Elevated PAI-1 is associated with poor clinical outcomes in pediatric patients with acute lung injury.

PurposeDeposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI.Design/methodsWe measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI.ResultsA total of 94 patients were included. The median age was 3.2 years (range 16 days-18 years), the PaO(2)/F(i)O(2) was 141 +/- 72 (mean +/- SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness.ConclusionsHigher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI

Evidence for long-term variability in the ultra high energy photon flux from Cygnus X-3

A time-correlation analysis of atmospheric Cerenkov pulses by a wide-angle photomultiplier system was previously shown to have present in it a nonrandom component which seemed associated with the Right Ascension (RA) range approx. 20+or-04h. A recent examination of multi-muon events recorded by a photon-decay detector shows a similar time-dependent effect, closely matching the previous results, supporting the suggestion that the effect is of cosmic origin. However, even though Cyg. X-3 lies well inside the region of peak intensity, it does not seem possible to ascribe to it the whole effect, for the implied photon flux appears too large to be reconciled to various gamma-ray measurements of Cyg. X-3. The original data were subjected to a phase-histogram analysis and it as found that only 2.5% of overall recorded data are compatible with a phase-dependent emission from Cyg. X-3. Assuming these events to be gamma rays yields a detected flux of (2.6 + or - 0.3) x 10 to the minus 12th power gamma cm -2s-1 above 5 x 10 to the 14th power eV. Comparing this value with more recent ultra high energy (UHE) photon data from the same source, it is suggested that the available data generally favor a long-term reduction in the Cyg. X-3 inferred luminosity ( 10 to the 13th power eV) by a factor of (1.8 + or - 0.3) per year

Periodic gamma-ray emissions from Geminga at or = 10(12) eV

Analysis of data from an atmospheric Cerenkov telescope indicated the periodic emission of gamma rays of energy 10 to the 12th power eV, at 60.25 second period, from 2CG 195+4. The gamma ray flux at 99% confidence level is estimated to be 9.5 x 10 to 12 photons/sq cm/s

Effect of some physiological factors and pharmacological agents on left ventricular function in man

In recent years, significant conceptual advances have helped to formulate a broad scheme of the mechanisms which regulate ventricular function. Likewise, methodological advances now enable a wide range of haemodynamic measurements to be made in human subjects, with reasonable precision and relative ease. It has thus become possible to relate changes in several haemodynamic variables recorded simultaneously. Although it is still not feasible to estimate the functional competence of the left ventricle (or the heart as a whole) in absolute terns, the qualitative changes can now be assessed with greater confidence. The studies reported here were designed to investigate the changes in left ventricular performance in man during dynamic exercise and following the administration of two pharmacological agents used in clinical practice. The two pharmacological agents, morphine and propranolol, were selected for different reasons. Morphine was chosen in order to determine the circulatory effects that may be attributable to the drug and thereby provide, if possible, a rational basis for its use in the treatment of acute left ventricular failure. The therapeutic efficacy of morphine in this disorder is widely acknowledged, but to date no attempts, other than the one reported here, seem to have been made, (or at least none reported) to delineate the precise mode of action of this drug in the treatment of acute left ventricular failure. A detailed investigation was, therefore, designed to study the haemodynamic changes, with particular reference to left ventricular function, following an intravenous injection of morphine in therapeutic amounts. The report on this study forms the subject matter of Chapter IV. The other pharmacological agent used was propranolol, which is an adrenergic JS-receptor blocking agent. It is generally agreed that the sympathetic nervous system (and the adrenal medulla) dominates in the regulation of the cardiovascular response during dynamic exercise. Since the sympathetic influence (both chronotropic and inotropic) on the heart is mediated through ^-receptors (Ahlquist, 1948), it was felt that with the help of propranolol it should be possible to assess the importance of the sympatho-adrenal system in the regulation of cardiac performance during dynamic exercise. A study was, therefore, designed to investigate the haemodynamic changes during supine leg exercise before and after ^-adrenergic block with propranolol. The report on this investigation is presented in Chapter V. An assessment of the changes in left ventricular performance rg supine leg exercise, which has been used as the standard physiological stimulus, was also undertaken in the course of the study reported in Chapter V. In Chapter I a summary of the present concepts (and some controversies) regarding the regulation cf left ventricular performance is presented. Also Included in this chapter is additional information relevant to the understanding of left ventricular function and the methods that may be used to assess this. A detailed critique of the methods used is given in Chapter II. Since it was not feasible to measure either end-diastolic fibre length or end-diastolic pressure in the left ventricle, the mean pulmonary wedge pressure has been used as an indirect estimate of left ventricular end-diastolic pressure and hence end-diastolic fibre length. It was felt necessary to determine the confidence with which the mean pulmonary wedge pressure could be used as an estimate of left ventricular end-diastolic pressure. To this end, therefore, another study was designed and the report on this is presented in Chapter III. A brief comment on the statistical methods used is given in the appendix. Since this thesis is being presented In two volumes, it was thought best, for ease of reference, to Include all the tables and references in the companion volume

Political Movement Through Cultural Identity: Lessons from the Présence Africaine

The Présence Africaine journal was unlike any of the time. Founded in Paris in 1947, its mission centered the expression of African cultures that had been suppressed under French colonial rule. The writers did not share a race or nationality but were united by a shared purpose of creating literary discourse around the colonization of Africa and the struggles of the pan-African movement. The founder, Alioune Diop, was a Senegalese professor who promoted a unique approach to political change. He was aware of the stark cultural losses that the French colonization of Africa was causing and saw the colonial suppression of African culture and its exclusion from the idea of “modernity” as a means of control by France. This paper explores the journal’s unique approach to African decolonization through cultural expression. Keywords: Colonialism, culture, Africa, journalism, art, Alioune Diop, Frantz Fanon, France, Présence Africaine, decolonization, dialogue Part of the panel: Exploring Global Cultural IdentitiesModerator: Professor Bright Alozi

Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie