Comparing Total Neoplasms, Breast & Prostate Cancer Mortality Rates of the UK and 20 Major Developed Countries 1989-91 v 2013- 15 - Identifying Progress

Introduction: Britain’s cancer survival results have been criticised as being significantly higher than twenty Major Developed Countries (MDC). Hence this comparison of current UK Total Age-StandardisedDeath-Rates (ASDR), female Breast and Prostate cancer mortality rates with twenty (MDC) between1989 to 2015 to determine any significant change. Method: WHO data ASDR per million (pm) for Total, Breast and Prostate cancer mortality rates examined for the years 1989-91 to 2013-15. Confidence Intervals (+/- 95%) are used to determine any significant differences between the UK and other country’s outcomes over the period. Chi square tests for each nation’s Breast and Prostate mortality. Results: Every country’s Total ASDR, Breast and Prostate cancer mortality fell except Greece and Japan. Total ASDR Male cancer mortality rates ranged from Portugal 1653pm to Sweden 1232pm. UK at 1475pm were 10th but had been 6th highest. Total ASDR Female rates went from Denmark’s 1176pm to Japan’s 740pm, the UK 1092pm now 5th but previously had been second highest. No country’s Total rates fell significantly more than Britain’s who had significantly bigger reductions than four other countries for both sexes. Breast mortality ranged from Ireland’s 206pm to Japan’s 99pm, UK rates fell significantly more than five countries. Whilst Breast mortality fell in every country Norway and UK had significantly bigger reductions in Breast than Prostate deaths, conversely France’s Prostate rates fell more than Breast mortality. Prostate mortality went from Norway 213pm Japan’s 60pm, the UK 167pm and five countries had greater reductions than Britain. Conclusions: Results reflect well on UK services for Total and Breast cancers, showing the NHS achieving more with proportionately less as Britain spends less on health than most MDC. The need how to improve UK prostate results are briefly discussed, such as a public information campaign to match the successful Breast cancer aware programme of the 1990’s

AMI-LA Observations of the SuperCLASS Super-cluster

We present a deep survey of the SuperCLASS super-cluster - a region of sky known to contain five Abell clusters at redshift $z\sim0.2$ - performed using the Arcminute Microkelvin Imager (AMI) Large Array (LA) at 15.5$~$GHz. Our survey covers an area of approximately 0.9 square degrees. We achieve a nominal sensitivity of $32.0~\mu$Jy beam$^{-1}$ toward the field centre, finding 80 sources above a $5\sigma$ threshold. We derive the radio colour-colour distribution for sources common to three surveys that cover the field and identify three sources with strongly curved spectra - a high-frequency-peaked source and two GHz-peaked-spectrum sources. The differential source count (i) agrees well with previous deep radio source count, (ii) exhibits no evidence of an emerging population of star-forming galaxies, down to a limit of 0.24$~$mJy, and (iii) disagrees with some models of the 15$~$GHz source population. However, our source count is in agreement with recent work that provides an analytical correction to the source count from the SKADS Simulated Sky, supporting the suggestion that this discrepancy is caused by an abundance of flat-spectrum galaxy cores as-yet not included in source population models.Comment: 17 pages, 14 figures, 3 tables. Accepted for publication in MNRA

Investigating Bayesian optimization for rail network optimization

Optimizing the operation of rail networks using simulations is an on-going task where heuristic methods such as Genetic Algorithms have been applied. However, these simulations are often expensive to compute and consequently, because the optimization methods require many (typically >104) repeat simulations, the computational cost of optimization is dominated by them. This paper examines Bayesian Optimization and benchmarks it against the Genetic Algorithm method. By applying both methods to test-tasks seeking to maximize passenger satisfaction by optimum resource allocation, it is experimentally determined that a Bayesian Optimization implementation finds ‘good’ solutions in an order of magnitude fewer simulations than a Genetic Algorithm. Similar improvement for real-world problems will allow the predictive power of detailed simulation models to be used for a wider range of network optimization tasks. To the best of the authors’ knowledge, this paper documents the first application of Bayesian Optimization within the field of rail network optimization

A Multi-telescope Campaign on FRB 121102: Implications for the FRB Population

We present results of the coordinated observing campaign that made the first subarcsecond localization of a Fast Radio Burst, FRB 121102. During this campaign, we made the first simultaneous detection of an FRB burst by multiple telescopes: the VLA at 3 GHz and the Arecibo Observatory at 1.4 GHz. Of the nine bursts detected by the Very Large Array at 3 GHz, four had simultaneous observing coverage at other observatories. We use multi-observatory constraints and modeling of bursts seen only at 3 GHz to confirm earlier results showing that burst spectra are not well modeled by a power law. We find that burst spectra are characterized by a ~500 MHz envelope and apparent radio energy as high as $10^{40}$ erg. We measure significant changes in the apparent dispersion between bursts that can be attributed to frequency-dependent profiles or some other intrinsic burst structure that adds a systematic error to the estimate of DM by up to 1%. We use FRB 121102 as a prototype of the FRB class to estimate a volumetric birth rate of FRB sources $R_{FRB} \approx 5x10^{-5}/N_r$ Mpc$^{-3}$ yr$^{-1}$, where $N_r$ is the number of bursts per source over its lifetime. This rate is broadly consistent with models of FRBs from young pulsars or magnetars born in superluminous supernovae or long gamma-ray bursts, if the typical FRB repeats on the order of thousands of times during its lifetime.Comment: 17 pages, 7 figures. Submitted to AAS Journal

AMI-LA observations of the SuperCLASS supercluster

We present a deep survey of the SuperCLASS super-cluster - a region of sky known to contain five Abell clusters at redshift $z\sim0.2$ - performed using the Arcminute Microkelvin Imager (AMI) Large Array (LA) at 15.5$~$GHz. Our survey covers an area of approximately 0.9 square degrees. We achieve a nominal sensitivity of $32.0~\mu$Jy beam$^{-1}$ toward the field centre, finding 80 sources above a $5\sigma$ threshold. We derive the radio colour-colour distribution for sources common to three surveys that cover the field and identify three sources with strongly curved spectra - a high-frequency-peaked source and two GHz-peaked-spectrum sources. The differential source count (i) agrees well with previous deep radio source count, (ii) exhibits no evidence of an emerging population of star-forming galaxies, down to a limit of 0.24$~$mJy, and (iii) disagrees with some models of the 15$~$GHz source population. However, our source count is in agreement with recent work that provides an analytical correction to the source count from the SKADS Simulated Sky, supporting the suggestion that this discrepancy is caused by an abundance of flat-spectrum galaxy cores as-yet not included in source population models

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). PATIENTS AND METHODS: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSION: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes

Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): an open-label, multicenter, phase II trial.

PURPOSE: Resistance to HER2 (ErbB2)-targeted therapy may be mediated by other members of the ErbB family. We investigated the efficacy and safety of the irreversible ErbB family blocker, afatinib, alone as first-line therapy in the advanced setting and in combination with vinorelbine or paclitaxel for those who progressed on afatinib monotherapy, in female patients with metastatic breast cancer who had failed or progressed on prior HER2-targeted therapy in the early disease setting. METHODS: In this phase II, single-arm, two-part study (ClinicalTrials.gov: NCT01271725), patients in part A received afatinib 40 mg/day in 21-day cycles until disease progression or intolerable adverse events (AEs). Patients with progressive disease could then receive afatinib plus weekly vinorelbine 25 mg/m2 or paclitaxel 80 mg/m2 until disease progression or intolerable AEs (part B). The primary endpoint was confirmed objective response rate (RECIST v1.1). RESULTS: Eighty-seven patients were enrolled and 74 were treated in part A (median age: 51 years [range 27-76]; 31 [42%] estrogen receptor-positive, 26 [35%] progesterone receptor-positive). Of these, 39 (53%) patients went on to receive afatinib plus vinorelbine (13 patients) or paclitaxel (26 patients) in part B. Thirteen (18%) and 12 (31%) patients achieved an objective response in parts A and B, respectively. The most common treatment-related AEs with afatinib monotherapy (any/grade ≥ 3) were diarrhea (68%/8%) and rash (49%/4%). Combination therapy was generally well tolerated, with no additive toxicity observed. CONCLUSION: Afatinib treatment, alone or in combination with vinorelbine or paclitaxel, was associated with objective responses in ≥ 18% of patients with metastatic breast cancer for whom prior HER2-targeted therapy has failed. Treatment-related AEs were generally manageable, with few grade ≥ 3 AEs reported. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01271725, registered 1 July 2011