Scientific Highlights of the HETE-2 Mission

The HETE-2 mission has been highly productive. It has observed more than 250 GRBs so far. It is currently localizing 25 - 30 GRBs per year, and has localized 43 GRBs to date. Twenty-one of these localizations have led to the detection of X-ray, optical, or radio afterglows, and as of now, 11 of the bursts with afterglows have known redshifts. HETE-2 has confirmed the connection between GRBs and Type Ic supernovae, a singular achievement and certainly one of the scientific highlights of the mission so far. It has provided evidence that the isotropic-equivalent energies and luminosities of GRBs are correlated with redshift, implying that GRBs and their progenitors evolve strongly with redshift. Both of these results have profound implications for the nature of GRB progenitors and for the use of GRBs as a probe of cosmology and the early universe. HETE-2 has placed severe constraints on any X-ray or optical afterglow of a short GRB. It is also solving the mystery of "optically dark' GRBs, and revealing the nature of X-ray flashes.Comment: 10 pages, 9 figures, to appear in proc. "The Restless High-Energy Universe", Royal Tropical Institute, Amsterdam; revised text, added ref

Existence of superposition solutions for pulse propagation in nonlinear resonant media

Existence of self-similar, superposed pulse-train solutions of the nonlinear, coupled Maxwell-Schr\"odinger equations, with the frequencies controlled by the oscillator strengths of the transitions, is established. Some of these excitations are specific to the resonant media, with energy levels in the configurations of $\Lambda$ and $N$ and arise because of the interference effects of cnoidal waves, as evidenced from some recently discovered identities involving the Jacobian elliptic functions. Interestingly, these excitations also admit a dual interpretation as single pulse-trains, with widely different amplitudes, which can lead to substantially different field intensities and population densities in different atomic levels.Comment: 11 Pages, 6 Figures, presentation changed and 3 figures adde

Cost-effectiveness of adalimumab for early-stage Dupuytren’s disease

Aims: To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren’s disease (DD) and the value of further research from an NHS perspective. Methods: We used data from the Repurposing anti-TNF for Dupuytren’s disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded. Results: The within-trial economic evaluation found that adalimumab plus standard care cost £503,410 per quality-adjusted life year (QALY) gained versus standard care alone over a 12-month time horizon. The model-based extrapolation suggested that, over a lifetime, repeated courses of adalimumab could cost £14,593 (95% confidence interval £7,534 to £42,698) per QALY gained versus standard care alone. If the NHS was willing to pay £20,000/QALY gained, there is a 77% probability that adalimumab with retreatment is the best value for money. Conclusion: Repeated courses of adalimumab are likely to be a cost-effective treatment for progressive early-stage DD. The value of perfect parameter information that would eliminate all uncertainty around the parameters estimated in RIDD and the duration of quiescence was estimated to be £105 per patient or £272 million for all 2,584,411 prevalent cases in the UK

Geomorphological effectiveness of floods to rework gravel bars:insight from hyperscale topography and hydraulic modelling

Bars are key morphological units in river systems, fashioning the sediment regime and bedload transport processes within a reach. Reworking of these features underpins channel adjustment at larger scales, thereby acting as a key determinant of channel stability. Despite their importance to channel evolution, few investigations have acquired spatially continuous data on bar morphology and sediment‐size to investigate bar reworking. To this end, four bars along a 10 km reach of a wandering gravel‐bed river were surveyed with Terrestrial Laser Scanning (TLS), capturing downstream changes in slope, bed material size and channel planform. Detrended standard deviations (σz) were extracted from TLS point clouds and correlated to underlying physically measured median grain‐size (D50), across a greater range of σz values than have hitherto been reported. The resulting linear regression model was used to create a 1 m resolution median grain‐size map. A fusion of airborne LiDAR and optical‐empirical bathymetric mapping was used to develop reach‐scale Digital Elevation Models (DEMs) for rapid two‐dimensional hydraulic modelling using JFlow® software. The ratio of dimensionless shear stress over critical shear stress was calculated for each raster cell to calculate the effectiveness of a range of flood events (2.33‐100 year recurrence intervals) to entrain sediment and rework bar units. Results show that multiple bar forming discharges exist, whereby frequent flood flows rework tail and back‐channel areas, whilst much larger, less frequent floods are required to mobilise the coarser sediment fraction on bar heads. Valley confinement is shown to exert a primary influence on patterns of bar reworking. Historical aerial photography, hyperscale DEMs and hydraulic modelling are used to explain channel adjustment at the reach scale. The proportion of the bar comprised of more frequently entrained units (tail, back channel, supra‐platform) relative to more static units (bar head) exerts a direct influence upon geomorphic sensitivity

Exercise treatments for lumbar spinal stenosis: A systematic review and intervention component analysis of randomised controlled trials

Objective To analyse the components used in exercise interventions for people with symptoms of neurogenic claudication due to lumbar spinal stenosis and identify components associated with successful interventions. Data sources Eligible papers published up to April 2023 from MEDLINE, EMBASE, CINAHL, PEDro, CENTRAL, Web of Science, and trial registry websites. Review methods Literature searches were performed by an Information Specialist. We searched for randomised trials evaluating exercise interventions for people with neurogenic claudication symptoms (the primary symptom of lumbar spinal stenosis). Two authors independently performed study selection, data extraction, and quality assessments using the Cochrane Risk of Bias tool Version 2 and the TIDieR checklist for intervention reporting. Details of intervention components were extracted, tabulated, and synthesised using an intervention component analysis approach. Results We found thirteen trials reporting 23 exercise interventions delivered to 1440 participants. These featured 60 different components. Most exercise interventions included supervision and flexion-based exercises. Balance exercises were rarely included. Exercise components featured more frequently in successful interventions included stretches, strength or trunk muscle exercises, fitness exercises, especially cycling, and psychologically informed approaches. Interpretation is limited by low study numbers and heterogeneity. No conclusions could be drawn about exercise supervision or dose. Discussion Exercise interventions for people with neurogenic claudication typically feature multiple components. Common features such as supervision, lumbar flexion, and aerobic fitness exercises and also less common features such as stretches, strengthening exercises, and psychologically informed approaches warrant consideration for inclusion when designing and optimising exercise interventions for people with lumbar spinal stenosis

Surgical fixation with K-wires versus casting in adults with fracture of distal radius: DRAFFT2 multicentre randomised clinical trial

Objective To assess wrist function, quality of life, and complications in adult patients with a dorsally displaced fracture of the distal radius, treated with either a moulded cast or surgical fixation with K-wires. Design Multicentre randomised clinical superiority trial, Setting 36 hospitals in the UK National Health Service (NHS). Participants 500 adults aged 16 or over with a dorsally displaced fracture of the distal radius, randomised after manipulation of their fracture (255 to moulded cast; 245 to surgical fixation). Interventions Manipulation and moulded cast was compared with manipulation and surgical fixation with K-wires plus cast. Details of the application of the cast and the insertion of the K-wires were at the discretion of the treating surgeon, according to their normal clinical practice. Main outcome measures The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months (five questions about pain and 10 about function and disability; overall score out of 100 (best score=0 and worst score=100)). Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for surgery due to loss of fracture position in the first six weeks. Results The mean age of participants was 60 years and 417 (83%) were women; 395 (79%) completed follow-up. No statistically significant difference in the PRWE score was seen at 12 months (cast group (n=200), mean 21.2 (SD 23.1); K-wire group (n=195), mean 20.7 (22.3); adjusted mean difference −0.34 (95% confidence interval −4.33 to 3.66), P=0.87). No difference was seen at earlier time points. In the cast group, 33 (13%) of participants needed surgical fixation for loss of fracture position in the first six weeks compared with one revision surgery in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10). Conclusions Among patients with a dorsally displaced distal radius fracture that needed manipulation, surgical fixation with K-wires did not improve patients’ wrist function at 12 months compared with a cast. Trial registration ISRCTN registry ISRCTN1198054

Partial symmetry breaking and heteroclinic tangencies

We study some global aspects of the bifurcation of an equivariant family of volume-contracting vector fields on the three-dimensional sphere. When part of the symmetry is broken, the vector fields exhibit Bykov cycles. Close to the symmetry, we investigate the mechanism of the emergence of heteroclinic tangencies coexisting with transverse connections. We find persistent suspended horseshoes accompanied by attracting periodic trajectories with long periods

Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial

Background Dupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease. Methods In this phase 2b, randomised, double-blind, placebo-controlled trial adults with early-stage Dupuytren's disease and an established clinically distinct nodule with a clear history of progression in the preceding 6 months were recruited from two clinical centres in the UK and were randomly assigned 1:1 to receive four injections of adalimumab or saline every 3 months. Participants and assessors were masked. The primary outcome was nodule hardness measured with a durometer at 12 months. Data were analysed by linear mixed effects regression models in the intention-to-treat population with multiple imputation for missing primary outcome data. The trial is registered at the ISRCTN registry, ISRCTN 27786905 and is complete. Findings Between Feb 17, 2017, and Jan 11, 2019, 284 participants were screened in the UK and 140 were enrolled. 47 (34%) participants were female and 93 (66%) were male. Mean age of participants was 59·7 years (SD 10·0). Primary outcome data were available from 113 participants. Nodule hardness was lower (−4·6 AU [95% CI −7·1 to −2·2], p=0·0002) in the adalimumab compared with the saline group at 12 months. There were no related serious adverse events; the most common adverse events were minor injection site reactions. Interpretation Intranodular injections of adalimumab in participants with early-stage Dupuytren's disease resulted in softening and reduction in size of the nodules. Longer follow-up would be required to assess the effect of tumour necrosis factor inhibition on disease progression, extension deficit and hand function. Funding Health Innovation Challenge Fund (Wellcome Trust, Department of Health) and 180 Life Sciences

Pulsars and Their Nebulae as EGRET Sources

At the end of the EGRET mission, only 6-8 Galactic sources had been identified as young pulsars. Since then, several energetic pulsars have been discovered in EGRET error boxes along the Galactic plane, as well as several pulsar wind nebulae from which pulsations have not yet been discovered. Some of these nebulae are associated with moderately variable EGRET sources, suggesting that the gamma-ray emission might be coming from the nebula rather than from the pulsar magnetosphere. There is also a population of unidentified EGRET sources at mid-Galactic latitudes which have been proposed to be either nearby middle-aged pulsars or millisecond pulsars. I review the current status of observational studies of pulsars associated with EGRET sources and what they suggest the upcoming AGILE and GLAST gamma-ray missions might observe.Comment: 11 pages, proceedings of talk given at "Young Neutron Stars and Supernova Remnants" session of 35th COSPAR meeting held in Paris, France. To appear in Advances in Space Researc