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ObjectiveThe aim of this study was to analyse the 2020 burden of Systemic Lupus Erythematosus (SLE) in Europe, from the patients’ perspective.MethodsIn May 2020, Lupus Europe, the European umbrella patient association for SLE, designed and disseminated a multilingual anonymous online survey to individuals with a self-reported physician’s diagnosis of SLE living in Europe.ResultsData from 4375 SLE survey respondents (95.9% women, median age: 45 (IQR: 36–54) years, 70.7% Caucasians) from 35 European countries were analysed. The median age at SLE diagnosis was 30 years (IQR: 22–40) and the median diagnosis delay was 2 years (IQR: 0–6). The most commonly affected organ-systems included the joints (81.8%) and skin (59.4%), with renal involvement in 30%. Another diagnosis was given before that of SLE in 45.0%, including psychological/mental disorders in 9.1% and fibromyalgia in 5.9%. The median number of symptoms reported was 9 (IQR: 6–11) out of 21, with fatigue most common (85.3%) and most bothersome. The median number of SLE-related medications was 5 (IQR: 3–7), including antimalarials (75%), oral glucocorticoids (52.4%), immunosuppressants (39.8%) and biologics (10.9%). Respondents reported significant impact over their studies, career and emotional/sexual life in 50.7%, 57.9% and 38.2%, respectively. Appropriate access to care was highly variable across countries and care component.ConclusionThis survey underlines the 2020 burden and strong heterogeneity in the care of SLE across Europe, from the patient’s perspective. Altogether, these data may prove crucial to physicians, patients and policy-makers to improve the diagnosis and management of this rare and complex disease.

Medulloblastoma, a malignant childhood cerebellar tumour, segregates molecularly into biologically distinct subgroups, suggesting that a personalized approach to therapy would be beneficial 1 . Mouse modelling and cross-species genomics have provided increasing evidence of discrete, subgroup-specific developmental origins 2 . However, the anatomical and cellular complexity of developing human tissues 3 —particularly within the rhombic lip germinal zone, which produces all glutamatergic neuronal lineages before internalization into the cerebellar nodulus—makes it difficult to validate previous inferences that were derived from studies in mice. Here we use multi-omics to resolve the origins of medulloblastoma subgroups in the developing human cerebellum. Molecular signatures encoded within a human rhombic-lip-derived lineage trajectory aligned with photoreceptor and unipolar brush cell expression profiles that are maintained in group 3 and group 4 medulloblastoma, suggesting a convergent basis. A systematic diagnostic-imaging review of a prospective institutional cohort localized the putative anatomical origins of group 3 and group 4 tumours to the nodulus. Our results connect the molecular and phenotypic features of clinically challenging medulloblastoma subgroups to their unified beginnings in the rhombic lip in the early stages of human development. Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical location, and for the difficulty of modelling these tumours in mice.

Silk from silkworms and spiders is an exceptionally important natural material, inspiring a range of new products and applications due to its high strength, elasticity, and toughness at low density, as well as its unique conductive and optical properties. Transgenic and recombinant technologies offer great promise for the scaled-up production of new silkworm- and spider-silk-inspired fibres. However, despite considerable effort, producing an artificial silk that recaptures the physico-chemical properties of naturally spun silk has thus far proven elusive. The mechanical, biochemical, and other properties of pre-and post-development fibres accordingly should be determined across scales and structural hierarchies whenever feasible. We have herein reviewed and made recommendations on some of those practices for measuring the bulk fibre properties; skin-core structures; and the primary, secondary, and tertiary structures of silk proteins and the properties of dopes and their proteins. We thereupon examine emerging methodologies and make assessments on how they might be utilized to realize the goal of developing high quality bio-inspired fibres.

A shift in healthcare payment models from volume toward value-based incentives will require deliberate input into systems development from both perioperative clinicians and administrators to ensure appropriate recognition of the value of all services provided—particularly ones that are not reimbursable in current fee-for-service payment models. Time-driven activity-based costing (TDABC) methodology identifies cost drivers and reduces inaccurate costing based on siloed budgets. Inaccurate costing also results from the fact that current costing methods use charges and there has been tremendous cost shifting throughout health care. High cost, high variability processes can be identified for process improvement. As payment models inevitably evolve towards value-based metrics, it will be critical to knowledgably participate in the coordination of these changes. This document provides 8 practical Recommendations from the Society for Perioperative Assessment and Quality Improvement (SPAQI) aimed at outlining the principles of TDABC, creating process maps for patient workflows, understanding payment structures, establishing physician alignment across service lines to create integrated practice units to facilitate development of evidence-based pathways for specific patient risk groups, establishing consistent care delivery, minimizing variability between physicians and departments, utilizing data analytics and information technology tools to track progress and obtain actionable data, and using TDABC to create costing transparency.

BackgroundPatients’ motivations for undergoing direct-acting antiviral (DAA) therapy for chronic hepatitis C may include anticipation of treatment benefits not well described in the literature.AimsEvaluate patients’ anticipated and actualized improvements in several domains of functioning before and after viral cure.MethodsPre–post-study utilizing in-depth interviews with 28 patients prior to, and several months after, DAA therapy. Interviews were audio-recorded, transcribed, coded, and analyzed by two qualitative experts.ResultsPatients had a median age of 54 years, 43% were male, 57% white, 25% had cirrhosis, and 71% were treated with sofosbuvir/ledipasvir. Pre-treatment, patients hoped for improvements in several domains including psychological, emotional, physical, social, and occupational functioning. After viral cure, increased energy and less fear of transmission were pathways to better quality of life. Psychological and emotional improvements positively affected physical, social, and occupational functioning. Social improvements were due to better mood and motivation, fewer symptoms, and reduced fear of stigma and transmission. Occupational benefits were linked to increased stamina, self-confidence, and less pain, anxiety, and stigma. Reduced fear of stigma had a pervasive impact on all life improvements after cure. Patient characteristics such as the presence of cirrhosis or psychiatric issues influence treatment motivations. Qualitative data correspond with change in pre–post-survey scores.ConclusionsTremendous hope is placed on the ability of DAA therapy to bring about substantial improvements in life functioning after viral cure. Highly interconnected effects on quality of life worked synergistically through improved physical and psychological well-being. Stakeholders should appreciate the multi-dimensional benefits that viral eradication bestows upon individuals and society.

To enhance the solubility of orally administered pharmaceuticals, liquid capsules or amorphous tablets are often preferred over crystalline drug products. However, little is known regarding the variation in bonding mechanisms between pharmaceutical molecules in their different disordered forms. In this study, liquid and melt-quenched glassy carbamazepine have been studied using high energy X-ray diffraction and modeled using Empirical Potential Structure Refinement. The results show significant structural differences between the liquid and glassy states. The liquid shows a wide range of structures; from isolated molecules, to aromatic ring correlations and NH-O hydrogen bonding. Upon quenching from the liquid to the glass the number of hydrogen bonds per molecule increases by ~50% at the expense of a ~30% decrease in the close contact (non-bonded) carbon-carbon interactions between aromatic rings. During the cooling process, there is an increase in both singly and doubly hydrogen-bonded adjacent molecules. Although hydrogen-bonded dimers found in the crystalline states persist in the glassy state, the absence of a crystalline lattice also allows small, hydrogen-bonded NH-O trimers and tetramers to form. This proposed model for the structure of glassy carbamazepine is consistent with the results from vibrational spectroscopy and nuclear magnetic resonance.

We undertook a national survey of parental attitudes to childhood vaccinations and compared results with those in earlier comparable surveys covering a 10year period. We randomly selected 275 nationally representative sampling locations in England. Interviewers identified eligible primary care givers (referred to as parents) of children aged from 2months to <5years and conducted home-based interviews between January and April 2015. We aimed to recruit 1000 parents of children aged 0–2years and 1000 of children aged 3–4years. The questionnaire covered all aspects of the immunisation process, vaccines administered in pregnancy and from infancy to pre-school with a maximum of 86 mixed questions. Interviews were completed with 1792 parents of whom 1130 had children aged 0–2years and 999 had children aged 3–4years; 337 had children of both ages. The findings showed that confidence in and acceptance of the vaccination programme was high. Only 2% of parents reported refusing vaccination whilst 90% reported vaccinating their children automatically when due. Almost all parents (97%) had access to the internet and 34% consulted web-based resources for information on vaccination. Parents who used chat rooms or discussion forums for this purpose were significantly more likely to say they had seen something that would make them doubt having their child(ren) immunised (31% compared to 8% amongst all parents). Health professionals and the NHS were seen as the most trusted source of advice on immunisation (90% agreed/strongly agreed with each). Very few parents did not trust these sources (4% and 3% disagreed, respectively). Health professionals remain extremely important in communicating information about vaccination and are highly trusted by parents; a trust that has increased in recent years. Despite most parents seeking information on the Internet, trust in and advice from health care professionals appeared to be key factors influencing parental decisions.

•Wide variation in uptake of flu vaccine persists in English NHS hospitals.•Many factors of high uptake are linked to leadership and organisational culture.•Embedding the flu programme in well-being policy helps acceptability and adherence.•A supportive culture is likely to achieve higher uptake than a coercive one.•Middle managers’ facilitating role in delivering the programme is key to uptake. Health care workers are a priority group for seasonal influenza vaccination, which is recommended by the World Health Organisation. There is a wide variation in uptake between and within countries. England has achieved 69.5% of health care workers vaccinated overall in 2017/18 across NHS acute and community health care settings, but it varies between Trusts from 50% to over 92.3%. While attitudinal factors have been well researched, there is limited evidence on organisational factors associated with high uptake. In England, most NHS Trusts are now implementing a similar range of interventions as part of their flu programme, and it remains unclear why performance remains so variable. This qualitative study is the first to explore reasons for this variation and provide recommendations for lower performing Trusts on how to improve. Fifty-seven interviews of managers and vaccinators were conducted in nine hospitals with flu vaccination uptake ranging from just over 55% to above 90%. Our study found that while Trusts deployed a wide range of both demand generating and supply interventions to increase uptake, there were marked differences in the organisational and delivery models utilised. Our study suggests that organisational culture was possibly the most important ingredient when trying to differentiate between high and low performing Trusts. We found that a positive culture aimed at fostering continuous improvement and favouring non-coercion on balance yielded more adherence from staff. Where influenza vaccination was embedded in the organisation wellbeing strategy, rather than executed as a siloed seasonal programme, this tended to foster good performance. Improving performance of influenza vaccination in health care workers will involve not only deploying the right interventions, and following “best practices”. It will require the adaptation of flu progamme delivery strategies to the organisation context, and embedding vaccination into the organisational culture, thus supporting the normalisation of yearly vaccination.

Molecular structures and dynamics in amorphous materials present unique experimental challenges compared with the characterization of crystalline solids. Liquids and glassy solids have many applications in industry such as ionic liquids for fuel cells or biomolecule stabilizing agents, enhancing pharmaceuticals dissolution rates, and modified high performance biopolymers like silk for textile, biomedical, drug delivery, among many others. Amorphous materials are metastable, with kinetic profiles of phase transitions depending on relaxation dynamics, thermal history, plus factors such as temperature, pressure, and humidity. Understanding molecular structure and phase transitions of amorphous states of small molecules and biopolymers is broadly important for realizing their applications. The structure of liquid and glassy states of the drugs carbamazepine (CBZ) and indomethacin (IMC) were studied with solid-state nuclear magnetic resonance (ssNMR) spectroscopy, high energy X-ray diffraction, Fourier Infrared Transform Spectroscopy (FTIR), differential scanning calorimetry (DSC), and Empirical Potential Structure Refinement (EPSR). Both drugs have multiple crystalline polymorphs with slow dissolution kinetics, necessitating stable glassy or polymer dispersed formulations. More hydrogen bonds per CBZ molecule and a larger distribution of oligomeric states in the glass versus the liquid than expected. The chlorobenzyl ring of crystalline and glassy IMC measured with ssNMR were surprisingly found to have similar mobility. Crucially, humidity strongly affects glass structure, highlighting the importance of combining modeling techniques like EPSR with careful sample preparation for proper interpretation. Highly basic protic ionic liquids with low ∆pKa were synthesized with metathesis rather than proton transfer and characterized using NMR and dielectric spectroscopy. Finally, the protein secondary structure of spider egg sac silk was studied using ssNMR, FTIR, and scanning electron microscopy. Tubuliform silk found in spider egg sacs has extensive β-sheet domains which form nanocrystallites within an amorphous matrix. Structural predictions and spectroscopic measurements of tubuliform silk solution are mostly α-helical, with the mechanism of structural rearrangement to the β-sheet rich fiber unknown. The movement of spiders during egg silk spinning make in situ experiments difficult practically. This work is the first observation that tubuliform silk of Argiope aurantia after liquid crystalline spinning exits the spinneret as a predominantly (~70%) β-sheet fiber.