Rationale, design and methods of the Study of Work and Pain (SWAP): a cluster randomised controlled trial testing the addition of a vocational advice service to best current primary care for patients with musculoskeletal pain (ISRCTN 52269669)

Background Musculoskeletal pain is a major contributor to short and long term work absence. Patients seek care from their general practitioner (GP) and yet GPs often feel ill-equipped to deal with work issues. Providing a vocational case management service in primary care, to support patients with musculoskeletal problems to remain at or return to work, is one potential solution but requires robust evaluation to test clinical and cost-effectiveness. Methods/Design This protocol describes a cluster randomised controlled trial, with linked qualitative interviews, to investigate the effect of introducing a vocational advice service into general practice, to provide a structured approach to managing work related issues in primary care patients with musculoskeletal pain who are absent from work or struggling to remain in work. General practices (n = 6) will be randomised to offer best current care or best current care plus a vocational advice service. Adults of working age who are absent from or struggling to remain in work due to a musculoskeletal pain problem will be invited to participate and 330 participants will be recruited. Data collection will be through patient completed questionnaires at baseline, 4 and 12 months. The primary outcome is self-reported work absence at 4 months. Incremental cost-utility analysis will be undertaken to calculate the cost per additional QALY gained and incremental net benefits. A linked interview study will explore the experiences of the vocational advice service from the perspectives of GPs, nurse practitioners (NPs), patients and vocational advisors. Discussion This paper presents the rationale, design, and methods of the Study of Work And Pain (SWAP) trial. The results of this trial will provide evidence to inform primary care practice and guide the development of services to provide support for musculoskeletal pain patients with work-related issues. Trial registration Current Controlled Trials ISRCTN52269669

Alkali Metal Complexes of Phosphine-Borane-Substituted Benzyl Ligands and Their Application in the Synthesis of B-H\ub7\ub7\ub7Sn Stabilized Dialkylstannylenes

\ua9 2024 The Authors. Published by American Chemical Society.The benzyl-substituted phosphine-boranes PhCH2P(BH3)R2 [R = iPr (1H), Ph (2H), Cy (3H)] are accessible through either the reaction between R2PCl and PhCH2MgBr, followed by treatment with BH3\ub7SMe2 or the reaction between R2P(BH)3Li and PhCH2Br. Treatment of 1H, 2H, or 3H with nBuLi, PhCH2Na, or PhCH2K gave the corresponding alkali metal complexes [{iPr2P(BH3)CHPh}Li(THF)]2 (1Li), [{Ph2P(BH3)CHPh}Li(OEt2)2] (2Li), [{Cy2P(BH3)CHPh}Li(TMEDA)] (3Li), [iPr2P(BH3)CHPh]Na (1Na), [{Ph2P(BH3)CHPh}Na(THF)2]2 (2Na), [Cy2P(BH3)CHPh]Na(THF)0.5 (3Na), [{iPr2P(BH3)CHPh}K]∞ (1K), [{Ph2P(BH3)CHPh}K(THF)]∞ (2K), and [{Cy2P(BH3)CHPh}K.0.5PhMe]∞ (3K). X-ray crystallography revealed that, while 2Li and 3Li crystallize as monomers, 1Li and 2Na crystallize as borane-bridged dimers. The potassium complexes 1K, 2K, and 3K all crystallize with polymeric structures, in which the monomer units are linked to each other through a range of both bridging BH3 groups and multihapto interactions between the potassium cations and the aromatic rings. The reactions between two equivalents of either 1Li or 3Li and Cp2Sn gave the corresponding dialkylstannylenes [{R2P(BH3)CHPh}2Sn] [R = iPr (1Sn), Cy (3Sn)]. These compounds were isolated as mixtures of the rac and meso diastereomers. X-ray crystallography reveals that rac-1Sn and rac-3Sn crystallize as discrete monomers each exhibiting two agostic-type B-H\ub7\ub7\ub7Sn contacts

Impact of practice on quality of life of those living with an indwelling urinary catheter - an international evaluation

After completing this education activity, the learner will be able to compare the characteristics and quality of life of patients living with a long-term indwelling urinary catheter in the United Kingdom and the United States where catheter care policies differ with respect to types and routes of catheterization and timing of catheter changes

Comparison between resistive and collisionless double tearing modes for nearby resonant surfaces

The linear instability and nonlinear dynamics of collisional (resistive) and collisionless (due to electron inertia) double tearing modes (DTMs) are compared with the use of a reduced cylindrical model of a tokamak plasma. We focus on cases where two q = 2 resonant surfaces are located a small distance apart. It is found that regardless of the magnetic reconnection mechanism, resistivity or electron inertia, the fastest growing linear eigenmodes may have high poloidal mode numbers m ~ 10. The spectrum of unstable modes tends to be broader in the collisionless case. In the nonlinear regime, it is shown that in both cases fast growing high-m DTMs lead to an annular collapse involving small magnetic island structures. In addition, collisionless DTMs exhibit multiple reconnection cycles due to reversibility of collisionless reconnection and strong ExB flows. Collisionless reconnection leads to a saturated stable state, while in the collisional case resistive decay keeps the system weakly dynamic by driving it back towards the unstable equilibrium maintained by a source term.Comment: 15 pages, 9 figure

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Use of DNA–Damaging Agents and RNA Pooling to Assess Expression Profiles Associated with BRCA1 and BRCA2 Mutation Status in Familial Breast Cancer Patients

A large number of rare sequence variants of unknown clinical significance have been identified in the breast cancer susceptibility genes, BRCA1 and BRCA2. Laboratory-based methods that can distinguish between carriers of pathogenic mutations and non-carriers are likely to have utility for the classification of these sequence variants. To identify predictors of pathogenic mutation status in familial breast cancer patients, we explored the use of gene expression arrays to assess the effect of two DNA–damaging agents (irradiation and mitomycin C) on cellular response in relation to BRCA1 and BRCA2 mutation status. A range of regimes was used to treat 27 lymphoblastoid cell-lines (LCLs) derived from affected women in high-risk breast cancer families (nine BRCA1, nine BRCA2, and nine non-BRCA1/2 or BRCAX individuals) and nine LCLs from healthy individuals. Using an RNA–pooling strategy, we found that treating LCLs with 1.2 µM mitomycin C and measuring the gene expression profiles 1 hour post-treatment had the greatest potential to discriminate BRCA1, BRCA2, and BRCAX mutation status. A classifier was built using the expression profile of nine QRT–PCR validated genes that were associated with BRCA1, BRCA2, and BRCAX status in RNA pools. These nine genes could distinguish BRCA1 from BRCA2 carriers with 83% accuracy in individual samples, but three-way analysis for BRCA1, BRCA2, and BRCAX had a maximum of 59% prediction accuracy. Our results suggest that, compared to BRCA1 and BRCA2 mutation carriers, non-BRCA1/2 (BRCAX) individuals are genetically heterogeneous. This study also demonstrates the effectiveness of RNA pools to compare the expression profiles of cell-lines from BRCA1, BRCA2, and BRCAX cases after treatment with irradiation and mitomycin C as a method to prioritize treatment regimes for detailed downstream expression analysis

The Host Galaxy of FRB 20171020A Revisited

The putative host galaxy of FRB 20171020A was first identified as ESO 601-G036 in 2018, but as no repeat bursts have been detected, direct confirmation of the host remains elusive. In light of recent developments in the field, we re-examine this host and determine a new association confidence level of 98%. At 37 Mpc, this makes ESO 601-G036 the third closest FRB host galaxy to be identified to date and the closest to host an apparently non-repeating FRB (with an estimated repetition rate limit of < 0.011 bursts per day above 10 erg). Due to its close distance, we are able to perform detailed multi-wavelength analysis on the ESO 601-G036 system. Follow-up observations confirm ESO 601-G036 to be a typical star-forming galaxy with HI and stellar masses of log(M_HI/M_sol) ~ 9.2 and log(M_*/M_sol) = 8.64, and a star formation rate of SFR = 0.09 +/- 0.01 M_sol/yr. We detect, for the first time, a diffuse gaseous tail (log(M_HI/M_sol) ~ 8.3) extending to the south-west that suggests recent interactions, likely with the confirmed nearby companion ESO 601-G037. ESO 601-G037 is a stellar shred located to the south of ESO 601-G036 that has an arc-like morphology, is about an order of magnitude less massive, and has a lower gas metallicity that is indicative of a younger stellar population. The properties of the ESO 601-G036 system indicate an ongoing minor merger event, which is affecting the overall gaseous component of the system and the stars within ESO 601-G037. Such activity is consistent with current FRB progenitor models involving magnetars and the signs of recent interactions in other nearby FRB host galaxies.Comment: 16 pages, 9 figures, accepted for publication in PAS

A pilot survey for transients and variables with the Australian Square Kilometre Array Pathfinder

We present a pilot search for variable and transient sources at 1.4 GHz with the Australian Square Kilometre Array Pathfinder (ASKAP). The search was performed in a 30 deg2 area centred on the NGC 7232 galaxy group over eight epochs and observed with a near-daily cadence. The search yielded nine potential variable sources, rejecting the null hypothesis that the flux densities of these sources do not change with 99.9 per cent confidence. These nine sources displayed flux density variations with modulation indices m = 0.1 above our flux density limit of ~1.5mJy. They are identified to be compact active galactic nucleus (AGN)/quasars or galaxies hosting an AGN, whose variability is consistent with refractive interstellar scintillation.We also detect a highly variable source with modulation index m &gt; 0.5 over a time interval of a decade between the SydneyUniversity Molonglo Sky Survey (SUMSS) and our latest ASKAP observations. We find the source to be consistent with the properties of long-term variability of a quasar. No transients were detected on time-scales of days and we place an upper limit ?t &lt; 0.01 deg-2 with 95 per cent confidence for non-detections on near-daily time-scales. The future VAST-Wide survey with 36-ASKAP dishes will probe the transient phase space with similar cadence to our pilot survey, but better sensitivity, and will detect and monitor rarer brighter events

Predictors of stable return-to-work in non-acute, non-specific spinal pain: low total prior sick-listing, high self prediction and young age. A two-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Non-specific spinal pain (NSP), comprising back and/or neck pain, is one of the leading disorders in long-term sick-listing. During 2000-2004, 125 Swedish primary-care patients with non-acute NSP, full-time sick-listed 6 weeks-2 years, were included in a randomized controlled trial to compare a cognitive-behavioural programme with traditional primary care. This prospective cohort study is a re-assessment of the data from the randomized trial with the 2 treatment groups considered as a single cohort. The aim was to investigate which baseline variables predict a stable return-to-work during a 2-year period after baseline: objective variables from function tests, socioeconomic, subjective and/or treatment variables. Stable return-to-work was a return-to-work lasting for at least 1 month from the start of follow-up.</p> <p>Methods</p> <p><it>Stable return-to-work </it>was the outcome variable, the above-mentioned factors were the predictive variables in multiple-logistic regression models, one per follow-up at 6, 12, 18 and 24 months after baseline. The factors from univariate analyzes with a <it>p</it>-value of at most .10 were included. The non-significant variables were excluded stepwise to yield models comprising only significant factors (<it>p </it>< .05). As the comparatively few cases made it risky to associate certain predictors with certain time-points, we finally considered the predictors which were represented in at least 3 follow-ups. They are presented with odds ratios (OR) and 95% confidence intervals.</p> <p>Results</p> <p>Three variables qualified, all of them represented in 3 follow-ups: <it>Low total prior sick-listing </it>(including all diagnoses) was the strongest predictor in 2 follow-ups, 18 and 24 months, OR 4.8 [1.9-12.3] and 3.8 [1.6-8.7] respectively, <it>High self prediction </it>(the patients' own belief in return-to-work) was the strongest at 12 months, OR 5.2 [1.5-17.5] and <it>Young age </it>(max 44 years) the second strongest at 18 months, OR 3.5 [1.3-9.1].</p> <p>Conclusions</p> <p>In primary-care patients with non-acute NSP, the strong predictors of stable return-to-work were 2 socioeconomic variables, <it>Low total prior sick-listing </it>and <it>Young age</it>, and 1 subjective variable, <it>High self-prediction</it>. Objective variables from function tests and treatment variables were non-predictors. Except for <it>Young age</it>, the predictors have previously been insufficiently studied, and so our study should widen knowledge within clinical practice.</p> <p>Trial registration</p> <p>Trial registration number for the original trial NCT00488735.</p

A blind ATCA HI survey of the Fornax galaxy cluster:Properties of the HI detections

We present the first interferometric blind HI survey of the Fornax galaxy cluster, which covers an area of 15 deg2 out to the cluster virial radius. The survey has a spatial and velocity resolution of 67″ × 95″(∼6 × 9 kpc at the Fornax cluster distance of 20 Mpc) and 6.6 km s−1 and a 3σ sensitivity of NHI ∼ 2 × 1019 cm−2 and MHI ∼ 2 × 107 M⊙, respectively. We detect 16 galaxies out of roughly 200 spectroscopically confirmed Fornax cluster members. The detections cover about three orders of magnitude in HI mass, from 8 × 106 to 1.5 × 1010 M⊙. They avoid the central, virialised region of the cluster both on the sky and in projected phase-space, showing that they are recent arrivals and that, in Fornax, HI is lost within a crossing time, ∼2 Gyr. Half of these galaxies exhibit a disturbed HI morphology, including several cases of asymmetries, tails, offsets between HI and optical centres, and a case of a truncated HI disc. This suggests that these recent arrivals have been interacting with other galaxies, the large-scale potential or the intergalactic medium, within or on their way to Fornax. As a whole, our Fornax HI detections are HI-poorer and form stars at a lower rate than non-cluster galaxies in the same M⋆ range. This is particularly evident at M⋆  ≲  109 M⊙, indicating that low mass galaxies are more strongly affected throughout their infall towards the cluster. The MHI/M⋆ ratio of Fornax galaxies is comparable to that in the Virgo cluster. At fixed M⋆, our HI detections follow the non-cluster relation between MHI and the star formation rate, and we argue that this implies that thus far they have lost their HI on a timescale ≳1−2 Gyr. Deeper inside the cluster HI removal is likely to proceed faster, as confirmed by a population of HI-undetected but H2-detected star-forming galaxies. Overall, based on ALMA data, we find a large scatter in H2-to-HI mass ratio, with several galaxies showing an unusually high ratio that is probably caused by faster HI removal. Finally, we identify an HI-rich subgroup of possible interacting galaxies dominated by NGC 1365, where pre-processing is likely to have taken place