PET Molecular Imaging of Hypoxia in Ischemic Stroke: An Update.

Hypoxia, a condition of insufficient oxygen availability to support metabolism, occurs when the vascular supply is interrupted, as in stroke. The identification of the hypoxic and viable tissue in stroke as compared with irreversible lesions (necrosis) has relevant implications for the treatment of ischemic stroke. Traditionally, imaging by positron emission tomography (PET), using 15O-based radiotracers, allowed the measurement of perfusion and oxygen extraction in stroke, providing important insights in its pathophysiology. However, these multitracer evaluations are of limited applicability in clinical settings. More recently, specific tracers have been developed, which accumulate with an inverse relationship to oxygen concentration and thus allow visualizing the hypoxic tissue non invasively. These belong to two main groups: nitroimidazoles, and among these the 18F-Fluoroimidazole (18F-FMISO) is the most widely used, and the copper-based tracers, represented mainly by Cu-ATSM. While these tracers have been at first developed and tested in order to image hypoxia in tumors, they have also shown promising results in stroke models and preliminary clinical studies in patients with cardiovascular disorders, allowing the detection of hypoxic tissue and the prediction of the extent of subsequent ischemia and clinical outcome. These tracers have therefore the potential to select an appropriate subgroup of patients who could benefit from a hypoxia-directed treatment and provide prognosis relevant imaging. The molecular imaging of hypoxia made important progress over the last decade and has a potential for integration into the diagnostic and therapeutic workup of patients with ischemic stroke.

An episode mimicking a versive seizure in acute bilateral pontine stroke.

Pontine ischemia usually results in focal deficits such as hemiparesis, facial palsy, dysarthria, disorders of eye movements or vertigo. Although rarely described, involuntary abnormal movements and "convulsions" due to pontine lesions can also occur. Here we describe a 67-year-old woman with hypertension who presented with a tonic movement mimicking a versive seizure in the acute phase of bilateral pontine ischemia. Post-stroke movement disorders are well known. They are usually associated with supratentorial lesions and rarely occur in the acute phase, but "seizure-like" episodes can be seen in pontine ischemia. Awareness of this rare phenomenon is useful for the management of acute stroke patients.

PFO closure vs. medical therapy in cryptogenic stroke or transient ischemic attack: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: This study aims to assess whether patent foramen ovale (PFO) closure is superior to medical therapy in preventing recurrence of cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We searched PubMed for randomized trials which compared PFO closure with medical therapy in cryptogenic stroke/TIA using the items: "stroke or cerebrovascular accident or TIA" and "patent foramen ovale or paradoxical embolism" and "trial or study". RESULTS: Among 650 potentially eligible articles, 3 were included including 2303 patients. There was no statistically significant difference between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs. 2.94% respectively, OR: 0.64, 95%CI: 0.37-1.10), TIA (2.08% vs. 2.42% respectively, OR: 0.87, 95%CI: 0.50-1.51) and death (0.60% vs. 0.86% respectively, OR: 0.71, 95%CI: 0.28-1.82). In subgroup analysis, there was significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs. medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21-0.98, relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to-treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy, OR: 0.93, 95%CI: 0.45-2.11). Compared to medical therapy, the number of patients with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60-5.42) but higher in the STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47-27.84). CONCLUSIONS: This meta-analysis does not support PFO closure for secondary prevention with unselected devices in cryptogenic stroke/TIA. In subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset AF, however. This observation should be confirmed in further trials using inclusion criteria for patients with high likelihood of PFO-related stroke recurrence.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Spatial modelling of biodiversity at the community level

1. Statistical modelling is often used to relate sparse biological survey data to remotely derived environmental predictors, thereby providing a basis for predictively mapping biodiversity across an entire region of interest. The most popular strategy for such modelling has been to model distributions of individual species one at a time. Spatial modelling of biodiversity at the community level may, however, confer significant benefits for applications involving very large numbers of species, particularly if many of these species are recorded infrequently. 2. Community-level modelling combines data from multiple species and produces information on spatial pattern in the distribution of biodiversity at a collective community level instead of, or in addition to, the level of individual species. Spatial outputs from community-level modelling include predictive mapping of community types (groups of locations with similar species composition), species groups (groups of species with similar distributions), axes or gradients of compositional variation, levels of compositional dissimilarity between pairs of locations, and various macro-ecological properties (e.g. species richness). 3. Three broad modelling strategies can be used to generate these outputs: (i) 'assemble first, predict later', in which biological survey data are first classified, ordinated or aggregated to produce community-level entities or attributes that are then modelled in relation to environmental predictors; (ii) 'predict first, assemble later', in which individual species are modelled one at a time as a function of environmental variables, to produce a stack of species distribution maps that is then subjected to classification, ordination or aggregation; and (iii) 'assemble and predict together', in which all species are modelled simultaneously, within a single integrated modelling process. These strategies each have particular strengths and weaknesses, depending on the intended purpose of modelling and the type, quality and quantity of data involved. 4. Synthesis and applications. The potential benefits of modelling large multispecies data sets using community-level, as opposed to species-level, approaches include faster processing, increased power to detect shared patterns of environmental response across rarely recorded species, and enhanced capacity to synthesize complex data into a form more readily interpretable by scientists and decision-makers. Community-level modelling therefore deserves to be considered more often, and more widely, as a potential alternative or supplement to modelling individual species.

Bacterial community structure of a pesticide-contaminated site and assessment of changes induced in community structure during bioremediation.

The introduction of culture-independent molecular screening techniques, especially based on 16S rRNA gene sequences, has allowed microbiologists to examine a facet of microbial diversity not necessarily reflected by the results of culturing studies. The bacterial community structure was studied for a pesticide-contaminated site that was subsequently remediated using an efficient degradative strain Arthrobacter protophormiae RKJ100. The efficiency of the bioremediation process was assessed by monitoring the depletion of the pollutant, and the effect of addition of an exogenous strain on the existing soil community structure was determined using molecular techniques. The 16S rRNA gene pool amplified from the soil metagenome was cloned and restriction fragment length polymorphism studies revealed 46 different phylotypes on the basis of similar banding patterns. Sequencing of representative clones of each phylotype showed that the community structure of the pesticide-contaminated soil was mainly constituted by Proteobacteria and Actinomycetes. Terminal restriction fragment length polymorphism analysis showed only nonsignificant changes in community structure during the process of bioremediation. Immobilized cells of strain RKJ100 enhanced pollutant degradation but seemed to have no detectable effects on the existing bacterial community structure.

Implicit attitudes and self-concepts towards transgression and aggression: Differences between male community and offender adolescents, and associations with psychopathic traits.

Research suggests that implicit attitudes play a key role in the occurrence of antisocial behaviours. This study assessed implicit attitudes and self-concepts related to aggression and transgression in community and offender adolescents, using a new set of Implicit Association Tests (IATs), and examined their association with of psychopathic traits. Thirty-six offenders and 66 community adolescents performed 4 IATs assessing 1) implicit attitudes about a) aggression and b) transgression as good, and 2) implicit self-concepts about a) aggression and b) transgression as self-descriptive. They filled in self-report questionnaires: the Youth Psychopathic Traits Inventory, the Child Behaviour Checklist, and explicit measures of their attitudes and self-concepts towards transgression and aggression. Results showed few differences between community and offender adolescents on implicit attitudes and self-concepts, and unexpected negative associations between some implicit attitudes and psychopathic traits, while the association was positive for the corresponding explicit attitudes. Possible explanations of these findings are discussed.

Personal indebtedness, community characteristics and theft crimes

Becker (1968) and Stigler (1970) provide the germinal works for an economic analysis of crime, and their approach has been utilised to consider the response of crime rates to a range of economic, criminal and socioeconomic factors. Until recently however this did not extend to a consideration of the role of personal indebtedness in explaining the observed pattern of crime. This paper uses the Becker (1968) and Stigler (1970) framework, and extends to a fuller consideration of the relationship between economic hardship and theft crimes in an urban setting. The increase in personal debt in the past decade has been significant, which combined with the recent global recession, has led to a spike in personal insolvencies. In the context of the recent recession it is important to understand how increases in personal indebtedness may spillover into increases in social problems like crime. This paper uses data available at the neighbourhood level for London, UK on county court judgments (CCJ's) granted against residents in that neighbourhood, this is our measure of personal indebtedness, and examines the relationship between a range of community characteristics (economic, socio-economic, etc), including the number of CCJ's granted against residents, and the observed pattern of theft crimes for three successive years using spatial econometric methods. Our results confirm that theft crimes in London follow a spatial process, that personal indebtedness is positively associated with theft crimes in London, and that the covariates we have chosen are important in explaining the spatial variation in theft crimes. We identify a number of interesting results, for instance that there is variation in the impact of covariates across crime types, and that the covariates which are important in explaining the pattern of each crime type are largely stable across the three periods considered in this analysis.

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.