Effect of delayed acquisition times on Gadolinium-enhanced MRI of the presumably normal canine brain

A delay in imaging following intravenous contrast medium administration has been recommended to reduce misdiagnoses. However, the normal variation of contrast enhancement in dogs following a delay has not been characterized. Contrast enhanced MR imaging of 22 dogs was assessed, in terms of identification of normal anatomic structures, to investigate the variation associated with 10 minute delay between contrast medium administration and imaging. All dogs had a normal brain MR imaging study and unremarkable CSF. Specific ROIs were assessed both objectively, using computer software, and subjectively using three observers. Mean contrast enhancement greater than 10% was seen in the pituitary gland, choroid plexus, meninges, temporal muscle, trigeminal nerve and the trigeminal nerve root. Structures with an active blood-brain-barrier had minimal contrast enhancement (<6%). Enhancing structures had significantly more contrast enhancement at t=1min versus t=10min, except in temporal muscle, the trigeminal nerve and the trigeminal nerve root. Inter-observer agreement was moderate to good in favor of the initial post contrast T1w sequence. The observers found either no difference or poor agreement in identification of the non-vascular structures. Intra-observer agreement was very good with all vascular structures and most non-vascular structures. A degree of meningeal enhancement was a consistent finding. The initial acquisition had higher enhancement characteristics and observer agreement for some structures; however, contrast-to-noise was comparable in the delayed phase or not significantly different. We provide baseline references and suggest that the initial T1w post contrast sequence is preferable but not essential should a delayed post contrast T1w sequence be performed

The joint effects of water and sanitation on diarrhoeal disease: a multicountry analysis of the Demographic and Health Surveys

ObjectivesTo assess whether the joint effects of water and sanitation infrastructure, are acting antagonistically (redundant services preventing the same cases of diarrhoeal disease), independently, or synergistically; and to assess how these effects vary by country and over time.MethodsWe used data from 217 Demographic and Health Surveys conducted in 74 countries between 1986 and 2013. We used modified Poisson regression to assess the impact of water and sanitation infrastructure on the prevalence of diarrhoea among children under 5.ResultsThe impact of water and sanitation varied across surveys, and adjusting for socio‐economic status drove these estimates towards the null. Sanitation had a greater effect than water infrastructure when all 217 surveys were pooled; however, the impact of sanitation diminished over time. Based on survey data from the past 10 years, we saw no evidence for benefits in improving drinking water or sanitation alone, but we estimated a 6% reduction of both combined (prevalence ratio = 0.94, 95% confidence limit 0.91–0.98).ConclusionsWater and sanitation interventions should be combined to maximise the number of cases of diarrhoeal disease prevented in children under 5. Further research should identify the sources of variability seen between countries and across time. These national surveys likely include substantial measurement error in the categorisation of water and sanitation, making it difficult to interpret the roles of other pathways.ObjectifsEvaluer les effets conjoints des infrastructures de l'eau et d'assainissement afin de voir si elles sont des services redondants prévenant les mêmes cas de maladies diarrhéiques, si elles agissent indépendamment ou en synergie et d’évaluer comment ces effets varient selon les pays et au fil du temps.MéthodesNous avons utilisé les données de 217 enquêtes démographiques et santé menées dans 90 pays entre 1986 et 2013. Nous avons utilisé la régression de Poisson modifiée pour évaluer l'impact des infrastructures de l'eau et d'assainissement sur la prévalence de la diarrhée chez les enfants de moins de cinq ans.RésultatsL'impact de l'eau et de l'assainissement variait dans toutes les enquêtes et l'ajustement pour le statut socioéconomique conduisait ces estimations vers le néant. L'assainissement avait un effet plus important que l'infrastructure de l'eau lorsque toutes les 217 enquêtes ont été poolées. Toutefois, l'impact de l'assainissement a diminué au fil du temps. Basé sur des données d'enquêtes des dix dernières années, nous n'avons vu aucune preuve pour les bénéfices de l'amélioration de l'eau potable ou de l'assainissement seuls, mais nous avons estimé une réduction de 6% pour la combinaison des deux (rapport de prévalence = 0,94; IC95%: 0,91 à 0,98).ConclusionsLes interventions sur l'eau et l'assainissement devraient être combinées pour maximiser le nombre de cas de maladies diarrhéiques prévenus chez les enfants de moins de cinq ans. Des recherches supplémentaires devraient identifier les sources de variabilité observées entre les pays et dans le temps. Ces enquêtes nationales comportent probablement une erreur importante de mesure dans la catégorisation de l'eau et de l'assainissement, ce qui rend difficile l'interprétation des rôles des autres voies.ObjetivosEvaluar el efecto conjunto del agua e infraestructura sanitaria, y determinar si son servicios redundantes que previenen los mismos casos de enfermedad diarreica, actúan de forma independiente o actúan de forma sinérgica; y evaluar como dichos efectos varían según el país y a lo largo del tiempo.MétodosHemos utilizado los datos de 217 Censos Demográficos y de Salud realizados en 90 países entre 1986 y 2013. Hemos realizado una regresión de Poisson modificada para evaluar el impacto del agua y de la infraestructura sanitaria sobre la prevalencia de la diarrea en niños menores de cinco años.ResultadosEl impacto del agua y del saneamiento variaba a lo largo de los censos, y el ajustar según el estatus socioeconómico llevaba los resultados a cero. El saneamiento tenía un mayor efecto que la infraestructura para el agua si se agrupaban los 217 censos; sin embargo, el impacto del saneamiento disminuía a lo largo del tiempo. Basado en los datos censales de los últimos diez años, no encontramos evidencia de los beneficios de la mejora del agua para consumo o del saneamiento por sí solos, pero hemos estimado una reducción del 6% de las dos intervenciones combinadas (tasa de prevalencia = 0.94, IC 95% 0.91‐0.98).ConclusionesLas intervenciones en el agua o el saneamiento deberían combinarse para maximizar el número de casos de enfermedad diarréica prevenidas en niños menores de cinco años. Estudios futuros deberían identificar las fuentes de variabilidad observada entre países y a lo largo del tiempo. Es posible que los censos nacionales incluyan un error sustancial en la medición de las categorías de agua y saneamiento, lo cual complica la determinación del papel de vías alternativas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110633/1/tmi12441.pd

Réunion de chercheurs en éducation médicale à une conférence sur Twitter autour du sujet du professionnalisme et la construction de l’identité professionnelle

Implication Statement The Education Innovation Institute (EII) of Medical College of Georgia, Augusta University, hosted a conference on Twitter about Professional Identity Formation (PIF), #MCGConf2021PIF, on February 25, 2021. The conference featured five presentations by 15 authors from Canada and the U.S. A Twitter conference is a versatile, affordable, and accessible digital option for medical education groups interested in diversifying conference offerings and reaching a broader audience. It was low-cost, organized in six months, and garnered over 9,000 Twitter impressions. Small networks and interest groups can organize Twitter conferences for their constituencies and larger conference organizations can host online mini-conferences to supplement in-person events.Énoncé des implications de la recherche Le 25 février 2021, l’Educational Innovation Institute (EII) du Medical College of Georgia de l’Université Augusta a tenu une conférence sur la construction de l’identité professionnelle sur le réseau social Twitter (#MCGConf2021PIF). Cinq communications y ont été présentées par 15 chercheurs du Canada et des États-Unis. Elle a été organisée en six mois, à coût modeste, et elle a recueilli plus de 9 000 impressions sur Twitter. La conférence Twitter s’avère être une option numérique polyvalente, abordable et accessible pour les membres du milieu de l’éducation médicale désireux de diversifier leur offre de symposiums et de toucher un public plus large. Twitter offre aux petits réseaux et groupes d’intérêt la possibilité de convier leurs membres à des conférences restreintes et aux organisateurs de conférences plus importantes la possibilité de tenir des mini-conférences en ligne pour compléter leurs activités en personne

A comparison of fragmenting lead-based and lead-free bullets for aerial shooting of wild pigs

In response to the health threats posed by toxic lead to humans, scavenging wildlife and the environment, there is currently a focus on transitioning from lead-based to lead-free bullets for shooting of wild animals. We compared efficiency metrics and terminal ballistic performance for lead-based and lead-free (non-lead) bullets for aerial shooting of wild pigs (Sus scrofa) in eastern Australia. Ballistic testing revealed that lead-based and lead-free bullets achieved similar performance in precision and muzzle kinetic energy (E-0) levels (3337.2 J and 3345.7 J, respectively). An aerial shooting trial was conducted with wild pigs shot with one type of lead-based and one type of lead-free bullets under identical conditions. Observations were made from 859 shooting events (n = 430 and 429 respectively), with a sub-set of pigs examined via gross post-mortem (n = 100 and 108 respectively), and a further sub-set examined via radiography (n = 94 and 101 respectively). The mean number of bullets fired per pig killed did not differ greatly between lead-based and lead-free bullets respectively (4.09 vs 3.91), nor did the mean number of bullet wound tracts in each animal via post-mortem inspection (3.29 vs 2.98). However, radiography revealed a higher average number of fragments per animal (median >300 vs median = 55) and a broader distribution of fragments with lead-based bullets. Our results suggest that lead-based and lead-free bullets are similarly effective for aerial shooting of wild pigs, but that the bullet types behave differently, with lead-based bullets displaying a higher degree of fragmentation. These results suggest that aerial shooting may be a particularly important contributor to scavenging wildlife being exposed to lead and that investigation of lead-free bullets for this use should continue

The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells

AbstractA recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a ⩾10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC50=160μM; 22GSCs: IC50=44μM) compared to MGMT non-expressing (33GSCs: IC50=1.5μM; 114GSCs: IC50=5.2μM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50–500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74±2.9% and 38±3.2%, respectively; 22GSC: 61±11% and 38±2.6%, respectively; 33GSC: 56±9.5% and 60±7.1%, respectively; 114 GSC: 79±3.5% and 41±4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., ± MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications

Interplay between IL-10, IFN-γ, IL-17A and PD-1 Expressing EBNA1-Specific CD4+ and CD8+ T Cell Responses in the Etiologic Pathway to Endemic Burkitt Lymphoma

Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized for eBL. Using a bespoke flow cytometry assay we measured intracellular IFN-γ, IL-10, IL-17A expression and phenotyped CD4+ and CD8+ T cell effector memory subsets specific to EBNA1 for eBL patients compared to two groups of healthy children with divergent malaria exposures. In response to EBNA1 and a malaria antigen (PfSEA-1A), the three study groups exhibited strikingly different cytokine expression and T cell memory profiles. EBNA1-specific IFN-γ-producing CD4+ T cell response rates were lowest in eBL (40%) compared to children with high malaria (84%) and low malaria (66%) exposures (p < 0.0001 and p = 0.0004, respectively). However, eBL patients did not differ in CD8+ T cell response rates or the magnitude of IFN-γ expression. In contrast, eBL children were more likely to have EBNA1-specific CD4+ T cells expressing IL-10, and less likely to have polyfunctional IFN-γ+IL-10+ CD4+ T cells (p = 0.02). They were also more likely to have IFN-γ+IL-17A+, IFN-γ+ and IL-17A+ CD8+ T cell subsets compared to healthy children. Cytokine-producing T cell subsets were predominantly CD45RA+CCR7+ TNAIVE-LIKE cells, yet PD-1, a marker of persistent activation/exhaustion, was more highly expressed by the central memory (TCM) and effector memory (TEM) T cell subsets. In summary, our study suggests that IL-10 mediated immune regulation and depletion of IFN-γ+ EBNA1-specific CD4+ T cells are complementary mechanisms that contribute to impaired T cell cytotoxicity in eBL pathogenesis

SSWAP: A Simple Semantic Web Architecture and Protocol for semantic web services

<p>Abstract</p> <p>Background</p> <p>SSWAP (<b>S</b>imple <b>S</b>emantic <b>W</b>eb <b>A</b>rchitecture and <b>P</b>rotocol; pronounced "swap") is an architecture, protocol, and platform for using reasoning to semantically integrate heterogeneous disparate data and services on the web. SSWAP was developed as a hybrid semantic web services technology to overcome limitations found in both pure web service technologies and pure semantic web technologies.</p> <p>Results</p> <p>There are currently over 2400 resources published in SSWAP. Approximately two dozen are custom-written services for QTL (Quantitative Trait Loci) and mapping data for legumes and grasses (grains). The remaining are wrappers to Nucleic Acids Research Database and Web Server entries. As an architecture, SSWAP establishes how clients (users of data, services, and ontologies), providers (suppliers of data, services, and ontologies), and discovery servers (semantic search engines) interact to allow for the description, querying, discovery, invocation, and response of semantic web services. As a protocol, SSWAP provides the vocabulary and semantics to allow clients, providers, and discovery servers to engage in semantic web services. The protocol is based on the W3C-sanctioned first-order description logic language OWL DL. As an open source platform, a discovery server running at <url>http://sswap.info</url> (as in to "swap info") uses the description logic reasoner Pellet to integrate semantic resources. The platform hosts an interactive guide to the protocol at <url>http://sswap.info/protocol.jsp</url>, developer tools at <url>http://sswap.info/developer.jsp</url>, and a portal to third-party ontologies at <url>http://sswapmeet.sswap.info</url> (a "swap meet").</p> <p>Conclusion</p> <p>SSWAP addresses the three basic requirements of a semantic web services architecture (<it>i.e</it>., a common syntax, shared semantic, and semantic discovery) while addressing three technology limitations common in distributed service systems: <it>i.e</it>., <it>i</it>) the fatal mutability of traditional interfaces, <it>ii</it>) the rigidity and fragility of static subsumption hierarchies, and <it>iii</it>) the confounding of content, structure, and presentation. SSWAP is novel by establishing the concept of a canonical yet mutable OWL DL graph that allows data and service providers to describe their resources, to allow discovery servers to offer semantically rich search engines, to allow clients to discover and invoke those resources, and to allow providers to respond with semantically tagged data. SSWAP allows for a mix-and-match of terms from both new and legacy third-party ontologies in these graphs.</p

Study protocol for a type III hybrid effectiveness-implementation trial of strategies to implement firearm safety promotion as a universal suicide prevention strategy in pediatric primary care

BACKGROUND: Insights from behavioral economics, or how individuals\u27 decisions and behaviors are shaped by finite cognitive resources (e.g., time, attention) and mental heuristics, have been underutilized in efforts to increase the use of evidence-based practices in implementation science. Using the example of firearm safety promotion in pediatric primary care, which addresses an evidence-to-practice gap in universal suicide prevention, we aim to determine: is a less costly and more scalable behavioral economic-informed implementation strategy (i.e., Nudge ) powerful enough to change clinician behavior or is a more intensive and expensive facilitation strategy needed to overcome implementation barriers? METHODS: The Adolescent and child Suicide Prevention in Routine clinical Encounters (ASPIRE) hybrid type III effectiveness-implementation trial uses a longitudinal cluster randomized design. We will test the comparative effectiveness of two implementation strategies to support clinicians\u27 use of an evidence-based firearm safety practice, S.A.F.E. Firearm, in 32 pediatric practices across two health systems. All pediatric practices in the two health systems will receive S.A.F.E. Firearm materials, including training and cable locks. Half of the practices (k = 16) will be randomized to receive Nudge; the other half (k = 16) will be randomized to receive Nudge plus 1 year of facilitation to target additional practice and clinician implementation barriers (Nudge+). The primary implementation outcome is parent-reported clinician fidelity to the S.A.F.E Firearm program. Secondary implementation outcomes include reach and cost. To understand how the implementation strategies work, the primary mechanism to be tested is practice adaptive reserve, a self-report practice-level measure that includes relationship infrastructure, facilitative leadership, sense-making, teamwork, work environment, and culture of learning. DISCUSSION: The ASPIRE trial will integrate implementation science and behavioral economic approaches to advance our understanding of methods for implementing evidence-based firearm safety promotion practices in pediatric primary care. The study answers a question at the heart of many practice change efforts: which strategies are sufficient to support change, and why? Results of the trial will offer valuable insights into how best to implement evidence-based practices that address sensitive health matters in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04844021 . Registered 14 April 2021