Addressing our planetary crisis: Consensus statement from the presenters and International Advisory Committee of the Regional Action on Climate Change (RACC) Symposium held in conjunction with the Kyoto-based Science and Technology in Society (STS) Forum, 1 October 2021.

12 month embargo; published: 01 November 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

3-month versus 6-month adjuvant chemotherapy for patients with high-risk stage II and III colorectal cancer: 3-year follow-up of the SCOT non-inferiority RCT.

BACKGROUND: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. OBJECTIVES: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. DESIGN: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. SETTING: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. PARTICIPANTS: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. INTERVENTIONS: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. RESULTS: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand-foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p < 0.001). Quality-of-life scores were better in the 3-month treatment group over months 4-6. A cost-effectiveness analysis showed 3-month treatment to cost £4881 less over the 8-year analysis period, with an incremental net monetary benefit of £7246 per patient. CONCLUSIONS: The study achieved its primary end point, showing that 3-month oxaliplatin-containing adjuvant chemotherapy is non-inferior to 6 months of the same regimen; 3-month treatment showed a better safety profile and cost less. For future work, further follow-up will refine long-term estimates of the duration effect on disease-free survival and overall survival. The health economic analysis will be updated to include long-term extrapolation for subgroups. We expect these analyses to be available in 2019-20. The Short Course Oncology Therapy (SCOT) study translational samples may allow the identification of patients who would benefit from longer treatment based on the molecular characteristics of their disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN59757862 and EudraCT 2007-003957-10. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 64. See the NIHR Journals Library website for further project information. This research was supported by the Medical Research Council (transferred to NIHR Evaluation, Trials and Studies Coordinating Centre - Efficacy and Mechanism Evaluation; grant reference G0601705), the Swedish Cancer Society and Cancer Research UK Core Clinical Trials Unit Funding (funding reference C6716/A9894)

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK

Nuclear energy in the public sphere: Anti-nuclear movements vs. industrial lobbies in Spain (1962-1979)

The final publication is available at Springer via http://dx.doi.org/10.1007/s11024-014-9263-0This article examines the role of the Spanish Atomic Forum as the representative of the nuclear sector in the public arena during the golden years of the nuclear power industry from the 1960s to 1970s. It focuses on the public image concerns of the Spanish nuclear lobby and the subsequent information campaigns launched during the late 1970s to counteract demonstrations by the growing and heterogeneous anti-nuclear movement. The role of advocacy of nuclear energy by the Atomic Forum was similar to that in other countries, but the situation in Spain had some distinguishing features. Anti-nuclear protest in Spain peaked in 1978 paralleling the debates of a new National Energy Plan in Congress, whose first draft had envisaged a massive nuclearization of the country. We show how the approval of the Plan in July 1979, with a significant reduction in the nuclear energy component, was influenced by the anti-nuclear protest movements in Spain. Despite the efforts of the Spanish Atomic Forum to counter its message, the anti-nuclear movement was strengthened by reactions to the Three Mile Island accident in March 1979

The Inner-Shelf Dynamics Experiment

17 USC 105 interim-entered record; under review.The article of record as published may be found at http://dx.doi.org/10.1175/BAMS-D-19-0281.1The inner shelf, the transition zone between the surfzone and the midshelf, is a dynamically complex region with the evolution of circulation and stratification driven by multiple physical processes. Cross-shelf exchange through the inner shelf has important implications for coastal water quality, ecological connectivity, and lateral movement of sediment and heat. The Inner-Shelf Dynamics Experiment (ISDE) was an intensive, coordinated, multi-institution field experiment from September–October 2017, conducted from the midshelf, through the inner shelf, and into the surfzone near Point Sal, California. Satellite, airborne, shore- and ship-based remote sensing, in-water moorings and ship-based sampling, and numerical ocean circulation models forced by winds, waves, and tides were used to investigate the dynamics governing the circulation and transport in the inner shelf and the role of coastline variability on regional circulation dynamics. Here, the following physical processes are highlighted: internal wave dynamics from the midshelf to the inner shelf; flow separation and eddy shedding off Point Sal; offshore ejection of surfzone waters from rip currents; and wind-driven subtidal circulation dynamics. The extensive dataset from ISDE allows for unprecedented investigations into the role of physical processes in creating spatial heterogeneity, and nonlinear interactions between various inner-shelf physical processes. Overall, the highly spatially and temporally resolved oceanographic measurements and numerical simulations of ISDE provide a central framework for studies exploring this complex and fascinating region of the ocean.U.S. Office of Naval Research (ONR)ONR Departmental Research Initiative (DRI)Inner-Shelf Dynamics Experiment (ISDE

The DUNE Far Detector Interim Design Report, Volume 3: Dual-Phase Module

The DUNE IDR describes the proposed physics program and technical designs of the DUNE far detector modules in preparation for the full TDR to be published in 2019. It is intended as an intermediate milestone on the path to a full TDR, justifying the technical choices that flow down from the high-level physics goals through requirements at all levels of the Project. These design choices will enable the DUNE experiment to make the ground-breaking discoveries that will help to answer fundamental physics questions. Volume 3 describes the dual-phase module's subsystems, the technical coordination required for its design, construction, installation, and integration, and its organizational structure

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe