Showing papers by "University of Southern Denmark published in 2019"
University of Bristol1, University Hospitals Bristol NHS Foundation Trust2, Monash University3, French Institute of Health and Medical Research4, Paris Descartes University5, Cochrane Collaboration6, St George's, University of London7, University of York8, Queen Mary University of London9, Clinical Trial Service Unit10, Harvard University11, University of Oxford12, Odense University Hospital13, University of Southern Denmark14, University of Alberta15, University of Toronto16, University of Manchester17, Johns Hopkins University18, McGill University19, University College London20
TL;DR: The Cochrane risk-of-bias tool has been updated to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
Abstract: Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.
9,228 citations
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
698 citations
Lund University1, University of Copenhagen2, Molecular Medicine Partnership Unit3, ETH Zurich4, Fudan University5, German Cancer Research Center6, University of São Paulo7, University of Trento8, European Institute of Oncology9, Tokyo Institute of Technology10, Japan Society for the Promotion of Science11, University of Tokyo12, Osaka University13, National Presto Industries14, City University of New York15, National Institutes of Health16, Huntsman Cancer Institute17, University of Southern Denmark18
TL;DR: A meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer identified a core set of 29 species significantly enriched in CRC metagenomes, establishing globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
Abstract: Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10−5). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics. Cross-study analysis defines fecal microbial species associated with colorectal cancer.
615 citations
university of lille1, University of Southern Denmark2, University of Calgary3, University of Wolverhampton4, Karolinska Institutet5, University of Melbourne6, Heidelberg University7, National University of Ireland, Galway8, University of Alberta9, Harvard University10, Centre Hospitalier Universitaire de Toulouse11, University of Caen Lower Normandy12, University of Paris13, Genmab14, Janssen Pharmaceutica15
TL;DR: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among thosewho received lenalidmide and Dexameth asone alone.
Abstract: Background Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought...
609 citations
University of Texas MD Anderson Cancer Center1, University of Chicago2, Roswell Park Cancer Institute3, Seattle Cancer Care Alliance4, University of Southern Denmark5, University of New South Wales6, Jikei University School of Medicine7, University of Oklahoma8, Kaplan Medical Center9, University of Utah10, Texas Oncology11, University of Pennsylvania12, University of Ulsan13, University of Alabama at Birmingham14, University of Oxford15, Washington University in St. Louis16, Kaiser Permanente17, Memorial Sloan Kettering Cancer Center18, AbbVie19
TL;DR: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliporib maintenance therapy led to significantly longer progression-free survival than carboplati plus pac Litaxel induction therapy alone.
Abstract: Background Data are limited regarding the use of poly(adenosine diphosphate [ADP]–ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance...
557 citations
University of São Paulo1, University of Trento2, European Institute of Oncology3, University of Turin4, Japan Society for the Promotion of Science5, Tokyo Institute of Technology6, University of Tokyo7, Osaka University8, National Presto Industries9, German Cancer Research Center10, Huntsman Cancer Institute11, University of Copenhagen12, University of Southern Denmark13, Virginia Bioinformatics Institute14, City University of New York15
TL;DR: The combined analysis of heterogeneous CRC cohorts identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.
Abstract: Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies. Multicohort analysis identifies microbial signatures of colorectal cancer in fecal microbiomes.
478 citations
Laboratory of Molecular Biology1, University of Victoria2, University of Colorado Boulder3, National University of Singapore4, Pasteur Institute5, Biogen Idec6, Northeastern University7, University of Pennsylvania8, Novo Nordisk9, Scripps Research Institute10, Washington University in St. Louis11, University of Washington12, Johnson & Johnson13, Utrecht University14, University of Southern Denmark15, University of Massachusetts Amherst16, University of California, Berkeley17, University of Western Ontario18, Academy of Sciences of the Czech Republic19, Hebrew University of Jerusalem20, Iowa State University21, Hoffmann-La Roche22, Genentech23, University of Kansas24, York University25, University of Maryland, Baltimore26, Amgen27, University of Calgary28, University of Copenhagen29
TL;DR: Recommendations arising from community discussions emerging out of the first International Conference on Hydrogen-Exchange Mass Spectrometry (IC-HDX; 2017) are provided, meant to represent both a consensus viewpoint and an opportunity to stimulate further additions and refinements as the field advances.
Abstract: Hydrogen deuterium exchange mass spectrometry (HDX-MS) is a powerful biophysical technique being increasingly applied to a wide variety of problems. As the HDX-MS community continues to grow, adoption of best practices in data collection, analysis, presentation and interpretation will greatly enhance the accessibility of this technique to nonspecialists. Here we provide recommendations arising from community discussions emerging out of the first International Conference on Hydrogen-Exchange Mass Spectrometry (IC-HDX; 2017). It is meant to represent both a consensus viewpoint and an opportunity to stimulate further additions and refinements as the field advances.
401 citations
TL;DR: The role of mountains as refugia for biodiversity may well come under threat, with ongoing global changes in climate and land use, likely playing a key role in generating and maintaining diversity.
Abstract: Mountains contribute disproportionately to the terrestrial biodiversity of Earth, especially in the tropics, where they host hotspots of extraordinary and puzzling richness. With about 25% of all land area, mountain regions are home to more than 85% of the world’s species of amphibians, birds, and mammals, many entirely restricted to mountains. Biodiversity varies markedly among these regions. Together with the extreme species richness of some tropical mountains, this variation has proven challenging to explain under traditional climatic hypotheses. However, the complex climatic characteristics of rugged mountain regions differ fundamentally from those of lowland regions, likely playing a key role in generating and maintaining diversity. With ongoing global changes in climate and land use, the role of mountains as refugia for biodiversity may well come under threat.
394 citations
TL;DR: Results indicate that VRET is an effective and equal medium for exposure therapy and relatively consistent across disorders.
387 citations
Nicole M. Warrington1, Robin N Beaumont2, Momoko Horikoshi3, Felix R. Day4 +242 more•Institutions (79)
TL;DR: An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.
Abstract: Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
323 citations
TL;DR: The high biodiversity of certain mountains reflects the interplay of multiple evolutionary mechanisms: enhanced speciation rates with distinct opportunities for coexistence and persistence of lineages, shaped by long-term climatic changes interacting with topographically dynamic landscapes.
Abstract: Mountain regions are unusually biodiverse, with rich aggregations of small-ranged species that form centers of endemism. Mountains play an array of roles for Earth’s biodiversity and affect neighboring lowlands through biotic interchange, changes in regional climate, and nutrient runoff. The high biodiversity of certain mountains reflects the interplay of multiple evolutionary mechanisms: enhanced speciation rates with distinct opportunities for coexistence and persistence of lineages, shaped by long-term climatic changes interacting with topographically dynamic landscapes. High diversity in most tropical mountains is tightly linked to bedrock geology—notably, areas comprising mafic and ultramafic lithologies, rock types rich in magnesium and poor in phosphate that present special requirements for plant physiology. Mountain biodiversity bears the signature of deep-time evolutionary and ecological processes, a history well worth preserving.
TL;DR: This review covers the use of blood flow restriction to enhance muscular strength and hypertrophy via training with resistance and aerobic exercise and preventing muscle atrophy using the technique passively.
Abstract: The current manuscript sets out a position stand for blood flow restriction (BFR) exercise, focusing on the methodology, application and safety of this mode of training. With the emergence of this technique and the wide variety of applications within the literature, the aim of this position stand is to set out a current research informed guide to BFR training to practitioners. This covers the use of BFR to enhance muscular strength and hypertrophy via training with resistance and aerobic exercise and preventing muscle atrophy using the technique passively. The authorship team for this article was selected from the researchers focused in BFR training research with expertise in exercise science, strength and conditioning and sports medicine.
Queen's University Belfast1, University of Düsseldorf2, Boston Children's Hospital3, Charles University in Prague4, Oslo University Hospital5, Medical University of Vienna6, University of Pécs7, Copenhagen University Hospital8, University of Leeds9, University of Bristol10, Umeå University11, Medical University of Silesia12, Lithuanian University of Health Sciences13, Trinity College, Dublin14, Dresden University of Technology15, Vrije Universiteit Brussel16, University of Luxembourg17, University of Southern Denmark18
TL;DR: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013, suggesting a doubling in incidence rate within approximately 20 years in Europe.
Abstract: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004–2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.
Erasmus University Rotterdam1, University of Southampton2, University Hospital Southampton NHS Foundation Trust3, University of Porto4, Paris Descartes University5, Sorbonne6, University of Southern California7, University of Crete8, Maastricht University9, National and Kapodistrian University of Athens10, University Medical Center Groningen11, Université de Sherbrooke12, Norwegian Institute of Public Health13, University of Bologna14, Nofer Institute of Occupational Medicine15, University of California, Davis16, Harvard University17, University of Illinois at Chicago18, University of Valencia19, National Institutes of Health20, University of Turku21, University of Bristol22, Helmholtz Centre for Environmental Research - UFZ23, Jagiellonian University Medical College24, Åbo Akademi University25, Harokopio University26, Public Health Research Institute27, University of Southern Denmark28, University of Copenhagen29, La Trobe University30, University of Helsinki31, University of Turin32, Radboud University Nijmegen33, University of Trieste34, University of Bergen35, Ludwig Maximilian University of Munich36, Slovak Medical University37, Utrecht University38, Pompeu Fabra University39
TL;DR: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights, however, the optimal gestations weight gain ranges had limited predictive value for the outcomes assessed.
Abstract: Importance Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures Gestational weight gain. Main Outcomes and Measures The main outcome termedany adverse outcomewas defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI Conclusions and Relevance In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.
TL;DR: Data is outlined from population-based studies on recent and long-term trends in diabetes-related complications that suggest the economic and social burden of diabetes is expected to rise due to changing demographics and lifestyle especially in middle- and low-income countries.
Abstract: The global prevalence of diabetes is predicted to increase dramatically in the coming decades as the population grows and ages, in parallel with the rising burden of overweight and obesity, in both developed and developing countries. Cardiovascular disease represents the principal cause of death and morbidity among people with diabetes, especially in those with type 2 diabetes mellitus. Adults with diabetes have 2-4 times increased cardiovascular risk compared with adults without diabetes, and the risk rises with worsening glycaemic control. Diabetes has been associated with 75% increase in mortality rate in adults, and cardiovascular disease accounts for a large part of the excess mortality. Diabetes-related macrovascular and microvascular complications, including coronary heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, chronic renal disease, diabetic retinopathy and cardiovascular autonomic neuropathy are responsible for the impaired quality of life, disability and premature death associated with diabetes. Given the substantial clinical impact of diabetes as a cardiovascular risk factor, there has been a growing focus on diabetes-related complications. While some population-based studies suggest that the epidemiology of such complications is changing and that rates of all-cause and cardiovascular mortality among individuals with diabetes are decreasing in high-income countries, the economic and social burden of diabetes is expected to rise due to changing demographics and lifestyle especially in middle- and low-income countries. In this review we outline data from population-based studies on recent and long-term trends in diabetes-related complications.
Roswell Park Cancer Institute1, Carolinas Healthcare System2, Mayo Clinic3, Cedars-Sinai Medical Center4, Emory University5, Universidade Nova de Lisboa6, Harvard University7, VU University Medical Center8, Sarah Cannon Research Institute9, National and Kapodistrian University of Athens10, University of Bologna11, Chartered Institute of Management Accountants12, University Hospital Heidelberg13, Memorial Sloan Kettering Cancer Center14, Oslo University Hospital15, University of Southern Denmark16, University of Rochester17, Boston University18, Columbia University19
TL;DR: Recommendations on imaging within and outside of clinical trials will help standardise imaging for monoclonal plasma cell disorders worldwide to allow the comparison of results and the unification of treatment approaches for multiple myeloma.
Abstract: Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in the investigation of multiple myeloma and often dictates the decision to start treatment. Furthermore, detection of minimal residual disease is important for prognosis determination and treatment planning, and it has underscored an unmet need for sensitive imaging methods that accurately assess patient response to multiple myeloma treatment. Low-dose whole-body CT has increased sensitivity compared with conventional skeletal survey in the detection of bone disease, which can reveal information leading to changes in therapy and disease management that could prevent or delay the onset of clinically significant morbidity and mortality as a result of skeletal-related events. Given the multiple options available for the detection of bone and bone marrow lesions, ranging from conventional skeletal survey to whole-body CT, PET/CT, and MRI, the International Myeloma Working Group decided to establish guidelines on optimal use of imaging methods at different disease stages. These recommendations on imaging within and outside of clinical trials will help standardise imaging for monoclonal plasma cell disorders worldwide to allow the comparison of results and the unification of treatment approaches for multiple myeloma.
Erasmus University Medical Center1, Medical University of Warsaw2, University of Valencia3, University of Porto4, Stockholm County Council5, Paris Descartes University6, Sorbonne7, Maastricht University8, University of Southern California9, University of Crete10, French Institute of Health and Medical Research11, National and Kapodistrian University of Athens12, University Medical Center Groningen13, University of Southampton14, Liverpool School of Tropical Medicine15, Norwegian Institute of Public Health16, Karolinska Institutet17, University of Bologna18, University Hospital Southampton NHS Foundation Trust19, Ludwig Maximilian University of Munich20, Nofer Institute of Occupational Medicine21, University of California, Davis22, University of Illinois at Chicago23, University of Western Australia24, National Institutes of Health25, University College Cork26, University of Bristol27, University of Turku28, Helmholtz Centre for Environmental Research - UFZ29, Jagiellonian University Medical College30, Åbo Akademi University31, Harokopio University32, University College Dublin33, University of Calgary34, Public Health Research Institute35, University of Copenhagen36, University of Southern Denmark37, La Trobe University38, Harvard University39, University of Helsinki40, University of Turin41, University of Trieste42, University of Bergen43, Slovak Medical University44, Boston Children's Hospital45, Utrecht University46, Pompeu Fabra University47, Bradford Royal Infirmary48
TL;DR: In this article, the authors conducted an individual participant data meta-analysis of data from 162,129 mothers and children from 37 pregnancy and birth cohort studies from Europe, North-America and Australia, using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal socio-demographic and life style related characteristics.
Abstract: Background:
Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these risks differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.
Methods and Findings:
We conducted an individual participant data meta-analysis of data from 162,129 mothers and children from 37 pregnancy and birth cohort studies from Europe, North-America and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges with the risks of overweight/obesity in early- (2.0-5.0 years), mid- (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal socio-demographic and life style related characteristics. We observed that a higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (Odds Ratios (OR) for overweight/obesity in early-, mid- and late childhood, respectively: 1.66 (95% Confidence Interval (CI): 1.56, 1.78), OR 1.91 (95% CI: 1.85, 1.98), and OR 2.28 (95% CI: 2.08, 2.50) for maternal overweight, OR 2.43 (95% CI: 2.24, 2.64), OR 3.12 (95% CI: 2.98, 3.27), and OR 4.47 (95% CI: 3.99, 5.23) for maternal obesity, and OR 1.39 (95% CI: 1.30, 1.49), OR 1.55 (95% CI: 1.49, 1.60), and 1.72 (95% CI: 1.56, 1.91) for excessive gestational weight gain. The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity and excessive gestational weight gain ranged from 10.2 to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (P-values for interactions of maternal BMI with gestational weight gain: p=0.038, p<0.001 and p=0.637, in early-, mid- and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North-America and Australia, results need to be interpreted with caution with respect to other populations.
Conclusions:
In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.
TL;DR: The cell biology of the post-stroke inflammatory response is summarized and pharmacological interventions targeting inflammation in the acute phase after a stroke that may be used alone or in combination with recanalization therapies are discussed.
Abstract: Inflammation is currently considered a prime target for the development of new stroke therapies. In the acute phase of ischemic stroke, microglia are activated and then circulating immune cells invade the peri-infarct and infarct core. Resident and infiltrating cells together orchestrate the post-stroke inflammatory response, communicating with each other and the ischemic neurons, through soluble and membrane-bound signaling molecules, including cytokines. Inflammation can be both detrimental and beneficial at particular stages after a stroke. While it can contribute to expansion of the infarct, it is also responsible for infarct resolution, and influences remodeling and repair. Several pre-clinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological interventions that target inflammation post-stroke. Experimental evidence shows that targeting certain inflammatory cytokines, such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-10, holds promise. However, as these cytokines possess non-redundant protective and immunoregulatory functions, their neutralization or augmentation carries a risk of unwanted side effects, and clinical translation is, therefore, challenging. This review summarizes the cell biology of the post-stroke inflammatory response and discusses pharmacological interventions targeting inflammation in the acute phase after a stroke that may be used alone or in combination with recanalization therapies. Development of next-generation immune therapies should ideally aim at selectively neutralizing pathogenic immune signaling, enhancing tissue preservation, promoting neurological recovery and leaving normal function intact.
TL;DR: There remains a need to better understand the fundamental mechanisms underlying the molecular pathways they mediate to design more effective anti-inflammatory and anti-cancer therapies.
Abstract: The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies (TNFSF/TNFRSF) include 19 ligands and 29 receptors that play important roles in the modulation of cellular functions. The commu...
TL;DR: In this paper, the authors investigated the relationship between green supply chain management and green innovation practices and the influence of these practices on the environmental performance in 123 manufacturing organizations with ISO 14001 certification.
Woolcock Institute of Medical Research1, University of British Columbia2, University of Cape Town3, St. Louis Children's Hospital4, University of Manitoba5, Ghent University Hospital6, University of Mainz7, Federal University of Bahia8, Imperial College London9, Kagoshima University10, The Chinese University of Hong Kong11, University of Illinois at Chicago12, China-Japan Friendship Hospital13, University of Southern Denmark14, University of Edinburgh15, Celal Bayar University16, Laval University17
TL;DR: The Global Initiative for Asthma no longer recommends treating adults/adolescents with asthma with short-acting bronchodilators alone and they should receive symptom-driven or a daily corticosteroid-containing inhaler, to reduce risk of severe exacerbations.
Abstract: GINA no longer recommends treating adults/adolescents with asthma with short-acting bronchodilators alone. Instead, they should receive symptom-driven (in mild asthma) or a daily corticosteroid-containing inhaler, to reduce risk of severe exacerbations.http://bit.ly/310LLzE
TL;DR: This review summarizes the presentations given at the International Union of Physiological Sciences Congress in Rio de Janeiro, Brazil, in 2017, during the symposium entitled “The Renin-Angiotensin System: Going Beyond the Classical Paradigms,” in which the signaling and physiological actions of ANG-(1−7), ACE2, AT2R, and alatensins were reported (with a focus on noncentral nervous system-related tissues).
Abstract: Thirty years ago, a novel axis of the renin-angiotensin system (RAS) was unveiled by the discovery of angiotensin-(1−7) [ANG-(1−7)] generation in vivo. Later, angiotensin-converting enzyme 2 (ACE2)...
TL;DR: The challenge presented by these drugs is defined, contemporary strategies to solve this challenge are outlined, and consequent in silico and in vitro evaluation of the delivery technologies for poorly water-soluble drugs are proposed.
Leiden University1, Max Planck Society2, California Pacific Medical Center3, Johns Hopkins University4, VU University Amsterdam5, Delft University of Technology6, University of Southern Denmark7, Washington University in St. Louis8, University of Washington9, Erasmus University Rotterdam10, Yeshiva University11, University of Haifa12, University of Michigan13, Boston University14, Newcastle University15, University of Kiel16, Mount Sinai Hospital17, Council on Education for Public Health18, University of Copenhagen19, University of Montpellier20, University of Paris21, University of Iceland22, National Institutes of Health23, University of Amsterdam24, Harvard University25, Bar-Ilan University26, Zhejiang University27, University of Pittsburgh28, Oregon Health & Science University29, Kaiser Permanente30, University of Turku31, University of California, Los Angeles32, University of Bristol33, University of Oxford34, Peking University35, Duke University36, Broad Institute37
TL;DR: A case–control design based on phenotype definitions of individuals surviving at or beyond the age corresponding to the 90th and 99th survival percentile, and two additional loci located in the APOE locus and near GPR78 are reported, revealing a role for tissue-specific expression of multiple genes in longevity.
Abstract: Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) e4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE e2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.
TL;DR: Testing whether a lesson presented in either immersive VR or as a video could benefit from the pre-training principle, as a means of reducing cognitive load, showed an interaction between media and method, indicating that pre- training had a positive effect on knowledge, transfer, and self-efficacy.
Abstract: Immersive virtual reality (VR) is predicted to have a significant impact on education; but most studies investigating learning with immersive VR have reported mixed results when compared to low-immersion media. In this study, a sample of 118 participants was used to test whether a lesson presented in either immersive VR or as a video could benefit from the pre-training principle, as a means of reducing cognitive load. Participants were randomly assigned to one of two method conditions (with/without pre-training), and one of two media conditions (immersive VR/video). The results showed an interaction between media and method, indicating that pre-training had a positive effect on knowledge (d = 0.81), transfer (d = 0.62), and self-efficacy (d = 0.64) directly following the intervention; and on self-efficacy (d = 0.84) in a one-week delayed post-test in the immersive VR condition. No effect was found for any of these variables within the video condition.
TL;DR: The challenges of DC microgrid protection are investigated from various aspects including, dc fault current characteristics, ground systems, fault detection methods, protective devices, and fault location methods.
Abstract: DC microgrids have attracted significant attention over the last decade in both academia and industry. DC microgrids have demonstrated superiority over AC microgrids with respect to reliability, efficiency, control simplicity, integration of renewable energy sources, and connection of dc loads. Despite these numerous advantages, designing and implementing an appropriate protection system for dc microgrids remains a significant challenge. The challenge stems from the rapid rise of dc fault current which must be extinguished in the absence of naturally occurring zero crossings, potentially leading to sustained arcs. In this paper, the challenges of DC microgrid protection are investigated from various aspects including, dc fault current characteristics, ground systems, fault detection methods, protective devices, and fault location methods. In each part, a comprehensive review has been carried out. Finally, future trends in the protection of DC microgrids are briefly discussed.
TL;DR: The Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment.
Abstract: Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
University of Hawaii1, European Space Research and Technology Centre2, Sea Education Association3, Utrecht University4, University of Oldenburg5, University of Southampton6, IFREMER7, Plymouth Marine Laboratory8, University of the Highlands and Islands9, University of Plymouth10, University of Southern Denmark11, University of California, San Diego12, University of Copenhagen13, Atlantic Oceanographic and Meteorological Laboratory14, National Institute of Oceanography, India15, Kyushu University16, Shirshov Institute of Oceanology17, California Institute of Technology18, Carnegie Institution for Science19, Williams College20, United States Environmental Protection Agency21, University of Exeter22, Commonwealth Scientific and Industrial Research Organisation23, International Council for the Exploration of the Sea24, VU University Amsterdam25, National Oceanic and Atmospheric Administration26, Dartmouth College27, Catholic University of the North28, University of São Paulo29
TL;DR: In this article, the authors discuss the structure of the future integrated marine debris observing system (IMDOS) that is required to provide long-term monitoring of the state of the anthropogenic pollution and support operational activities to mitigate impacts on the ecosystem and safety of maritime activity.
Abstract: Plastics and other artificial materials pose new risks to health of the ocean. Anthropogenic debris travels across large distances and is ubiquitous in the water and on the shorelines, yet, observations of its sources, composition, pathways and distributions in the ocean are very sparse and inaccurate. Total amounts of plastics and other man-made debris in the ocean and on the shore, temporal trends in these amounts under exponentially increasing production, as well as degradation processes, vertical fluxes and time scales are largely unknown. Present ocean circulation models are not able to accurately simulate drift of debris because of its complex hydrodynamics. In this paper we discuss the structure of the future integrated marine debris observing system (IMDOS) that is required to provide long-term monitoring of the state of the anthropogenic pollution and support operational activities to mitigate impacts on the ecosystem and safety of maritime activity. The proposed observing system integrates remote sensing and in situ observations. Also, models are used to optimize the design of the system and, in turn, they will be gradually improved using the products of the system. Remote sensing technologies will provide spatially coherent coverage and consistent surveying time series at local to global scale. Optical sensors, including high-resolution imaging, multi- and hyperspectral, fluorescence, and Raman technologies, as well as SAR will be used to measure different types of debris. They will be implemented in a variety of platforms, from hand-held tools to ship-, buoy-, aircraft-, and satellite-based sensors. A network of in situ observations, including reports from volunteers, citizen scientists and ships of opportunity, will be developed to provide data for calibration/validation of remote sensors and to monitor the spread of plastic pollution and other marine debris. IMDOS will interact with other observing systems monitoring physical, chemical, and biological processes in the ocean and on shorelines as well as state of the ecosystem, maritime activities and safety, drift of sea ice, etc. The synthesized data will support innovative multi-disciplinary research and serve diverse community of users.
TL;DR: Whole-transcriptome analysis of 3D-cultured T cells revealed that a high-density matrix induces downregulation of cytotoxic activity markers and upregulation of regulatory T cell markers that could be essential for suppression of T cell activity in the tumor microenvironment.
Abstract: Tumor progression is accompanied by dramatic remodeling of the surrounding extracellular matrix leading to the formation of a tumor-specific ECM, which is often more collagen-rich and of increased stiffness. The altered ECM of the tumor supports cancer growth and metastasis, but it is unknown if this effect involves modulation of T cell activity. To investigate if a high-density tumor-specific ECM could influence the ability of T cells to kill cancer cells, we here studied how T cells respond to 3D culture in different collagen densities. T cells cultured in 3D conditions surrounded by a high or low collagen density were imaged using confocal fluorescent microscopy. The effects of the different collagen densities on T cell proliferation, survival, and differentiation were examined using flow cytometry. Cancer cell proliferation in similar 3D conditions was also measured. Triple-negative breast cancer specimens were analyzed for the number of infiltrating CD8+ T cells and for the collagen density. Whole-transcriptome analyses were applied to investigate in detail the effects of collagen density on T cells. Computational analyses were used to identify transcription factors involved in the collagen density-induced gene regulation. Observed changes were confirmed by qRT-PCR analysis. T cell proliferation was significantly reduced in a high-density matrix compared to a low-density matrix and prolonged culture in a high-density matrix led to a higher ratio of CD4+ to CD8+ T cells. The proliferation of cancer cells was unaffected by the surrounding collagen-density. Consistently, we observed a reduction in the number of infiltrating CD8+ T-cells in mammary tumors with high collagen-density indicating that collagen-density has a role in regulating T cell abundance in human breast cancer. Whole-transcriptome analysis of 3D-cultured T cells revealed that a high-density matrix induces downregulation of cytotoxic activity markers and upregulation of regulatory T cell markers. These transcriptional changes were predicted to involve autocrine TGF-β signaling and they were accompanied by an impaired ability of tumor-infiltrating T cells to kill autologous cancer cells. Our study identifies a new immune modulatory mechanism, which could be essential for suppression of T cell activity in the tumor microenvironment.
TL;DR: An inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality is demonstrated and highlighted, highlighting the potential to reduce mortality through recommendations to increase intakes of flavonoids-rich foods, particularly in smokers and high alcohol consumers.
Abstract: Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (>20 g/d) vs. low-moderate (<20 g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers. The studies showing health benefits of flavonoids and their impact on cancer mortality are incomplete. Here, the authors perform a prospective cohort study in Danish participants and demonstrate an inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality.