Barrier-properties of Nup98 FG phases ruled by FG motif identity and inter-FG spacer length

Nup98 FG repeat domains comprise hydrophobic FG motifs linked through uncharged spacers. FG motifs capture nuclear transport receptors (NTRs) during nuclear pore complex (NPC) passage, confer inter-repeat cohesion, and condense the domains into a selective phase with NPC-typical barrier properties. We found that shortening inter-FG spacers enhances cohesion, increases phase density, and tightens such barrier – consistent with a sieve-like phase. Phase separation tolerated mutations of Nup98-typical GLFG motifs, provided the domain-hydrophobicity remained preserved. NTR-entry, however, was sensitive to (certain) deviations from canonical FG motifs, suggesting a co-evolutionary adaptation. Unexpectedly, we found that arginines promote efficient FG-phase entry also by means other than cation-π interactions. Although incompatible with NTR·cargo complexes, a YG phase displayed remarkable transport selectivity, particularly for evolved GFPNTR-variants. GLFG to FSFG mutations made the FG phase hypercohesive, precluding NTR-entry. Longer spacers relieved this hypercohesive phenotype. The antagonism between cohesion and NTR·FG interactions appears thus key to transport selectivity

Resonator-Enhanced Optical Dipole Trap for Fermionic Lithium Atoms

We demonstrate a novel optical dipole trap which is based on the enhancement of the optical power density of a Nd:YAG laser beam in a resonator. The trap is particularly suited for experiments with ultracold gases, as it combines a potential depth of order 1 mK with storage times of several tens of seconds. We study the interactions in a gas of fermionic lithium atoms in our trap and observe the influence of spin-changing collisions and off-resonant photon scattering. A key element in reaching long storage times is an ultra-low noise laser. The dependence of the storage time on laser noise is investigated.Comment: 4 pages 3 figures Revised 17.07.2001; Corrected calibration of noise measm

Elucidating the structural composition of a Fe-N-C catalyst by nuclear and electron resonance techniques

Fe–N–C catalysts are very promising materials for fuel cells and metal–air batteries. This work gives fundamental insights into the structural composition of an Fe–N–C catalyst and highlights the importance of an in‐depth characterization. By nuclear‐ and electron‐resonance techniques, we are able to show that even after mild pyrolysis and acid leaching, the catalyst contains considerable fractions of α‐iron and, surprisingly, iron oxide. Our work makes it questionable to what extent FeN4 sites can be present in Fe–N–C catalysts prepared by pyrolysis at 900 °C and above. The simulation of the iron partial density of phonon states enables the identification of three FeN4 species in our catalyst, one of them comprising a sixfold coordination with end‐on bonded oxygen as one of the axial ligands

Improving the use of research evidence in guideline development: 9. Grading evidence and recommendations

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the ninth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on grading evidence and recommendations in guidelines. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct a full systematic review ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: Should WHO grade the quality of evidence and the strength of recommendations? • Users of recommendations need to know how much confidence they can place in the underlying evidence and the recommendations. The degree of confidence depends on a number of factors and requires complex judgments. These judgments should be made explicitly in WHO recommendations. A systematic and explicit approach to making judgments about the quality of evidence and the strength of recommendations can help to prevent errors, facilitate critical appraisal of these judgments, and can help to improve communication of this information. What criteria should be used to grade evidence and recommendations? • Both the quality of evidence and the strength of recommendations should be graded. The criteria used to grade the strength of recommendations should include the quality of the underlying evidence, but should not be limited to that. • The approach to grading should be one that has wide international support and is suitable for a wide range of different types of recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which is currently suggested in the Guidelines for WHO Guidelines, is being used by an increasing number of other organizations internationally. It should be used more consistently by WHO. Further developments of this approach should ensure its wide applicability. Should WHO use the same grading system for all of its recommendations? • Although there are arguments for and against using the same grading system across a wide range of different types of recommendations, WHO should use a uniform grading system to prevent confusion for developers and users of recommendations

Improving the use of research evidence in guideline development: 15. Disseminating and implementing guidelines

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 15(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: In this review we address strategies for the implementation of recommendations in health care. METHODS: We examined overviews of systematic reviews of interventions to improve health care delivery and health care systems prepared by the Cochrane Effective Practice and Organisation of Care (EPOC) group. We also conducted searches using PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: What should WHO do to disseminate and facilitate the uptake of recommendations? • WHO should choose strategies to implement their guidelines from among those which have been evaluated positively in the published literature on implementation research • Because the evidence base is weak and modest to moderate effects, at best, can be anticipated, WHO should promote rigorous evaluations of implementation strategies. What should be done at headquarters, by regional offices and in countries? • Adaptation and implementation of WHO guidelines should be done locally, at the national or sub-national level. • WHO headquarters and regional offices should support the development and evaluation of implementation strategies by local authorities

A systematic review on randomized controlled trials : Coaching elements of digital services to support chronically ill adolescents during transition of care

Aims To define digital health services that have been studied among chronically ill adolescents and to describe e-health coaching elements that may have an impact on transition outcomes. Design Systematic review without meta-analysis. Data sources MEDLINE (Ovid), Pub Med, Scopus and CINAHL on 28 May 2018. Review methods Peer-reviewed articles published between January 2008-May 2018 were reviewed following the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Results Twelve randomized controlled trials were included. The interventions varied significantly in duration and content. E-coaching that included human and social support showed positive impact on transition outcomes. Digital health services incorporated into usual care provide efficient and accessible care. Conclusion E-coaching elements enable tailoring and personalization and present a tool for supporting and motivating chronically ill adolescents during transition of care. Future research should evaluate the effectiveness of e-coaching elements. Impact Digital services are considered a means for increasing adolescents' motivation for self-care and for increasing their accessibility to health care. The coaching elements in digital services consist of a theoretical basis, human support, interactive means and social support. Included interventions varied in terms of duration, dose, content and design. Our results may serve the development of digital health services for adolescents in transition. E-coaching can be used to engage and motivate chronically ill adolescents to improve health behaviour and self-management during transition of care.Peer reviewe

Ultra-cold atoms in an optical cavity: two-mode laser locking to the cavity avoiding radiation pressure

The combination of ultra-cold atomic clouds with the light fields of optical cavities provides a powerful model system for the development of new types of laser cooling and for studying cooperative phenomena. These experiments critically depend on the precise tuning of an incident pump laser with respect to a cavity resonance. Here, we present a simple and reliable experimental tuning scheme based on a two-mode laser spectrometer. The scheme uses a first laser for probing higher-order transversal modes of the cavity having an intensity minimum near the cavity's optical axis, where the atoms are confined by a magnetic trap. In this way the cavity resonance is observed without exposing the atoms to unwanted radiation pressure. A second laser, which is phase-locked to the first one and tuned close to a fundamental cavity mode drives the coherent atom-field dynamics.Comment: 7 pages, 7 figure

Beverage specific alcohol intake in a population-based study: Evidence for a positive association between pulmonary function and wine intake

BACKGROUND: Lung function is a strong predictor of cardiovascular and all-cause mortality. Previous studies suggest that alcohol exposure may be linked to impaired pulmonary function through oxidant-antioxidant mechanisms. Alcohol may be an important source of oxidants; however, wine contains several antioxidants. In this study we analyzed the relation of beverage specific alcohol intake with forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) in a random sample of 1555 residents of Western New York, USA. METHODS: We expressed pulmonary function as percent of predicted normal FEV(1) (FEV(1)%) and FVC (FVC%) after adjustment for height, age, gender and race. To obtain information on alcohol intake we used a questionnaire that reliably queries total alcohol and beverage specific recent (past 30 days) and lifetime alcohol consumption. Results: Using multiple linear regression analysis after adjustment for covariates (pack-years of smoking, weight, smoking status, education, nutritional factors and for FEV(1)%, in addition, eosinophil count), we observed no significant correlation between total alcohol intake and lung function. However, we found positive associations of recent and lifetime wine intake with FEV(1)% and FVC%. When we analyzed white and red wine intake separately, the association of lung function with red wine was weaker than for white wine. CONCLUSION: While total alcohol intake was not related to lung function, wine intake showed a positive association with lung function. Although we cannot exclude residual confounding by healthier lifestyle in wine drinkers, differential effects of alcoholic beverages on lung health may exist

Improving the use of research evidence in guideline development: 3. Group composition and consultation process

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the third of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVE: In this review we address the composition of guideline development groups and consultation processes during guideline development. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: What should be the composition of a WHO-panel that is set up to develop recommendations? The existing empirical evidence suggests that panel composition has an impact on the content of the recommendations that are made. There is limited research evidence to guide the exact composition of a panel. Based on logical arguments and the experience of other organisations we recommend the following: • Groups that develop guidelines or recommendations should be broadly composed and include important stakeholders such as consumers, health professionals that work within the relevant area, and managers or policy makers. • Groups should include or have access to individuals with the necessary technical skills, including information retrieval, systematic reviewing, health economics, group facilitation, project management, writing and editing. • Groups should include or have access to content experts. • To work well a group needs an effective leader, capable of guiding the group in terms of the task and process, and capable of facilitating collaboration and balanced contribution from all of the group members. • Because many group members will not be familiar with the methods and processes that are used in developing recommendations, groups should be offered training and support to help ensure understanding and facilitate active participation. What groups should be consulted when a panel is being set up? We did not identify methodological research that addressed this question, but based on logical arguments and the experience of other organisations we recommend that as many relevant stakeholder groups as practical should be consulted to identify suitable candidates with an appropriate mix of perspectives, technical skills and expertise, as well as to obtain a balanced representation with respect to regions and gender. What methods should WHO use to ensure appropriate consultations? We did not find any references that addressed issues related to this question. Based on logical arguments and the experience of other organisations we believe that consultations may be desirable at several stages in the process of developing guidelines or recommendations, including: • Identifying and setting priorities for guidelines and recommendations • Commenting on the scope of the guidelines or recommendations • Commenting on the evidence that is used to inform guidelines or recommendations • Commenting on drafts of the guidelines or recommendations • Commenting on plans for disseminating and supporting the adaptation and implementation of the guidelines or recommendations. • Key stakeholder organisations should be contacted directly whenever possible. • Consultation processes should be transparent and should encourage feedback from interested parties