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Background: Diabetes and cardiovascular disease increase the risk of incident cognitive dysfunction. Identification of novel biochemical markers for cognitive dysfunction may identify people at the highest risk while yielding insights regarding the pathophysiology of cognitive dysfunction. Objective: To identify cardiovascular biomarkers in serum that are independent predictors of cognitive dysfunction in individuals with dysglycemia. Methods: This analysis was conducted in 8,365 participants in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial whose stored serum was analyzed for 238 cardio-metabolic biomarkers and completed a baseline Mini-Mental State Examination (MMSE). Fine and Gray sub distribution hazard models accounting for the competing risk of death accounting for clinical risk factors and the baseline MMSE were used to identify biomarkers that predicted incident cognitive dysfunction (MMSE

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

Following the outbreak of COVID-19, social distancing restrictions limited access to face-to-face mental health services in Western Australia (WA), necessitating a rapid transition to non-face-to-face alternatives, including telehealth. The current study investigated barriers and facilitators to telehealth access and engagement, and preferences for child and youth mental health service delivery during and beyond COVID-19. Three participant groups were recruited via social media and partner organisations, and completed a tailored online survey: i) young people (14–25 years) who had ever accessed or attempted to access mental health support or services (n = 84), ii) parents of young people with a child aged 0–25 years who had ever accessed or attempted to access mental health support or services with or on behalf of their child (n = 68), and iii) professionals working in the child or youth mental health sector (n = 167). Regarding barriers to engagement, young people were primarily concerned with the privacy implications of telehealth and its efficacy relative to face-to-face alternatives. Parents and clinicians were more concerned with the technological pitfalls of telehealth (e.g., internet-connectivity, picture/sound issues). Telehealth’s accessibility was highlighted as a facilitator for all groups. Although certain participant groups were considered to be more suited to telehealth than others, most participants endorsed a blended approach to the future provision of mental health services. To facilitate a blended approach to the delivery of child and youth mental health services, participants recommended more reliable and affordable internet access, implementing funding models that support telehealth delivery, and training for clinical staff. What is already known about this topic:At the time of writing, Western Australia has been fortunate enough to resist a large-scale outbreak of COVID-19, making the state relatively unique in its experience of the pandemic. Despite this, the state has experienced periods of social distancing requirements and associated impact on mental health service provision.Young people have been especially susceptible to mental health decline during the pandemic.Social distancing requirements have necessitated the rapid transition of mental health service provision from face-to-face to non-face-to-face alternatives. At the time of writing, Western Australia has been fortunate enough to resist a large-scale outbreak of COVID-19, making the state relatively unique in its experience of the pandemic. Despite this, the state has experienced periods of social distancing requirements and associated impact on mental health service provision. Young people have been especially susceptible to mental health decline during the pandemic. Social distancing requirements have necessitated the rapid transition of mental health service provision from face-to-face to non-face-to-face alternatives. What this topic adds:Findings from this study provide localised insights into barriers and facilitators to engagement with non-face-to-face service delivery from the perspective of children and young people, carers and mental health professionals.Despite concerns about the relative efficacy of telehealth compared to traditional face-to-face services and challenges with technology, the majority of young people, parents, and mental health professionals in the study felt that moving forwards, child and youth mental health services should be provided using a flexible, blended approach where both face-to-face and non-face-to-face options are available. Findings from this study provide localised insights into barriers and facilitators to engagement with non-face-to-face service delivery from the perspective of children and young people, carers and mental health professionals. Despite concerns about the relative efficacy of telehealth compared to traditional face-to-face services and challenges with technology, the majority of young people, parents, and mental health professionals in the study felt that moving forwards, child and youth mental health services should be provided using a flexible, blended approach where both face-to-face and non-face-to-face options are available.

Objective To review and synthesise qualitative literature regarding the psychological outcomes following paediatric burn injuries, and to determine if children and adolescents who experience a burn injury have elevated risk of psychopathology following the injury. Design Systematic review of quantitative and qualitative studies. Data sources Informit health, Medline, Embase, and PsycINFO were searched from January 2010 to December 2020. Data extraction and synthesis Two reviewers screened articles, and one reviewer extracted data (with cross-checking from another reviewer) from the included studies and assessed quality using an established tool. Narrative synthesis was used to synthesise the findings from the quantitative studies, and thematic synthesis was used to synthesise the findings of included qualitative studies. Results Searches yielded 1240 unique titles, with 130 retained for full-text screening. Forty-five studies from 17 countries were included. The psychological outcomes included in the studies were mental health diagnoses, medication for mental illness, depression, anxiety, stress, fear, post-traumatic stress, post-traumatic growth, emotional issues, self-harm, self-esteem, self-concept, stigmatisation, quality of life, level of disability, resilience, coping, and suicidality. Conclusions Our findings highlight paediatric burn patients as a particularly vulnerable population following a burn injury. Studies suggest elevated anxiety and traumatic stress symptoms, and higher rates of psychopathology in the long-term. Further research is recommended to determine the psychological outcomes in the other mental health domains highlighted in this review, as findings were mixed. Clinical care teams responsible for the aftercare of burn patients should involve psychological support for the children and families to improve outcomes.

Summary Background The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries. Methods We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events. Findings Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all p trend trend trend =0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol. Interpretation Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk. Funding Full funding sources listed at the end of the paper (see Acknowledgments).

This paper explores the complex structures of recent free-trade agreements (FTAs) between the European Union and developing countries, surveys the main factors determining their economic effects, and presents quantitative simulations of the effects of these agreements. Limitations of product coverage substantially reduce the potential benefits of the agreements compared to full bilateral free trade, while only the Mexico, Chile, and Turkey agreements have trade related commitments which are wider and deeper than the preferential reduction in tariffs. In the case of Egypt, existing levels of protection mean that it is moving toward regional free trade with many domestic distortions still in place, producing a significant loss for the Egyptian economy.

Since the middle of the1990s the EU has vigorously pursued a policy of replacing non– reciprocal preferences for the developing countries in the Mediterranean, Latin America and with South Africa, with bilateral free–trade agreements. This article examines the content of these agreements and the empirical evidence on their likely effects and concludes that they are ‘broad’ but ‘shallow’ agreements. The static effect are likely to be very small or negative while the potential dynamic gains are problematic, especially regarding the concept of a ‘lock in’ to trade liberalisation, unless there are greater commitments to trade related issues by both sides and especially by the EU.

The EU has opened up its market to duty and quota free imports from the least developed countries. This article outlines the key elements of this initiative and the factors determining its likely effects and argues that the EU must also liberalise and reform its prefernntial rules of origin if the initiative is to be effective in achieving its objectives.

Background: Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study's four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated abnormal laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

The establishment of the World Trade Organisation (WTO) in 1995 reflected and reinforced significant shifts in global orthodoxies in favour of the liberalisation of world trade, and posed problems for trading arrangements such as the Lome Conventions between the European Union (EU) and the 70 African, Caribbean and Pacific (ACP) states, which had initially been established in the very different setting of the mid-1970s. Integral to the Lome Conventions has been the principle of non-reciprocity, under which the EU offered preferential conditions for access to its markets by products originating in the ACP states, without any requirement for reciprocal concessions (other than most-favoured-nation status) by the ACP. These preferences are due to expire with the 4th Lome Convention in February 2000. Because they are non-reciprocal, these preferences cannot qualify under Article XXIV of the General Agreement on Tariffs and Trade (GATT) of 1947. Being available only to a particular group of developing countries, they are discriminatory and cannot be regarded as being covered by Part IV of the GATT, or the Enabling Clause of 1979, since these measures only sanction special, differential and preferential treatment for all developing countries. As a result of the changed climate of opinion in the World Trade Organisation (WTO), emphasising the obligation of members to bring their trade measures into conformity with WTO disciplines, the EU sought and obtained a waiver from Article I (principle of non-discrimination) for the remaining duration of the Convention, leaving open the arrangements to be put into effect after 2000.In the public discussions and consultations on a successor arrangement to Lome, the European Commission has emphasised the need for such an arrangement to be compatible with WTO requirements, so as to ensure the legal security of preferences. It is therefore envisaged that Lome preferences will be available only to the least developed countries (LLDCs), but will be generalised to all of the least developed countries, including for example Bangladesh, Bhutan, Cambodia, Lao D.R., Maldives, Nepal and Yemen, and not just to members of the ACP Group. The Commission has proposed that the non-LLDC ACP countries should be offered a series of regional and sub-regional free trade agreements. Not only would such arrangements seek to be WTO compatible, but the Commission also sees reciprocal regional agreements as stepping stones to fully liberalised trade and the integration of the developing countries into the world economy – an important development cooperation objective of the Maastricht Treaty.This article examines the Commission's proposals, and analyses the likely static and dynamic effects of a free trade agreement on the African ACP countries. It concludes by questioning whether the Commission's proposals would assist, rather than hinder, the regional integration and greater participation of these countries in the world economy.

We conducted a systematic review and meta-analysis to determine if pre-operative brain natriuretic peptide (BNP) (i.e., BNP or N-terminal pro-B-type natriuretic peptide [NT-proBNP]) is an independent predictor of 30-day adverse cardiovascular outcomes after noncardiac surgery.Pre-operative clinical cardiac risk indices have only modest predictive power. BNP predicts adverse cardiovascular outcomes in a variety of nonsurgical settings and may similarly predict these outcomes in the perioperative setting.We employed 5 search strategies (e.g., searching bibliographic databases), and we included all studies that assessed the independent prognostic value of pre-operative BNP measurement as a predictor of cardiovascular complications after noncardiac surgery. We determined study eligibility and conducted data abstraction independently and in duplicate. We calculated a pooled odds ratio using a random effects model.Nine studies met eligibility criteria, and included a total of 3,281 patients, among whom 314 experienced 1 or more perioperative cardiovascular complications. The average proportion of patients with elevated BNP was 24.8% (95% confidence interval [CI]: 20.1 to 30.4%; I(2) = 89%). All studies showed a statistically significant association between an elevated pre-operative BNP level and various cardiovascular outcomes (e.g., a composite of cardiac death and nonfatal myocardial infarction; atrial fibrillation). Data pooled from 7 studies demonstrated an odds ratio (OR) of 19.3 (95% CI: 8.5 to 43.7; I(2) = 58%). The pre-operative BNP measurement was an independent predictor of perioperative cardiovascular events among studies that only considered the outcomes of death, cardiovascular death, or myocardial infarction (OR: 44.2, 95% CI: 7.6 to 257.0, I(2) = 51.6%), and those that included other outcomes (OR: 14.7, 95% CI: 5.7 to 38.2, I(2) = 62.2%); the p value for interaction was 0.28.These results suggest that an elevated pre-operative BNP or NT-proBNP measurement is a powerful, independent predictor of cardiovascular events in the first 30 days after noncardiac surgery.

A substantial body of opinion argues that, at best, trade preferences for developing countries have had little or no trade stimulating effect. This paper argues that this view fails to distinguish between the effects of EU and US preferences and, in the case of EU preferences, can be rejected on the basis of recent empirical evidence. The implications of the Appellate Body ruling on EU special preferences and the Commission's proposals for the reform of the rules of origin are then examined. The paper concludes with an examination of proposals to increase the effectiveness of the GSP+.

Raised glucose levels extending from normal into the diabetic range (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial.Glucose tolerance, HbA1c, other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent.The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA1c in all participants (P0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P0.0001) descent. This progressive curvilinear relationship was most apparent at HbA1c levels5.7%. The HbA1c-AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P0.004). Both diabetes (P = 0.002) and HbA1c (P0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA1c (P0.0001) but not diabetes (P = 0.6) was a significant determinant.The degree of AS is related to the level of HbA1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA1c and AS was observed within different ethnic groups.

The ACP countries and the EU recognise that the present non-reciprocal and discriminatory Lome preferences must be replaced with WTO compatible arrangements. This means that the agreements conform either to the free trade area provisions of Article XXIV or to the GSP. This article sets out the key elements of ACP preferences and examines the potential advantages and disadvantages for various groups of ACP countries of possible forms of free trade areas and a ‘Lome-equivalent’ GSP.

The Lome IV Convention, which provides the framework for development cooperation between the European Union (EU) and 71 African, Caribbean and Pacific (ACP) states, expires in the year 2000. The form that a successor arrangement would take, will be of considerable importance to the ACP countries, more than half of which belong to the Commonwealth. This study examines the possible options for the next phase of ACPEU cooperation, addressing the diverse trade and development interests of ACP countries.

This paper presents comprehensive data on the growth, structure and forms of involvement of multinational enterprises in the international hotel industry, and uses this data to provide empirical support for the eclectic theory of international production. Our understanding of the international hotel industry is that the ownership of a hotel often has the characteristics of portfolio investment and that the owners may have little knowledge of hotel operations. In these circumstances they will invariably employ a professional management company to run the hotel under a long term contract providing them with full control over the operation of the hotel. A particular feature of this paper is therefore to distinguish between, what we term, ‘equity-based control’ and ‘contract-based control’ of the enterprise and to point out the implications of this distinction for the analysis of the multinational enterprise.

Despite the prevalence of international hotel chains in the tourism sector of developing countries, little research has been carried out on the structure of the industry, the sources of the competitive advantages of the hotel chains over indigenous hotels, reasons for the alternative forms of involvement of the hotel chains and deriving from this, their potential and actual impact on host countries. This article applies theories developed for the multinational enterprise in the manufacturing sector, to original data and observations on the international hotel industry. Given the state of the art and the limited information on the impact of MNE hotels, the paper is principally concerned with generating potentially useful hypotheses for consideration by host governments and to provide a framework for further research. Certain policy conclusions however, are drawn from the analysis, especially regarding the appropriate from of involvement by the international hotels.

Original data are presented on the growth of foreign-based international hotel chains and their distribution by home and host countries as well as by the principal sphere of economic activity of the parent company. A feature of the paper is the analysis of the source of competitive advantage of the international hotel chains and the non-equity forms of involvement which particularly characterize the industry. These characteristics may require that a clear distinction be made between ownership of an international-class hotel and control over its operations.