Correlations of projectile like fragments in heavy ion reactions at Fermi energy

Correlations between pairs of projectile-like fragments, emitted by the system ${^{16}O}+{^{197}Au}$ at the laboratory bombarding energy of 515 MeV, have been studied under two stipulated conditions: (1) at least one member of the pair is emitted at an angle less than the grazing angle for the system, (2) both the members of the pair are emitted at angles larger than the grazing angle. A surprisingly large difference, by more than an order of magnitude, is found between the correlations for the two cases. This observation could be explained on the basis of a simple semi-classical break up model. Further analysis of the variation of the charge correlation function with the difference in the nuclear charges of the correlated pair showed trends which are consistent with an "inelastic break up process", in which the projectile breaks up at the radius of contact, in such a way that, one fragment (preferably the lighter) is emitted to one side within the grazing angle, while the other orbits around the target nucleus for a while and emerges on the other side, at a negative scattering angle, much like in a deep inelastic scattering.Comment: 19 pages, 12 figures accepted by Eurp. Physics Journal

Metasubtract: an R‐package to analytically produce leave‐one‐out meta‐analysis GWAS summary statistics

SUMMARY: statistics from a meta-analysis of genome-wide association studies (meta-GWAS) can be used for many follow-up analyses. One valuable application is the creation of polygenic scores. However, if polygenic scores are calculated in a validation cohort that was part of the meta-GWAS consortium, this cohort is not independent and analyses will therefore yield inflated results. The R package 'MetaSubtract' was developed to subtract the results of the validation cohort from meta-GWAS summary statistics analytically. The statistical formulas for a meta-analysis were inverted to compute corrected summary statistics of a meta-GWAS leaving one (or more) cohort(s) out. These formulas have been implemented in MetaSubtract for different meta-analyses methods (fixed effects inverse variance or square root sample size weighted z-score) accounting for no, single or double genomic control correction. Results obtained by MetaSubtract correlate very well to those calculated using the traditional way, i.e. by performing a meta-analysis leaving out the validation cohort. In conclusion, MetaSubtract allows researchers to compute meta-GWAS summary statistics that are independent of the GWAS results of the validation cohort without requiring access to the cohort level GWAS results of the corresponding meta-GWAS consortium. AVAILABILITY AND IMPLEMENTATION: https://cran.r-project.org/web/packages/MetaSubtract. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Attenuation of leukocyte sequestration by selective blockade of PECAM-1 or VCAM-1 in murine endotoxemia

Background: Molecular mechanisms regulating leukocyte sequestration into the tissue during endotoxemia and/or sepsis are still poorly understood. This in vivo study investigates the biological role of murine PECAM-1 and VCAM-1 for leukocyte sequestration into the lung, liver and striated skin muscle. Methods: Male BALB/c mice were injected intravenously with murine PECAM-1 IgG chimera or monoclonal antibody (mAb) to VCAM-1 ( 3 mg/kg body weight); controls received equivalent doses of IgG2a ( n = 6 per group). Fifteen minutes thereafter, 2 mg/kg body weight of Salmonella abortus equi endotoxin was injected intravenously. At 24 h after the endotoxin challenge, lungs, livers and striated muscle of skin were analyzed for their myeloperoxidase activity. To monitor intravital leukocyte-endothelial cell interactions, fluorescence videomicroscopy was performed in the skin fold chamber model of the BALB/c mouse at 3, 8 and 24 h after injection of endotoxin. Results: Myeloperoxidase activity at 24 h after the endotoxin challenge in lungs (12,171 +/- 2,357 mU/g tissue), livers ( 2,204 +/- 238 mU/g) and striated muscle of the skin ( 1,161 +/- 110 mU/g) was significantly reduced in both treatment groups as compared to controls, with strongest attenuation in the PECAM-1 IgG treatment group. Arteriolar leukocyte sticking at 3 h after endotoxin (230 +/- 46 cells x mm(-2)) was significantly reduced in both treatment groups. Leukocyte sticking in postcapillary venules at 8 h after endotoxin ( 343 +/- 69 cells/mm(2)) was found reduced only in the VCAM-1-mAb-treated animals ( 215 +/- 53 cells/mm(2)), while it was enhanced in animals treated with PECAM-1 IgG ( 572 +/- 126 cells/mm(2)). Conclusion: These data show that both PECAM-1 and VCAM-1 are involved in endotoxin-induced leukocyte sequestration in the lung, liver and muscle, presumably through interference with arteriolar and/or venular leukocyte sticking. Copyright (C) 2004 S. Karger AG, Basel

Does health care save lives? Avoidable mortality revisited.

Does health care save lives? Commentators such as McKeown and Illich, writing in the 1960s, argued that it played very little part, and might even be harmful. However they were writing about a period when health care had relatively little to offer compared to today. Since then, several writers have described often quite substantial improvements in death rates from conditions for which effective interventions have been introduced. But the debate continues, with some arguing that health care is making an increasingly important impact on overall levels of health while others contend that it is in the realm of broader policies, such as education, transport and housing, that we should look to for future advances in health. Inevitably this is to a considerable extent a false dichotomy. Both are important. But how much does health care contribute to population health? One way in which this question has been addressed previously is to look at deaths that should not occur in the presence of effective and timely health care, so-called ‘avoidable’ mortality. However much of this work was undertaken in the 1980s and early 1990s, since when health care has advanced considerably. In addition, ‘avoidable’ deaths were often limited to those before, for example, the age of 65, a figure that seems inappropriately low in the light of life expectancies that are now about 80 in many countries. In this review we have traced the evolution of the concept of ‘avoidable’ mortality from its inception in the 1970s. We have undertaken a detailed methodological critique of this concept, examining questions of attribution, issues relating to comparisons over time and place, and relationships with other indicators of health service provision. To help future researchers we have produced a comprehensive, annotated review of the work that has been undertaken worldwide so far. We note that ‘avoidable’ mortality was never intended to be more than an indicator of potential weaknesses in health care that can then be investigated in more depth. We describe examples of where this approach has been successful, drawing attention to problems that might otherwise have been missed. In contrast, many of the critics of ‘avoidable’ mortality, or more specifically, mortality amenable to health care (amenable mortality), have asked that it do something it was not intended to do, to be a definitive source of evidence of differences in effectiveness of health care. Thus, it is not unexpected that studies seeking to link amenable mortality with health care resources have failed to do so, especially when undertaken within countries, although it is notable that where gross differences exist, as between western and eastern Europe, the gap in amenable mortality is especially high. For these reasons, it seems justifiable to continue and extend the extensive body of research that has already been undertaken to look at ‘avoidable’ mortality, updating the list of conditions included to reflect the changing scope of health care and extending the age limit to reflect increasing expectation of life. However it must be recognised that the concept of ‘avoidable’ mortality does have important limitations, relating to comparability of data, attribution of causes, and coverage of the range of health outcomes. Comparisons of health system performance are now firmly on the international policy agenda, especially since the publication of the 2000 World Health Report. Incorporation of concept of mortality amenable to medical care into the methodology used to generate the rankings of health systems in that report would be an advance on the current situation. We show how, within Europe, this would lead to different rankings from those based on overall disability adjusted life expectancy, which is used in the current rankings. However, any approach based on aggregate data would not address one of the major criticisms of such comparisons, that they do not indicate what needs to be done when faced with evidence of sub-optimal performance. This requires a more detailed analysis of the specific issues facing health systems. Here we propose a new method, in which analyses of amenable mortality identify areas of potential concern that are then examined in more detail by studying the processes and outcomes of care for tracer conditions, selected on the basis of their ability to assess a wide range of health system components. The second part of the review applies the refined method of amenable mortality analysis to patterns of mortality in the countries of the European Union over the past two decades. This shows that deaths that could be prevented by timely and effective care were still relatively common in many countries in 1980. Reductions in these deaths contributed substantially to the overall change in life expectancy between birth and age 75 during the 1980s. The largest contribution was from falling infant mortality but in some countries reductions in deaths among the middle aged was equally or even more important. These countries were Denmark, The Netherlands, the United Kingdom, France (for men) and Sweden (for women). In contrast, during the 1990s, reductions in amenable mortality made a somewhat smaller contribution to improved life expectancy, especially in the northern European countries. However they remained important in southern Europe, especially in Portugal and Greece, where the initial death rates had been higher. These findings provide clear evidence that improvements in access to effective health care have had a measurable impact in many countries during the 1980s and 1990s, in particular through reductions in infant mortality and in deaths among the middle aged and elderly, especially women. However the scale of impact has, to a considerable extent, reflected the starting point. Thus, those countries where infant mortality was relatively high at the beginning of the 1980s, and which had the greatest scope for improvement, such as Greece and Portugal, unsurprisingly saw the greatest reductions in amenable mortality in infancy. In contrast, in countries with infant mortality rates that had already reached very low rates by the beginning of the 1990s, such as Sweden, the scope for further improvement was small. Similarly, the scope for improvement in amenable deaths in adulthood was greatest in those countries where initial rates were highest. The corollary of this is that as rates fall in all countries, the extent of variation decreases. As a consequence, it seems likely that, in the 21st century, the ability to compare health system performance using mortality data at the aggregate level is likely to be limited, simply because the differences will be relatively small. This does not, however, mean that there is not scope for analyses that use amenable mortality rates to screen for potential problems that can then be explored in more depth. It also does not exclude the use of amenable mortality to gain new insights into inequalities in access to care within populations