Tau-Rex I: A Next Generation Retrieval Code for Exoplanetary Atmospheres

Spectroscopy of exoplanetary atmospheres has become a well established method for the characterisation of extrasolar planets. We here present a novel inverse retrieval code for exoplanetary atmospheres. T-REx (Tau Retrieval for Exoplanets) is a line-by-line radiative transfer fully Bayesian retrieval framework. T-REx includes the following features: 1) the optimised use of molecular line-lists from the ExoMol project; 2) an unbiased atmospheric composition prior selection, through custom built pattern recognition software; 3) the use of two independent algorithms to fully sample the Bayesian likelihood space: nested sampling as well as a more classical Markov Chain Monte Carlo approach; 4) iterative Bayesian parameter and model selection using the full Bayesian Evidence as well as the Savage-Dickey Ratio for nested models, and 5) the ability to fully map very large parameter spaces through optimal code parallelisation and scalability to cluster computing. In this publication we outline the T-REx framework and demonstrate, using a theoretical hot-Jupiter transmission spectrum, the parameter retrieval and model selection. We investigate the impact of Signal-to-Noise and spectral resolution on the retrievability of individual model parameters, both in terms of error bars on the temperature and molecular mixing ratios as well as its effect on the model's global Bayesian evidence

τ-REx. II. Retrieval of emission spectra

τ-REx (Tau Retrieval of Exoplanets) is a novel, fully Bayesian atmospheric retrieval code custom built for extrasolar atmospheres. In Waldmann et al., the transmission spectroscopic case was introduced, and here we present the emission spectroscopy spectral retrieval for the τ-REx framework. Compared to transmission spectroscopy, the emission case is often significantly more degenerate due to the need to retrieve the full atmospheric temperature–pressure (TP) profile. This is particularly true in the case of current measurements of exoplanetary atmospheres, which are either of low signal-to-noise, low spectral resolution, or both. We present a new way of combining two existing approaches to the modeling of the said TP profile: (1) the parametric profile, where the atmospheric TP structure is analytically approximated by a few model parameters, (2) the layer-by-layer approach, where individual atmospheric layers are modeled. Both of these approaches have distinct advantages and disadvantages in terms of convergence properties and potential model biases. The τ-REx hybrid model presented here is a new two-stage TP profile retrieval, which combines the robustness of the analytic solution with the accuracy of the layer-by-layer approach. The retrieval process is demonstrated using simulations of the hot-Jupiter WASP-76b and the hot-super-Earth 55 Cnc e as well as the secondary eclipse measurements of HD 189733b

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial

\ua9 The Author(s) 2024.Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. Methods: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. Results: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43–2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29–0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). Conclusion: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF. Graphical Abstract: (Figure presented.)

Geriatric hip fracture clinical pathway: the Hong Kong experience

Geriatric hip fracture is one of the commonest fractures in orthopaedic trauma. There is a trend of further increase in its incidence in the coming decades. Besides the development of techniques and implants to overcome the difficulties in fixation of osteoporosis bone, the general management of the hip fracture is also very challenging in terms of the preparation of the generally poorer pre-morbid state and complicate social problems associated with this group of patients. In order to cope with the increasing demand, our hospital started a geriatric hip fracture clinical pathway in 2007. The aim of this pathway is to provide better care for this group of patients through multidisciplinary approach. From year 2007 to 2009, we had managed 964 hip fracture patients. After the implementation of the pathway, the pre-operative and the total length of stay in acute hospital were shortened by over 5 days. Other clinical outcomes including surgical site infection, 30 days mortality and also incidence of pressure sore improved when compared to the data before the pathway. The rate of surgical site infection was 0.98%, and the 30 days mortality was 1.67% in 2009. The active participation of physiotherapists, occupational therapists as well as medical social workers also helped to formulate the discharge plan as early as the patient is admitted. In conclusion, a well-planned and executed clinical pathway for hip fracture can improve the clinical outcomes of the geriatric hip fractures

Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis

Genome-wide association studies (GWAS) conducted using commercial single nucleotide polymorphisms (SNP) arrays have proven to be a powerful tool for the detection of common disease susceptibility variants. However, their utility for the detection of lower frequency variants is yet to be practically investigated. Here we describe the application of a rare variant collapsing method to a large genome-wide SNP dataset, the Wellcome Trust Case Control Consortium rheumatoid arthritis (RA) GWAS. We partitioned the data into gene-centric bins and collapsed genotypes of low frequency variants (defined here as MAF ≤0.05) into a single count coupled with univariate analysis. We then prioritised gene regions for further investigation in an independent cohort of 3,355 cases and 2,427 controls based on rare variant signal p value and prior evidence to support involvement in RA. A total of 14,536 gene bins were investigated in the primary analysis and signals mapping to the TNFAIP3 and chr17q24 loci were selected for further investigation. We detected replicating association to low frequency variants in the TNFAIP3 gene (combined p = 6.6 × 10−6). Even though rare variants are not well-represented and can be difficult to genotype in GWAS, our study supports the application of low frequency variant collapsing methods to genome-wide SNP datasets as a means of exploiting data that are routinely ignored

An Evolutionary Framework for Association Testing in Resequencing Studies

Sequencing technologies are becoming cheap enough to apply to large numbers of study participants and promise to provide new insights into human phenotypes by bringing to light rare and previously unknown genetic variants. We develop a new framework for the analysis of sequence data that incorporates all of the major features of previously proposed approaches, including those focused on allele counts and allele burden, but is both more general and more powerful. We harness population genetic theory to provide prior information on effect sizes and to create a pooling strategy for information from rare variants. Our method, EMMPAT (Evolutionary Mixed Model for Pooled Association Testing), generates a single test per gene (substantially reducing multiple testing concerns), facilitates graphical summaries, and improves the interpretation of results by allowing calculation of attributable variance. Simulations show that, relative to previously used approaches, our method increases the power to detect genes that affect phenotype when natural selection has kept alleles with large effect sizes rare. We demonstrate our approach on a population-based re-sequencing study of association between serum triglycerides and variation in ANGPTL4

Motion direction, speed and orientation in binocular matching

The spatial differences between the images seen by the two eyes, called binocular disparities, can be used to recover the volumetric (three-dimensional) aspects of a scene. The computation of disparity depends upon the correct identi®cation of corresponding features in the two images. Understanding what image features are used by the brain to solve this matching problem is one of the main issues in stereoscopic vision. Many cortical neurons in visual areas V1 (ref. 2), MT (refs 3, 4) and MST (refs 5, 6) that are tuned to binocular disparity are also tuned to orientation, motion direction and speed. Although psychophysical work has shown that motion direction can facilitate binocular matching, the psychophysical literature on the role of orientation is mixed^8,9 , and it has been argued that speed differences are ineffective in aiding correspondence^7. Here we use a different psychophysical paradigm to show that the visual system uses similarities in orientation, motion direction and speed to achieve binocular correspondence. These results indicate that cells that multiplex orientation, motion direction, speed and binocular disparity may help to solve the binocular matching problem

Development of a Core Outcome Set for effectiveness trials aimed at optimising prescribing in older adults in care homes

Background: Prescribing medicines for older adults in care homes is known to be sub-optimal. Whilst trials testing interventions to optimise prescribing in this setting have been published, heterogeneity in outcome reporting has hindered comparison of interventions, thus limiting evidence synthesis. The aim of this study was to develop a core outcome set (COS), a list of outcomes which should be measured and reported, as a minimum, for all effectiveness trials involving optimising prescribing in care homes. The COS was developed as part of the Care Homes Independent Pharmacist Prescribing Study (CHIPPS). Methods: A long-list of outcomes was identified through a review of published literature and stakeholder input. Outcomes were reviewed and refined prior to entering a two-round online Delphi exercise and then distributed via a web link to the CHIPPS Management Team, a multidisciplinary team including pharmacists, doctors and Patient Public Involvement representatives (amongst others), who comprised the Delphi panel. The Delphi panellists (n = 19) rated the importance of outcomes on a 9-point Likert scale from 1 (not important) to 9 (critically important). Consensus for an outcome being included in the COS was defined as ≥70% participants scoring 7–9 and <15% scoring 1–3. Exclusion was defined as ≥70% scoring 1–3 and <15% 7–9. Individual and group scores were fed back to participants alongside the second questionnaire round, which included outcomes for which no consensus had been achieved. Results: A long-list of 63 potential outcomes was identified. Refinement of this long-list of outcomes resulted in 29 outcomes, which were included in the Delphi questionnaire (round 1). Following both rounds of the Delphi exercise, 13 outcomes (organised into seven overarching domains: medication appropriateness, adverse drug events, prescribing errors, falls, quality of life, all-cause mortality and admissions to hospital (and associated costs)) met the criteria for inclusion in the final COS. Conclusions: We have developed a COS for effectiveness trials aimed at optimising prescribing in older adults in care homes using robust methodology. Widespread adoption of this COS will facilitate evidence synthesis between trials. Future work should focus on evaluating appropriate tools for these key outcomes to further reduce heterogeneity in outcome measurement in this context