Spin-ice physics in cadmium cyanide

Spin-ices are frustrated magnets that support a particularly rich variety of emergent physics. Typically, it is the interplay of magnetic dipole interactions, spin anisotropy, and geometric frustration on the pyrochlore lattice that drives spin-ice formation. The relevant physics occurs at temperatures commensurate with the magnetic interaction strength, which for most systems is 1–5 K. Here, we show that non-magnetic cadmium cyanide, Cd(CN)2, exhibits analogous behaviour to magnetic spin-ices, but does so on a temperature scale that is nearly two orders of magnitude greater. The electric dipole moments of cyanide ions in Cd(CN)2 assume the role of magnetic pseudospins, with the difference in energy scale reflecting the increased strength of electric vs magnetic dipolar interactions. As a result, spin-ice physics influences the structural behaviour of Cd(CN)2 even at room temperature.ISSN:2041-172

OMERACT Definitions for Ultrasonographic Pathology and Elementary Lesions Of Rheumatic Disorders Fifteen Years On

Objective. The Outcome Measures in Rheumatology (OMERACT) ultrasound (US) working group (WG) operates research activities for the validation of US as an outcome measurement instrument according to the Filter 2.0 framework Methods. From the onset of the WG research in 2005 through now, original publications on definitions and scoring systems for pathophysiological manifestations and elementary lesions of various rheumatic disorders were reviewed Results. Definitions and scoring systems according to new terminology are provided Conclusions. We have redefined OMERACT definitions of US pathology and elementary lesions as well as scoring systems which are now proposed for OMERACT approval for application in clinical trial

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ABSTRACT. Objective. To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Working Group on the validation of US as a potential outcome measure in gout. Methods. Based on the lack of definitions, highlighted in a recent literature review on US as an outcome tool in gout, a series of iterative exercises were carried out to obtain consensus-based definitions on US elementary components in gout using a Delphi exercise and subsequently testing these definitions in static images and in patients with proven gout. Cohen's κ was used to test agreement, and values of 0-0.20 were considered poor, 0.20-0.40 fair, 0.40-0.60 moderate, 0.60-0.80 good, and 0.80-1 excellent. Results. With an agreement of > 80%, consensus-based definitions were obtained for the 4 elementary lesions highlighted in the literature review: tophi, aggregates, erosions, and double contour (DC). In static images interobserver reliability ranged from moderate to almost perfect, and similar results were found for the intrareader reliability. In patients the intraobserver agreement was good for all lesions except DC (moderate). The Outcome Measures in Rheumatology (OMERACT) US Working Group (Appendix 1) developed a gout subgroup with the purpose of validating US as an imaging tool for gout. If this objective is achieved, US may be implemented as an outcome measure in gout. Is Ultrasound a Validated Outcome Measure in Gout? In 2013, a systematic literature review was published evaluating US as an outcome tool in gout and asymptomatic hyperuricemia 10 . The report found 18 out of 67 articles published since 1975 to be eligible for review. Described in the literature were 4 main pathologies related solely to gout: tophi, double contour sign (DC), soft tissue abnormalities, and bony lesions. The review highlighted that US was able to detect tophi using magnetic resonance imaging (MRI) as a gold standard, and this measure was found sensitive to change. The DC is an articular cartilage abnormality related to the deposition of crystals on the surface of the hyaline cartilage, which seemed specific to gout, with excellent inter-reader reliability and sensitive to change (the latter only in a very small patient population). Soft tissue pathology such as intrasynovial hyperechogenicity may be indicative of gout. US was less sensitive than MRI for diagnosing erosions (bony lesions) but more sensitive than conventional radiography, as is also known from rheumatoid arthritis studies Criterion and construct validity were assessed only for tophi, and overall there was a lack of consensus on the definitions of the 4 elementary lesions and their validity according to the OMERACT filter 13 . Current Limitations of US in Gout Assessment Despite clear interest in this imaging technique for the management of gout, the literature review clearly pointed to a lack of clear US definitions for the main 4 elementary lesions identified: tophi, DC, soft tissue hyperechogenicity (punctuate crystal aggregates), and bony lesions (erosions). This lack of consensus-based definitions impairs the ability to validate US according to the OMERACT filter and hampers widespread use of US in therapeutic clinical trials, due to the difficulty to measure the same phenomenon. In order to implement US in the management of patients with established or suspected gout the "gout subgroup of the OMERACT US Working Group" initiated a validation process. The first step was to obtain consensus-based definitions for the US elementary lesion as indicated by the literature review. This was accomplished by performing a Delphi exercise 14 . Thirty-five rheumatologists performing US and with an interest in gout were invited to participate, and 32 responded positively. After 3 Delphi rounds, > 80% agreement was obtained for each definition Agreement was obtained to use the existing definitions for both synovitis and tenosynovitis 15 because these may be co-components in gout disease. Agreement could not be obtained to include synovitis (including Doppler activity) as an elementary lesion indicative of gout, because the presence of synovitis alone was not considered specific enough to define gout disease because it is a key component in other inflammatory arthropathies as well 14 . On the other hand, even if erosions may also be seen in other arthropathy conditions, since they may also be found extraarticularly in gout and may possibly have a slightly different appearance, it was decided to test, as part of the Delphi exercise, whether the existing definition worked also in gout. Perfect agreement was obtained to keep the definition close to the definition used for erosions in general. The second step was to test the reliability of the obtained definitions in a Web exercise consisting of static images of the elementary lesions. The Web exercise included 110 US images of the 4 lesions obtained from feet and knees and 20 of these images were shown twice in order to test both interand intrareader reliability. Twenty-seven of the 35 rheumatologists participating in the Delphi exercise participated in the reliability study. Cohen's κ was used to evaluate interand intrareader reliability. Κ values 0-0.20 were considered poor; 0.20-0.40 fair; 0.40-0.60 moderate; 0.60-0.80 good; and 0.80-1 excellent The third step was to test the agreement and reliability of the elementary lesions in a cohort of patients with gout. Sixteen of the rheumatologists previously involved in the first and second step participated in a workshop with 8 patients with crystal-proven gout. Both intra-and inter-reader reliability was assessed by scanning the patients twice within the same day. The areas of attention were the intercondylar region of the knee, the 1st metatarsophalangeal (MTP) joint, and the patellar tendon. Cohen's κ was used to evaluate inter-and intrareader reliability. Κ values of 0-0.20 were considered poor; 0.20-0.40 fair; 0.40-0.60 moderate; 0.60-0.80 good; and 0.80-1 excellen

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

The prevalence of underpowered randomized clinical trials in rheumatology

OBJECTIVE: The conduct of underpowered randomized controlled trials (RCT) has recently been criticized in medical journals. We investigated the current prevalence of underpowered RCT in rheumatology. METHODS: We searched to identify randomized, prospective RCT assessing clinical efficacy of treatments for adult rheumatic diseases published in English in 2001 and 2002. RCT were assessed as positive or negative based on the result of the primary outcome measure. For phase III RCT with negative results without power analysis, we calculated adequate sample size using beta = 0.20 and alpha = 0.05. We also examined trial quality by assessing the adequacy of reported random sequence generation, allocation concealment, and analysis, and compared the quality of reporting of RCT with adequate and inadequate sample size. RESULTS: A total of 228 RCT met inclusion criteria; of the 205 phase III trials, 119 were positive, 81 were negative. The remaining 5 trials made no statistical comparison between interventions, and did not supply enough information for a result to be calculated. Of the 86 negative or indeterminate RCT, 37 reported sample size calculations (all but 4 had adequate power). Of the 49 remaining phase III trials that did not report power calculations, we conducted sample size calculations; only 10 were adequately powered. Few of the underpowered RCT studied rare rheumatic diseases. Negative RCT with inadequate sample size were less likely to describe adequate random sequence generation or allocation concealment than positive RCT or negative RCT with adequate sample size. CONCLUSION: The conduct of underpowered trials is not an infrequent occurrence in rheumatology, with only 50% of negative or indeterminate phase III rheumatology RCT in 2001-2002 having adequate sample size