New England Medical Center Posterior Circulation Stroke Registry II. Vascular Lesions

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, the extracranial (ECVA) and intracranial vertebral arteries (ICVA) were the commonest sites of severe occlusive disease followed by the basilar artery (BA). Severe occlusive lesions were found in >1 large artery in 148 patients; 134 had unilateral or bilateral severe disease at one arterial location. Single arterial site occlusive disease occurred most often in the ECVA (52 patients, 15 bilateral) followed by the ICVA (40 patients, 12 bilateral) and the BA (46 patients). Involvement of the ICVAs and the BA was very common and some patients also had ECVA lesions. Hypertension, smoking, and coronary and peripheral vascular disease were most prevalent in patients with extracranial disease while diabetes and hyperlipidemia were more common when occlusive lesions were only intracranial. Intra-arterial embolism was the most common mechanism of brain infarction in patients with ECVA and ICVA occlusive disease. ICVA occlusive lesions infrequently caused infarction limited to the proximal territory (medulla and posterior inferior cerebellum). BA lesions most often caused infarcts limited to the middle posterior circulation territory (pons and anterior inferior cerebellum). Posterior cerebral artery occlusive lesions were predominantly embolic. Penetrating artery disease caused mostly pontine and thalamic infarcts. Prognosis was poorest in patients with BA disease. The best prognosis surprisingly was in patients who had multiple arterial occlusive lesions; they often had position-sensitive transient ischemic attacks during months or years

New England Medical Center Posterior Circulation Stroke Registry: I. Methods, Data Base, Distribution of Brain Lesions, Stroke Mechanisms, and Outcomes

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs before strokes, and 16% had only posterior circulation TIAs. Embolism was the commonest stroke mechanism accounting for 40% of cases (24% cardiac origin, 14% arterial origin, 2% had potential cardiac and arterial sources). In 32%, large artery occlusive lesions caused hemodynamic brain infarction. Stroke mechanisms in the posterior and anterior circulation are very similar. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes), while the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Infarcts that included the distal territory were twice as common as those that included the proximal or middle territories. Most distal territory infarcts were attributable to embolism. Thirty day mortality was low (3.6%). Embolic stroke mechanism, distal territory location, and basilar artery occlusive disease conveyed the worst prognosis

Platelet-Activating Factor Induces TLR4 Expression in Intestinal Epithelial Cells: Implication for the Pathogenesis of Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF), bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs) are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC) lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line). PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC

Star Formation in Galaxies Along the Hubble Sequence

Observations of star formation rates (SFRs) in galaxies provide vital clues to the physical nature of the Hubble sequence, and are key probes of the evolutionary properties of galaxies. The focus of this review is on the broad patterns in the star formation properties of galaxies along the Hubble sequence, and their implications for understanding galaxy evolution and the physical processes that drive the evolution. Star formation in the disks and nuclear regions of galaxies are reviewed separately, then discussed within a common interpretive framework. The diagnostic methods used to measure SFRs are also reviewed, and a self-consistent set of SFR calibrations is presented as an aid to workers in the field.Comment: 41 pages, with 9 figures. To appear in Volume 36 of the Annual Review of Astronomy and Astrophysic

Gram Negative Bacteria Are Associated with the Early Stages of Necrotizing Enterocolitis

Introduction: Necrotizing enterocolitis (NEC) affects 5–10 % of infants born weighing less than 1500 g. Most models of NEC recapitulate late-stage disease with gut necrosis and elevated inflammatory mediators. Evaluation of NEC at earlier, less lethal stages of disease will allow investigation of initial disease triggers and may advance our understanding of temporal relationships between factors implicated in NEC pathogenesis. In this manuscript, we describe our investigation of early NEC and test the hypothesis that bacteria and inflammatory mediators differ between animals with early NEC and disease fre

Branched Chain Fatty Acids Reduce the Incidence of Necrotizing Enterocolitis and Alter Gastrointestinal Microbial Ecology in a Neonatal Rat Model

Branched chain fatty acids (BCFA) are found in the normal term human newborn's gut, deposited as major components of vernix caseosa ingested during late fetal life. We tested the hypothesis that premature infants' lack of exposure to gastrointestinal (GI) BCFA is associated with their microbiota and risk for necrotizing enterocolitis (NEC) using a neonatal rat model.Pups were collected one day before scheduled birth. The pups were exposed to asphyxia and cold stress to induce NEC. Pups were assigned to one of three experimental treatments. DF (dam-fed); Control, hand-fed rat milk substitute; BCFA, hand-fed rat milk substitute with 20%w/w BCFA. Total fat was equivalent (11%wt) for both the Control and BCFA groups. Cecal microbiota were characterized by 16S rRNA gene pyrosequencing, and intestinal injury, ileal cytokine and mucin gene expression, interleukin-10 (IL-10) peptide immunohistochemistry, and BCFA uptake in ileum phospholipids, serum and liver were assessed.NEC incidence was reduced by over 50% in the BCFA group compared to the Control group as assessed in ileal tissue; microbiota differed among all groups. BCFA-fed pups harbored greater levels of BCFA-associated Bacillus subtilis and Pseudomonas aeruginosa compared to Controls. Bacillus subtilis levels were five-fold greater in healthy pups compared to pups with NEC. BCFA were selectively incorporated into ileal phospholipids, serum and liver tissue. IL-10 expression increased three-fold in the BCFA group versus Controls and no other inflammatory or mucosal mRNA markers changed.At constant dietary fat level, BCFA reduce NEC incidence and alter microbiota composition. BCFA are also incorporated into pup ileum where they are associated with enhanced IL-10 and may exert other specific effects

Representation of the verb's argument-structure in the human brain

<p>Abstract</p> <p>Background</p> <p>A verb's argument structure defines the number and relationships of participants needed for a complete event. One-argument (intransitive) verbs require only a subject to make a complete sentence, while two- and three-argument verbs (transitives and ditransitives) normally take direct and indirect objects. Cortical responses to verbs embedded into sentences (correct or with syntactic violations) indicate the processing of the verb's argument structure in the human brain. The two experiments of the present study examined whether and how this processing is reflected in distinct spatio-temporal cortical response patterns to isolated verbs and/or verbs presented in minimal context.</p> <p>Results</p> <p>The magnetoencephalogram was recorded while 22 native German-speaking adults saw 130 German verbs, presented one at a time for 150 ms each in experiment 1. Verb-evoked electromagnetic responses at 250 – 300 ms after stimulus onset, analyzed in source space, were higher in the left middle temporal gyrus for verbs that take only one argument, relative to two- and three-argument verbs. In experiment 2, the same verbs (presented in different order) were preceded by a proper name specifying the subject of the verb. This produced additional activation between 350 and 450 ms in or near the left inferior frontal gyrus, activity being larger and peaking earlier for one-argument verbs that required no further arguments to form a complete sentence.</p> <p>Conclusion</p> <p>Localization of sources of activity suggests that the activation in temporal and frontal regions varies with the degree by which representations of an event as a part of the verbs' semantics are completed during parsing.</p

Reciprocity as a foundation of financial economics

This paper argues that the subsistence of the fundamental theorem of contemporary financial mathematics is the ethical concept ‘reciprocity’. The argument is based on identifying an equivalence between the contemporary, and ostensibly ‘value neutral’, Fundamental Theory of Asset Pricing with theories of mathematical probability that emerged in the seventeenth century in the context of the ethical assessment of commercial contracts in a framework of Aristotelian ethics. This observation, the main claim of the paper, is justified on the basis of results from the Ultimatum Game and is analysed within a framework of Pragmatic philosophy. The analysis leads to the explanatory hypothesis that markets are centres of communicative action with reciprocity as a rule of discourse. The purpose of the paper is to reorientate financial economics to emphasise the objectives of cooperation and social cohesion and to this end, we offer specific policy advice

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Adipose derived pericytes rescue fractures from a failure of healing – non-union

Atrophic non-union is attributed to biological failure of the fracture repair process. It occurs in up to 10% of fractures, results in significant morbidity to patients, and treatment often requires complex reconstructive procedures. We tested the ability of human bone derived marrow mesenchymal stem cells (MSC), and human adipose derived pericytes (the native ancestor of the MSC) delivered percutaneously to the fracture gap to prevent the formation of atrophic non-union in a rat model. At eight weeks, 80% of animals in the cell treatment groups showed evidence of bone healing compared to only 14% of those in the control group. Radiographic parameters showed significant improvement over the eight-week period in the cell treatment groups, and histology confirmed bone bridges at the fracture gap in the both treatment groups. The quality of bone produced and its biomechanical properties were significantly enhanced in both treatment groups. The results from this study demonstrate that MSC and pericytes have significant bone regeneration potential in an atrophic non-union model. These cells may have a role in the prevention of atrophic non-union and could enable a paradigm shift in the treatment of fractures at high risk of failing to heal and developing non-union