Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker

Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS. © 2014 Abhinav, Yeh, El-Dokla, Ferrando, Chang, Lacomis, Friedlander and Fernandez-Miranda

Marcadores sorológicos de hepatite B em indivíduos submetidos a exames de sangue em unidades de saúde

OBJECTIVE: To study some of the epidemiological aspects of hepatitis B in a non-representative sample of patients seen in health care clinics. METHODS: The study population comprised 632 patients who were seen at health care clinics in the city of Ribeirão Preto, Brazil, for the purpose of blood testing, regardless the reason. After signing a written consent, an additional amount of blood was drawn from the same venous puncture site used to collect the original sample for the testing assigned to the patient at the health care clinic. A questionnaire was applied to each participant, looking for the presence of risk factors for hepatitis B. The blood samples were tested for HBV markers, using immunoenzimatic techniques. RESULTS: The prevalences of HBsAg and anti-HBcAg were 0.3% and 13.9%, respectively. By a logistic regression model, the following variables were significantly associated with the infection: age, time of residency in the city (higher risk among those living for a period less than one year), past history of hepatitis, incarceration and sexual behavior (higher risk among homosexual and bisexual males). CONCLUSIONS: The growing difficulties in obtaining blood samples from a representative group of patients, as done in classic surveys, make it necessary to look for alternative methodologies which can provide information concerning the presence of infectious agents in a community. Though the results cannot be generalized to the population as a whole, the methodology used conveyed some knowledge regarding the circulation of hepatitis B virus. In addition, it makes much easier to obtain agreement from the participants, since it does not add any invasive procedure. Despite the limitations, this methodology may be helpful in epidemiological surveillance of infectious agents known as producing asymptomatic infections in much of the population.OBJETIVO: Estudar aspectos da epidemiologia da hepatite B em pessoas submetidas à coleta de sangue em unidades de saúde. MÉTODOS: Indivíduos dos quais se coletou sangue em unidades de saúde de Ribeirão Preto, independentemente do motivo, foram solicitados a fornecer uma quantidade adicional de material, obtida no momento da coleta e submetida à detecção de marcadores de hepatite B. Simultaneamente, por meio de questionário padronizado, foram obtidas informações de possíveis fatores de risco para a doença. Os dados foram analisados por meio de um modelo de regressão logística. RESULTADOS: As prevalências de HBsAg e de anti-HBcAg foram de 0,3% e 13,9%, respectivamente. Os fatores de risco associados à infecção foram: idade, residência na cidade há menos de um ano, antecedente de hepatite, exposição prévia a casas de correção e homo/bissexualismo masculino. CONCLUSÕES: Devido a dificuldades crescentes de obtenção de sangue de indivíduos sadios, essa pode ser uma alternativa para estudos que objetivem fornecer informações sobre a circulação de agentes infecciosos na população. Embora não se possa generalizar os dados obtidos pela metodologia usada, ela traz conhecimento referente à circulação do vírus de hepatite B

Deterministic diffusion fiber tracking improved by quantitative anisotropy

Diffusion MRI tractography has emerged as a useful and popular tool for mapping connections between brain regions. In this study, we examined the performance of quantitative anisotropy (QA) in facilitating deterministic fiber tracking. Two phantom studies were conducted. The first phantom study examined the susceptibility of fractional anisotropy (FA), generalized factional anisotropy (GFA), and QA to various partial volume effects. The second phantom study examined the spatial resolution of the FA-aided, GFA-aided, and QA-aided tractographies. An in vivo study was conducted to track the arcuate fasciculus, and two neurosurgeons blind to the acquisition and analysis settings were invited to identify false tracks. The performance of QA in assisting fiber tracking was compared with FA, GFA, and anatomical information from T 1-weighted images. Our first phantom study showed that QA is less sensitive to the partial volume effects of crossing fibers and free water, suggesting that it is a robust index. The second phantom study showed that the QA-aided tractography has better resolution than the FA-aided and GFA-aided tractography. Our in vivo study further showed that the QA-aided tractography outperforms the FA-aided, GFA-aided, and anatomy-aided tractographies. In the shell scheme (HARDI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 30.7%, 32.6%, and 24.45% of the false tracks, respectively, while the QA-aided tractography has 16.2%. In the grid scheme (DSI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 12.3%, 9.0%, and 10.93% of the false tracks, respectively, while the QA-aided tractography has 4.43%. The QA-aided deterministic fiber tracking may assist fiber tracking studies and facilitate the advancement of human connectomics. © 2013 Yeh et al

Complex Transition to Cooperative Behavior in a Structured Population Model

Cooperation plays an important role in the evolution of species and human societies. The understanding of the emergence and persistence of cooperation in those systems is a fascinating and fundamental question. Many mechanisms were extensively studied and proposed as supporting cooperation. The current work addresses the role of migration for the maintenance of cooperation in structured populations. This problem is investigated in an evolutionary perspective through the prisoner's dilemma game paradigm. It is found that migration and structure play an essential role in the evolution of the cooperative behavior. The possible outcomes of the model are extinction of the entire population, dominance of the cooperative strategy and coexistence between cooperators and defectors. The coexistence phase is obtained in the range of large migration rates. It is also verified the existence of a critical level of structuring beyond that cooperation is always likely. In resume, we conclude that the increase in the number of demes as well as in the migration rate favor the fixation of the cooperative behavior

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. RESULTS: There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P 0.05). Furthermore, changes in corticomotor plasticity were not related to changes in motor performance. CONCLUSION: These results indicate that tDCS induced behavioural changes in the non-dominant hand as a consequence of mechanisms associated with use-dependant cortical plasticity that is independent of the electrode arrangement