SN2010jp (PTF10aaxi): A Jet-Driven Type II Supernova

We present photometry and spectroscopy of the peculiar TypeII supernova (SN) 2010jp, also named PTF10aaxi. The light curve exhibits a linear decline with a relatively low peak absolute magnitude of only -15.9, and a low radioactive decay luminosity at late times that suggests a nickel mass below 0.003 $M_{\odot}$. Spectra of SN2010jp display an unprecedented triple-peaked H$\alpha$ line profile, showing: (1) a narrow (800 km/s) central component that suggests shock interaction with dense CSM; (2) high-velocity blue and red emission features centered at -12600 and +15400 km/s; and (3) broad wings extending from -22000 to +25000 km/s. These features persist during 100 days after explosion. We propose that this line profile indicates a bipolar jet-driven explosion, with the central component produced by normal SN ejecta and CSM interaction at mid latitudes, while the high-velocity bumps and broad line wings arise in a nonrelativistic bipolar jet. Two variations of the jet interpretation seem plausible: (1) A fast jet mixes 56Ni to high velocities in polar zones of the H-rich envelope, or (2) the reverse shock in the jet produces blue and red bumps in Balmer lines when a jet interacts with dense CSM. Jet-driven SNeII are predicted for collapsars resulting from a wide range of initial masses above 25 $M_{\odot}$ at sub-solar metallicity. This seems consistent with the SN host environment, which is either an extremely low-luminosity dwarf galaxy or very remote parts of an interacting pair of star-forming galaxies. It also seems consistent with the low 56Ni mass that may accompany black hole formation. We speculate that the jet survives to produce observable signatures because the star's H envelope was mostly stripped away by previous eruptive mass loss.Comment: 11 pages, 9 figures, submitted to MNRA

Understanding the Changing Cultural Value of the BBC World Service and the British Council

This project investigated the changing cultural value of the BBC World Service (WS) and the British Council (BC) and how their cultural value can be assessed and measured. For eight decades, these organisations have been the face and voice of Britain overseas. Our research found that their attraction and influence abroad remains strong, but is on the wane, reflecting the UK’s declining economic and political significance on the world stage. Among the key findings of our historical and contemporary research: Cultural value is the catalyst of all aspects of value at WS and BC, founded on their capacity to act as transcultural intermediaries, fostering international understanding, and setting benchmarks in global standards for journalism and cultural relations work. Cultural value is relational, never independent of political and economic value. It is perspectival: audiences trust the quality and credibility of outputs; high professional standards and prestige benefit staff; funders appreciate the diplomatic and soft power assets. Cultural value accrues slowly over time but can be quickly lost. Social media afford new ways of connecting, informing and engaging citizens at home and abroad. Our case studies analysing the uses of Twitter and Facebook by BC and WS around global media events underscore the so far limited role of social media in democratising participation and promoting intercultural dialogue. We developed an innovative, theoretically grounded and empirically informed Cultural Value Model (CVM). This is an innovative device for conceptualising, analysing and assessing value in a multidimensional, composite, visual way. The CVM is designed for planning, monitoring and evaluating projects and organisations over time, alongside existing performance indicators and impact measures. It is currently being tested and developed on further projects at WS and BC as well as at the Swedish Institute

Adopt to adapt: Efforts to Keep the RAMPART Trial of Adjuvant Immunotherapy in Renal Cancer on Track in the COVID-19 Era

Introduction: The RAMPART trial is an international, UCL-led, multi-arm multi-stage (MAMS) platform trial investigating the use of immune checkpoint inhibitors after nephrectomy in patients with renal cell carcinoma. It was initiated with a control (active monitoring) and two research arms (durvalumab monotherapy and durvalumab with tremelimumab) and has been open to recruitment since July 2018. Due to the COVID-19 pandemic, recruitment and treatment delivery was suspended for four months in the Spring/Summer of 2020 and accrual has only recovered in 2022. / Methods/Approach: The RAMPART team provided clear communication to sites on how to manage priorities during the temporary suspension and relaunch of the trial. The protocol was amended to ensure the safe treatment of patients and to offer flexibility to conduct consent and certain assessments remotely. Sites were asked to focus on the submission of high priority data to permit continued oversight of patient safety and allow primary outcome data to be collected. Data completeness has been carefully monitored and targeted data chases have been conducted to maximise data integrity. We have explored the extent to which the pandemic will prolong recruitment and follow-up, and the timelines for our primary analyses. To maximise options for patients and to aid accrual, we examined the impact of re-randomisation of control arm patients within the protocol, an approach that has been employed in other trials within the CTU in other disease areas. / Results Structure & Timelines: This section will contain an update on compliance, recruitment, sites open and timelines for analysis. In order to be able to present these adequately and robustly, we will use data up to September 2022. / Potential Relevance & Impact: The pandemic era has been challenging for clinical trials. Adaptations can be made to prioritise patient safety, to allow activity to continue where there is capacity and to ensure trial integrity is maintained

Stature estimation equations for South Asian skeletons based on DXA scans of contemporary adults.

OBJECTIVES: Stature estimation from the skeleton is a classic anthropological problem, and recent years have seen the proliferation of population-specific regression equations. Many rely on the anatomical reconstruction of stature from archaeological skeletons to derive regression equations based on long bone lengths, but this requires a collection with very good preservation. In some regions, for example, South Asia, typical environmental conditions preclude the sufficient preservation of skeletal remains. Large-scale epidemiological studies that include medical imaging of the skeleton by techniques such as dual-energy X-ray absorptiometry (DXA) offer new potential datasets for developing such equations. MATERIALS AND METHODS: We derived estimation equations based on known height and bone lengths measured from DXA scans from the Andhra Pradesh Children and Parents Study (Hyderabad, India). Given debates on the most appropriate regression model to use, multiple methods were compared, and the performance of the equations was tested on a published skeletal dataset of individuals with known stature. RESULTS: The equations have standard errors of estimates and prediction errors similar to those derived using anatomical reconstruction or from cadaveric datasets. As measured by the number of significant differences between true and estimated stature, and the prediction errors, the new equations perform as well as, and generally better than, published equations commonly used on South Asian skeletons or based on Indian cadaveric datasets. CONCLUSIONS: This study demonstrates the utility of DXA scans as a data source for developing stature estimation equations and offer a new set of equations for use with South Asian datasets

RAMPART : a model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting

AstraZeneca LP have provided an educational grant for the trial and free of charge durvalumab and tremelimumab. A small grant is also provided by Kidney Cancer UK. MRC CTU at UCL provides funding for staff working on the trial.The development of therapeutics in oncology is a highly active research area for the pharmaceutical and biotechnology industries, but also has a strong academic base. Many new agents have been developed in recent years, most with specific biological targets. This has mandated the need to look at different ways to streamline the evaluation of new agents. One solution has been the development of adaptive trial designs that allow the evaluation of multiple agents, concentrating on the most promising agents while screening out those which are unlikely to benefit patients. Another way forward has been the growth of partnerships between academia and industry with the shared goal of designing and conducting high quality clinical trials which answer important clinical questions as efficiently as possible. The RAMPART trial (NCT03288532) brings together both of these processes in an attempt to improve outcomes for patients with locally advanced renal cell carcinoma (RCC), where no globally acceptable adjuvant strategy after nephrectomy currently exist. RAMPART is led by the MRC CTU at University College London (UCL), in collaboration with other international academic groups and industry. We aim to facilitate the use of data from RAMPART, (dependent on outcomes), for a future regulatory submission that will extend the license of the agents being investigated. We share our experience in order to lay the foundations for an effective trial design and conduct framework and to guide others who may be considering similar collaborations.Publisher PDFPeer reviewe

RAMPART : a phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

AstraZeneca LP have provided an educational grant for the trial and free of charge durvalumab and tremelimumab. A small grant is also provided by Kidney Cancer UK. MRC CTU at UCL also provides funding for staff working on the trial. The TransRAMPART sample collection is being funded by a Prospective Sample Collection award from Cancer Research UK.Background 20–60% of patients with initially locally advanced Renal Cell Carcinoma (RCC) develop metastatic disease despite optimal surgical excision. Adjuvant strategies have been tested in RCC including cytokines, radiotherapy, hormones and oral tyrosine-kinase inhibitors (TKIs), with limited success. The predominant global standard-of-care after nephrectomy remains active monitoring. Immune checkpoint inhibitors (ICIs) are effective in the treatment of metastatic RCC; RAMPART will investigate these agents in the adjuvant setting. Methods/design RAMPART is an international, UK-led trial investigating the addition of ICIs after nephrectomy in patients with resected locally advanced RCC. RAMPART is a multi-arm multi-stage (MAMS) platform trial, upon which additional research questions may be addressed over time. The target population is patients with histologically proven resected locally advanced RCC (clear cell and non-clear cell histological subtypes), with no residual macroscopic disease, who are at high or intermediate risk of relapse (Leibovich score 3–11). Patients with fully resected synchronous ipsilateral adrenal metastases are included. Participants are randomly assigned (3,2:2) to Arm A - active monitoring (no placebo) for one year, Arm B - durvalumab (PD-L1 inhibitor) 4-weekly for one year; or Arm C - combination therapy with durvalumab 4-weekly for one year plus two doses of tremelimumab (CTLA-4 inhibitor) at day 1 of the first two 4-weekly cycles. The co-primary outcomes are disease-free-survival (DFS) and overall survival (OS). Secondary outcomes include safety, metastasis-free survival, RCC specific survival, quality of life, and patient and clinician preferences. Tumour tissue, plasma and urine are collected for molecular analysis (TransRAMPART).Publisher PDFPeer reviewe

Analysis of reach-scale elevation distribution in braided rivers: Definition of a new morphologic indicator and estimation of mean quantities

This work has been carried out within the SMART Joint Doctorate (Science forthe MAnagement of Rivers and theirTidal systems) funded with the support of the Erasmus Mundus programme of the European Union. Data of the Rees River were derived as part of UKNatural Environment Research Council grant (NE/G005427/1) awarded to PI Brasington, along with further support from the NERC Geophysical Equipmen tFacility (Loan 892) and Leverhulme Trust IAF2014-03

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London