International differences in alcohol use according to sexual orientation.

Most research on sexual orientation and alcohol use in the United States has found higher rates of alcohol use and abuse among gay men and lesbians. Studies from other countries have found smaller or no differences between sexual minority and heterosexual women and men. The present study used general population survey data from 14 countries to examine high-volume and risky single-occasion drinking by sexual orientation. Data from 248 gay men and lesbians and 3720 heterosexuals were analyzed in a case-control design. In several countries partnered or recently partnered gay men and lesbians had no greater risk of heavy drinking or engaging in heavy drinking than heterosexual controls. Only lesbians in North America showed higher risk for both indicators. Future general population health research should include larger samples of gays and lesbians and use more comprehensive measures of sexual orientation for investigating the prevalence of health risk factors.

Catechol-binding serines of beta(2)-adrenergic receptors control the equilibrium between active and inactive receptor states.

The binding free energy for the interaction between serines 204 and 207 of the fifth transmembrane helix of the beta(2)-adrenergic receptor (beta(2)-AR) and catecholic hydroxyl (OH) groups of adrenergic agonists was analyzed using double mutant cycles. Binding affinities for catecholic and noncatecholic agonists were measured in wild-type and mutant receptors, carrying alanine replacement of the two serines (S204A, S207A beta(2)-AR), a constitutive activating mutation, or both. The free energy coupling between the losses of binding energy attributable to OH deletion from the ligand and from the receptor indicates a strong interaction (nonadditivity) as expected for a direct binding between the two sets of groups. However, we also measured a significant interaction between the deletion of OH groups from the receptor and the constitutive activating mutation. This suggests that a fraction of the decrease in agonist affinity caused by serine mutagenesis may involve a shift in the conformational equilibrium of the receptor toward the inactive state. Direct measurements using a transient transfection assay confirm this prediction. The constitutive activity of the (S204A, S207A) beta(2)-AR mutant is 50 to 60% lower than that of the wild-type beta(2)-AR. We conclude that S204 and S207 do not only provide a docking site for the agonist, but also control the equilibrium of the receptor between active (R*) and inactive (R) forms.

Efeito do fósforo suplementar sobre o desempenho reprodutivo de vacas de corte em pastagem de Brachiaria humidicola

O objetivo deste experimento foi observar e quantificar o efeito de duas misturas minerais (ad libitum), uma sem (M) e outra com fósforo suplementar (MP), sobre o desempenho produtivo e reprodutivo de vacas de cria neloradas em pastejo de Brachiaria humidicola. O trabalho foi realizado na Fazenda Modelo (Embrapa-Centro Nacional de Pesquisa de Gado de Corte), localizada em Terenos, MS, em duas fases, a primeira, em 1988/92, e a segunda, em 1992/94. Na segunda fase, reduziu-se a carga animal durante a seca e os dias de amamentação (de 1,0 para 0,5 vacas/ha e de 210 para 90 dias, respectivamente). Foram realizadas medidas de consumo da mistura mineral (M = 76 e MP = 112 g/cab./dia); teor médio de fósforo na forrageira (época das chuvas = 0,16%, época seca = 0,11%); peso vivo (primeira fase: M = 363±3,3 e MP = 371±3,8 kg; segunda fase: M = 407± 5,7 e MP = 417± 6,5 kg); taxa de natalidade (primeira fase: M = 67±3,3 e MP = 66± 3,5%; segunda fase: M = 74± 6,3 e MP = 80± 5,7%) e bezerros desmamados (primeira fase: M = 86± 5,0 e MP = 91± 5,3; segunda fase: M = 55± 6,4 e MP = 67± 5,7). As vacas de cria não responderam ao fósforo suplementar.

Targeting Notch signaling in pancreatic cancer.

IMPORTANCE OF THE FIELD: With some 220,000 new cases/year in the world, pancreatic adenocarcinoma is the fourth highest cause of death by cancers. Among newly diagnosed patients about 210,000 will die within 9 months following diagnosis. Therefore, effective adjuncts to current treatment strategies are necessary. Because embryological signaling pathways are upregulated in pancreatic adenocarcinoma, they represent potential targets for future therapies. AREAS COVERED IN THIS REVIEW: Our aim is to present the Notch pathway, and to describe its involvement in pancreatic pathophysiology/carcinogenesis. This pathway appeared as a prime target for pancreatic cancer therapy. In the light of the crosstalk of Notch with other survival/embryologic pathways, drugs affecting more than one pathway may have to be combined. WHAT THE READER WILL GAIN: Drugs against gamma-secretases could thus serve in cancer treatment and can be combined with drugs targeting survival pathways interplaying with Notch such as Hedgehog. TAKE HOME MESSAGE: Downregulation of Notch contributes to the inhibition and apoptosis of pancreatic cancer cells whereas Hedgehog inhibition will allow for enhanced delivery of drugs to the tumor. Both pathway inhibitors appear to have synergistic effects for future therapeutics for pancreatic adenocarcinoma, once safety issues of compounds are overcome.

Innovations in hypoxic training

Athletes seem compelled to include some forms of altitude training in their preparation expecting additional performance gains compared to equivalent training at sea-level. For the general population, altitude training often only consists in spending weeks at altitude to enhance red blood cell production, hemoglobin mass and thus oxygen delivery to the muscles. Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea-level but train in hypobaric hypoxia (HH, real altitude) or normobaric hypoxia (NH, simulated altitude) was shown to induce exclusive adaptations directly at the muscular level that may support performance improvements. Our work first demonstrated significant differences between exposure and exercise in HH vs. NH that may help disentangling hypoxia and hypobaria for athletes or mountaineers who use NH to prepare for altitude competitions or expeditions. Second, we produced a comprehensive review of the strikingly poor and controversial benefits of IHT for performance enhancement in team or racket sports. Using evidence of peripheral muscular adaptations with the recruitment of fast-twitch fibers playing a major role, we then developed and assessed the potential of a new training method in hypoxia based on the repetitions of "all-out" sprints interspersed with incomplete recovery periods, the so called "repeated sprint training in hypoxia" (RSH). We have consequently shown RSH to delay fatigue when sprints with incomplete recoveries are repeated until exhaustion both in cycling and cross-country ski double poling. We definitely outlined RSH as a promising training strategy and proposed new studies to judge the efficacy of RSH in team sports and determine the specific mechanisms that may enhance team game results. In conclusion, our work allowed updating the panorama over the contemporary hypoxic training possibilities. It provides an overview of the current scientific knowledge about intermittent hypoxic training and repeated sprint training in hypoxia (RSH). This will benefit athletes and teams in intermittent sports looking to include a hypoxic stimulus to their training to gain a specific competitive edge.

Model development for capercaillie (Tetrao urogallus) habitat in the Jura Mountains (Western Switzerland)

Capercaillie, Tetrao urogallus, is a threatened species in central Europe, and Swiss populations declined 40 to 50 % between 1970 and 1985. Capercaillie are sensitive to forest structure, and loss of habitat is a major cause of their decline. Knowledge of habitat characteristics is therefore essential for capercaillie conservation. Here, we present models predicting capercaillie probability of occurrence, based on relevant structural habitat variables. Models were built using multiple logistic regression analyses on capercaillie presence/absence data. Vegetation survey was carried out in July 1999 in a 170-km2 forested area (Jura mountains, canton de Vaud, western Switzerland) inhabited by capercaillie and presence/absence of the species was assessed according to dropping presence/absence. The survey was based on 10-m-radius sample plots each in a 1-km2 forest patch (n = 76 with capercaillie droppings, n = 80 without). A first model included seven out of 27 measured habitat variables and a second model only four. The latter model best represents practical needs. It includes three variables which had a negative impact on capercaillie presence: tree and shrub covers and spruce, Picea excelsa, shrub cover, and one which had a positive effect: bilberry, Vaccinium myrtillus, cover, highlighting that capaercaillie selected open forest with high bilberry abundance. The model can be used to map potential capercaillie habitat distribution and to manage the habitat in favour of capercaillie (protection and adapted forestry practices) in the Swiss Jura mountains.

Thin Bonded Portland Cement Concrete Overlay, HR-520, 1990

A four and one-half inch thick, bonded portland cement concrete (PCC) overlay and integral widening were used to rehabilitate a 4.5 mile section of Iowa route 141 from US 169 to Iowa 210 in Dallas County. There was a substantial amount of cracking in the old 20 feet wide PCC pavement. Most of the widening, which was tied to the original slab by dowel bars, was placed as a four feet wide section on one side. Coring has shown that the overlay is well bonded and testing with the Delamtect has shown less than 1% debonding. Midpanel transverse cracks in the old pavement have reflected through the overlay (as expected). Some new transverse cracking has occurred. This cracking has not caused any significant problems. In general, the overlay is performing quite well.

Improving Subgrade Support Values with Longitudinal Drains, MLR-84-3, 1984

This report is a brief summary of research on the effect of longitudinal drains on subgrade support. The Iowa DOT began installing longitudinal subdrains at a depth of 24" in 1978. The trend in Iowa has been to deeper longitudinal drains with the present standard being 48" deep. A very limited amount of data would indicate that the deeper longitudinal drains are providing a greater benefit to the subgrade support value. The 24# deep drains of the Poweshiek Interstate 80 project yielded a spring subgrade support value of 165. The 30" deep drains on Pottawattamie Interstate 80 yielded a K value of 170 while the 48"deep drains on Cass County Interstate 80 yielded a K value of 210. This limited amount of data would indicate that the deeper drains provide greater benefit to improvement of the subgrade support values.

Efeitos da solarização do solo na densidade populacional da tiririca e na produtividade de hortaliças sob manejo orgânico

Foi conduzido um ensaio de campo em Seropédica, Estado do Rio de Janeiro, para avaliar o efeito da solarização do solo na população infestante de tiririca (Cyperus rotundus) e na produtividade de hortaliças submetidas a manejo orgânico. A solarização correspondeu à cobertura do solo com polietileno transparente (50 mim) por um período de 210 dias. Houve um aumento da temperatura média da camada superficial do solo (0-10 cm) da ordem de 23%, em relação ao das parcelas não-solarizadas. Após a retirada do plástico, cultivaram-se: cenoura (Daucus carota 'Brasília'), repolho (Brassica oleracea var. capitata 'Astrus'), beterraba (Beta vulgaris 'Tall Top Early Wonder') e vagem-anã (Phaseolus vulgaris 'Alessa'). Em termos gerais, a solarização reduziu em 59% a reinfestação pela tiririca. Nas parcelas solarizadas, houve significativo incremento das produtividades de cenoura (28%), vagem (32%), beterraba (37%) e repolho (34%). A fixação biológica do nitrogênio, a julgar pela nodulação da vagem, não foi afetada pela solarização, mas a população de nematóides do solo sofreu considerável redução.

Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.

BACKGROUND: High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). METHODS: We assessed the association between the genetic bottleneck of HIV at transmission and the prevalence and incidence of HCV coinfection in HIV-infected MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the transmission bottleneck, we used the fraction of ambiguous nucleotides detected by genotypic resistance tests sampled during early HIV infection. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously established threshold (0.5%). RESULTS: From the SHCS, we identified 671 MSM with available results of HCV serologic tests and with an HIV genotypic resistance test performed during early HIV infection. Of those, 161 (24.0%) exhibited a broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV transmission bottlenecks exhibited a 2-fold higher odds of having ever experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI}, 1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission bottlenecks. CONCLUSIONS: Our results indicate that the currently occurring sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV transmission bottlenecks. This is consistent with an important role of high-risk behavior and mucosal barrier impairment in the transmission of HCV among MSM.