The Periglacial Landscape of Mars: Insight into the \u27Decameter-scale Rimmed Depressions\u27 in Utopia Planitia

Currently, Mars appears to be in a ‘frozen’ and ‘dry’ state, with the clear majority of the planet’s surface maintaining year-round sub-zero temperatures. However, the discovery of features consistent with landforms found in periglacial environments on Earth, suggests a climate history for Mars that may have involved freeze and thaw cycles. Such landforms include hummocky, polygonised, scalloped, and pitted terrains, as well as ice-rich deposits and gullies, along the mid- to high-latitude bands, typically with no lower than 20o N/S. The detection of near-surface and surface ice via the Phoenix lander, excavation of ice via recent impact cratering activity as monitored by High Resolution Imaging Science Experiment (HiRISE), Context Camera (CTX), and Compact Reconnaissance Imaging Spectrometer (CRISM), complemented by interpreted results from the SHAllow RADar (SHARAD) instrument, further unveil a landscape enriched in water/ice. Studies of the orbital behaviour of Mars have equally inferred that climate-forcing, triggered by cyclic shifts in the obliquity of Mars, controls the atmospheric stability of water-ice on the surface, allowing the mid- to high-latitudes to host a, so-called, periglacial environment. Still, there is much debate regarding just how ‘wet’ the paleoclimate of Mars has been, with concurrent water-related and ‘dry’ hypotheses having been put forth to explain the landscape evolution of the planet. We advocate that, considering the current limitations in studying Mars, geomorphological analysis is a reliable avenue in inferring the genetic nature of a landscape. As such, via a geomorphologic survey, we report on the landscape analysis of a region within Utopia Planitia. This region hosts a diverse abundance of potential periglacial features, including an intriguing ‘rimmed’ feature found within our study area. This feature, which we have dubbed ‘Decameter-scale Rimmed Depression’, serves as a valuable stratigraphic marker for rebuilding the geologic history of Utopia Planitia within the recent late Amazonian period, as it is both relatively young and potentially periglacial in nature. Ultimately, our aim is to unveil an additional piece to the periglacial ‘puzzle’ of Mars, via focusing on the prevalent process(es), responsible in shaping the landscape in question, and suggest a scenario for the late-Amazonian climate history, specific to Utopia Planitia

Efficacy of two artemisinin-based combinations for the treatment of malaria in pregnancy in India: a randomized controlled trial.

BACKGROUND: In India, the recommended first-line treatment for malaria in the second and third trimester of pregnancy is artesunate + sulfadoxine-pyrimethamine (AS+SP). However, data on safety and efficacy of artemisinin-based combination therapy (ACT) in pregnancy is limited. This study assessed the safety and efficacy of AS+SP and artesunate + mefloquine (AS+MQ) for treatment of Plasmodium falciparum in pregnancy in India. METHODS: This open-label, randomized clinical trial was conducted from October 2010 to December 2013 at three sites in India (Ranchi and Jamshedpur in Jharkhand state, and Rourkela in Odisha state). Pregnant women in the second or third trimester who had P. falciparum mono-infection of any parasite density with or without fever were randomized to receive AS+SP or AS+MQ. Blood slides and filter paper samples for Polymerase Chain Reaction (PCR) were collected on days 0, 1, 2, 3, 14, 21, 28, 42 and 63 post treatment. Women were followed up at delivery and at day 42 postpartum. FINDINGS: Two hundred and forty-eight women of 7064 pregnant women (3.5%) who were screened at monthly antenatal clinics had a P. falciparum mono-infection and were randomized to receive AS+SP (125) or AS+MQ (123) and all of these women were included in the intention to treat (ITT) analysis. The primary endpoint of an adequate clinical and parasite response (ACPR) on day 63 was not available for 9 women who were counted as treatment failure in the ITT analysis. In the ITT population, the ACPR was 121/125 (96.8%; 95% Confidence interval (CI) 92.0-99.1%) in the AS+SP group and 117/123 (95.1%; 95% CI 89.7-98.2) in the AS+MQ group. Among the 239 women (121 from the AS+SP arm and 118 from the AS+MQ arm) who completed the day 63 follow up (per protocol analysis) the ACPR was 100% in the AS+SP group and 99.2% (117/118) in the AS+MQ group. There were five serious adverse events (SAE) among pregnant women (4 in the AS+SP group and 1 in the AS+MQ group) and 13 fetal/neonatal SAEs (7 in the AS+SP group and 6 in the AS+MQ) but none of them were related to the study drugs. A higher proportion of women in the AS+MQ arm reported vomiting within 7 days post-treatment than did women in the AS+SP arm (6.9 vs. 1.6%; p = 0.001). CONCLUSION: Both AS+SP and AS+MQ are safe and effective for treatment of uncomplicated falciparum malaria in pregnancy in India. Trial registration CTRI This study is registered with Clinical Trial Registry India (CTRI), number CTRI/2009/091/001055. Date of Registration 11 January 2010, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=1185&EncHid=&userName=anvikar

Multiparametric ultrasound versus multiparametric MRI to diagnose prostate cancer (CADMUS): a prospective, multicentre, paired-cohort, confirmatory study

BACKGROUND: Multiparametric MRI of the prostate followed by targeted biopsy is recommended for patients at risk of prostate cancer. However, multiparametric ultrasound is more readily available than multiparametric MRI. Data from paired-cohort validation studies and randomised, controlled trials support the use of multiparametric MRI, whereas the evidence for individual ultrasound methods and multiparametric ultrasound is only derived from case series. We aimed to establish the overall agreement between multiparametric ultrasound and multiparametric MRI to diagnose clinically significant prostate cancer. METHODS: We conducted a prospective, multicentre, paired-cohort, confirmatory study in seven hospitals in the UK. Patients at risk of prostate cancer, aged 18 years or older, with an elevated prostate-specific antigen concentration or abnormal findings on digital rectal examination underwent both multiparametric ultrasound and multiparametric MRI. Multiparametric ultrasound consisted of B-mode, colour Doppler, real-time elastography, and contrast-enhanced ultrasound. Multiparametric MRI included high-resolution T2-weighted images, diffusion-weighted imaging (dedicated high B 1400 s/mm2 or 2000 s/mm2 and apparent diffusion coefficient map), and dynamic contrast-enhanced axial T1-weighted images. Patients with positive findings on multiparametric ultrasound or multiparametric MRI underwent targeted biopsies but were masked to their test results. If both tests yielded positive findings, the order of targeting at biopsy was randomly assigned (1:1) using stratified (according to centre only) block randomisation with randomly varying block sizes. The co-primary endpoints were the proportion of positive lesions on, and agreement between, multiparametric MRI and multiparametric ultrasound in identifying suspicious lesions (Likert score of ≥3), and detection of clinically significant cancer (defined as a Gleason score of ≥4 + 3 in any area or a maximum cancer core length of ≥6 mm of any grade [PROMIS definition 1]) in those patients who underwent a biopsy. Adverse events were defined according to Good Clinical Practice and trial regulatory guidelines. The trial is registered on ISRCTN, 38541912, and ClinicalTrials.gov, NCT02712684, with recruitment and follow-up completed. FINDINGS: Between March 15, 2016, and Nov 7, 2019, 370 eligible patients were enrolled; 306 patients completed both multiparametric ultrasound and multiparametric MRI and 257 underwent a prostate biopsy. Multiparametric ultrasound was positive in 272 (89% [95% CI 85-92]) of 306 patients and multiparametric MRI was positive in 238 patients (78% [73-82]; difference 11·1% [95% CI 5·1-17·1]). Positive test agreement was 73·2% (95% CI 67·9-78·1; κ=0·06 [95% CI -0·56 to 0·17]). Any cancer was detected in 133 (52% [95% CI 45·5-58]) of 257 patients, with 83 (32% [26-38]) of 257 being clinically significant by PROMIS definition 1. Each test alone would result in multiparametric ultrasound detecting PROMIS definition 1 cancer in 66 (26% [95% CI 21-32]) of 257 patients who had biopsies and multiparametric MRI detecting it in 77 (30% [24-36]; difference -4·3% [95% CI -8·3% to -0·3]). Combining both tests detected 83 (32% [95% CI 27-38]) of 257 clinically significant cancers as per PROMIS definition 1; of these 83 cancers, six (7% [95% CI 3-15]) were detected exclusively with multiparametric ultrasound, and 17 (20% [12-31]) were exclusively detected by multiparametric MRI (agreement 91·1% [95% CI 86·9-94·2]; κ=0·78 [95% CI 0·69-0·86]). No serious adverse events were related to trial activity. INTERPRETATION: Multiparametric ultrasound detected 4·3% fewer clinically significant prostate cancers than multiparametric MRI, but it would lead to 11·1% more patients being referred for a biopsy. Multiparametric ultrasound could be an alternative to multiparametric MRI as a first test for patients at risk of prostate cancer, particularly if multiparametric MRI cannot be carried out. Both imaging tests missed clinically significant cancers detected by the other, so the use of both would increase the detection of clinically significant prostate cancers compared with using each test alone. FUNDING: The Jon Moulton Charity Trust, Prostate Cancer UK, and UCLH Charity and Barts Charity

MOESM1 of Efficacy of two artemisinin-based combinations for the treatment of malaria in pregnancy in India: a randomized controlled trial

Additional file 1. Kaplan–Meier failure estimates

The CanMars Mars Sample Return analogue mission

The return of samples from known locations on Mars is among the highest priority goals of the international planetary science community. A possible scenario for Mars Sample Return (MSR) is a series of 3 missions: sample cache, fetch, and retrieval. The NASA Mars 2020 mission represents the first cache mission and was the focus of the CanMars analogue mission described in this paper. The major objectives for CanMars included comparing the accuracy of selecting samples remotely using rover data versus a traditional human field party, testing the efficiency of remote science operations with periodic pre-planned strategic observations (Strategic Traverse Days), assessing the utility of realistic autonomous science capabilities to the remote science team, and investigating the factors that affect the quality of sample selection decision-making in light of returned sample analysis. CanMars was conducted over two weeks in November 2015 and continued over three weeks in October and November 2016 at an analogue site near Hanksville, Utah, USA, that was unknown to the Mission Control Team located at the University of Western Ontario (Western) in London, Ontario, Canada. This operations architecture for CanMars was based on the Phoenix and Mars Exploration Rover missions together with previous analogue missions led by Western with the Mission Control Team being divided into Planning and Science sub-teams. In advance of the 2015 operations, the Science Team used satellite data, chosen to mimic datasets available from Mars-orbiting instruments, to produce a predictive geological map for the landing ellipse and a set of hypotheses for the geology and astrobiological potential of the landing site. The site was proposed to consist of a series of weakly cemented multi-coloured sedimentary rocks comprising carbonates, sulfates, and clays, and sinuous ridges with a resistant capping unit, interpreted as inverted paleochannels. Both the 2015 CanMars mission, which achieved 11 sols of operations, and the first part of the 2016 mission (sols 12–21), were conducted with the Mars Exploration Science Rover (MESR) and a series of integrated and hand-held instruments designed to mimic the payload of the Mars 2020 rover. Part 2 of the 2016 campaign (sols 22–39) was implemented without the MESR rover and was conducted exclusively by the field team as a Fast Motion Field Test (FMFT) with hand-carried instruments and with the equivalent of three sols of operations being executed in a single actual day. A total of 8 samples were cached during the 39 sols from which the Science Team prioritized 3 for “return to Earth”. Various science autonomy capabilities, based on flight-proven or near-future techniques intended for actual rover missions, were tested throughout the 2016 CanMars activities, with autonomous geological classification and targeting and autonomous pointing refinement being used extensively during the FMFT. Blind targeting, contingency sequencing, and conditional sequencing were also employed. Validation of the CanMars cache mission was achieved through various methods and approaches. The use of dedicated documentarians in mission control provided a detailed record of how and why decisions were made. Multiple separate field validation exercises employing humans using traditional geological techniques were carried out. All 8 of the selected samples plus a range of samples from the landing site region, collected out-of-simulation, have been analysed using a range of laboratory analytical techniques. A variety of lessons learned for both future analogue missions and planetary exploration missions are provided, including: dynamic collaboration between the science and planning teams as being key for mission success; the more frequent use of spectrometers and micro-imagers having remote capabilities rather than contact instruments; the utility of strategic traverse days to provide additional time for scientific discussion and meaningful interpretation of the data; the benefit of walkabout traverse strategies along with multi-sol plans with complex decisions trees to acquire a large amount of contextual data; and the availability of autonomous geological targeting, which enabled complex multi-sol plans gathering large suites of geological and geochemical survey data. Finally, the CanMars MSR activity demonstrated the utility of analogue missions in providing opportunities to engage and educate children and the public, by providing tangible hands-on linkages between current robotic missions and future human space missions. Public education and outreach was a priority for CanMars and a dedicated lead coordinated a strong presence on social media (primarily Twitter and Facebook), articles in local, regional, and national news networks, and interaction with the local community in London, Ontario. A further core objective of CanMars was to provide valuable learning opportunities to students and post-doctoral fellows in preparation for future planetary exploration missions. A learning goals survey conducted at the end of the 2016 activities had 90% of participants “somewhat agreeing” or “strongly agreeing” that participation in the mission has helped them to increase their understanding of the four learning outcomes