Development and validation of a patient-reported outcome measure for systemic sclerosis: the EULAR Systemic Sclerosis Impact of Disease (ScleroID) questionnaire

OBJECTIVES: Patient-reported outcome measures (PROMs) are important for clinical practice and research. Given the high unmet need, our aim was to develop a comprehensive PROM for systemic sclerosis (SSc), jointly with patient experts. METHODS: This European Alliance of Associations for Rheumatology (EULAR)-endorsed project involved 11 European SSc centres. Relevant health dimensions were chosen and prioritised by patients. The resulting Systemic Sclerosis Impact of Disease (ScleroID) questionnaire was subsequently weighted and validated by Outcome Measures in Rheumatology criteria in an observational cohort study, cross-sectionally and longitudinally. As comparators, SSc-Health Assessment Questionnaire (HAQ), EuroQol Five Dimensional (EQ-5D), Short Form-36 (SF-36) were included. RESULTS: Initially, 17 health dimensions were selected and prioritised. The top 10 health dimensions were selected for the ScleroID questionnaire. Importantly, Raynaud's phenomenon, impaired hand function, pain and fatigue had the highest patient-reported disease impact. The validation cohort study included 472 patients with a baseline visit, from which 109 had a test-retest reliability visit and 113 had a follow-up visit (85% female, 38% diffuse SSc, mean age 58 years, mean disease duration 9 years). The total ScleroID score showed strong Pearson correlation coefficients with comparators (SSc-HAQ, 0.73; Patient's global assessment, Visual Analogue Scale 0.77; HAQ-Disability Index, 0.62; SF-36 physical score, -0.62; each p<0.001). The internal consistency was strong: Cronbach's alpha was 0.87, similar to SSc-HAQ (0.88) and higher than EQ-5D (0.77). The ScleroID had excellent reliability and good sensitivity to change, superior to all comparators (intraclass correlation coefficient 0.84; standardised response mean 0.57). CONCLUSIONS: We have developed and validated the EULAR ScleroID, which is a novel, brief, disease-specific, patient-derived, disease impact PROM, suitable for research and clinical use in SSc

Security Limitations of Classical-Client Delegated Quantum Computing

Secure delegated quantum computing allows a computationally weak client to outsource an arbitrary quantum computation to an untrusted quantum server in a privacy-preserving manner. One of the promising candidates to achieve classical delegation of quantum computation is classical-client remote state preparation ($RSP_{CC}$), where a client remotely prepares a quantum state using a classical channel. However, the privacy loss incurred by employing $RSP_{CC}$ as a sub-module is unclear. In this work, we investigate this question using the Constructive Cryptography framework by Maurer and Renner (ICS'11). We first identify the goal of $RSP_{CC}$ as the construction of ideal RSP resources from classical channels and then reveal the security limitations of using $RSP_{CC}$. First, we uncover a fundamental relationship between constructing ideal RSP resources (from classical channels) and the task of cloning quantum states. Any classically constructed ideal RSP resource must leak to the server the full classical description (possibly in an encoded form) of the generated quantum state, even if we target computational security only. As a consequence, we find that the realization of common RSP resources, without weakening their guarantees drastically, is impossible due to the no-cloning theorem. Second, the above result does not rule out that a specific $RSP_{CC}$ protocol can replace the quantum channel at least in some contexts, such as the Universal Blind Quantum Computing (UBQC) protocol of Broadbent et al. (FOCS '09). However, we show that the resulting UBQC protocol cannot maintain its proven composable security as soon as $RSP_{CC}$ is used as a subroutine. Third, we show that replacing the quantum channel of the above UBQC protocol by the $RSP_{CC}$ protocol QFactory of Cojocaru et al. (Asiacrypt '19), preserves the weaker, game-based, security of UBQC.Comment: 40 pages, 12 figure

Verification of Quantum Computation: An Overview of Existing Approaches

International audienc

Long-term safety of gamma knife radiosurgery (SRS) for acromegaly

Purpose Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke. Methods 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed. Results 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27–3.96; SIR = 0.52, 95% CI 0.06–1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity. Conclusion Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications

Catalysing sustainable fuel and chemical synthesis

Concerns over the economics of proven fossil fuel reserves, in concert with government and public acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from such combustible carbon, are driving academic and commercial research into new sustainable routes to fuel and chemicals. The quest for such sustainable resources to meet the demands of a rapidly rising global population represents one of this century’s grand challenges. Here, we discuss catalytic solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels, and oxygenated organic molecules for the manufacture of fine and speciality chemicals to meet future societal demands

Using machine learning to identify important predictors of COVID-19 infection prevention behaviors during the early phase of the pandemic

Before vaccines for coronavirus disease 2019 (COVID-19) became available, a set of infection-prevention behaviors constituted the primary means to mitigate the virus spread. Our study aimed to identify important predictors of this set of behaviors. Whereas social and health psychological theories suggest a limited set of predictors, machine-learning analyses can identify correlates from a larger pool of candidate predictors. We used random forests to rank 115 candidate correlates of infection-prevention behavior in 56,072 participants across 28 countries, administered in March to May 2020. The machine-learning model predicted 52% of the variance in infection-prevention behavior in a separate test sample—exceeding the performance of psychological models of health behavior. Results indicated the two most important predictors related to individual-level injunctive norms. Illustrating how data-driven methods can complement theory, some of the most important predictors were not derived from theories of health behavior—and some theoretically derived predictors were relatively unimportant

The emerging application of semi-quantitative and quantitative capillaroscopy in systemic sclerosis

Systemic sclerosis (SSc) is a connective tissue disease with high morbidity and mortality, characterized by autoimmunity, obliterative vasculopathy involving mainly the microvasculature, and fibrosis. SSc-specific nailfold capillaroscopic changes have been defined, and nailfold capillaroscopy (NFC) is now unequivocally accepted to be a cornerstone for the early diagnosis of SSc. However, the use of NFC in patients already diagnosed with SSc is still not standardized. Several studies have shown that NFC abnormalities correlate with disease activity and severity and are predictive for disease worsening, such as occurrence of new digital ulcers. More importantly, successful treatment has been shown to diminish NFC abnormalities in severe SSc cases. These findings support the importance of NFC in monitoring patients with SSc and even its role as an outcome measure in SSc clinical trials. It is a matter of debate if Semi-quantitative and Quantitative NFC would be a more sensitive tool than qualitative NFC for meeting these objectives. This review is presenting the emerging application of Semi-quantitative and Quantitative NFC in SSc and its potential benefits

Digital ulcer debridement in systemic sclerosis: a systematic literature review

Optimal wound care is an essential component in the management of systemic sclerosis (SSc) digital ulcers (DUs). DU debridement has been suggested to reduce ulcer-related pain and improve tissue healing. However, only a minority of rheumatologists perform DU debridement, and there is no standard of care/protocol. Our objectives were to (i) evaluate the current evidence for the use of debridement in DU management and (ii) assess whether there are any specific protocols. A systematic literature review was performed searching the PubMed database (between 01/01/1950–01/03/2019) in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts. Articles in English, which focussed on SSc-DU debridement/curettage, were included. Exclusion criteria included studies of juvenile/paediatric patients and basic/non-clinical research. Our search identified 1497 studies of which 4 studies were included in our final analysis. Three studies used scalpel debridement, and one study used this in combination with autolytic debridement. No studies specifically reported the effect on DU healing from debridement. Autolytic debridement with hyaluronate-based products was associated with significant ulcer pain and inflammation. Local anaesthetic significantly reduces pain both during and after debridement. Combined local and oral analgesia is often required for more severe or infected DUs. DU (scalpel and autolytic) debridement is being used by some clinicians in rheumatology; however, there are no standardised protocols. To improve wound care for SSc-DUs, future research should focus on developing a standardised protocol for SSc-DU debridement, with a view to facilitate randomised controlled trials to demonstrate safety and treatment efficacy