Low-cost, multi-agent systems for planetary surface exploration

The use of off-the-shelf consumer electronics combined with top-down design methodologies have made small and inexpensive satellites, such as CubeSats, emerge as viable, low-cost and attractive space-based platforms that enable a range of new and exciting mission scenarios. In addition, to overcome some of the resource limitation issues encountered with these platforms, distributed architectures have emerged to enable complex tasks through the use of multiple low complexity units. The low-cost characteristics of such systems coupled with the distributed architecture allows for an increase in the size of the system beyond what would have been feasible with a monolithic system, hence widening the operational capabilities without significantly increasing the control complexity of the system. These ideas are not new for Earth orbiting devices, but excluding some distributed remote sensing architectures they are yet to be applied for the purpose of planetary exploration. Experience gained through large rovers demonstrates the value of in-situ exploration, which is however limited by the associated high-cost and risk. The loss of a rover can and has happened because of a number of possible failures: besides the hazards directly linked to the launch and journey to the target-body, hard landing and malfunctioning of parts are all threats to the success of the mission. To overcome these issues this paper introduces the concept of using off-the-shelf consumer electronics to deploy a low-cost multi-rover system for future planetary surface exploration. It is shown that such a system would significantly reduce the programmatic-risk of the mission (for example catastrophic failure of a single rover), while exploiting the inherent advantages of cooperative behaviour. These advantages are analysed with a particular emphasis put upon the guidance, navigation and control of such architectures using the method of artificial potential field. Laboratory tests on multi-agent robotic systems support the analysis. Principal features of the system are identified and the underlying advantages over a monolithic single-agent system highlighted

The deglacial history of 79N glacier and the Northeast Greenland Ice Stream

Acknowledgements This work was funded by NERC Standard Grant NE/N011228/1. We thank the Alfred Wegner Institute, and particularly Hicham Rafiq and Daniel Steinhage, for their significant logistic support through the iGRIFF project. Additional support was provided from Station Nord (Jørgen Skafte), Nordland Air, Air Greenland, the Joint Arctic Command and the Department of Geography, Durham University. Naalakkersuisut, Government of Greenland, provided Scientific Survey (VU-00121) and Export (046/2017) licences for this work. We would also like to thank our Field Ranger Isak (Nanu-Travel) and dog Ooni for keeping us safe in the field. TCN Sample preparation was carried out at the National Environmental Isotope Facility, Scottish Universities Environmental Research Centre under grant allocation 9185.0814. Chris Orton in the Cartographic Unit, Geography, Durham University edited several figures. This paper is dedicated to Mr Arnold Jones – a true Quaternarist.Peer reviewe

The deglacial history of 79N glacier and the Northeast Greenland Ice Stream

The Northeast Greenland Ice Stream (NEGIS) is the main artery for ice discharge from the northeast sector of the Greenland Ice Sheet (GrIS) to the North Atlantic. Understanding the past, present and future stability of the NEGIS with respect to atmospheric and oceanic forcing is of global importance as it drains around 17% of the GrIS and has a sea-level equivalent of 1.6 m. This paper reconstructs the deglacial and Holocene history of Nioghalvfjerdsbræ (or 79N Glacier); a major outlet of the NEGIS.At high elevation (>900 m asl) autochthonous blockfield, a lack of glacially moulded bedrock and pre LGM exposure ages point to a complex exposure/burial history extending back over half a million years. However, post Marine Isotope Stage 12, enhanced glacial erosion led to fjord incision and plateaux abandonment. Between 900 and 600 m asl the terrain is largely unmodified by glacial scour but post LGM erratics indicate the advection of cold-based ice through the fjord. In contrast, below ∼600 m asl Nioghalvfjerdsfjorden exhibits a geomorphological signal indicative of a warm-based ice stream operating during the last glacial cycle. Dated ice marginal landforms and terrain along the fjord walls show initial thinning rates were slow between ∼23 and 10 ka, but post-10 ka it is evident that Nioghalvfjerdsfjorden deglaciated extremely quickly with complete fjord deglaciation below ∼500 m asl between 10.0 and 8.5 ka.Both increasing air and ocean temperatures were pivotal in driving surface lowering and submarine melt during deglaciation, but the final withdrawal of ice through Nioghalvfjerdsfjorden was facilitated by the action of marine ice sheet instability. Our estimates show that thinning and retreat rates reached a maximum of 5.29 ma−1 and 613 ma−1, respectively, as the ice margin withdrew westwards. This would place the Early Holocene disintegration of this outlet of the NEGIS at the upper bounds of contemporary thinning and retreat rates seen both in Greenland and Antarctica. Combined with recent evidence of ice stream shutdown during the Holocene, as well as predictions of changing ice flow dynamics within downstream sections of the NEGIS catchment, this suggests that significant re-organisation of the terminal zone of the ice stream is imminent over the next century

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease

Reply to Comment on "The UK consensus position on the treatment of pancreatic cancer during the COVID-19 pandemic".

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/50110000028

The deglacial history of 79N glacier and the Northeast Greenland Ice Stream

The Northeast Greenland Ice Stream (NEGIS) is the main artery for ice discharge from the northeast sector of the Greenland Ice Sheet (GrIS) to the North Atlantic. Understanding the past, present and future stability of the NEGIS with respect to atmospheric and oceanic forcing is of global importance as it drains around 17% of the GrIS and has a sea-level equivalent of 1.6 m. This paper reconstructs the deglacial and Holocene history of Nioghalvfjerdsbræ (or 79N Glacier); a major outlet of the NEGIS. At high elevation (>900 m asl) autochthonous blockfield, a lack of glacially moulded bedrock and pre LGM exposure ages point to a complex exposure/burial history extending back over half a million years. However, post Marine Isotope Stage 12, enhanced glacial erosion led to fjord incision and plateaux abandonment. Between 900 and 600 m asl the terrain is largely unmodified by glacial scour but post LGM erratics indicate the advection of cold-based ice through the fjord. In contrast, below ∼600 m asl Nioghalvfjerdsfjorden exhibits a geomorphological signal indicative of a warm-based ice stream operating during the last glacial cycle. Dated ice marginal landforms and terrain along the fjord walls show initial thinning rates were slow between ∼23 and 10 ka, but post-10 ka it is evident that Nioghalvfjerdsfjorden deglaciated extremely quickly with complete fjord deglaciation below ∼500 m asl between 10.0 and 8.5 ka. Both increasing air and ocean temperatures were pivotal in driving surface lowering and submarine melt during deglaciation, but the final withdrawal of ice through Nioghalvfjerdsfjorden was facilitated by the action of marine ice sheet instability. Our estimates show that thinning and retreat rates reached a maximum of 5.29 ma−1 and 613 ma−1, respectively, as the ice margin withdrew westwards. This would place the Early Holocene disintegration of this outlet of the NEGIS at the upper bounds of contemporary thinning and retreat rates seen both in Greenland and Antarctica. Combined with recent evidence of ice stream shutdown during the Holocene, as well as predictions of changing ice flow dynamics within downstream sections of the NEGIS catchment, this suggests that significant re-organisation of the terminal zone of the ice stream is imminent over the next century

Global outbreak research: harmony not hegemony

No abstract available

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men