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Selected AbstractsMANAGEMENT OF THE BILE DUCT STONE: CURRENT SITUATION IN JAPANDIGESTIVE ENDOSCOPY, Issue 2010Ichiro Yasuda Endoscopic treatment is now recognized as the standard treatment for common bile duct stones worldwide. Endoscopic treatment routinely involves endoscopic sphincterotomy in most countries including Japan and endoscopic papillary balloon dilation is also a widely used alternative to endoscopic sphincterotomy in Japan. Surgery in any form, including laparoscopic surgery, is mainly performed when endoscopic treatments are unsuccessful or unfavorable. Other therapeutic modalities considered under certain circumstances include lithotripsy under the guidance of percutaneous transhepatic cholangioscopy, peroral cholangioscopy, or enteroscopy; electrohydraulic lithotripsy or laser lithotripsy; and extracorporeal shock-wave lithotripsy. [source] A one-dimensional model for simulating armouring and erosion on hillslopes: 2.EARTH SURFACE PROCESSES AND LANDFORMS, Issue 10 2007Long term erosion, armouring predictions for two contrasting mine spoils Abstract This paper investigates the dynamics of soil armouring as a result of fluvial erosion for a non-cohesive sandy gravel spoil from the Ranger Mine, Australia, and a cohesive silt loam spoil from the Northparkes Mine, Australia, using a model for hillslope soil armouring. These long term predictions concentrate on the temporal and spatial changes of the spoil grading and erosion over 100,200 years for the flat cap regions (1,2%) and steep batter edges (10,30%) typically encountered on waste rock dumps. The existence of a significant rock fragment fraction in the Ranger spoil means that it armours readily, while Northparkes does not. For Ranger the waste rock showed reductions in (1) cumulative erosion of up to 81% from that obtained by extrapolating the initial erosion rate out 100 years and (2) the erosion/year by more than 10-fold. For Northparkes reductions were less marked, with the maximum reduction in erosion/year being 37% after 200 years. For Ranger the reductions were greatest and fastest for intermediate gradient hillslopes. For the steepest hillslopes the armouring decreased because the flow shear stresses were large enough to mobilize all material in the armour layer. Model uncertainty was assessed with probabilistic confidence limits demonstrating that these erodibility reductions were statistically significant. A commonly used hillslope erosion model (sediment flux = ,1 discharge m1 slope n1) was fitted to these predictions. The erodibility, ,1, and m1 decreased with time, which was consistent with our physical intuition about armouring. At Ranger the parameter m1 asymptoted to 1·5,1·6 while at Northparkes it asymptoted to 1·2,1·3. At Ranger transient spatial trends in armouring led to a short term (50,200 years in the future) reduction in n1, to below zero under certain circumstances, recovering to an asymptote of about 0·5,1. At Northparkes n1 asymptoted to about 0·6, with no negative transients predicted. The m1 and n1 parameters predicted for Ranger were shown to be consistent with field data from a 10-year-old armoured hillslope and consistent with published relationships between erodibility and rock content for natural hillslopes. Copyright © 2007 John Wiley & Sons, Ltd. [source] Adaptive Offspring Sex Ratio Depends on Male Tail Length in the GuppyETHOLOGY, Issue 11 2006Kenji Karino A biased sex ratio in a brood is considered to be an adaptive strategy under certain circumstances. For example, if the expected reproductive success of one sex is greater than that of the other, parents should produce more offspring of the former sex than the latter. A previous study has documented that in the guppy, Poecilia reticulata, the female offspring of males possessing proportionally longer tails exhibit smaller body sizes and show decreased reproductive outputs than those of males having shorter tails. On the other hand, the total lengths of the male offspring of the long-tailed males are larger because of their longer tails; consequently, they exhibit greater sexual attractiveness to females. Therefore, it has been hypothesized that this asymmetry in the expected reproductive success between the male and female offspring of long-tailed males may result in a biased sex ratio that is dependent on the tail lengths of their fathers. This hypothesis was tested in the present study. The results showed that the females that mated with long-tailed males produced more male offspring than those that mated with short-tailed males. Logistic regression analysis showed that the ratio of tail length to the standard length of the fathers is a determinant factor of the sex of their offspring. These results suggest that the manipulation of the offspring sex ratios by parents enhances the overall fitness of the offspring. [source] Memory, Trauma, and Embodied Distress: The Management of Disruption in the Stories of Cambodians in ExileETHOS, Issue 3 2000Professor Gay Becker Embodied memories of terror and violence create new meaning and reorder the world, but in doing so they encompass the inexplicable aspects of cultural processes that have allowed the world one lives in to become an unspeakable place, hostile and death-ridden. In this article, we examine the narratives of Cambodian refugees'experiences of the Khmer Rouge regime against the backdrop of an ethnographic study of older Cambodians' lives in an inner-city neighborhood. The stories from this study of 40 Cambodians between the ages of 50 and 79 illustrate the relationship between bodily distress and memory, and between personal history and collective experience. These narratives reveal how people strive to create continuity in their lives but under certain circumstances are unable to do so. [source] New insights into the pathophysiology of diabetic nephropathy: from haemodynamics to molecular pathologyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2004G. Wolf Abstract Although debated for many years whether haemodynamic or structural changes are more important in the development of diabetic nephropathy, it is now clear that these processes are interwoven and present two sides of one coin. On a molecular level, hyperglycaemia and proteins altered by high blood glucose such as Amadori products and advanced glycation end-products (AGEs) are key players in the development of diabetic nephropathy. Recent evidence suggests that an increase in reactive oxygen species (ROS) formation induced by high glucose-mediated activation of the mitochondrial electron-transport chain is an early event in the development of diabetic complications. A variety of growth factors and cytokines are then induced through complex signal transduction pathways involving protein kinase C, mitogen-activated protein kinases, and the transcription factor NF-,B. High glucose, AGEs, and ROS act in concert to induce growth factors and cytokines. Particularly, TGF-, is important in the development of renal hypertrophy and accumulation of extracellular matrix components. Activation of the renin-angiotensin system by high glucose, mechanical stress, and proteinuria with an increase in local formation of angiotensin II (ANG II) causes many of the pathophysiological changes associated with diabetic nephropathy. In fact, it has been shown that angiotensin II is involved in almost every pathophysiological process implicated in the development of diabetic nephropathy (haemodynamic changes, hypertrophy, extracellular matrix accumulation, growth factor/cytokine induction, ROS formation, podocyte damage, proteinuria, interstitial inflammation). Consequently, blocking these deleterious effects of ANG II is an essential part of every therapeutic regiment to prevent and treat diabetic nephropathy. Recent evidence suggests that regression of diabetic nephropathy could be achieved under certain circumstances. [source] Choice versus sensitivity: Party reactions to public concernsEUROPEAN JOURNAL OF POLITICAL RESEARCH, Issue 6 2004Michael D. McDonald Under certain circumstances, however, party convergence on these may preclude electoral choice, thus creating conflict between two democratic ,goods'. We examine possible tradeoffs between choice and responsiveness, and see which actually occur in 16 postwar democracies. Party policy positions turn out to be more strongly related to party ideology than popular concerns, thus privileging differentiation and choice over sensitivity and responsiveness. Implications for democratic theory and practice are considered. [source] Testing the group polarization hypothesis by using logit modelsEUROPEAN JOURNAL OF SOCIAL PSYCHOLOGY, Issue 1 2002María F. Rodrigo This paper focuses on methodological aspects of group polarization research and has two well-defined parts. The first part presents a methodological overview of group polarization research together with an examination of the inadequacy, under certain circumstances, of the traditional parametric approach usually used to test this phenomenon based on pre-test/post-test means comparison across groups. It is shown that this approach will produce masks effects when groups are heterogeneous with regard to the observed change from pre-test to post-test. The second part suggests an alternative methodological approach based on logit models for the analysis of contingency tables from a categorization of the variable ,kind of shift'. This approach is illustrated and compared with the parametric approach with a simulated data set. Copyright © 2002 John Wiley & Sons, Ltd. [source] The Jurisprudence of Constitutional Conflict: Constitutional Supremacy in Europe before and after the Constitutional TreatyEUROPEAN LAW JOURNAL, Issue 3 2005Mattias Kumm With the inclusion in the recently adopted Constitutional Treaty of a clause explicitly confirming the ,primacy of EU Law' appearances suggest that the EU is about to establish a characteristic of mature, vertically integrated, federal states such as the USA. This article argues that this view is mistaken. It develops a comprehensive jurisprudential framework for addressing constitutional conflicts, ,Constitutionalism Beyond the State' (CBC). CBS detaches the discussion of supremacy and constitutional conflict from a statist framework; provides a jurisprudential account that explains and justifies the highly differentiated, context-sensitive and dynamic set of conflict rules that national courts have in the past adopted; and provides the lacking theoretical basis for the more attractive, but undertheorised sui generis accounts of European constitutional practice that have recently gained ground in the literature. CBS provides a jurisprudentially grounded reconstructive account of why the issue of constitutional conflict is as rich and complicated in Europe as it is and why it is likely to remain so even if the Constitutional Treaty is ratified. The article then goes on to make concrete proposals addressed to national constitutional courts and the Court of Juctise respectively about how, in application of the developed approach, constitutional conflicts ought to be addressed doctrinally. It includes a proposal to read the new ,constitutional identity' clause as authorising Member States as a matter of EU Law to set aside EU Law on constitutional grounds under certain circumstances. [source] RAPID ANTAGONISTIC COEVOLUTION BETWEEN PRIMARY AND SECONDARY SEXUAL CHARACTERS IN HORNED BEETLESEVOLUTION, Issue 9 2008Harald F. Parzer Different structures may compete during development for a shared and limited pool of resources to sustain growth and differentiation. The resulting resource allocation trade-offs have the potential to alter both ontogenetic outcomes and evolutionary trajectories. However, little is known about the evolutionary causes and consequences of resource allocation trade-offs in natural populations. Here, we explore the significance of resource allocation trade-offs between primary and secondary sexual traits in shaping early morphological divergences between four recently separated populations of the horned beetle Onthophagus taurus as well as macroevolutionary divergence patterns across 10 Onthophagus species. We show that resource allocation trade-offs leave a strong signature in morphological divergence patterns both within and between species. Furthermore, our results suggest that genital divergence may, under certain circumstances, occur as a byproduct of evolutionary changes in secondary sexual traits. Given the importance of copulatory organ morphology for reproductive isolation our findings begin to raise the possibility that secondary sexual trait evolution may promote speciation as a byproduct. We discuss the implications of our results on the causes and consequences of resource allocation trade-offs in insects. [source] ALLEE EFFECT AND SELF-FERTILIZATION IN HERMAPHRODITES: REPRODUCTIVE ASSURANCE IN DEMOGRAPHICALLY STABLE POPULATIONSEVOLUTION, Issue 12 2004Pierre-Olivier Cheptou Abstract The fact that selfing increases seed set (reproductive assurance) has often been put forward as an important selective force for the evolution of selfing. However, the role of reproductive assurance in hermaphroditic populations is far from being clear because of a lack of theoretical work. Here, I propose a theoretical model that analyzes selffertilization in the presence of reproductive assurance. Because reproductive assurance directly influences the per capita growth rate, I developed an explicit demographic model for partial selfers in the presence of reproductive assurance, specifically when outcrossing is limited by the possibility of pollen transfer (Allee effect). Mating system parameters are derived as a function of the underlying demographical parameters. The functional link between population demography and mating system parameters (reproductive assurance, selfing rate) can be characterized. The demographic model permits the analysis of the evolution of self-fertilization in stable populations when reproductive assurance occurs. The model reveals some counterintuitive results such as the fact that increasing the fraction of selfed ovules can, in certain circumstances, increase the fraction of outcrossed ovules. Moreover, I demonstrate that reproductive assurance per se cannot account for the evolution of stable mixed selfing rates. Also, the model reveals that the extinction of outcrossing populations depends on small changes in population density (ecological perturbations), while the transition from outcrossing to selfing can, in certain cases, lead the population to extinction (evolutionary suicide). More generally, this paper highlights the fact that self-fertilization affects both the dynamics of individuals and the dynamics of selfing genes in hermaphroditic populations. [source] Cryptic variation in butterfly eyespot development: the importance of sample size in gene expression studiesEVOLUTION AND DEVELOPMENT, Issue 1 2007Robert D. Reed SUMMARY Previous studies have shown that development can be robust to variation in parameters such as the timing or level of gene expression. This leads to the prediction that natural populations should be able to host developmental variation that has little phenotypic effect. Cryptic variation is of particular interest because it can result in selectable phenotypes when "released" by environmental or genetic factors. Currently, however, we have little idea of how variation is distributed between genes or over time in pattern formation processes. Here we survey expression of Notch (N), Spalt (Sal), and Engrailed (En) during butterfly eyespot determination to better understand how pattern formation may vary within a population. We observed substantial heterochronic variance in the progress of spatial expression patterns for all three proteins, suggesting some degree of developmental buffering in eyespot development. Peak variance for different proteins was found at both early and late stages of development, contrasting with previous models suggesting that the distribution of variance should be more temporally focused during pattern formation. We speculate that our observations are representative of a standing reservoir of cryptic variation that may contribute to phenotypic evolution under certain circumstances. Our results also provide a strong cautionary message that gene expression studies with limited sample sizes can be positively misleading in terms of inferring expression pattern time series, as well as for making cross-species phylogenetic comparisons. [source] The Equality Deficit: Protection against Discrimination on the Grounds of Sexual Orientation in EmploymentGENDER, WORK & ORGANISATION, Issue 4 2001Nicole Busby The provisions of UK law offer no specific protection to gay men and lesbians suffering discrimination in the workplace on the grounds of sexual orientation. Such discrimination may take many forms and can result in ,fair' dismissal in certain circumstances. This article considers the degree of legal protection available under current provisions and investigates possible sources for the development of specific anti-discrimination legislation. It is concluded that, despite the application of certain aspects of employment law, the level of protection afforded to this group of workers amounts to an equality deficit in comparison to the legal redress available to those discriminated against on other grounds. Although the development of human rights legislation may have some application in this context, the combination of institutionalized discrimination and wider public policy concerns suggest that the introduction of specific legislation aimed at eliminating such discrimination in the United Kingdom is still some way off. [source] Genetic association tests in the presence of epistasis or gene-environment interactionGENETIC EPIDEMIOLOGY, Issue 7 2008Kai WangArticle first published online: 24 APR 200 Abstract A genetic variant is very likely to manifest its effect on disease through its main effect as well as through its interaction with other genetic variants or environmental factors. Power to detect genetic variants can be greatly improved by modeling their main effects and their interaction effects through a common set of parameters or "generalized association parameters" (Chatterjee et al. [2006] Am. J. Hum. Genet. 79:1002,1016) because of the reduced number of degrees of freedom. Following this idea, I propose two models that extend the work by Chatterjee and colleagues. Particularly, I consider not only the case of relatively weak interaction effect compared to the main effect but also the case of relatively weak main effect. This latter case is perhaps more relevant to genetic association studies. The proposed methods are invariant to the choice of the allele for scoring genotypes or the choice of the reference genotype score. For each model, the asymptotic distribution of the likelihood ratio statistic is derived. Simulation studies suggest that the proposed methods are more powerful than existing ones under certain circumstances. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Biogeochemical modelling of the rise in atmospheric oxygenGEOBIOLOGY, Issue 4 2006M. W. CLAIRE ABSTRACT Understanding the evolution of atmospheric molecular oxygen levels is a fundamental unsolved problem in Earth's history. We develop a quantitative biogeochemical model that simulates the Palaeoproterozoic transition of the Earth's atmosphere from a weakly reducing state to an O2 -rich state. The purpose is to gain an insight into factors that plausibly control the timing and rapidity of the oxic transition. The model uses a simplified atmospheric chemistry (parameterized from complex photochemical models) and evolving redox fluxes in the Earth system. We consider time-dependent fluxes that include organic carbon burial and associated oxygen production, reducing gases from metamorphic and volcanic sources, oxidative weathering, and the escape of hydrogen to space. We find that the oxic transition occurs in a geologically short time when the O2 -consuming flux of reducing gases falls below the flux of organic carbon burial that produces O2. A short timescale for the oxic transition is enhanced by a positive feedback due to decreasing destruction of O2 as stratospheric ozone forms, which is captured in our atmospheric chemistry parameterization. We show that one numerically self-consistent solution for the rise of O2 involves a decline in flux of reducing gases driven by irreversible secular oxidation of the crust caused by time-integrated hydrogen escape to space in the preoxic atmosphere, and that this is compatible with constraints from the geological record. In this model, the timing of the oxic transition is strongly affected by buffers of reduced materials, particularly iron, in the continental crust. An alternative version of the model, where greater fluxes of reduced hydrothermal cations from the Archean seafloor consume O2, produces a similar history of O2 and CH4. When climate and biosphere feedbacks are included in our model of the oxic transition, we find that multiple ,Snowball Earth' events are simulated under certain circumstances, as methane collapses and rises repeatedly before reaching a new steady-state. [source] The Impact of Medicaid Managed Care on Pregnant Women in Ohio: A Cohort AnalysisHEALTH SERVICES RESEARCH, Issue 4p1 2004Embry M. Howell Objective. To examine the impact of mandatory HMO enrollment for Medicaid-covered pregnant women on prenatal care use, smoking, Cesarean section (C-section) use, and birth weight. Data Sources/Study Setting. Linked birth certificate and Medicaid enrollment data from July 1993 to June 1998 in 10 Ohio counties, 6 that implemented mandatory HMO enrollment, and 4 with low levels of voluntary enrollment (under 15 percent). Cuyahoga County (Cleveland) is analyzed separately; the other mandatory counties and the voluntary counties are grouped for analysis, due to small sample sizes. Study Design. Women serve as their own controls, which helps to overcome the bias from unmeasured variables such as health beliefs and behavior. Changes in key outcomes between the first and second birth are compared between women who reside in mandatory HMO enrollment counties and those in voluntary enrollment counties. County of residence is the primary indicator of managed care status, since, in Ohio, women are allowed to "opt out" of HMO enrollment in mandatory counties in certain circumstances, leading to selection. As a secondary analysis, we compare women according to their HMO enrollment status at the first and second birth. Data Collection/Extraction Methods. Linked birth certificate/enrollment data were used to identify 4,917 women with two deliveries covered by Medicaid, one prior to the implementation of mandatory HMO enrollment (mid-1996) and one following implementation. Data for individual births were linked over time using a scrambled maternal Medicaid identification number. Principal Findings. The effects of HMO enrollment on prenatal care use and smoking were confined to Cuyahoga County, Ohio's largest county. In Cuyahoga, the implementation of mandatory enrollment was related to a significant deterioration in the timing of initiation of care, but an improvement in the number of prenatal visits. In that county also, women who smoked in their first pregnancy were less likely to smoke during the second pregnancy, compared to women in voluntary counties. Women residing in all the mandatory counties were less likely to have a repeat C-section. There were no effects on infant birth weight. The effects of women's own managed care status were inconsistent depending on the outcome examined; an interpretation of these results is hampered by selection issues. Changes over time in outcomes, both positive and negative, were more pronounced for African American women. Conclusions. With careful implementation and attention to women's individual differences as in Ohio, outcomes for pregnant women may improve with Medicaid managed care implementation. Quality monitoring should continue as Medicaid managed care becomes more widespread. More research is needed to identify the types of health maintenance organization activities that lead to improved outcomes. [source] An efficient triplet-based algorithm for evidential reasoning,INTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 4 2008Yaxin Bi Linear-time computational techniques based on the structure of an evidence space have been developed for combining multiple pieces of evidence using Dempster's rule (orthogonal sum), which is available on a number of contending hypotheses. They offer a means of making the computation-intensive calculations involved more efficient in certain circumstances. Unfortunately, they restrict the orthogonal sum of evidential functions to the dichotomous structure that applies only to elements and their complements. In this paper, we present a novel evidence structure in terms of a triplet and a set of algorithms for evidential reasoning. The merit of this structure is that it divides a set of evidence into three subsets, distinguishing the trivial evidential elements from the important ones,focusing particularly on some elements of an evidence space. It avoids the deficits of the dichotomous structure in representing the preference of evidence and estimating the basic probability assignment of evidence. We have established a formalism for this structure and the general formulae for combining pieces of evidence in the form of the triplet, which have been theoretically and empirically justified. © 2008 Wiley Periodicals, Inc. [source] Challenging the Bioethical Application of the Autonomy Principle within Multicultural SocietiesJOURNAL OF APPLIED PHILOSOPHY, Issue 1 2004Andrew Fagan abstract,This article critically re-examines the application of the principle of patient autonomy within bioethics. In complex societies such as those found in North America and Europe health care professionals are increasingly confronted by patients from diverse ethnic, cultural, and religious backgrounds. This affects the relationship between clinicians and patients to the extent that patients' deliberations upon the proposed courses of treatment can, in various ways and to varying extents, be influenced by their ethnic, cultural, and religious commitments. The principle of patient autonomy is the main normative constraint imposed upon medical treatment. Bioethicists typically appeal to the principle of patient autonomy as a means for generally attempting to resolve conflict between patients and clinicians. In recent years a number of bioethicists have responded to the condition of multiculturalism by arguing that the autonomy principle provides the basis for a common moral discourse capable of regulating the relationship between clinicians and patients in those situations where patients' beliefs and commitments do or may contradict the ethos of biomedicine. This article challenges that claim. I argue that the precise manner in which the autonomy principle is philosophically formulated within such accounts prohibits bioethicists' deployment of autonomy as a core ideal for a common moral discourse within multicultural societies. The formulation of autonomy underlying such accounts cannot be extended to simply assimilate individuals' most fundamental religious and cultural commitments and affiliations per se. I challenge the assumption that respecting prospective patients' fundamental religious and cultural commitments is necessarily always compatible with respecting their autonomy. I argue that the character of some peoples' relationship with their cultural or religious community acts to significantly constrain the possibilities for acting autonomously. The implication is clear. The autonomy principle may be presently invalidly applied in certain circumstances because the conditions for the exercise of autonomy have not been fully or even adequately satisfied. This is a controversial claim. The precise terms of my argument, while addressing the specific application of the autonomy principle within bioethics, will resonate beyond this sphere and raises questions for attempts to establish a common moral discourse upon the ideal of personal autonomy within multicultural societies generally. [source] Douglas Darden's Sex Shop: An Immodest ProposalJOURNAL OF ARCHITECTURAL EDUCATION, Issue 2 2004PETER SCHNEIDER When once we resort to the arena of representation, we remove the weightiest and most obvious restrictions on imaginative flight. We are free at least to depict those things which architecture might do in certain circumstances,circumstances bounded only by the remotest confines of probability. Here is the sphere of the maker of architectural fantasies. He can explore a great margin of territory,nearly virgin territory,capable of yielding architectural treasure, unique and enthralling. [source] CYP3A4 and pregnane X receptor humanized miceJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2007Frank J. Gonzalez Abstract Marked species differences exist in P450 expression and activities. In order to produce mouse models that can be used to more accurately predict human drug and carcinogen metabolism, P450- and xenobiotic receptor humanized mice are being prepared using bacterial artificial chromosomes (BAC) and P1 phage artificial chromosomes (PAC) genomic clones. In some cases, transgenic mice carrying the human genes are bred with null-mice to produce fully humanized mice. Mice expressing human CYP1A1, CYP1A2, CYP2E1, CYP2D6, CYP3A4, and CYP3A7 were generated and characterized. Studies with the CYP3A4-humanized (hCYP3A4) mouse line revealed new information on the physiological function of this P450 and its role in drug metabolism in vivo. With this mouse line, CYP3A4, under certain circumstances, was found to alter the serum levels of estrogen resulting in deficient lactation and low pup survival as a result of underdeveloped mammary glands. This hCYP3A4 mouse established the importance of intestinal CYP3A4 in the pharmacokinetics of orally administered drugs. The hCYP3A4 mice were also used to establish the mechanisms of potential gender differences in CYP3A4 expression (adult female > adult male) that could account for human gender differences in drug metabolism and response. The pregnane X receptor (PXR) is also involved in induction of drug metabolism through its target genes including CYP3A4. Since species differences exist in ligand specificity between human and mice, a PXR -humanized mouse (hPXR) was produced that responds to human PXR activators such as rifampicin but does not respond to the rodent activator pregnenalone 16,-carbonitrile. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:158,162, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20173 [source] The Role of the Kidneys in HypertensionJOURNAL OF CLINICAL HYPERTENSION, Issue 9 2005L. Gabriel Navar PhD The devastating long-term consequences of high blood pressure include stroke, heart disease, atherosclerosis, renal disease, and other end-organ damage. From a physiologic perspective, it is not apparent why the propensity for hypertension is so widespread in the general population. Clearly, an adequate arterial pressure is essential for perfusion of the tissues to provide adequate oxygenation and nutrition to the brain and other critical organs. Although the various microcirculatory beds have the capability to adjust vascular resistance to autoregulate blood flow, systemic arterial pressure is usually maintained at levels greater than required for requisite tissue perfusion. The myriad of neurohumoral mechanisms designed to protect against decreases in systemic arterial pressure provide a reserve capacity for increased perfusion when there are increased tissue demands. The unfortunate consequence of having these powerful physiologic control mechanisms is that they may be inappropriately activated in certain circumstances or by genetically determined traits, leading to hypertension and cardiovascular injury. Evidence continues to accumulate indicating that the kidney not only is victim to hypertension-related injury, but also contributes as a villain to the hypertensinogenic process. [source] Balancing treatment allocations by clinician or center in randomized trials allows unacceptable levels of treatment predictionJOURNAL OF EVIDENCE BASED MEDICINE, Issue 3 2009Robert K Hills Abstract Objective Randomized controlled trials are the standard method for comparing treatments because they avoid the selection bias that might arise if clinicians were free to choose which treatment a patient would receive. In practice, allocation of treatments in randomized controlled trials is often not wholly random with various ,pseudo-randomization' methods, such as minimization or balanced blocks, used to ensure good balance between treatments within potentially important prognostic or predictive subgroups. These methods avoid selection bias so long as full concealment of the next treatment allocation is maintained. There is concern, however, that pseudo-random methods may allow clinicians to predict future treatment allocations from previous allocation history, particularly if allocations are balanced by clinician or center. We investigate here to what extent treatment prediction is possible. Methods Using computer simulations of minimization and balanced block randomizations, the success rates of various prediction strategies were investigated for varying numbers of stratification variables, including the patient's clinician. Results Prediction rates for minimization and balanced block randomization typically exceed 60% when clinician is included as a stratification variable and, under certain circumstances, can exceed 80%. Increasing the number of clinicians and other stratification variables did not greatly reduce the prediction rates. Without clinician as a stratification variable, prediction rates are poor unless few clinicians participate. Conclusion Prediction rates are unacceptably high when allocations are balanced by clinician or by center. This could easily lead to selection bias that might suggest spurious, or mask real, treatment effects. Unless treatment is blinded, randomization should not be balanced by clinician (or by center), and clinician,center effects should be allowed for instead by retrospectively stratified analyses. [source] Red blood cells labelling with 99mTc-d,l-HMPAO: an alternative method for specific casesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2003F.J. Pérez Abstract The effectiveness of the classic methods for red blood cells (RBCs) labelling with 99mTc has been demonstrated in nuclear medicine. However, nuclear physicians have found, in certain circumstances, this diagnostic technique fails and poor quality images are obtained. In this work we report on an alternative method that is of useful in these occasions, for in vitro labelling RBCs with 99mTc-d,l-HMPAO complex. The study shows a high and reproducible labelling efficiency (94.14±0.38), using low amount of tin. The RBCs were isolated from plasma and other interfering blood cells before adding 99mTc-d,l-HMPAO. The tracer was retained and the elution rate from RBCs was low (less than 6% after 120 min). The preclinical results indicate that this new method could be a good alternative to the standard classic methods for specific cases. Copyright © 2003 John Wiley & Sons, Ltd. [source] Molecular basis for detection of invading pathogens in the brainJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2008Jeppe Falsig Abstract Classical immunology textbooks have described the central nervous system as an immune-privileged site, i.e., as devoid of inflammatory and host-vs.-graft immunoreactions. This view has been refined, since we now know that hematopoietic cells infiltrate the CNS under certain circumstances and that CNS-resident cells are capable of launching an innate immune response. Microglia cells express an extensive repertoire of pattern-recognition receptors and act as sentinels surveilling the CNS for possible damage or infection. Astrocytes are the most abundant cell type in the brain, and they are capable of launching a strong supportive innate immune response. Novel findings show that both astrocytes and, surprisingly, even neurons express pattern-recognition receptors. Activation of these receptors leads to a functional response, indicating that cells other than microglia are capable of initiating a primary innate immune response against CNS-invading pathogens. Here, we put these findings into context with what has been learned from recent in vitro and in vivo experiments about the initiation of an innate immune response in the brain. © 2007 Wiley-Liss, Inc. [source] Synthesis and use of a pseudo-cysteine for native chemical ligationJOURNAL OF PEPTIDE SCIENCE, Issue 4 2003David A. Alves Abstract The process of native chemical ligation (NCL) is well described in the literature. An N -terminal cysteine-containing peptide reacts with a C -terminal thioester-containing peptide to yield a native amide bond after transesterification and acyl transfer. An N -terminal cysteine is required as both the N -terminal amino function and the sidechain thiol participate in the ligation reaction. In certain circumstances it is desirable, or even imperative, that the N -terminal region of a peptidic reaction partner remain unmodified, for instance for the retention of biological activity after ligation. This work discusses the synthesis of a pseudo- N -terminal cysteine building block for incorporation into peptides using standard methods of solid phase synthesis. Upon deprotection, this building block affords a de factoN -terminal cysteine positioned on an amino acid sidechain, which is capable of undergoing native chemical ligation with a thioester. The syntheses of several peptides and structures containing this motif are detailed, their reactions discussed, and further applications of this technology proposed. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Commodity Taxes, Wage Determination, and ProfitsJOURNAL OF PUBLIC ECONOMIC THEORY, Issue 2 2001Sophia Delipalla We examine the effects of two different types of commodity taxation, specific and ad valorem, on wages and profits. We analyze two models of wage determination, one with efficiency wage setting and one with union-firm bargaining. In the former, a (locally) revenue-neutral shift from specific to ad valorem taxation leads to an increase in both employment and wages and a reduction in profitability. In the latter, the effect on wages and profits may be reversed: predominantly ad valorem taxation raises employment but lowers wages, and under certain circumstances, the net effect is an increase in profits. [source] Effect of pea and soya bean interaction on zinc dialyzability in weaning foodsJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 10 2005F Rincón Abstract Higher values are reported for Zn dialyzability of homogenized infant formulas when pea content is high and soya bean content is low, but also when the reverse is the case, ie low pea content and high soya bean content. This apparent paradox is examined in terms of a potential antagonistic effect of the pea × soya bean interaction on Zn dialyzability. The antagonistic effect is traced to the linear combined effect of the two ingredients on pH over a narrow interval around 5.90 and on calcium content. This combined effect may account for the difference in results between in vivo and in vitro studies reported by several authors. The combination of certain vegetables in an infant formula may, in certain circumstances, enhance Zn dialyzability, contradicting the general view that increased legume content diminishes Zn dialyzability due to an increase in phytic acid levels. Copyright © 2005 Society of Chemical Industry [source] Trade Unions, Wage Bargaining Coordination, and Foreign Direct InvestmentLABOUR, Issue 4 2008Roxana Radulescu Conventional wisdom is that a high trade union bargaining strength and a system of coordinated wage bargaining reduce the attractiveness of an economy as a location for foreign direct investment, although there is limited evidence for this. The paper takes panel data for 19 OECD economies to examine the relationship between trade union bargaining strength, bargaining coordi nation, and a range of incentives for inward foreign direct investment. It finds a strong negative effect of trade union density on inward foreign direct investment, which is dependent on the degree of wage bargaining coordination. A high degree of coordination weakens the deterrent effect of high union density, which is consistent with the notion that under certain circumstances a coordinated increase in wages can increase profits of the multinationals by hurting domestic firms. [source] Scientific rationale for the Finnish Allergy Programme 2008,2018: emphasis on prevention and endorsing toleranceALLERGY, Issue 5 2009L. C. Von Hertzen ,In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. ,Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. ,Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. ,Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008,2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level. [source] Spermatozoal RNAs: What about their functions?MICROSCOPY RESEARCH AND TECHNIQUE, Issue 8 2009Jean-Pierre Dadoune Abstract The profound architectural changes that transform spermatids into spermatozoa result in a high degree of DNA packaging within the sperm head. However, the mature sperm chromatin that harbors imprinted genes exhibits a dual nucleoprotamine/nucleohistone structure with DNase-sensitive regions, which could be implicated in the establishment of efficient epigenetic information in the developing embryo. Despite its apparent transcriptionally inert state, the sperm nucleus contains diverse RNA populations, mRNAs, antisense and miRNAs, that have been transcribed throughout spermatogenesis. There is also an endogenous reverse transcriptase that may be activated under certain circumstances. It is now commonly accepted that sperm can deliver some RNAs to the ovocyte at fertilization. This review presents potential links between male-specific genomic imprinting, chromatin organization, and the presence of diverse RNA populations within the sperm nucleus and discusses the functional significance of these RNAs in the spermatozoon itself and in the early embryo following fertilization. Some recent data are provided, supporting the view that analyzing the profile of spermatozoal RNAs could be useful for assessment of male fertility. Microsc. Res. Tech. 2009. © 2009 Wiley-Liss, Inc. [source] The GRB early optical flashes from internal shocks: application to GRB 990123, GRB 041219a and GRB 060111bMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2007D. M. Wei ABSTRACT With the successful launch of the Swift Gamma-ray Burst Explorer, it is widely expected that the prompt optical flashes like GRB 990123 would be easily detected. However, the observations show that for a number of Gamma-ray bursts (GRBs) no early optical flash has been detected, which indicates that the reverse shock emission must be suppressed. Here we explore the possibility that the optical flash may arise from the internal shock emission. For GRB 990123 and GRB 060111b, although their optical emission are not correlated with the gamma-ray emission, we propose here that their optical and gamma-ray emission may arise from different internal shocks (which can be formed by collision of different shells), and find that, under certain circumstances, the optical flashes of GRB 990123 and GRB 060111b can well be explained by the internal shock model. For GRB 041219a, the prompt optical emission was correlated with the gamma-ray emission, which can also be explained by the internal shock model if we assume the optical emission was the low-energy extension of the gamma-ray emission, and we find its redshift is about z, 0.2. As for GRB 050904, we have shown in previous paper that the optical flash was produced by synchrotron radiation and the X-ray flare was produced by the synchrotron,self-Compton (SSC) mechanism. Therefore we conclude that the early optical flashes of GRBs can usually arise from the internal shock emission. Meanwhile in our model since the shells producing the optical flashes would be easily disrupted by other shells, so we suggest that the bright optical flash should not be common in GRBs. In addition, we also discussed the SSC emission in the internal shock model, and find that for different values of parameters, there would be several kinds of high-energy emission (at ,100 keV, ,10 MeV or GeV) accompanying the optical flash. For a burst like GRB 990123, a GeV flare with fluence about 10,8 erg cm,2 s,1 is expected, which might be detected by the GLAST satellite. [source] | ||||||||||||||||||||||||||||||||||||||||||||||