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First discoveries and localisations of Fast Radio Bursts with MeerTRAP: a real-time, commensal MeerKAT survey
No full textWe report on the discovery and localization of fast radio bursts (FRBs) from the MeerTRAP project, a commensal fast radiotransient-detection programme at MeerKAT in South Africa. Our hybrid approach combines a coherent search with an averagefield-of-view of 0.4 deg2 with an incoherent search utilizing a field-of-view of 1.27 deg2 (both at 1284 MHz). Here, wepresent results on the first three FRBs: FRB 20200413A (DM=1990.05 pc cm􀀀3), FRB 20200915A (DM=740.65 pc cm􀀀3),and FRB 20201123A (DM=433.55 pc cm􀀀3). FRB 20200413A was discovered only in the incoherent beam. FRB 20200915A(also discovered only in the incoherent beam) shows speckled emission in the dynamic spectrum which cannot be explained byinterstellar scintillation in our Galaxy or plasma lensing, and might be intrinsic to the source. FRB 20201123A shows a faintpost-cursor burst about 200 ms after the main burst and warrants further follow-up to confirm whether it is a repeating FRB.FRB 20201123A also exhibits significant temporal broadening consistent with scattering by a turbulent medium. The broadeningexceeds that predicted for medium along the sightline through our Galaxy.We associate this scattering with the turbulent mediumin the environment of the FRB in the host galaxy. Within the approximately 10 localization region of FRB 20201123A , weidentify one luminous galaxy (A 15•67; J173438.35􀀀504550.4) that dominates the posterior probability for a host association.The galaxy’s measured properties are consistent with other FRB hosts with secure associations
Multilevel modelling approach to analysing life course socioeconomic status and understanding missingness
No full textThis paper investigated the extent to which parental socioeconomic status was associated with life course socioeconomic status heterogeneity between adult cohort members of the 1958 National Child Development Study and how this association differed depending on methods used to address longitudinal missing data. We compared three variants of the full information maximum likelihood approach, namely available case, complete case and partially observed case and two methods designed to compensate for missing at random data, namely multilevel multiple imputation and multiple imputation chained equations. Our results highlighted the important contribution of parental socioeconomic status in explaining the divergence in achieved socioeconomic status over the adult life course, how the available case approach increasingly overestimated socioeconomic attainment as age increased and survey sample size decreased, and how the complete case approach downwardly biased the effect of parental socioeconomic status on adult socioeconomic status
Counter-Example Guided Neural Network Compression Refinement (CEG4N)
No full textNeural networks are essential components of learning-basedsoftware systems. However, their high compute, memory, and power requirements make using them in low resources domains challenging. For this reason, neural networks are often compressed before deployment. Existing compression techniques tend to degrade the network accuracy.We propose Counter-Example Guided Neural Network Compression Refinement (CEG4N). This technique combines search-based quantization and equivalence verification: the former minimizes the computational requirements, while the latter guarantees that the network’s output does not change after compression. We evaluate CEG4N on a diverse set of benchmarks that include large and small networks. Our technique was successful at compressing the networks in our evaluation while producing models with up to 72% better accuracy than state-of-the-art techniques
Physical activity, sedentary time and breast cancer risk: A Mendelian randomization study
No full textObjectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomization (MR) assesses causality by simulating randomized trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130,957 European-ancestry women (69,838 invasive cases), and published UK Biobank data (n=91,105-377,234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.Results: Greater genetically-predicted overall activity was associated with lower breast cancer risk, overall (OR=0.59; 95%CI 0.42-0.83 per-standard deviation [SD; ~8 milligravities acceleration]) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95%CI 0.45-0.87, ≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95%CI 1.07-2.92 per-SD [~7% time spent sedentary]), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.<br/
Bridging disconnected networks of first and second lines of biologic therapies in rheumatoid arthritis with registry data: Bayesian evidence synthesis with target trial emulation
No full textObjective: We aim to utilise real world data in evidence synthesis to optimise an evidence base for the effectiveness of biologic therapies in rheumatoid arthritis in order to allow for evidence on first-line therapies to inform second-line effectiveness estimates.Study design and setting: We use data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) to supplement RCT evidence obtained from the literature, by emulating target trials of treatment sequences to estimate treatment effects in each line of therapy. Treatment effects estimates from the target trials inform a bivariate network meta-analysis (NMA) of first and second-line treatments.Results: Summary data were obtained from 21 trials of biologic therapies including 2 for second-line treatment and results from six emulated target trials of both treatment lines. Bivariate NMA resulted in a decrease in uncertainty around the effectiveness estimates of the second-line therapies, when compared to the results of univariate NMA, and allowed for predictions of treatment effects not evaluated in second-line RCTs.Conclusion: Bivariate NMA provides effectiveness estimates for all treatments in first- and second-line, including predicted effects in second-line where these estimates did not exist in the data. This novel methodology may have further applications, for example for bridging networks of trials in children and adults
Comparing the Utility and Disclosure Risk of Synthetic Data with Samples of Microdata
No full textMost statistical agencies release randomly selected samples of Census microdata, usually with sample fractions under 10% and with other forms of statistical disclosure control (SDC) applied. An alternative to SDC is data synthesis, which has been attracting growing interest, yet there is no clear consensus on how to measure the associated utility and disclosure risk of the data. The ability to produce synthetic Census microdata, where the utility and associated risks are clearly understood, could mean that more timely and wider-ranging access to microdata would be possible. This paper follows on from previous work by the authors which mapped synthetic Census data on a risk-utility (R-U) map. The paper presents a framework to measure the utility and disclosure risk of synthetic data by comparing it to samples of the original data of varying sample fractions, thereby identifying the sample fraction which has equivalent utility and risk to the synthetic data. Three commonly used data synthesis packages are compared with some interesting results. Further work is needed in several directions but the methodology looks very promising.</p
Time restricted feeding – a free and effective method of managing hypertension by ameliorating inflammation?
No full textPalliative radiotherapy in cancers of female genital tract: Outcomes and prognostic factors
No full textBackground and purposeMetastatic and incurable cancers of the gynaecological tract (FGTC) represent a major global health burden. Systemic treatment has modest efficacy and radiotherapy is often used for local symptoms. This study combines experience from two large UK centres in palliative radiotherapy for gynaecological cancers. Materials and methodsPooled data from two major centres was analysed. Advanced FGTC patients who received at least one fraction of palliative radiotherapy to the pelvis between 2013 to 2018 were included. Data collected included demographic and tumour details, radiotherapy dose fractionation and details of previous and subsequent treatment. Response was defined in terms of toxicity, symptomatic response and survival. Comorbidities were recorded using a modified ACE 27 score which is adjusted for the presence of uncontrolled FGTC in all the patients.ResultsA total of 184 patients were included for treatment response and toxicity; survival data was available for 165 patients. Subjective response in pre-radiotherapy symptoms was documented in 80.4%. Grade 3 or worse gastrointestinal, urinary and other(vomiting, fatigue, pain ) toxicity incidence was 2.2%, 3.8%, and 2.7% respectively. No statistically significant correlation between the prescribed EQD210 and symptom control or toxicity was seen. 1 year overall survival was 25.1% (median 5.9 months). Absent distant metastases, completion of the intended course of radiotherapy, response to radiotherapy, and receipt of further lines of treatment were independent prognostic factors. Conclusion.Palliative radiotherapy is effective for symptoms of advanced FGTC with low toxicity. The absence of a dose response argues for short low dose palliative radiotherapy schedules to be used.<br/
ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma.
No full textBackground & Aims: Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.Methods: Demographic, tumour, and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary end point was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0-1 after sorafenib discontinuation.Results: Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0-1; 43 patients (24%) were both CP-A and PS 0-1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72-8.25, p=0.0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (p=0.008). Conclusions: Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.<br/
Antiplatelet resistance: a review of concepts, mechanisms and implications for management in acute ischaemic stroke and transient ischaemic attack
No full textAcute ischaemic stroke is a leading cause of death and major disability worldwide. Approximately 50% of ischaemic strokes are caused by atherothrombotic occlusion of the cerebral arteries and antiplatelets are the mainstay of secondary stroke preventative treatment. Aspirin is beneficial if given early and short-term treatment using aspirin and clopidogrel is increasingly used for patients with intracranial atherosclerotic disease, minor stroke and/or transient ischemic attack. However, up to 50% of patients continue to have recurrent stroke and major vascular events, which may be partly due to resistance to aspirin and/or clopidogrel. Although the precise mechanisms are unknown, clinical and genetic factors associated with bioavailability and binding to target receptors are implicated. This narrative review begins with the concept of aspirin and clopidogrel resistance in ischaemic stroke and transient ischaemic attack (TIA), potential mechanisms including genetic polymorphisms and an overview of platelet function measures and limitations. We conclude by highlighting practical issues in the management of patients with aspirin and/or clopidogrel resistance including the emerging interest in ticagrelor, prasugrel and cilostazol and directions for future trials in TIA and acute ischaemic stroke