Blinded interpretation of study results can feasibly and effectively diminish interpretation bias

Peer reviewe

Ancient DNA suggests modern wolves trace their origin to a late Pleistocene expansion from Beringia.

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that have maintained a wide geographic distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single late Pleistocene population. Both the geographic origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a dataset of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore, and provides an insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.L.L., K.D. and G.L. were supported by the Natural Environment Research Council, UK (grant numbers NE/K005243/1, NE/K003259/1); LL was also supported by the European Research Council grant (339941‐ADAPT); A.M. and A.E. were supported by the European Research Council Consolidator grant (grant number 647787‐LocalAdaptation); L.F. and G.L. were supported by the European Research Council grant (ERC‐2013‐StG 337574‐UNDEAD); T.G. was supported by a European Research Council Consolidator grant (681396‐Extinction Genomics) & Lundbeck Foundation grant (R52‐5062); O.T. was supported by the National Science Center, Poland (2015/19/P/NZ7/03971), with funding from EU's Horizon 2020 programme under the Marie Skłodowska‐Curie grant agreement (665778) and Synthesys Project (BETAF 3062); V.P., E.P. and P.N. were supported by the Russian Science Foundation grant (N16‐18‐10265 RNF); A.P. was supported by the Max Planck Society; M.L‐G. was supported by a Czech Science Foundation grant (GAČR15‐06446S)

Ancient DNA suggests modern wolves trace their origin to a late Pleistocene expansion from Beringia.

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that have maintained a wide geographic distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single late Pleistocene population. Both the geographic origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a dataset of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore, and provides an insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.L.L., K.D. and G.L. were supported by the Natural Environment Research Council, UK (grant numbers NE/K005243/1, NE/K003259/1); LL was also supported by the European Research Council grant (339941‐ADAPT); A.M. and A.E. were supported by the European Research Council Consolidator grant (grant number 647787‐LocalAdaptation); L.F. and G.L. were supported by the European Research Council grant (ERC‐2013‐StG 337574‐UNDEAD); T.G. was supported by a European Research Council Consolidator grant (681396‐Extinction Genomics) & Lundbeck Foundation grant (R52‐5062); O.T. was supported by the National Science Center, Poland (2015/19/P/NZ7/03971), with funding from EU's Horizon 2020 programme under the Marie Skłodowska‐Curie grant agreement (665778) and Synthesys Project (BETAF 3062); V.P., E.P. and P.N. were supported by the Russian Science Foundation grant (N16‐18‐10265 RNF); A.P. was supported by the Max Planck Society; M.L‐G. was supported by a Czech Science Foundation grant (GAČR15‐06446S)

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.Peer reviewe

Randomisation to protect against selection bias in healthcare trials

Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison groups (selection bias). Differences due to chance will still occur and these are minimised by randomising a sufficiently large number of people

German-language translation of the PANELVIEW instrument to evaluate the guideline development process from the perspective of the guideline group

Introduction: The development process for clinical guidelines is influenced by factors that are relevant to the validity of a guideline but often are not captured sufficiently in the final guideline documents. PANELVIEW is an English-language tool that can be used to explore the guideline development process from the perspective of guideline group members. Our aim was to translate the PANELVIEW tool into German, taking into account national contexts and linguistic differences.Methods: The PANELVIEW tool was initially translated by a core team, then refined and approved by a group of experts in a consensus-based Delphi process. The experts were selected on the basis of their experience in guideline development covering different fields (clinical, methodological, organisational, health professional, patient perspective) and geographical regions (Germany, Austria, Switzerland). A representative of the original PANELVIEW team was also involved. The Delphi steps included an online survey, an online consensus conference and final approval by circulating the results via email. Individual items were seen as generally agreed upon if the level of agreement in the respective steps was 75 % or more.Results: The expert group consisted of 12 persons. Of these, 11 (92 %) participated in the online survey and 10 (83 %) in the subsequent consensus conference. After the first Delphi step, sufficient agreement was achieved for 19 of 34 items (56 %). The remaining 15 items were discussed in the consensus conference and finally obtained 100 % agreement. The discussion focused on clarifying and adapting terms whose meaning was ambiguous or inadequate in the German context, which led to a deviation from the original wording in some instances.Discussion: The PANELVIEW tool was translated into German by means of a Delphi process. PANELVIEW complements existing instruments for assessing the methodological quality of guidelines by capturing the perspective of the guideline group. This will enable guideline developers and organisations to identify problems in the drafting process and avoid them in future projects. User testing and validation of the German-language PANELVIEW tool are planned for the future.Conclusion: The German-language translation of PANELVIEW will enable guideline developers in German-speaking countries to continuously evaluate and, where necessary, improve the process and methods of guideline development

Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease:A Clinical Practice Guideline Update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society

Description: This guideline is an official statement of the American College of Physicians (ACP), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and European Respiratory Society (ERS). It represents an update of the 2007 ACP clinical practice guideline on diagnosis and management of stable chronic obstructive pulmonary disease (COPD) and is intended for clinicians who manage patients with COPD. This guideline addresses the value of history and physical examination for predicting airflow obstruction; the value of spirometry for screening or diagnosis of COPD; and COPD management strategies, specifically evaluation of various inhaled therapies (anticholinergics, long-acting beta-agonists, and corticosteroids), pulmonary rehabilitation programs, and supplemental oxygen therapy. Methods: This guideline is based on a targeted literature update from March 2007 to December 2009 to evaluate the evidence and update the 2007 ACP clinical practice guideline on diagnosis and management of stable COPD. Recommendation 1: ACP, ACCP, ATS, and ERS recommend that spirometry should be obtained to diagnose airflow obstruction in patients with respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). Spirometry should not be used to screen for airflow obstruction in individuals without respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). Recommendation 2: For stable COPD patients with respiratory symptoms and FEV(1) between 60% and 80% predicted, ACP, ACCP, ATS, and ERS suggest that treatment with inhaled bronchodilators may be used (Grade: weak recommendation, low-quality evidence). Recommendation 3: For stable COPD patients with respiratory symptoms and FEV(1) Recommendation 4: ACP, ACCP, ATS, and ERS recommend that clinicians prescribe monotherapy using either long-acting inhaled anticholinergics or long-acting inhaled beta-agonists for symptomatic patients with COPD and FEV(1) Recommendation 5: ACP, ACCP, ATS, and ERS suggest that clinicians may administer combination inhaled therapies (long-acting inhaled anticholinergics, long-acting inhaled beta-agonists, or inhaled corticosteroids) for symptomatic patients with stable COPD and FEV(1) <60% predicted (Grade: weak recommendation, moderate-quality evidence). Recommendation 6: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe pulmonary rehabilitation for symptomatic patients with an FEV(1) 50% predicted. (Grade: weak recommendation, moderate-quality evidence). Recommendation 7: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe continuous oxygen therapy in patients with COPD who have severe resting hypoxemia (PaO(2