Showing papers by "University of Gothenburg published in 2017"
Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
Gregory A. Roth1, Catherine O. Johnson1, Amanuel Alemu Abajobir2, Foad Abd-Allah3 +170 more•Institutions (99)
TL;DR: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden, finding that CVDs remain a major cause of health loss for all regions of the world.
2,525 citations
Wayne State University1, Columbia University2, Trinity College, Dublin3, Imperial College London4, University of Glasgow5, French Institute of Health and Medical Research6, University of Western Ontario7, Children's Hospital Oakland Research Institute8, University of the Witwatersrand9, Technische Universität München10, University of Western Australia11, Sahlgrenska University Hospital12, Oregon Health & Science University13, University of Texas Southwestern Medical Center14, University of Adelaide15, University of Copenhagen16, Copenhagen University Hospital17, University Medical Center Groningen18, Helsinki University Central Hospital19, Hacettepe University20, Charité21, Saarland University22, University of Gothenburg23, University of Milan24
TL;DR: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
Abstract: Aims
To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).
2,003 citations
TL;DR: The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries, and the contributions of changes in prevalence versus population growth and ageing to the increase.
1,573 citations
TL;DR: The gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals, which adds AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
1,115 citations
University of Gothenburg1, Carlos III Health Institute2, University of Girona3, University of Toulouse4, Barcelona Supercomputing Center5, Catalan Institution for Research and Advanced Studies6, French Institute of Health and Medical Research7, Paul Sabatier University8, Sahlgrenska University Hospital9, University of Copenhagen10
TL;DR: It is shown that metformin affected pathways with common biological functions in species from two different phyla, and many of the met formin-regulated genes in these species encoded metalloproteins or metal transporters, which provides support for the notion that altered gut microbiota mediates some of metformIn's antidiabetic effects.
Abstract: Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.
1,022 citations
University of Cambridge1, University of the Basque Country2, National Autonomous University of Mexico3, University of Córdoba (Spain)4, Corvinus University of Budapest5, University of Southern Denmark6, University of Gothenburg7, University of East Anglia8, Lund University9, University of Kiel10, United Nations11, Helmholtz Centre for Environmental Research - UFZ12, University of Khartoum13, King Abdulaziz City for Science and Technology14, University of Washington15, University of Oxford16, Ministry of Forestry17, University College Dublin18, National University of Cordoba19, Carthage University20, University of Chile21, Harvard University22, Norwegian University of Life Sciences23, University of Pretoria24, University of Antwerp25, Wetlands International26, Universidade Federal Rural do Rio de Janeiro27, International Union for Conservation of Nature and Natural Resources28, Council for Scientific and Industrial Research29, University of Western Australia30, National University of General Sarmiento31, Calcutta Institute of Engineering and Management32, European Commission33, Government of Canada34, Finnish Environment Institute35, Federal University of Rio de Janeiro36, Pontifical Catholic University of Rio de Janeiro37, International Institute of Minnesota38, Victoria University of Wellington39, Indian Institute of Forest Management40, University of Tokyo41
TL;DR: In this paper, the authors present the rationale for the inclusive valuation of nature's contributions to people (NCP) in decision making, as well as broad methodological steps for doing so, and argue that transformative practices aiming at sustainable futures would benefit from embracing such diversity, which require recognizing and addressing power relationships across stakeholder groups that hold different values on human nature-relations and NCP.
985 citations
VU University Medical Center1, University of Glasgow2, Paris Descartes University3, Medical University of Vienna4, University of Southern Denmark5, Umeå University6, University of Oslo7, University of Gothenburg8, Katholieke Universiteit Leuven9, University of Cantabria10, Dudley Group NHS Foundation Trust11, University of Debrecen12, University of Manchester13
TL;DR: The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased, which underscores the need for CVDrisk management in these patients.
Abstract: Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.
865 citations
TL;DR: In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls.
Abstract: BackgroundLong-term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes. MethodsWe included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population. ResultsAmong patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person-years were as follows: death from any cause, −31.4 (95% confidence interval [CI], −56.1 to −6.7); death from cardiovascular disease, −26.0 (95% CI, −42.6 to −9.4); death from coronary heart disease, −21.7 (95% CI, −37.1 to −6.4); and hospitalization for cardiovascular disease, −45.7 (95% CI, −71.4 to −20.1). Absolute changes per 10,000 p...
845 citations
TL;DR: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality.
786 citations
Simon Fraser University1, Population Health Research Institute2, University of Edinburgh3, Aga Khan University4, St. John's University5, Post Graduate Institute of Medical Education and Research6, University of Gothenburg7, Centers for Disease Control and Prevention8, Government Medical College, Thiruvananthapuram9, Dubai Health Authority10, Mount Sinai Hospital11, Isfahan University of Medical Sciences12, Istanbul Medeniyet University13, University of Wrocław14, University of La Frontera15
TL;DR: Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle- income, and high-income countries.
Catholic University of the Sacred Heart1, University of Belgrade2, University of Helsinki3, Pierre-and-Marie-Curie University4, University of Gothenburg5, Otto-von-Guericke University Magdeburg6, Wageningen University and Research Centre7, Helsinki University Central Hospital8, VU University Medical Center9
TL;DR: This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
Abstract: Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
TL;DR: The value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS) is explored.
Abstract: OBJECTIVE
Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).
METHODS
sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow-up = 3.1 years, interquartile range [IQR] = 2.0-4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.
RESULTS
sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2-65.3) or both brain and spinal gadolinium-enhancing lesions (62.5pg/ml, IQR = 42.7-71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9-41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease-modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC-based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval [CI] = 1.21-3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07-5.42, p = 0.034).
INTERPRETATION
These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857-870.
Mayo Clinic1, Yale University2, Case Western Reserve University3, Children's National Medical Center4, University of California, San Diego5, University of Miami6, Virginia Commonwealth University7, University of Calgary8, Cleveland Clinic9, University of Gothenburg10, University of British Columbia11, Saint Louis University12, Johns Hopkins University13, Dartmouth College14, University of Washington15, University of Texas MD Anderson Cancer Center16, Veterans Health Administration17, Royal Melbourne Hospital18, Cedars-Sinai Medical Center19, University of Colorado Denver20
TL;DR: Fred M. Kusumoto,MD, FHRS, FACC, Chair, Mark H. Schoenfeld, MD, F hrs, F ACC, FAHA, CCDS, Vice-Chair, Bruce L. Wilkoff, MD; Ulrika M. Birgersdotter-Green, MD.
TL;DR: The beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
TL;DR: It is suggested that Aβ fibrils start to accumulate predominantly within certain parts of the DMN in preclinical AD and already then affect brain connectivity before neurodegeneration occurs.
Abstract: It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer's disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who subsequently convert to having abnormal CSF Aβ42. The earliest Aβ accumulation is further associated with hypoconnectivity within the DMN and between the DMN and the frontoparietal network, but not with brain atrophy or glucose hypometabolism. Our results suggest that Aβ fibrils start to accumulate predominantly within certain parts of the DMN in preclinical AD and already then affect brain connectivity.
TL;DR: In this article, the variation of anti-corruption and anti-elite saliency in party positioning across Europe was studied. And it was shown that while anticorruption salience is primarily related to the (regional) context in which a party operates, anti-ELite salience was primarily a function of party ideology, and extreme left and extreme conservative (TAN) parties are significantly more likely to emphasize antielite views.
Abstract: This article addresses the variation of anti-corruption and anti-elite salience in party positioning across Europe. It demonstrates that while anti-corruption salience is primarily related to the (regional) context in which a party operates, anti-elite salience is primarily a function of party ideology. Extreme left and extreme conservative (TAN) parties are significantly more likely to emphasize anti-elite views. Through its use of the new 2014 Chapel Hill Expert Survey wave, this article also introduces the dataset.
TL;DR: The present article summarizes the most important co-morbidities of obesity and their prevalence and describes classification and grading systems that can be used to assess the individual and combined impact of co-Morbid conditions on mortality risk.
Abstract: Obesity and its repercussions constitute an important source of morbidity, impaired quality of life and its complications can have a major bearing on life expectancy. The present article summarizes the most important co-morbidities of obesity and their prevalence. Furthermore, it describes classification and grading systems that can be used to assess the individual and combined impact of co-morbid conditions on mortality risk. The literature was screened for assessment tools that can be deployed in the quantification of morbidity and mortality risk in individual patients. Thirteen specific domains have been identified that account for morbidity and mortality in obesity. Cardiovascular disease (CVD) and cancer account for the greatest mortality risk associated with obesity. The King’s Criteria and Edmonton Obesity Staging System (EOSS) were identified as useful tools for the detection and monitoring of individual patient mortality risk in obesity care. The stark facts on the complications of obesity should be capitalized on to improve patient management and knowledge and referred to in the wider dissemination of public health messages aimed at improving primary prevention.
TL;DR: It is found that macromolecular crowding drives assembly of the key PCM scaffold protein SPD-5 into spherical condensates that morphologically and dynamically resemble in vivo PCM.
TL;DR: Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c.
Abstract: IMPORTANCE The majority of individuals with type 1 diabetes do not meet recommended glycemic targets. OBJECTIVE To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections. DESIGN, SETTING, AND PARTICIPANTS Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5%(58 mmol/mol) treated with multiple daily insulin injections. INTERVENTIONS Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks. MAIN OUTCOMES AND MEASURES Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied. RESULTS Among 161 randomized participants, mean age was 43.7 years, 45.3%were women, and mean HbA1c was 8.6%(70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92%(63 mmol/mol) during continuous glucose monitoring use and 8.35%(68 mmol/mol) during conventional treatment (mean difference, -0.43%[95%CI, -0.57%to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia. CONCLUSIONS AND RELEVANCE Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Furthe. (Less)
York University1, Royal Berkshire NHS Foundation Trust2, RMIT University3, University of Washington4, University of Gothenburg5, Churchill Hospital6, JDRF7, Université de Montréal8, University of Dundee9, University College London Hospitals NHS Foundation Trust10, University of California, Irvine11, AstraZeneca12, Princess Margaret Hospital for Children13, University of Western Australia14, Telethon Institute for Child Health Research15, University of Colorado Denver16, University of Southern California17, Joslin Diabetes Center18, Boston Children's Hospital19
TL;DR: This Review provides an up-to-date consensus on exercise management for individuals with type 1 diabetes who exercise regularly, including glucose targets for safe and effective exercise, and nutritional and insulin dose adjustments to protect against exercise-related glucose excursions.
University of Antwerp1, University of Gothenburg2, Norwegian University of Science and Technology3, University of Zurich4, University of Amsterdam5, University of Vienna6, University of Southern Denmark7, University of Lisbon8, Paris-Sorbonne University9, Adam Mickiewicz University in Poznań10, National and Kapodistrian University of Athens11, King Juan Carlos University12, University of Pavia13, Ludwig Maximilian University of Munich14, Hebrew University of Jerusalem15, Loughborough University16
TL;DR: In this article, the authors review research on key changes and trends in political information environments and assess their democratic implications, focusing on advanced postindustrial democracies and six concerns that are all closely linked to the dissemination and acquisition of political knowledge: (1) declining supply of political information, (2) declining quality of news, (3) increasing media concentration and declining diversity of news.
Abstract: During the last decennia media environments and political communication systems have changed fundamentally. These changes have major ramifications for the political information environments and the extent to which they aid people in becoming informed citizens. Against this background, the purpose of this article is to review research on key changes and trends in political information environments and assess their democratic implications. We will focus on advanced postindustrial democracies and six concerns that are all closely linked to the dissemination and acquisition of political knowledge: (1) declining supply of political information, (2) declining quality of news, (3) increasing media concentration and declining diversity of news, (4) increasing fragmentation and polarization, (5) increasing relativism and (6) increasing inequality in political knowledge.
TL;DR: A significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4 is identified and identified.
Abstract: Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the
understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried
by the true risk variants and the corresponding statistical power to observe such effects given the study design and
sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however,
these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).
Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping
data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide
genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary
statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).
Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription
factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social
skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia
which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P=9 ×10−6). We further
combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to
identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12
novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a
‘neurodevelopmental hub’ on chromosome 8p11.23.
Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common
variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia
and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
University of Exeter1, Boston University2, German Center for Neurodegenerative Diseases3, Stockholm University4, French Institute of Health and Medical Research5, Indiana University6, Kyushu University7, Erasmus University Rotterdam8, University of Michigan9, University of Zaragoza10, Newcastle University11, University of Gothenburg12, University of Cambridge13
TL;DR: In this article, the authors synthesize the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria.
Abstract: Dementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.
TL;DR: Variation in the prevalence of obesity across the European continent suggests the existence of different profiles of risk or protection factors operating in different countries, which could indicate suitable targets for interventions to help manage the obesity epidemic in Europe.
Abstract: Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the ‘Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe.
University of Geneva1, Sahlgrenska University Hospital2, University of Gothenburg3, Istituto Universitario Di Studi Superiori Di Pavia4, VU University Amsterdam5, Stockholm County Council6, University Hospital of Lausanne7, University of Zurich8, Lund University9, University of Manchester10, Mayo Clinic11, University of Genoa12, European Association of Nuclear Medicine13, Karolinska University Hospital14, Alzheimer's Association15, University of Amsterdam16, Vita-Salute San Raffaele University17, Queen Mary University of London18, Beta19, University of Bern20, University of Brescia21, Geneva College22, Alzheimer Europe23, University of Malta24, University College London25, Stanford University26, University of Rostock27, German Center for Neurodegenerative Diseases28, Imperial College London29, Maastricht University30, St. Jude Children's Research Hospital31, Karolinska Institutet32
TL;DR: A strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers is developed.
Abstract: The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.
TL;DR: IBS symptom severity is found to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species.
Karolinska University Hospital1, Leipzig University2, Ludwig Maximilian University of Munich3, Greifswald University Hospital4, Indiana University – Purdue University Indianapolis5, University of Hamburg6, Aarhus University7, Technische Universität München8, University of Gothenburg9, Radboud University Nijmegen10, University of Giessen11, University of Verona12, Aalborg University13, Erasmus University Rotterdam14
TL;DR: The 2016 HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence and should serve as a reference standard for existing management of the disease and as a guide for future clinical research.
Abstract: BackgroundThere have been substantial improvements in the management of chronic pancreatitis, leading to the publication of several national guidelines during recent years. In collaboration with Un...
TL;DR: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion.
Abstract: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies – original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms. A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990–2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1–5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used. Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout. While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.
TL;DR: In this paper, the authors use the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to improve and expand the quantification of personal health-care access and quality for 195 countries and territories from 1990 to 2015.