The role of nω-nitro-L-arginine in modulation of pulmonary vascular tone in the maturing newborn pig

AbstractCurrent therapeutic modalities for treatment of newborn pulmonary hypertensive crisis include but are not limited to the administration of nitric oxide (endothelium-derived relaxing factor). However, few data are available on the role of endogenously produced endothelium-derived relaxing factor in the modulation of pulmonary vascular tone in the neonate. In the current study, we investigated the acute effects of Nω-nitro- L -arginine (a potent competitive inhibitor of endothelium-derived relaxing factor synthase) on the pulmonary vasculature of anesthetized open-chest 48-hour-old ( n = 8) and 2-week-old ( n = 7) Yorkshire pigs. After baseline data were acquired, all animals received a 10 mg/kg per minute infusion of Nω-nitro- L -arginine for 10 minutes. To discern distal and proximal pulmonary arterial vessel changes, input mean and characteristic impedance were respectively determined. Pulmonary vascular resistance was also calculated (units determined in dyne • sec • cm -5 plus or minus the standard errorof the mean). Results showed Nω-nitro- L -arginine infusion did not significantly alter baseline pulmonary arterial pressure (22,370 ±1473 dyne/cm2 ), pulmonary vascular resistance (5171 ±805 dyne • sec • cm -5 ), input impedance (6343 ±806 dyne • sec • cm -5 ), or characteristic impedance (2073 ±418 dyne • sec • cm -5 ) in 48-hour-old pigs. In 2-week-old pigs, infusion of Nω-nitro- L -arginine elevated pulmonary arterial pressure (18,162 ±1415 dyne/cm 2 versus 23,838 ±1810 dyne/cm 2 , p = 0.015), pulmonary vascular resistance (810 ±137 dyne • sec • cm -5 versus 1519 dyne • sec • cm -5 , p = 0.030), and input impedance (2302 ±251 dyne • sec • cm -5 versus 2900 ±255 dyne • sec • cm -5 , p = 0.018). Characteristic impedance was not altered in 2-week-old pigs. These data indicate that Nω-nitro- L -arginine infusion resulted in pulmonary arteriolar vasoconstriction in 2-week-old pigs, but not in 48-hour-old pigs. This finding suggests that endothelium-derived relaxing factor does not modulate basal pulmonary arteriolar tone during the early newborn period, but does play a significant role in 2-week-old pigs. These data also suggest that the functional role for endothelium-derived relaxing factor is confined to the distal arteriolar pulmonary bed and does not extend to the larger proximal arterial vessels. (J THORAC CARDIOVASC SURG 1995;110:1486-92

Contribution of genetic effects to genetic variance components with epistasis and linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Cockerham genetic models are commonly used in quantitative trait loci (QTL) analysis with a special feature of partitioning genotypic variances into various genetic variance components, while the F_∞genetic models are widely used in genetic association studies. Over years, there have been some confusion about the relationship between these two type of models. A link between the additive, dominance and epistatic effects in an F_∞model and the additive, dominance and epistatic variance components in a Cockerham model has not been well established, especially when there are multiple QTL in presence of epistasis and linkage disequilibrium (LD).</p> <p>Results</p> <p>In this paper, we further explore the differences and links between the F_∞and Cockerham models. First, we show that the Cockerham type models are allelic based models with a special modification to correct a confounding problem. Several important moment functions, which are useful for partition of variance components in Cockerham models, are also derived. Next, we discuss properties of the F_∞models in partition of genotypic variances. Its difference from that of the Cockerham models is addressed. Finally, for a two-locus biallelic QTL model with epistasis and LD between the loci, we present detailed formulas for calculation of the genetic variance components in terms of the additive, dominant and epistatic effects in an F_∞model. A new way of linking the Cockerham and F_∞model parameters through their coding variables of genotypes is also proposed, which is especially useful when reduced F_∞models are applied.</p> <p>Conclusion</p> <p>The Cockerham type models are allele-based models with a focus on partition of genotypic variances into various genetic variance components, which are contributed by allelic effects and their interactions. By contrast, the F_∞regression models are genotype-based models focusing on modeling and testing of within-locus genotypic effects and locus-by-locus genotypic interactions. When there is no need to distinguish the paternal and maternal allelic effects, these two types of models are transferable. Transformation between an F_∞model's parameters and its corresponding Cockerham model's parameters can be established through a relationship between their coding variables of genotypes. Genetic variance components in terms of the additive, dominance and epistatic genetic effects in an F_∞model can then be calculated by translating formulas derived for the Cockerham models.</p

Mobility time style: for an integrated view of time and mobility in societies with a future

This paper aims (i) to demonstrate the relevance of deepening the study of time usage from the individual and family perspectives and (ii) to put in dialog perceptions and uses of time with daily mobility patterns. It is increasingly imperative to consider mobility and the uses of time as central axes of lifestyles, highlighting the weight of several variables in the definition of lifestyle choices, namely transportation options. This reflection is based on an empirical study carried out in Portugal through interviews in the metropolitan areas of Lisbon and Porto. The analysis leads to the conclusion that, in addition to physical distances people have to cover, the choice of specific means of transportation is strongly dependent on the perceptions and uses of time. It is also evident that time is simultaneously dependent on the way technologies are absorbed into daily life and that time remains a matter of constraint and social opportunity.FCT -Fundação para a Ciência e a Tecnologia (UID/SOC/03126/2019

Psychosocial primary care – what patients expect from their General Practitioners A cross-sectional trial

BACKGROUND: Psychosocial Primary Care (PPC) is a model of service delivery for patients with mental disorders and psychosocial problems which was established in Germany in 1987. This study was performed as part of the evaluation of a PPC training program. We investigated patients' expectations of the psychosocial treatment offered by GPs trained in PPC. METHODS: Ten general practitioners trained in PPC were randomly selected. Two hundred and twenty patients were surveyed in the waiting room regarding their expectations concerning psychological treatment. RESULTS: Eighty-five per cent of patients could envisage making use of psychosocial treatments. Counselling by the GP was considered most important (65%). Fifty-four per cent of patients indicated that there was sufficient counselling, but further distinctions revealed dissatisfaction with both the extent and content of the counselling. Lack of time was the most frequent reason (53%) cited for insufficient counselling. A willingness to discuss the psychological aspects of illness was exhibited by between 55% (current illness) and 79% of patients. Two-thirds of patients believed that discussing psychological aspects and counselling by the doctor could exert a healing effect or contribute to symptomatic improvement in physical illnesses. Younger patients and patients with experience in psychotherapy expected referral to mental health services. CONCLUSIONS: Primary care patients desire and accept psychological treatment from their GP. Training in psychosocial competence in primary care should be offered more frequently

Alcohol and fatal life trajectories in Russia: understanding narrative accounts of premature male death in the family

Background: In the post-Soviet period, Russian working-age men have suffered unusually high mortality rates. Earlier quantitative work found that part of this is attributable to hazardous and harmful patterns of alcohol consumption, which increased in the period of transition at a time of massive social and economic disruption and uncertainty. However, there has been very little work done to document and understand in detail the downward life trajectories of individual men who died prematurely from alcohol-related conditions. Building on an earlier case-control study, this unique qualitative study investigates the perceived interplay between men's drinking careers, their employment and family history, health and eventual death.Methods: In-depth interviews were conducted with close relatives (most often the widow) of 19 men who died between 2003 and 2005 aged 25-54 years whose close relatives reported that alcohol contributed to their death. The study was conducted in a typical medium-sized Russian city. The relative's accounts were analysed using thematic content analysis.Results: The accounts describe how hazardous drinking both contributed to serious employment, family and health problems, and was simultaneously used as a coping mechanism to deal with life crises and a decline in social status. The interviews highlighted the importance of the workplace and employment status for shaping men's drinking patterns. Common themes emerged around a culture of drinking in the workplace, peer pressure from colleagues to drink, use of alcohol as remuneration, consuming non-beverage alcohols,Russian-specific drinking patterns, attitudes to treatment, and passive attitudes towards health and drinking.Conclusions: The study provides a unique insight into the personal decline that lies behind the extremely high working-age mortality due to heavy drinking in Russia, and highlights how health status and hazardous drinking are often closely intertwined with economic and social functioning. Descriptions of the development of drinking careers, hazardous drinking patterns and treatment experiences can be used to plan effective interventions relevant in the Russian context

The State Socialist Mortality Syndrome

Death rates for working-age men in European state socialist countries deviated from general improvements in survival observed in the rest of Europe during the 20th century. The magnitude of structural labor force changes across countries correlates with lagged increases in death rates for men in the working ages. This pattern is consistent with a hypothesis that hyper-development of heavy industry and stagnation (even contraction) of the service sector created anomic conditions leading to unhealthy lifestyles and self-destructive behavior among men moving from primary-sector to secondary-sector occupations. Occupational contrasts within countries similarly show concentration of rising male death rates among blue collar workers. Collapse of state socialist systems produced rapid corrections in labor force structure after 1990, again correlated with a fading of the state socialist mortality syndrome in following decades

Understanding and using quantitative genetic variation

Quantitative genetics, or the genetics of complex traits, is the study of those characters which are not affected by the action of just a few major genes. Its basis is in statistical models and methodology, albeit based on many strong assumptions. While these are formally unrealistic, methods work. Analyses using dense molecular markers are greatly increasing information about the architecture of these traits, but while some genes of large effect are found, even many dozens of genes do not explain all the variation. Hence, new methods of prediction of merit in breeding programmes are again based on essentially numerical methods, but incorporating genomic information. Long-term selection responses are revealed in laboratory selection experiments, and prospects for continued genetic improvement are high. There is extensive genetic variation in natural populations, but better estimates of covariances among multiple traits and their relation to fitness are needed. Methods based on summary statistics and predictions rather than at the individual gene level seem likely to prevail for some time yet

Seismicity along the Pacific-North American plate boundary in California and western Nevada, 1980-81

Beginning in 1980, the number and distribution of telemetered, high-gain seismic stations operated in California and western Nevada provided the capability for locating earthquakes of M ≥ 2.0 occurring throughout the broadly-deforming Pacific-North American plate boundary from the Salton Trough to the Mendocino triple junction and as far inland as the western Great Basin. Four networks combine to provide this capability: (1) the 300-station Central California Network operated by the U.S. Geological Survey from Menlo Park, CA; (2) the 200-station Southern California Network operated jointly by the California Institute of Technology (CIT) and the U. S. Geological Survey from Pasadena, CA; (3) the 40-station Western Nevada-Eastern California Network operated by the University of Nevada from Reno, NV; and (4) the 55-station Southern Nevada Network operated by the U.S. Geological Survey from Golden, CO. The distribution of earthquake hypocenters located by this combination of networks for 1980 and 1981 brings into focus detailed seismicity patterns within the broad bands of earthquake activity that have persisted for SO years or more based on locations of M ≥ 3 earthquakes from the regional networks operated by CIT and the University of California, Berkeley, since the early 1930's. The precise focal parameters of M ≥ 2.0 earthquakes afforded by these four telemetered networks provide critical constraints on the kinematics of seismogenic deformation of the western margin of the North American plate adjacent to the San Andreas transform-fault system