is not known. Here, we describe two chemically induced mouse mutations in Nadk2-S326L and S330P-which cause severe neuromuscular disease and shorten lifespan. The S330P allele was characterized in detail and shown to have marked denervation of neuromuscular junctions by 5 weeks of age and muscle atrophy by 11 weeks of age. Cerebellar Purkinje cells also showed progressive degeneration in this model. Transcriptome profiling on brain and muscle was performed at early and late disease stages. In addition, metabolomic profiling was performed on the brain, muscle, liver and spinal cord at the same ages and on plasma at 5 weeks. Combined transcriptomic and metabolomic analyses identified hyperlysinemia, DECR deficiency and generalized metabolic dysfunction in Nadk2 mutant mice, indicating relevance to the human disease. We compared findings from the Nadk model to equivalent RNA sequencing and metabolomic datasets from a mouse model of infantile neuroaxonal dystrophy, caused by recessive mutations in Pla2g6. This enabled us to identify disrupted biological processes that are common between these mouse models of neurological disease, as well as those processes that are gene-specific. These findings improve our understanding of the pathophysiology of neuromuscular diseases and describe mouse models that will be useful for future preclinical studies.

The integrated stress response contributes to tRNA synthetase-associated peripheral neuropathy.

Dominant mutations in ubiquitously expressed transfer RNA (tRNA) synthetase genes cause axonal peripheral neuropathy, accounting for at least six forms of Charcot-Marie-Tooth (CMT) disease. Genetic evidence in mouse and Drosophila models suggests a gain-of-function mechanism. In this study, we used in vivo, cell type­specific transcriptional and translational profiling to show that mutant tRNA synthetases activate the integrated stress response (ISR) through the sensor kinase GCN2 (general control nonderepressible 2). The chronic activation of the ISR contributed to the pathophysiology, and genetic deletion or pharmacological inhibition of Gcn2 alleviated the peripheral neuropathy. The activation of GCN2 suggests that the aberrant activity of the mutant tRNA synthetases is still related to translation and that inhibiting GCN2 or the ISR may represent a therapeutic strategy in CMT.

Musculoskeletal case-mix adjustment in a UK primary/community care cohort: Testing musculoskeletal models to make recommendations in this setting.

Benchmarking musculoskeletal (MSK) services is limited by the need to adjust for differences in patient characteristics/case-mix. Without this providers and services cannot be usefully compared. This paper investigates the predictive ability of case-mix adjustment models in a primary/community care cohort. OBJECTIVES: To investigate the predictive ability of two existing MSK case-mix adjustment models and compare to the predictive ability of an evidence informed and statistically informed model. METHOD: A secondary analysis of the 'Subgrouping for Targeted Treatment in Musculoskeletal Conditions' cluster randomised controlled trial data (n = 1211). Stepwise linear regression models were built and compared using available baseline variables. The MSK-HQ was used as the primary functional status outcome. RESULTS: Two existing models were compared (UK National PROMs Model, US FOTO Model) using available variables. Of these models the modified US FOTO model showed the best predictive ability in this cohort predicting 44% of the variation in MSK-HQ outcome, the modified UK National PROMs model predicted 41%. A newly developed evidence informed model (Keele Model 1) performed no better than the existing models, and a statistically informed model (Keele Model 2) gave only an additional 2% increase in model power compared to the modified US FOTO model. CONCLUSION: All models showed strong predictive ability. The modified US FOTO model looks to be best suited to the UK primary/community care cohort of the existing models. This model performed so well that we recommend that this model is used in a UK setting moving forwards rather than development of an alternative UK model.

Resilience as a communal concept: Understanding adolescent resilience in the context of the Syrian refugee crisis in Bar Elias, Lebanon.

BACKGROUND: The conflict in Syria has led to the displacement of 1.5 million refugees into the neighboring country of Lebanon, with a majority that have yet to return to their homeland. Syrian adolescents in the town of Bar Elias in the Bekaa Valley, Lebanon have lived and grown in the face of resource-limited environments, restricted movement, and a longing for return. Resilience is manifested in the adaptation to such circumstances through close supportive relationships, social engagement, employment, and religion. There is a communal aspect to resilience that is important to the adolescent refugee experience and to the efforts supporting these communities. METHODS: Fifteen one-to-one interviews and two focus groups, with a total of eighteen Syrian adolescents, were analyzed using an inductive thematic analysis informed by grounded theory principles. Participants were recruited through partnering non-governmental organizations (NGOs) in the area, and ethical approval was granted through UCL and the American University in Beirut (AUB). RESULTS: Syrian adolescents highlighted supportive relationships, communal activities and spaces, memories of home, employment, and shared environments as integral elements to their personal adaptation. Methods of resilience involved social cohesion and establishing stability for one's family and close community. Adaptation to the present is intertwined with facing the consequences of displacement in this new context and maintaining aspirations for a bright future. Engaging with the environments they share and help create is an important facet of resilience and occurs through group gatherings , hobbies, and online communication. Additionally, inner strength can be derived from religious activities and empowers individual processing. CONCLUSION: This study illuminates the elements and mechanisms embodied in these adolescents' communities and relationships that allow for adaptation to life in Bar Elias. These factors strengthen their approach to overcome social barriers and practice resilience. These communal aspects of the adolescents' lives also connect to their memories of home, current environment, and future aspirations.

Developing a core outcome set for community and primary care musculoskeletal services: A consensus approach.

BACKGROUND: At present there is no core outcome set (COS) for use in community and primary care Musculoskeletal (MSK) services across the UK. Services are therefore collecting different MSK outcomes and metrics in different ways and at different times. Standardising MSK data collection is essential in order for fair and impactful benchmarking to improve the quality of care delivered to the millions of patients presenting each year with MSK disorders. OBJECTIVE: To gain consensus on a proposed set of metrics that could be used to develop a COS for use in routine practice in community and primary care MSK services in the UK and to make recommendations to inform a future national MSK audit. METHODS: A consensus process involving researchers, healthcare professionals and patients. Previous research generated an initial list of proposed metrics. This proposal was then taken to wider stakeholder consensus via an online survey designed for both healthcare professionals and MSK service users. RESULTS: 199 respondents completed the survey, 166 healthcare professionals and 33 service users (25/33 eligible to answer all items within the survey). Metrics that reached strong consensus were; age, pain site, comorbidities, duration of symptoms, work status, work absence, work absence duration. No Patient Reported Outcome Measures (PROMs) met strong consensus and all Patient Reported Experience Measures (PREMs) other than timeliness/convenience met strong consensus criteria. CONCLUSION: 7 baseline factors and 9 PREM domains reached strong consensus. The MSK-HQ PROM was the highest rated outcome measure so was also recommended for inclusion in an MSK COS.

Dominant negative effects by inactive Spa47 mutants inhibit T3SS function and Shigella virulence.

Type three secretion systems (T3SS) are complex nano-machines that evolved to inject bacterial effector proteins directly into the cytoplasm of eukaryotic cells. Many high-priority human pathogens rely on one or more T3SSs to cause disease and evade host immune responses, underscoring the need to better understand the mechanisms through which T3SSs function and their role(s) in supporting pathogen virulence. We recently identified the Shigella protein Spa47 as an oligomerization-activated T3SS ATPase that fuels the T3SS and supports overall Shigella virulence. Here, we provide both in vitro and in vivo characterization of Spa47 oligomerization and activation in the presence and absence of engineered ATPase-inactive Spa47 mutants. The findings describe mechanistic details of Spa47-catalyzed ATP hydrolysis and uncover critical distinctions between oligomerization mechanisms capable of supporting ATP hydrolysis in vitro and those that support T3SS function in vivo. Concentration-dependent ATPase kinetics and experiments combining wild-type and engineered ATPase inactive Spa47 mutants found that monomeric Spa47 species isolated from recombinant preparations exhibit low-level ATPase activity by forming short-lived oligomers with active site contributions from at least two protomers. In contrast, isolated Spa47 oligomers exhibit enhanced ATP hydrolysis rates that likely result from multiple preformed active sites within the oligomeric complex, as is predicted to occur within the context of the type three secretion system injectisome. High-resolution fluorescence microscopy, T3SS activity, and virulence phenotype analyses of Shigella strains co-expressing wild-type Spa47 and the ATPase inactive Spa47 mutants demonstrate that the N-terminus of Spa47, not ATPase activity, is responsible for incorporation into the injectisome where the mutant strains exhibit a dominant negative effect on T3SS function and Shigella virulence. Together, the findings presented here help to close a significant gap in our understanding of how T3SS ATPases are activated and define restraints with respect to how ATP hydrolysis is ultimately coupled to T3SS function in vivo.

Models used for case-mix adjustment of patient reported outcome measures (PROMs) in musculoskeletal healthcare: A systematic review of the literature.

BACKGROUND: Case-mix adjustment is an established method to take account of variations across cohorts in baseline patient factors, when comparing health outcomes. Although commonplace, there is a lack of evidence as to the most appropriate case-mix adjustment model to use to enable fair comparisons of PROM data in musculoskeletal services. OBJECTIVES: To conduct a systematic review summarising evidence of the development, validation, and performance of musculoskeletal case-mix adjustment models, and to make recommendations for future methods. DATA SOURCES: Searches included; AMED, CINAHL, EMBASE, HMIC, MEDLINE, and grey literature. ELIGIBILITY CRITERIA: Studies; from January 1992-May 2017, English language, musculoskeletal adult population, developing or validating a case-mix adjustment model, using a relevant PROM, and using patient factors feasible for clinical collection. DATA SYNTHESIS: Two reviewers evaluated selected papers. The CASP Cohort Tool was used to assess quality. RESULTS: Fourteen studies were included; eight US studies on the Focus on Therapeutic Outcomes model (pooled n=546,726 patients (with pre/post treatment data)) and six UK studies related to the UK National PROMs Programme model (pooled n=282,424 patients (with pre/post treatment data)). The majority used retrospective data, restricted to complete datasets. Both US and UK models showed good predictive ability (R2 18-42%). Common model variables were; baseline PROM score, age, sex, comorbidities, symptom duration, and surgical history. Reduced quality scores were mainly due to acceptability of patient recruitment, and completeness and length of patient follow up. CONCLUSION: Significant methodological crossover was found. Further studies are however needed to externally validate and develop models across musculoskeletal settings. PROSPERO database(CRD42017055948).

Visible-Light-Driven Valorization of Biomass Intermediates Integrated with H2 Production Catalyzed by Ultrathin Ni/CdS Nanosheets.

Photocatalytic upgrading of crucial biomass-derived intermediate chemicals (i.e., furfural alcohol, 5-hydroxymethylfurfural (HMF)) to value-added products (aldehydes and acids) was carried out on ultrathin CdS nanosheets (thickness ∼1 nm) decorated with nickel (Ni/CdS). More importantly, simultaneous H2 production was realized upon visible light irradiation under ambient conditions utilizing these biomass intermediates as proton sources. The remarkable difference in the rates of transformation of furfural alcohol and HMF to their corresponding aldehydes in neutral water was observed and investigated. Aided by theoretical computation, it was rationalized that the slightly stronger binding affinity of the aldehyde group in HMF to Ni/CdS resulted in the lower transformation of HMF to 2,5-diformylfuran compared to that of furfural alcohol to furfural. Nevertheless, photocatalytic oxidation of furfural alcohol and HMF under alkaline conditions led to complete transformation to the respective carboxylates with concomitant production of H2.

Factors associated with survival of horses following relaparotomy.

REASONS FOR PERFORMING STUDY: Relaparotomy may be required to investigate and manage complications that occur following surgical management of colic. OBJECTIVES: To report factors associated with survival following relaparotomy. STUDY DESIGN: Retrospective cohort study. METHODS: Records of horses that had undergone exploratory laparotomy for treatment of colic over a 10-year period (2002-2012) and had undergone relaparotomy <8 weeks following the initial surgery were reviewed. Descriptive data were generated and association with survival time was modelled using Cox proportional hazards models. RESULTS: Relaparotomy was performed in 96 horses at <8 weeks following initial surgery at a median of 4 days. This represented 6.3% of horses that underwent laparotomy during the study period (n = 1531). Relaparotomy was most frequently undertaken based on signs of persistent post-operative colic (76%; n = 73). Short-term survival for horses undergoing relaparotomy due to persistent colic was 53%, incisional dehiscence 50%, post-operative reflux 37%, haemoperitoneum 17% and septic peritonitis 0%. Median survival was 6 days for all horses undergoing relaparotomy and 778 days for those that recovered following anaesthesia. Nonsurvival was associated with increased packed cell volume at 24 h following initial laparotomy (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04-1.10, P = 0.009), peritonitis as a reason for undertaking relaparotomy (HR 4.41, 95% CI 1.43-13.6, P = 0.01) and adhesions found at relaparotomy (HR 1.77, 95% CI 1.03-3.04, P = 0.04). Increased likelihood of survival was associated with colic signs being the reason for performing relaparotomy (HR 0.48, 95% CI 0.26-0.88, P = 0.02) and small intestinal distension found at relaparotomy (HR 0.53, 95% CI 0.29-0.96, P = 0.04). CONCLUSIONS: This study has provided information about survival rates and risk factors for survival in horses undergoing relaparotomy that can assist clinicians and owners when determining whether to perform relaparotomy and in predicting the likely surgical outcome.

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.

Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis.

Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Barriers to transition in young adults with neurogenic bladder.

INTRODUCTION: 'Transition' not only involves finding an adult healthcare provider, but also includes the process of developing the patient's ability to care for him/herself. Recent literature states that 40% of young adults with special healthcare needs are receiving the tools needed for transition. Pediatric urologists treating patients with complex anomalies, such as spina bifida, often anticipate poor outcomes for patients who are ill equipped for transition to adult care. The goal of this study was to identify potential barriers for young adults with neurogenic bladder when transitioning to independent care. STUDY DESIGN: A prospective IRB-approved study was performed on all patients with neurogenic bladder referred to the transitional urology clinic. Reasons for missed appointments were tracked, and all patients were asked to complete the Transition Readiness Assessment Questionnaire (TRAQ) in private prior to an appointment. The TRAQ responses are scaled 1-5, with higher numbers corresponding to higher transition readiness of each individual skill. The mean score for each question was calculated across all patients, and the mean TRAQ score was calculated across all questions for each patient. To assess if certain subgroups were more prepared for transition, mean scores were compared between sexes, patients aged <19 and ≥19 years old, and between ambulatory and full-time wheelchair users with unpaired t-tests. RESULTS: A total of 73% (58/79) of patients referred to the transitional clinic came to their appointment. The most common reason for missed clinic appointments was related to health insurance coverage (47%). A total of 42 patients completed the TRAQ at a mean age of 19.5 years old; 90% (38/42) had spina bifida. Females, ambulatory patients, and those ≥19 years old had higher overall mean TRAQ scores, but these differences were not statistically significant. The highest TRAQ scores were related to taking and ordering medications, utilization of medical supplies, communication with healthcare providers, and assisting with household duties. The majority of the patients indicated 'I am learning to do this'. The lowest scores were in response to questions about health insurance coverage, payments for medications or medical equipment, financial help, and utilization of community services. Most patients responded 'I do not know how but I want to learn'. CONCLUSIONS: Young adults with neurogenic bladder needed the most guidance during transition to independent care, with management of health insurance and finances. Based on these findings, dedicated social work and nurse visits have been included into the transition process.

Novel axon projection after stress and degeneration in the Dscam mutant retina.

The Down syndrome cell adhesion molecule gene (Dscam) is required for normal dendrite patterning and promotes developmental cell death in the mouse retina. Loss-of-function studies indicate that Dscam is required for refinement of retinal ganglion cell (RGC) axons in the lateral geniculate nucleus, and in this study we report and describe a requirement for Dscam in the maintenance of RGC axon projections within the retina. Mouse Dscam loss of function phenotypes related to retinal ganglion cell axon outgrowth and targeting have not been previously reported, despite the abundance of axon phenotypes reported in Drosophila Dscam1 loss and gain of function models. Analysis of the Dscam deficient retina was performed by immunohistochemistry and Western blot analysis during postnatal development of the retina. Conditional targeting of Dscam and Jun was performed to identify factors underlying axon-remodeling phenotypes. A subset of RGC axons were observed to project and branch extensively within the Dscam mutant retina after eye opening. Axon remodeling was preceded by histological signs of RGC stress. These included neurofilament accumulation, axon swelling, axon blebbing and activation of JUN, JNK and AKT. Novel and extensive projection of RGC axons within the retina was observed after upregulation of these markers, and novel axon projections were maintained to at least one year of age. Further analysis of retinas in which Dscam was conditionally targeted with Brn3b or Pax6α Cre indicated that axon stress and remodeling could occur in the absence of hydrocephalus, which frequently occurs in Dscam mutant mice. Analysis of mice mutant for the cell death gene Bax, which executes much of Dscam dependent cell death, identified a similar axon misprojection phenotype. Deleting Jun and Dscam resulted in increased axon remodeling compared to Dscam or Bax mutants. Retinal ganglion cells have a very limited capacity to regenerate after damage in the adult retina, compared to the extensive projections made in the embryo. In this study we find that DSCAM and JUN limit ectopic growth of RGC axons, thereby identifying these proteins as targets for promoting axon regeneration and reconnection.

Ictal infraslow activity in stereoelectroencephalography: Beyond the "DC shift".

OBJECTIVES: The significance of infraslow activity (ISA) in focal epilepsies is largely unknown. Recent work has demonstrated ictal ISA to be more widespread in expression than originally understood. Analysis of ISA by stereoelectroencephalography (SEEG) may help to clarify its localizing value, namely the focal versus widespread expression of ISA. METHODS: The ictal SEEG records for fifteen consecutive adult patients were retrospectively analyzed, using both conventional (1.6-70 Hz) and infraslow (0.01-0.1 Hz) bandpass filters. When justified, seizures were averaged in the infraslow band to clarify their stereotypy. Wavelets were used to quantify the time-frequency characteristics of ISA. RESULTS: All clinical seizures were found to possess ISA, and this was markedly invariant across seizures in a given patient. ISA showed biphasic peaks in power, both at ictal onset and offset, with this most prominent in the anatomical structures implicated by conventional analysis. In addition, ISA demonstrated an association with low voltage fast activity, and possessed a more restricted field than conventional activity. CONCLUSIONS: ISA is both widespread (anatomically distributed) and focal (closed electric field). Seizures possess an infraslow spatiotemporal signature. SIGNIFICANCE: Beyond representing a "focus" of paroxysmal activity, ISA must arise from a network process as a component of wideband ictal dynamics. How this relates to clinical definition of the epileptogenic zone requires further study.

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland.

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations.

A magnetoencephalography study of multi-modal processing of pain anticipation in primary sensory cortices.

Pain anticipation plays a critical role in pain chronification and results in disability due to pain avoidance. It is important to understand how different sensory modalities (auditory, visual or tactile) may influence pain anticipation as different strategies could be applied to mitigate anticipatory phenomena and chronification. In this study, using a countdown paradigm, we evaluated with magnetoencephalography the neural networks associated with pain anticipation elicited by different sensory modalities in normal volunteers. When encountered with well-established cues that signaled pain, visual and somatosensory cortices engaged the pain neuromatrix areas early during the countdown process, whereas the auditory cortex displayed delayed processing. In addition, during pain anticipation, the visual cortex displayed independent processing capabilities after learning the contextual meaning of cues from associative and limbic areas. Interestingly, cross-modal activation was also evident and strong when visual and tactile cues signaled upcoming pain. Dorsolateral prefrontal cortex and mid-cingulate cortex showed significant activity during pain anticipation regardless of modality. Our results show pain anticipation is processed with great time efficiency by a highly specialized and hierarchical network. The highest degree of higher-order processing is modulated by context (pain) rather than content (modality) and rests within the associative limbic regions, corroborating their intrinsic role in chronification.