Showing papers by "Ludwig Maximilian University of Munich published in 2017"
Columbia University1, University of Pittsburgh2, Florey Institute of Neuroscience and Mental Health3, Stanford University4, German Cancer Research Center5, Ludwig Maximilian University of Munich6, Yale University7, Memorial Sloan Kettering Cancer Center8, Dresden University of Technology9, Wistar Institute10, National University of Mar del Plata11, University of Texas Health Science Center at San Antonio12, Guangzhou Medical University13, University of Connecticut Health Center14, Nagoya University15, New York University16, University of Arizona17
TL;DR: The mechanisms underlying ferroptosis are reviewed, connections to other areas of biology and medicine are highlighted, and tools and guidelines for studying this emerging form of regulated cell death are recommended.
3,356 citations
Icahn School of Medicine at Mount Sinai1, Pure Earth2, World Bank3, University of Arizona4, McGill University5, Indian Ministry of Environment and Forests6, Qatar Airways7, University of Health Sciences Antigua8, Ludwig Maximilian University of Munich9, Johns Hopkins University10, Boston College11, Chulabhorn Research Institute12, University of Maryland, College Park13, University of Ghana14, Centro Nacional de Investigaciones Cardiovasculares15, University of Chicago16, University of London17, University of Oxford18, Indian Institute of Technology Delhi19, Simon Fraser University20, Consortium of Universities for Global Health21, University of Ottawa22, Columbia University23, Stockholm Resilience Centre24, Massachusetts Institute of Technology25, University of Queensland26, University of California, Berkeley27, New York University28, National Institutes of Health29, Public Health Research Institute30, United Nations Industrial Development Organization31, Renmin University of China32
TL;DR: This book is dedicated to the memory of those who have served in the armed forces and their families during the conflicts of the twentieth century.
2,628 citations
Gdańsk Medical University1, Institut Gustave Roussy2, Pontifícia Universidade Católica do Rio Grande do Sul3, Karolinska University Hospital4, Fortis Healthcare5, European Institute of Oncology6, Curie Institute7, American University of Beirut8, Brighton and Sussex Medical School9, Peter MacCallum Cancer Centre10, BC Cancer Agency11, Ludwig Maximilian University of Munich12, Memorial Sloan Kettering Cancer Center13, Sheba Medical Center14, Harvard University15, Université libre de Bruxelles16, Paris Descartes University17, University of California, San Francisco18, Johns Hopkins University19, Indiana University20, University of Washington21, Martin Luther University of Halle-Wittenberg22, King's College London23, Peking Union Medical College24
TL;DR: This ESO-ESMO ABC 5 Clinical Practice Guideline provides key recommendations for managing advanced breast cancer patients, and provides updates on managing patients with all breast cancer subtypes, LABC, follow-up, palliative and supportive care.
1,514 citations
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Massachusetts Institute of Technology1, Broad Institute2, Howard Hughes Medical Institute3, Wellcome Trust Sanger Institute4, European Bioinformatics Institute5, University of Cambridge6, Harvard University7, Weizmann Institute of Science8, University of Zurich9, Laboratory of Molecular Biology10, Utrecht University11, École Polytechnique Fédérale de Lausanne12, University of Pennsylvania13, German Cancer Research Center14, Heidelberg University15, Ludwig Maximilian University of Munich16, John Radcliffe Hospital17, Newcastle University18, Stanford University19, University of Oxford20, University of California, San Francisco21, Allen Institute for Brain Science22, Karolinska Institutet23, Royal Institute of Technology24, Icahn School of Medicine at Mount Sinai25, University of Cape Town26, University Medical Center Groningen27, Radboud University Nijmegen28, Kettering University29, University of Edinburgh30, Babraham Institute31, New York University32, Netherlands Cancer Institute33, Ragon Institute of MGH, MIT and Harvard34, University of Texas Health Science Center at Houston35, Technische Universität München36, Technical University of Denmark37, University of California, Berkeley38, King's College London39, California Institute of Technology40
TL;DR: An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease.
Abstract: The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.
1,391 citations
31 Jul 2017
TL;DR: In new experiments, it is shown that the new SIGMOD 2015 methods do not appear to offer practical benefits if the DBSCAN parameters are well chosen and thus they are primarily of theoretical interest.
Abstract: At SIGMOD 2015, an article was presented with the title “DBSCAN Revisited: Mis-Claim, Un-Fixability, and Approximation” that won the conference’s best paper award. In this technical correspondence, we want to point out some inaccuracies in the way DBSCAN was represented, and why the criticism should have been directed at the assumption about the performance of spatial index structures such as R-trees and not at an algorithm that can use such indexes. We will also discuss the relationship of DBSCAN performance and the indexability of the dataset, and discuss some heuristics for choosing appropriate DBSCAN parameters. Some indicators of bad parameters will be proposed to help guide future users of this algorithm in choosing parameters such as to obtain both meaningful results and good performance. In new experiments, we show that the new SIGMOD 2015 methods do not appear to offer practical benefits if the DBSCAN parameters are well chosen and thus they are primarily of theoretical interest. In conclusion, the original DBSCAN algorithm with effective indexes and reasonably chosen parameter values performs competitively compared to the method proposed by Gan and Tao.
1,192 citations
Ludwig Maximilian University of Munich1, Uppsala University2, Tel Aviv University3, Oregon State University4, Medical University Plovdiv5, Wageningen University and Research Centre6, Pompeu Fabra University7, University of British Columbia8, Technische Universität München9, University of Edinburgh10, University of Wollongong11
TL;DR: In this article, potential pathways linking greenspace to health are presented in three domains, which emphasize three general functions of greenspace: reducing harm (e.g., reducing exposure to air pollution, noise and heat), restoring capacities (i.e., attention restoration and physiological stress recovery), and encouraging physical activity and facilitating social cohesion). Interrelations between among the three domains are also noted.
1,187 citations
Paris 12 Val de Marne University1, University of Göttingen2, University Hospital of Lausanne3, French Institute of Health and Medical Research4, University of Milan5, University of Otago6, University of Regensburg7, University of Marburg8, Ruhr University Bochum9, Ludwig Maximilian University of Munich10, University of Siena11, University of Texas at Dallas12, University of Tübingen13
TL;DR: It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting.
1,062 citations
TL;DR: In this article, the authors review recent experimental progress in quantum many-body simulation and comment on future directions, and present a review of the current state-of-the-art in this field.
Abstract: Quantum simulation, a subdiscipline of quantum computation, can provide valuable insight into difficult quantum problems in physics or chemistry. Ultracold atoms in optical lattices represent an ideal platform for simulations of quantum many-body problems. Within this setting, quantum gas microscopes enable single atom observation and manipulation in large samples. Ultracold atom–based quantum simulators have already been used to probe quantum magnetism, to realize and detect topological quantum matter, and to study quantum systems with controlled long-range interactions. Experiments on many-body systems out of equilibrium have also provided results in regimes unavailable to the most advanced supercomputers. We review recent experimental progress in this field and comment on future directions.
1,056 citations
TL;DR: Power simulations at different sequencing depths showed that Drop-seq is more cost-efficient for transcriptome quantification of large numbers of cells, while MARS-seq, SCRB- sequencing, and Smart-seq2 are more efficient when analyzing fewer cells.
1,041 citations
Kyriaki Michailidou1, Kyriaki Michailidou2, Sara Lindström3, Sara Lindström4 +393 more•Institutions (127)
TL;DR: A genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry finds that heritability of Breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2–5-fold enriched relative to the genome- wide average.
Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
1,014 citations
TL;DR: The results show that badges, leaderboards, and performance graphs positively affect competence need satisfaction, as well as perceived task meaningfulness, while avatars, meaningful stories, and teammates affect experiences of social relatedness.
Harvard University1, Hoffmann-La Roche2, Genentech3, Dresden University of Technology4, Katholieke Universiteit Leuven5, University of Barcelona6, Southend University Hospital NHS Foundation Trust7, University of Erlangen-Nuremberg8, Ludwig Maximilian University of Munich9, Hospital for Special Surgery10
TL;DR: Tocilizumab, received weekly or every other week, combined with a 26‐week prednisone taper was superior to either 26‐ week or 52‐weekprednisone tapering plus placebo with regard to sustained glucocorticoid‐free remission in patients with giant‐cell arteritis.
Abstract: BackgroundGiant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis. MethodsIn this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone an...
TL;DR: In this paper, an overview is given of some of the most important techniques available to tackle the dynamics of an OQS beyond the Markov approximation, which requires a large separation of system and environment time scales.
Abstract: Open quantum systems (OQSs) cannot always be described with the Markov approximation, which requires a large separation of system and environment time scales. An overview is given of some of the most important techniques available to tackle the dynamics of an OQS beyond the Markov approximation. Some of these techniques, such as master equations, Heisenberg equations, and stochastic methods, are based on solving the reduced OQS dynamics, while others, such as path integral Monte Carlo or chain mapping approaches, are based on solving the dynamics of the full system. The physical interpretation and derivation of the various approaches are emphasized, how they are connected is explored, and how different methods may be suitable for solving different problems is examined.
University of Mainz1, University of Freiburg2, University of Würzburg3, Federal Institute for Drugs and Medical Devices4, RWTH Aachen University5, University of Regensburg6, University of Göttingen7, University of Tübingen8, Innsbruck Medical University9, University of Bern10, Ludwig Maximilian University of Munich11, Technische Universität München12, Max Planck Society13, University of Lausanne14
TL;DR: Following the new guidelines for therapeutic drug monitoring in psychiatry holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
Abstract: Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
TL;DR: In this article, the Gordon and Betty Moore Foundation (GBMF5076) and the Heising-Simons Foundation (HSPF) have contributed to the creation of the DES-Brazil Consortium.
Abstract: NSF [AST-1411763, AST-1714498, DGE 1144152, PHY-1707954, AST-1518052]; NASA [NNX15AE50G, NNX16AC22G]; National Science Foundation; Kavli Foundation; Danish National Research Foundation; Niels Bohr International Academy; DARK Cosmology Centre; Gordon & Betty Moore Foundation; Heising-Simons Foundation; UCSC; Alfred P. Sloan Foundation; David and Lucile Packard Foundation; European Research Council [ERC-StG-335936]; Gordon and Betty Moore Foundation [GBMF5076]; DOE (USA); NSF (USA); MISE (Spain); STFC (UK); HEFCE (UK); NCSA (UIUC); KICP (U. Chicago); CCAPP (Ohio State); MIFPA (Texas AM); MINECO (Spain); DFG (Germany); CNPQ (Brazil); FAPERJ (Brazil); FINEP (Brazil); Argonne Lab; UC Santa Cruz; University of Cambridge; CIEMAT-Madrid; University of Chicago; University College London; DES-Brazil Consortium; University of Edinburgh; ETH Zurich; Fermilab; University of Illinois; ICE (IEEC-CSIC); IFAE Barcelona; Lawrence Berkeley Lab; LMU Munchen; Excellence Cluster Universe; University of Michigan; NOAO; University of Nottingham; Ohio State University; University of Pennsylvania; University of Portsmouth; SLAC National Lab; Stanford University; University of Sussex; Texas AM University; Gemini Observatory [GS-2017B-Q-8, GS-2017B-DD-4]
Harvard University1, Medical University of Vienna2, Institut Jules Bordet3, University of St. Gallen4, Kantonsspital St. Gallen5, Institut Gustave Roussy6, Memorial Sloan Kettering Cancer Center7, Karolinska Institutet8, University of Bordeaux9, University of North Carolina at Chapel Hill10, Queen Mary University of London11, Charité12, Marmara University13, Mount Sinai Hospital, Toronto14, Ludwig Maximilian University of Munich15, University of Michigan16, National Taiwan University17, University of Ulm18, National Institutes of Health19, Gdańsk Medical University20, Sahlgrenska University Hospital21, Baylor College of Medicine22, University of Toronto23, Netherlands Cancer Institute24, Paracelsus Private Medical University of Salzburg25, Fudan University26, The Royal Marsden NHS Foundation Trust27, Kyoto University28, Institute of Cancer Research29, University of Milan30, McMaster University31
TL;DR: The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer, and recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence.
Christian R. Marshall, Daniel P. Howrigan1, Daniel P. Howrigan2, Daniele Merico +326 more•Institutions (98)
TL;DR: In this article, a centralized analysis pipeline was applied to a SCZ cohort of 21,094 cases and 20,227 controls, and a global enrichment of copy number variants (CNVs) was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies.
Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
University of Zurich1, Erasmus University Rotterdam2, Ludwig Maximilian University of Munich3, Medical University of Vienna4, Umeå University5, Aix-Marseille University6, University Hospital Heidelberg7, VU University Amsterdam8, Institut Gustave Roussy9, University of Cambridge10, University of Portsmouth11, University of Bonn12, Leiden University13, University of Lausanne14, University of Hamburg15, University of Düsseldorf16, German Cancer Research Center17
TL;DR: The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas, based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline.
Abstract: The European Association for Neuro-Oncology guideline provides recommendations for the clinical care of adult patients with astrocytic and oligodendroglial gliomas, including glioblastomas. The guideline is based on the 2016 WHO classification of tumours of the central nervous system and on scientific developments since the 2014 guideline. The recommendations focus on pathological and radiological diagnostics, and the main treatment modalities of surgery, radiotherapy, and pharmacotherapy. In this guideline we have also integrated the results from contemporary clinical trials that have changed clinical practice. The guideline aims to provide guidance for diagnostic and management decisions, while limiting unnecessary treatments and costs. The recommendations are a resource for professionals involved in the management of patients with glioma, for patients and caregivers, and for health-care providers in Europe. The implementation of this guideline requires multidisciplinary structures of care, and defined processes of diagnosis and treatment.
TL;DR: It is demonstrated that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis and the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX 4, thereby preventing fatal epileptic seizures.
TL;DR: Three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease are observed, providing additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's Disease.
Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
University of Oxford1, Wellington Management Company2, University of Barcelona3, University of Melbourne4, University of Amsterdam5, Ghent University Hospital6, Erasmus University Rotterdam7, National Institutes of Health8, Imperial College London9, Université de Montréal10, University of California, San Francisco11, Boston Children's Hospital12, University of Newcastle13, John Hunter Hospital14, Queen's University Belfast15, University of Western Australia16, French Institute of Health and Medical Research17, Université Paris-Saclay18, University of New South Wales19, University of Arizona20, Ludwig Maximilian University of Munich21, University of Pittsburgh22, University of Cape Town23
TL;DR: The only way to make progress in the future is to be much more clear about the meaning of the labels used for asthma and to acknowledge the assumptions associated with them, which are believed to be the most important causes of the stagnation in key clinical outcomes observed in the past 10 years.
TL;DR: In this article, the authors discuss the building blocks of carbon nitride materials and examine how strategies in synthesis, templating and post-processing translate from the molecular level to macroscopic properties, such as optical and electronic bandgap.
Abstract: In the past decade, research in the field of artificial photosynthesis has shifted from simple, inorganic semiconductors to more abundant, polymeric materials For example, polymeric carbon nitrides have emerged as promising materials for metal-free semiconductors and metal-free photocatalysts Polymeric carbon nitride (melon) and related carbon nitride materials are desirable alternatives to industrially used catalysts because they are easily synthesized from abundant and inexpensive starting materials Furthermore, these materials are chemically benign because they do not contain heavy metal ions, thereby facilitating handling and disposal In this Review, we discuss the building blocks of carbon nitride materials and examine how strategies in synthesis, templating and post-processing translate from the molecular level to macroscopic properties, such as optical and electronic bandgap Applications of carbon nitride materials in bulk heterojunctions, laser-patterned memory devices and energy storage devices indicate that photocatalytic overall water splitting on an industrial scale may be realized in the near future and reveal a new avenue of ‘post-silicon electronics’ Carbon nitrides are potentially cheap and metal-free alternatives for catalysts, semiconductors, battery materials and memory devices In this Review, we discuss the synthesis, design and morphology of these materials, and reflect on the ability of methods such as templating, etching, dye sensitization, heteroatom doping and co-polymerization, as well as the assembly of various heterojunctions, to improve device performance
University of Göttingen1, City College of New York2, University of São Paulo3, University of Toronto4, University of Erlangen-Nuremberg5, Aalborg University6, Greifswald University Hospital7, Spaulding Rehabilitation Hospital8, Medical University of South Carolina9, University of Pennsylvania10, Technische Universität Ilmenau11, University of Oldenburg12, École Polytechnique Fédérale de Lausanne13, Paris 12 Val de Marne University14, University of New South Wales15, University of Aberdeen16, University of Trento17, University of Lisbon18, University of Kiel19, Ruhr University Bochum20, Technical University of Dortmund21, Ludwig Maximilian University of Munich22, Beth Israel Deaconess Medical Center23, Mannheim University of Applied Sciences24, University of Siena25, The Catholic University of America26, University College London27, University of Copenhagen28, Fukushima Medical University29, Massachusetts Institute of Technology30, University of Tübingen31
TL;DR: Structured interviews are provided and recommend their use in future controlled studies, in particular when trying to extend the parameters applied, to discuss recent regulatory issues, reporting practices and ethical issues.
TL;DR: This work was funded by a grant from The Health Foundation (London, UK) that supported HR, KG, and NS.
Erasmus University Rotterdam1, University of California, San Francisco2, San Francisco VA Medical Center3, University College Dublin4, Utrecht University5, Yale University6, University of North Carolina at Chapel Hill7, Queen's University8, Vrije Universiteit Brussel9, Maastricht University Medical Centre10, Lancaster University11, University of Sheffield12, Ludwig Maximilian University of Munich13, University Hospital of Lausanne14
TL;DR: A formal Delphi consensus process was used to help develop a definition of ACP and provide recommendations for its application, and it is believed that these recommendations can provide guidance for clinical practice, ACP policy, and research.
Abstract: Advance care planning (ACP) is increasingly implemented in oncology and beyond, but a definition of ACP and recommendations concerning its use are lacking. We used a formal Delphi consensus process to help develop a definition of ACP and provide recommendations for its application. Of the 109 experts (82 from Europe, 16 from North America, and 11 from Australia) who rated the ACP definitions and its 41 recommendations, agreement for each definition or recommendation was between 68-100%. ACP was defined as the ability to enable individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate. Recommendations included the adaptation of ACP based on the readiness of the individual; targeting ACP content as the individual's health condition worsens; and, using trained non-physician facilitators to support the ACP process. We present a list of outcome measures to enable the pooling and comparison of results of ACP studies. We believe that our recommendations can provide guidance for clinical practice, ACP policy, and research.
University of Freiburg1, University of Alberta2, University of Milan3, University Hospital Southampton NHS Foundation Trust4, Texas A&M University5, Ludwig Maximilian University of Munich6, Sapienza University of Rome7, University of Salford8, Nottingham University Hospitals NHS Trust9, University of Glasgow10, University of St. Gallen11, Technische Universität München12
TL;DR: The causes and consequences of cancer-related malnutrition are examined, treatment approaches currently available are reviewed, and the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice are built.
Wellcome Trust Centre for Human Genetics1, Imperial College London2, Agency for Science, Technology and Research3, University of Oulu4, National Institutes of Health5, King's College London6, Ealing Hospital7, National University of Singapore8, University of Turin9, University Medical Center Groningen10, University of Tartu11, University of Bristol12, University College London13, University of Eastern Finland14, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico15, University of Kiel16, Leiden University Medical Center17, Dresden University of Technology18, University of Düsseldorf19, University of Surrey20, Erasmus University Rotterdam21, Max Healthcare22, Technische Universität München23, University of Naples Federico II24, Science for Life Laboratory25, Wellcome Trust Sanger Institute26, University of Ulm27, Ludwig Maximilian University of Munich28, University of Kelaniya29, Institute of Cancer Research30, King Abdulaziz University31, Queen Mary University of London32, Massachusetts Institute of Technology33, Health Protection Agency34, University of Oxford35, Churchill Hospital36, Imperial College Healthcare37
TL;DR: In this article, the authors used epigenome-wide association to show that body mass index (BMI), a key measure of adiposity, is associated with widespread changes in DNA methylation.
Abstract: Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances1,2. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation3,4,5,6, a key regulator of gene expression and molecular phenotype7. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10−7, range P = 9.2 × 10−8 to 6.0 × 10−46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10−6, range P = 5.5 × 10−6 to 6.1 × 10−35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07–2.56); P = 1.1 × 10−54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
TL;DR: There is an urgent need for public health measures to prevent obesity in order to save societal resources and international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability.
Abstract: Background: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies. Methods: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016. Results: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies. Conclusions: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.
TL;DR: It is shown that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophage expressing connexin 43.
TL;DR: A protocol is presented for the creation of DNA origami test samples, in situ sample preparation, multiplexed data acquisition, data simulation, super-resolution image reconstruction and post-processing such as drift correction, molecule counting (qPAINT) and particle averaging, designed to be modular.
Abstract: Super-resolution techniques have begun to transform biological and biomedical research by allowing researchers to observe structures well below the classic diffraction limit of light DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) offers an easy-to-implement approach to localization-based super-resolution microscopy, owing to the use of DNA probes In DNA-PAINT, transient binding of short dye-labeled ('imager') oligonucleotides to their complementary target ('docking') strands creates the necessary 'blinking' to enable stochastic super-resolution microscopy Using the programmability and specificity of DNA molecules as imaging and labeling probes allows researchers to decouple blinking from dye photophysics, alleviating limitations of current super-resolution techniques, making them compatible with virtually any single-molecule-compatible dye Recent developments in DNA-PAINT have enabled spectrally unlimited multiplexing, precise molecule counting and ultra-high, molecular-scale (sub-5-nm) spatial resolution, reaching ∼1-nm localization precision DNA-PAINT can be applied to a multitude of in vitro and cellular applications by linking docking strands to antibodies Here, we present a protocol for the key aspects of the DNA-PAINT framework for both novice and expert users This protocol describes the creation of DNA origami test samples, in situ sample preparation, multiplexed data acquisition, data simulation, super-resolution image reconstruction and post-processing such as drift correction, molecule counting (qPAINT) and particle averaging Moreover, we provide an integrated software package, named Picasso, for the computational steps involved The protocol is designed to be modular, so that individual components can be chosen and implemented per requirements of a specific application The procedure can be completed in 1-2 d