The direct effect of drinking to cope on alcohol problems is not mediated by alcohol consumption: Invariance across gender and countries

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: Data will be made available on request.BACKGROUND: Drinking to cope with negative affect confers a direct risk of alcohol problems independently of greater alcohol consumption (i.e., confers susceptibility to the alcohol harm paradox). However, it remains unclear whether this risk is common across gender and countries. METHODS: The current study applied path analysis to two cross-sectional samples of 18-25-year-old undergraduate hazardous drinking students recruited from the UK (Study 1; N = 873) and internationally (Study 2; N = 4064 recruited in Argentina, Canada, South Africa, Spain, Uruguay, USA, and England). The Drinking Motives Questionnaire (DMQ) measured drinking to cope with negative affect and drinking to enhance positive affect (i.e., enhancement motives). The Alcohol Use Disorders Identification Test (AUDIT) measured alcohol consumption and problems. RESULTS: In both studies, drinking to cope with negative affect had a direct effect on alcohol problems (S1: β = 0.259, SE = 0.031, p <.001; S2: β = 0.255, SE = 0.017, p <.001), and only a negligible proportion of this effect was mediated by alcohol consumption (S1: 2.58 %, p =.550; S2: 0.79 %, p=.538). By contrast, drinking to enhance positive affect had a smaller direct effect on alcohol problems (S1: β = 0.000, SE = 0.033, p =.989; S2: β = 0.044, SE = 0.017, p =.009), and a substantial proportion of this effect was mediated by greater alcohol consumption (S1: 99.76 %, p <.001; S2: 60.36 %, p <.001). Crucially, in both studies, the direct effect of drinking to cope on alcohol problems was invariant across gender and countries. CONCLUSIONS: These findings suggest that individuals who endorse drinking to cope with negative affect are uniquely susceptible to the alcohol harm paradox, that is, greater alcohol problems which cannot be explained by greater alcohol consumption, and this susceptibility is common across gender and countries.Alcohol Change UKMedical Research Council (MRC

Risk Pathways Contributing to the Alcohol Harm Paradox: Socioeconomic Deprivation Confers Susceptibility to Alcohol Dependence via Greater Exposure to Aversive Experience, Internalizing Symptoms and Drinking to Cope

This is the final version. Available on open access from Frontiers MediaData Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Socioeconomic deprivation is associated with greater alcohol problems despite lower alcohol consumption, but the mechanisms underpinning this alcohol harm paradox remain obscure. Fragmented published evidence collectively supports a multistage causal risk pathway wherein socioeconomic deprivation increases the probability of exposure to aversive experience, which promotes internalizing symptoms (depression and anxiety), which promotes drinking alcohol to cope with negative affect, which in turn accelerates the transition from alcohol use to dependence. To evaluate this proposed risk pathway, 219 hazardous drinkers from an undergraduate population completed questionnaires assessing these constructs in a single, cross sectional, online survey. Partial correlation coefficients revealed that each variable showed the strongest unique association with the next variable in the proposed multistage model, when adjusting for the other variables. Bootstrapped serial mediation analysis revealed that the indirect pathway linking all the variables in the proposed serial order was significant, while all other permutations were non-significant. Network centrality analysis corroborated the serial order of this indirect path. Finally, risk ratios estimated by categorizing the variables suggested that socioeconomic deprivation increased the risk of aversive experience by 32%, which increased the risk of internalizing symptoms by 180%, which increased the risk of drinking to cope by 64%, which increased susceptibility to alcohol dependence by 59%. These preliminary findings need to be corroborated by future research, nevertheless, they call for prevention strategies founded on social justice and the minimization of aversive experience in socially deprived individuals to mitigate mental health problems, maladaptive coping and addiction.Alcohol Research UKMedical Research Council (MRC

Time course of airway remodelling after an acute chlorine gas exposure in mice

Accidental chlorine (Cl2) gas inhalation is a common cause of acute airway injury. However, little is known about the kinetics of airway injury and repair after Cl2 exposure. We investigated the time course of airway epithelial damage and repair in mice after a single exposure to a high concentration of Cl2 gas. Mice were exposed to 800 ppm Cl2 gas for 5 minutes and studied from 12 hrs to 10 days post-exposure. The acute injury phase after Cl2 exposure (≤ 24 hrs post-exposure) was characterized by airway epithelial cell apoptosis (increased TUNEL staining) and sloughing, elevated protein in bronchoalveolar lavage fluid, and a modest increase in airway responses to methacholine. The repair phase after Cl2 exposure was characterized by increased airway epithelial cell proliferation, measured by immunoreactive proliferating cell nuclear antigen (PCNA), with maximal proliferation occurring 5 days after Cl2 exposure. At 10 days after Cl2 exposure the airway smooth muscle mass was increased relative to controls, suggestive of airway smooth muscle hyperplasia and there was evidence of airway fibrosis. No increase in goblet cells occurred at any time point. We conclude that a single exposure of mice to Cl2 gas causes acute changes in lung function, including pulmonary responsiveness to methacholine challenge, associated with airway damage, followed by subsequent repair and airway remodelling

Prospects for progress on health inequalities in England in the post-primary care trust era : professional views on challenges, risks and opportunities

Background - Addressing health inequalities remains a prominent policy objective of the current UK government, but current NHS reforms involve a significant shift in roles and responsibilities. Clinicians are now placed at the heart of healthcare commissioning through which significant inequalities in access, uptake and impact of healthcare services must be addressed. Questions arise as to whether these new arrangements will help or hinder progress on health inequalities. This paper explores the perspectives of experienced healthcare professionals working within the commissioning arena; many of whom are likely to remain key actors in this unfolding scenario. Methods - Semi-structured interviews were conducted with 42 professionals involved with health and social care commissioning at national and local levels. These included representatives from the Department of Health, Primary Care Trusts, Strategic Health Authorities, Local Authorities, and third sector organisations. Results - In general, respondents lamented the lack of progress on health inequalities during the PCT commissioning era, where strong policy had not resulted in measurable improvements. However, there was concern that GP-led commissioning will fare little better, particularly in a time of reduced spending. Specific concerns centred on: reduced commitment to a health inequalities agenda; inadequate skills and loss of expertise; and weakened partnership working and engagement. There were more mixed opinions as to whether GP commissioners would be better able than their predecessors to challenge large provider trusts and shift spend towards prevention and early intervention, and whether GPs’ clinical experience would support commissioning action on inequalities. Though largely pessimistic, respondents highlighted some opportunities, including the potential for greater accountability of healthcare commissioners to the public and more influential needs assessments via emergent Health & Wellbeing Boards. Conclusions - There is doubt about the ability of GP commissioners to take clearer action on health inequalities than PCTs have historically achieved. Key actors expect the contribution from commissioning to address health inequalities to become even more piecemeal in the new arrangements, as it will be dependent upon the interest and agency of particular individuals within the new commissioning groups to engage and influence a wider range of stakeholders.</p

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Pleistocene Climate, Phylogeny, and Climate Envelope Models: An Integrative Approach to Better Understand Species' Response to Climate Change

Mean annual temperature reported by the Intergovernmental Panel on Climate Change increases at least 1.1°C to 6.4°C over the next 90 years. In context, a change in climate of 6°C is approximately the difference between the mean annual temperature of the Last Glacial Maximum (LGM) and our current warm interglacial. Species have been responding to changing climate throughout Earth's history and their previous biological responses can inform our expectations for future climate change. Here we synthesize geological evidence in the form of stable oxygen isotopes, general circulation paleoclimate models, species' evolutionary relatedness, and species' geographic distributions. We use the stable oxygen isotope record to develop a series of temporally high-resolution paleoclimate reconstructions spanning the Middle Pleistocene to Recent, which we use to map ancestral climatic envelope reconstructions for North American rattlesnakes. A simple linear interpolation between current climate and a general circulation paleoclimate model of the LGM using stable oxygen isotope ratios provides good estimates of paleoclimate at other time periods. We use geologically informed rates of change derived from these reconstructions to predict magnitudes and rates of change in species' suitable habitat over the next century. Our approach to modeling the past suitable habitat of species is general and can be adopted by others. We use multiple lines of evidence of past climate (isotopes and climate models), phylogenetic topology (to correct the models for long-term changes in the suitable habitat of a species), and the fossil record, however sparse, to cross check the models. Our models indicate the annual rate of displacement in a clade of rattlesnakes over the next century will be 2 to 3 orders of magnitude greater (430-2,420 m/yr) than it has been on average for the past 320 ky (2.3 m/yr)

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Fitness Cost of Resistance to Bt Cotton Linked with Increased Gossypol Content in Pink Bollworm Larvae

Fitness costs of resistance to Bacillus thuringiensis (Bt) crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella), resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives