Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity.

Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood-brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

Assessment of perivascular space filtering methods using a three-dimensional computational model.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO's performance does not deteriorate as PVS volume increases. Second, the performance of all "vesselness" filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

The development of transversal competence of health service managers.

In their pedagogical projects, health management courses focus on multidisciplinarity, interdisciplinarity, comprehensiveness and transversality, whose main merit is to question health issues from different theoretical perspectives. Analyzing these issues under many perspectives does not necessarily mean the development of transversal competences. The development and application of these competences suppose going beyond integrating curricular contents and theory/practice. They depend on how the knowledge will be articulated to changes at organizational, sectorial and institutional levels and on the coevolution between these competences and changes. It is understood that health services manager role is effectively transversal when he/she: (i) acts at organizational boundaries, fostering interaction between organizations and other actors in the system; (ii) provides (and receives) feedback to (and from) these actors; and (iii) these feedbacks help decision makers to undertake organizational changes to respond to the environment and shape it.

The development of transversal competence of health service managers / O desenvolvimento da competência transversal dos gestores de serviços de saúde

ABSTRACT In their pedagogical projects, health management courses focus on multidisciplinarity, interdisciplinarity, comprehensiveness and transversality, whose main merit is to question health issues from different theoretical perspectives. Analyzing these issues under many perspectives does not necessarily mean the development of transversal competences. The development and application of these competences suppose going beyond integrating curricular contents and theory/practice. They depend on how the knowledge will be articulated to changes at organizational, sectorial and institutional levels and on the coevolution between these competences and changes. It is understood that health services manager role is effectively transversal when he/she: (i) acts at organizational boundaries, fostering interaction between organizations and other actors in the system; (ii) provides (and receives) feedback to (and from) these actors; and (iii) these feedbacks help decision makers to undertake organizational changes to respond to the environment and shape it.

RESUMO Em seus projetos pedagógicos, os cursos de gestão de saúde privilegiam a multidisciplinaridade, interdisciplinaridade, integralidade e transversalidade, cujo principal mérito é problematizar as questões da saúde sob diferentes perspectivas teóricas. Analisar as questões da área da saúde a partir de diversos prismas não implica necessariamente no desenvolvimento de competências transversais. O desenvolvimento e a aplicação dessas competências pressupõem ir além da integração entre conteúdos curriculares e entre teoria e prática. Dependem de como os conhecimentos serão articulados às mudanças nos níveis organizacional, setorial e institucional e da coevolução entre essas competências e essas mudanças. Entende-se que a atuação do gestor de serviços de saúde é efetivamente transversal quando: (i) atua nas fronteiras organizacionais, fomentando a interação entre as organizações e outros atores do sistema; (ii) provê (e recebe) feedbacks para esses (desses) atores; e (iii) esses feedbacks auxiliam os tomadores de decisão a empreender mudanças organizacionais, de modo a responder ao ambiente e a moldá-lo.

Transfer of knowledge in international cooperation: the Farmanguinhos - SMM case.

OBJECTIVE: To analyze the influence of four mechanisms of knowledge transfer (training, technical visits, expatriation, and standard operating procedures) on the different dimensions (potential and realized) of absorptive capacity in international technical cooperation. METHODS: We examine the case of implementation of the Sociedade Moçambicana de Medicamentos. Data have been collected using semi-structured interviews (applied to 21 professionals of the Sociedade Moçambicana de Medicamentos, Farmanguinhos, FIOCRUZ, and Itamaraty) and official documents. The data of the interviews have been submitted to content analysis, using the software NVivo. RESULTS: Training and technical visits directly influenced the acquisition and, partly, the assimilation of knowledge. Expatriation contributed with the transformation of this knowledge from the development and refinement of operational routines. Finally, the definition of standard operating procedures allowed the Mozambican technicians to be the actors of the transformation of the knowledge previously acquired and assimilated and, at the same time, it laid the foundations for a future exploration of the knowledge. CONCLUSIONS: Training and technical visits mainly influence the potential absorptive capacity, while expatriation and standard operating procedures most directly affect the realized absorptive capacity.

Evidence for Chemical and Electronic Nonuniformities in the Formation of the Interface of RbF-Treated Cu(In,Ga)Se2 with CdS.

We report on the initial stages of CdS buffer layer formation on Cu(In,Ga)Se2 (CIGSe) thin-film solar cell absorbers subjected to rubidium fluoride (RbF) postdeposition treatment (PDT). A detailed characterization of the CIGSe/CdS interface for different chemical bath deposition (CBD) times of the CdS layer is obtained from spatially resolved atomic and Kelvin probe force microscopy and laterally integrating X-ray spectroscopies. The observed spatial inhomogeneity in the interface's structural, chemical, and electronic properties of samples undergoing up to 3 min of CBD treatments is indicative of a complex interface formation including an incomplete coverage and/or nonuniform composition of the buffer layer. It is expected that this result impacts solar cell performance, in particular when reducing the CdS layer thickness (e.g., in an attempt to increase the collection in the ultraviolet wavelength region). Our work provides important findings on the absorber/buffer interface formation and reveals the underlying mechanism for limitations in the reduction of the CdS thickness, even when an alkali PDT is applied to the CIGSe absorber.

Data quality in electronic medical records in Manitoba: Do problem lists reflect chronic disease as defined by prescriptions?

OBJECTIVE: To determine if the problem list (health conditions) in primary care electronic medical records (EMRs) accurately reflects the conditions for which chronic medications are prescribed in the EMR. DESIGN: A retrospective analysis of EMR data. SETTING: Eighteen primary care clinics across rural and urban Manitoba using the Accuro EMR. PARTICIPANTS: Data from the EMRs of active patients seen in an 18-month period (December 18, 2011, to June 18, 2013, or December 3, 2012, to June 3, 2014) were used. MAIN OUTCOME MEASURES: The likelihood of documentation in the EMR problem list of those specific chronic diseases for which drug prescriptions were documented in the EMR. Regression modeling was performed to determine the effect of clinic patient load and remuneration type on the completeness of EMR problem lists. RESULTS: Overall problem-list completeness was low but was highest for diabetes and lowest for insomnia. Fee-for-service clinics generally had lower problem-list completeness than salaried clinics did for all prescription medications examined. Panel size did not affect problem-list completeness rates. CONCLUSION: The low EMR problem-list completeness suggests that this field is not reliable for use in quality improvement initiatives or research until higher reliability has been demonstrated. Further research is recommended to explore the reasons for the poor quality and to support improvement efforts.

Transfer of knowledge in international cooperation: the Farmanguinhos - SMM case / Transferência de conhecimento na cooperação internacional: o caso Farmanguinhos - SMM

ABSTRACT OBJECTIVE To analyze the influence of four mechanisms of knowledge transfer (training, technical visits, expatriation, and standard operating procedures) on the different dimensions (potential and realized) of absorptive capacity in international technical cooperation. METHODS We examine the case of implementation of the Sociedade Moçambicana de Medicamentos. Data have been collected using semi-structured interviews (applied to 21 professionals of the Sociedade Moçambicana de Medicamentos, Farmanguinhos, FIOCRUZ, and Itamaraty) and official documents. The data of the interviews have been submitted to content analysis, using the software NVivo. RESULTS Training and technical visits directly influenced the acquisition and, partly, the assimilation of knowledge. Expatriation contributed with the transformation of this knowledge from the development and refinement of operational routines. Finally, the definition of standard operating procedures allowed the Mozambican technicians to be the actors of the transformation of the knowledge previously acquired and assimilated and, at the same time, it laid the foundations for a future exploration of the knowledge. CONCLUSIONS Training and technical visits mainly influence the potential absorptive capacity, while expatriation and standard operating procedures most directly affect the realized absorptive capacity.

RESUMO OBJETIVO Analisar a influência de quatro mecanismos de transferência de conhecimento (treinamentos, visitas técnicas, expatriação e procedimentos operacionais padrão) sobre as diferentes dimensões (potencial e realizada) da capacidade absortiva na cooperação técnica internacional. MÉTODOS Examina-se o caso da implementação da Sociedade Moçambicana de Medicamentos. Os dados foram coletados por meio de entrevistas semiestruturadas (aplicadas a 21 profissionais da Sociedade Moçambicana de Medicamentos, Farmanguinhos, Fiocruz e Itamaraty) e de documentos oficiais. Os dados das entrevistas foram submetidos à análise de conteúdo, com uso do software NVivo. RESULTADOS Os treinamentos e as visitas técnicas influenciaram diretamente a aquisição e, parcialmente, a assimilação do conhecimento. A expatriação contribuiu para a transformação desse conhecimento, por meio do desenvolvimento e refinamento das rotinas operacionais. Por fim, a definição dos procedimentos operacionais padrão permitiu que os técnicos moçambicanos fossem os atores da transformação do conhecimento adquirido e assimilado previamente e, ao mesmo tempo, criou as bases para uma futura exploração do conhecimento. CONCLUSÕES Os treinamentos e as visitas técnicas influenciam, principalmente, a capacidade absortiva potencial, enquanto a expatriação e os procedimentos operacionais padrão impactam mais diretamente a capacidade absortiva realizada.

Data quality of electronic medical records in Manitoba: do problem lists accurately reflect chronic disease billing diagnoses?

OBJECTIVE: To determine problem list completeness related to chronic diseases in electronic medical records (EMRs) and explore clinic and physician factors influencing completeness. METHODS: A retrospective analysis of primary care EMR data quality related to seven chronic diseases (hypertension, diabetes, asthma, congestive heart failure, coronary artery disease, hypothyroidism, and chronic obstructive pulmonary disorder) in Manitoba, Canada. We included 119 practices in 18 primary care clinics across urban and rural Manitoba. The main outcome measure was EMR problem list completeness. Completeness was measured by comparing the number of EMR-documented diagnoses to the number of billings associated with each disease. We calculated odds ratios for the effect of clinic patient load and salary type on EMR problem list completeness of the 7 chronic diseases. RESULTS: Completeness of EMR problem list for each disease varied widely among clinics. Factors that significantly affected EMR problem list completeness included the primary care provider, the patient load, and the clinic's funding and organization model (ie, salaried, fee-for-service, or residency training clinics). Average rates of completeness were: hypertension, 72%; diabetes, 80%; hypothyroidism, 63%; asthma, 56%; chronic obstructive pulmonary disorder, 43%; congestive heart failure, 54%; and coronary artery disease, 64%. CONCLUSION: This study demonstrates the high variability but generally low quality of problem lists (health condition records) related to 7 common chronic diseases in EMRs. There are systematic physician- and clinic-level factors associated with low data quality completeness. This information may be useful to support improvement in EMR data quality in primary care.

Molecular assay optimized by Taguchi experimental design method for venous thromboembolism investigation.

Two mutations - Factor V Leiden (1691G > A) and the 20210G > A on the Prothrombin gene - are key risk factors for a frequent and potentially fatal disorder called Venous Thromboembolism. These molecular alterations can be investigated using real-time Polymerase Chain Reaction (PCR) with Fluorescence Resonance Energy Transfer (FRET) probes and distinct DNA pools for both factors. The objective of this paper is to present an application of Taguchi Experimental Design Method to determine the best parameters adjustment of a Molecular Assays Process in order to obtain the best diagnostic result for Venous Thromboembolism investigation. The complete process contains six three-level factors which usually demands 729 experiments to obtain the final result, if using a Full Factorial Array. In this research, a Taguchi L27 Orthogonal Array is chosen to optimize the analysis and reduce the number of experiments to 27 without degrading the final result accuracy. The application of this method can lessen the time and cost necessary to achieve the best operation condition for a required performance. The results is proven in practice and confirmed that the Taguchi method can really offer a good approach for clinical assay efficiency and effectiveness improvement even though the clinical diagnostics can be based on the use of qualitative techniques.

Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients.

GOALS OF WORK: This is a prospective and observational study comparing the efficacy of risk-assessment models in patients with neutropenic fever in a reference treatment center. The meaning of the complex infection was evaluated. MATERIALS AND METHODS: Patients were recruited throughout a 9-month period. Inclusion criteria were histologic diagnosis of malignancy, neutropenic febrile secondary to chemotherapy and/or radiotherapy (absolute neutrophil count of <500/microl and axillary temperature > or = 38 degrees C), and > or = 18 years of age. MAIN RESULTS: Fifty-three febrile neutropenic patients were included. Twenty one of them were classified as low risk by the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the MASCC risk-index scores were, respectively 87.9, 85.0, 90.6, 80.9, and 86.8%. None of the low-risk patients died, but four patients classified as low risk by the MASCC model developed serious medical complications during febrile neutropenic episodes. When we subtracted patients with complex infections from the group of patients with the MASCC risk-index score of > or = 21, we got 15 patients that were classified as low risk by a proposed adjustment by complex infection (PACI) model. None of them developed serious medical complications. The sensitivity, specificity, PPV, NPV, and the accuracy of this new model were, respectively, 100, 75.0, 86.8, 100, and 90.6%. CONCLUSION: The MASCC risk-index score had high sensitivity and specificity to predict the absence of complications, but the PACI model was better than MASCC for predicting the absence of complications in this febrile neutropenic patients.

Vólvulo de la vesícula biliar: presentación de un caso / Gallblader volvulus: case report

El vólvulo o torsión de vesícula biliar, si bien, es un cuadro poco frecuente, que afecta con mayor frecuencia a mujeres (3 a 1) entre los 65 y 75 años, constituye una de las causas de dolor abdominal a ser tenidas en cuenta en el diagnóstico diferencial del abdomen agudo del anciano. Se presenta el caso de una paciente de sexo femenino de 84 años, que ingresó al servicio por cuadro de dolor en FID de 24 horas de evolución, con náuseas y vómitos. El examen físico demostró dolor en FID, por lo que se decidió la cirugía con el diagnóstico de apendicitis aguda, constatándose en la misma un vólvulo de vesícula biliar, con áreas necróticas, realizándose una colecistectomía convencional. La paciente evolucionó satisfactoriamente.

Neoplasia trofoblástica gestacional embrionada: apresentaçäo de um caso / Embryonate gestational trophoblastic neoplasm: a case report

É apresentado um caso de neoplasia trofoblástica gestacional, que evolui para quimioterapia após esvaziamento por histerotomia. Discorre-se inicialmente sobre as principais características da doença, apresenta-se o caso e comenta-se finalmente as possibilidades dessa evoluçäo fora dos padröes habituais