Correlations between life-detection techniques and implications for sampling site selection in planetary analog missions

We conducted an analog sampling expedition under simulated mission constraints to areas dominated by basaltic tephra of the Eldfell and Fimmvörðuháls lava fields (Iceland). Sites were selected to be “homogeneous” at a coarse remote sensing resolution (10–100 m) in apparent color, morphology, moisture, and grain size, with best-effort realism in numbers of locations and replicates. Three different biomarker assays (counting of nucleic-acid-stained cells via fluorescent microscopy, a luciferin/luciferase assay for adenosine triphosphate, and quantitative polymerase chain reaction (qPCR) to detect DNA associated with bacteria, archaea, and fungi) were characterized at four nested spatial scales (1 m, 10 m, 100 m, and >1 km) by using five common metrics for sample site representativeness (sample mean variance, group F tests, pairwise t tests, and the distribution-free rank sum H and u tests). Correlations between all assays were characterized with Spearman's rank test. The bioluminescence assay showed the most variance across the sites, followed by qPCR for bacterial and archaeal DNA; these results could not be considered representative at the finest resolution tested (1 m). Cell concentration and fungal DNA also had significant local variation, but they were homogeneous over scales of >1 km. These results show that the selection of life detection assays and the number, distribution, and location of sampling sites in a low biomass environment with limited a priori characterization can yield both contrasting and complementary results, and that their interdependence must be given due consideration to maximize science return in future biomarker sampling expeditions

Preferably Plinian and Pumaceous: Implications of Microbial Activity in Modern Volcanic Deposits at Askja Volcano, Iceland, and Relevancy for Mars Exploration

To search more efficiently for a record of past life on Mars, it is critical to know where to look and thus maximize the likelihood of success. Large-scale site selection for the Mars 2020 mission has been completed, but small (meter to 10 cm)-scale relationships of microenvironments will not be known until the rover reaches the surface. Over a 2 m transect at a modern volcanic deposit on the flank of Askja volcano in the barren highlands of Iceland, we compared two biological indicators (ATP activity and 16SrRNA amplicon sequence composition) to physical characteristics including bulk chemical composition, spectral signatures of mineralogy, and grain size. Using analytical instrumentation analogous to those available on Mars rovers, we were able to characterize the geological setting of the deposits and link physical parameters to microbial abundance and diversity. In general, methanogenesis, methanotrophy/methylotrophy, and nitrate reduction were the functional traits most associated with microbial community shift along the transect. Core microbiome members tended to be associated with nitrate reduction, and relative abundance of core microbes was strongly related to free water in the deposit. Community compositional shift of the rare microbiome was related to microenvironmental changes such as change in grain size, geochemistry, and age of deposit. These correlations lead us to suggest a sampling strategy that accounts for Martian geology, looking for undisturbed (not remobilized) explosive volcanic ash below pumice that could maximize diversity and abundance of different bioindicators. Our study also illustrates the importance of studying the variability across microenvironments in low biomass settings on earth

Biomarker and Geochemical Assay Validation in Mars Analog Sites: Lessons from the FELDSPAR (Field Exploration and Life Detection Sampling for Planetary Analog Research) Project

Missions looking for signs of life on other worlds can often only take a few samples once they arrive. Making sense of these "few and far between" observations is easier if we know what a "normal" level of variation for that kind of planet is. Recent eruption sites in Iceland are good places to learn about this, because they have very little life present and the same types of rocks as many places on Mars. We have visited several of these sites in Iceland and tested many different kinds of measurements: the energy available for life, the amount of DNA (an important biological molecule) present, the relative amounts of different kinds of micro-organisms, and the specific minerals that make up the rocks and ground. In addition to recommendations for future expeditions, we have also shown that using early on-site measurements to choose later on-site sample sites is very helpful in reducing the number of sample sites needed

Family Physicians’ Attitudes and Practices Regarding Assessments of Medical Fitness to Drive in Older Persons

BACKGROUND: Higher crash rates per mile driven in older drivers have focused attention on the assessment of older drivers. OBJECTIVE: To examine the attitudes and practices of family physicians regarding fitness-to-drive issues in older persons. DESIGN: Survey questionnaire. PARTICIPANTS: The questionnaire was sent to 1,000 randomly selected Canadian family physicians. Four hundred sixty eligible physicians returned completed questionnaires. MEASUREMENTS: Self-reported attitudes and practices towards driving assessments and the reporting of medically unsafe drivers. RESULTS: Over 45% of physicians are not confident in assessing driving fitness and do not consider themselves to be the most qualified professionals to do so. The majority (88.6%) feel that they would benefit from further education in this area. About 75% feel that reporting a patient as an unsafe driver places them in a conflict of interest and negatively impacts on the patient and the physician–patient relationship. Nevertheless, most (72.4%) agree that physicians should be legally responsible for reporting unsafe drivers to the licensing authorities. Physicians from provinces with mandatory versus discretionary reporting requirements are more likely to report unsafe drivers (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.58 to 4.91), but less likely to perform driving assessments (OR, 0.58; 95% CI, 0.39 to 0.85). Most driving assessments take between 10 and 30 minutes, with much variability in the components included. CONCLUSIONS: Family physicians lack confidence in performing driving assessments and note many negative consequences of reporting unsafe drivers. Education about assessing driving fitness and approaches that protect the physician–patient relationship when reporting occurs are needed

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Asymmetric dimethylarginine endogenous inhibition of nitric oxide synthase causes differential vasculature effects

Background: Asymmetric dimethylarginine (ADMA), produced during protein metabolism, is an endogenous inhibitor of nitric oxide synthase, but little is known about its direct vasoactive properties in different arterial beds. Material/Methods: Segments of canine coronary, renal, and femoral arteries were pretreated with increasing concentrations of ADMA, and endothelial function was evaluated in organ chambers. Results: In precontracted canine coronary arteries, the highest concentrations of ADMA inhibited endothelium-dependent relaxation mediated by acetylcholine (n=7), but no concentration of ADMA inhibited receptor-independent relaxation mediated by calcium ionophore (n=7) (P<.001). The effect of ADMA on acetylcholine-mediated relaxation was shown to be competitive inhibition of the nitric oxide synthase pathway, because the addition of L-arginine (10(-3) M), but not D-arginine (101 M), reversed the effect produced by 10(-5) M ADMA. Further, ADMA did not alter endothelium-independent relaxation mediated by sodium nitroprusside (10(-9) to 10(-6) M; n=7). Femoral arteries (n=7) and renal arteries (n=7) were more sensitive to ADMA than were coronary arteries, and they demonstrated significant ADMA inhibition to receptor dependent relaxation induced by acetylcholine (P=.03 and P=.01, respectively) and to receptor-independent relaxation induced by calcium ionophore (P=.02 and P=.01, respectively). Conclusions: Endothelium-dependent relaxation mediated by ADMA is more marked in femoral and renal arteries than in coronary arteries. The response in coronary arteries may be overall protective. Considering these different effects in various artery types, the role of ADMA as a confiable and specific cardiovascular risk factor is questioned

A study of presbycardia, with gender differences favoring ageing women

Background The impact of ageing on the human cardiovascular system has been the subject of several studies in recent years, but with insufficient emphasis on defining sex-specific differences. To rectify this, gender-specific differences in structure and function in the human cardiovascular system were studied in a European population during natural ageing. Methods Cardiac power output (CPO) was measured and integrated with changes in left ventricular (LV) mass, diastolic, systolic and limb blood flow, blood pressure and exercise capacity in 93 health-screened men and 122 women, aged 20 to 75 years. Results Correlating with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPOmax = Q̇max x MAPmax) and reserve (CR = CPOmax − CPOrest) capacities decreased 20–25% with age in male hearts. In contrast, CPOmax, CR and LV mass were all preserved in ageing women. Maximum cardiac output (Q̇max; 26–32%), peak forearm blood flow (FBFpeak; 61%) and exercise capacity (40–50%) all decreased, but more so in men than women. In contrast, systemic vascular resistance (68–75%) and mean arterial pressure (MAPmax; 14–26%) increased in both sexes. CPOrest decreased 27% in men, but was unchanged in women, despite lower early:late diastolic filling (48–51%), Q̇rest (19–23%) and FBFrest (56%) in both sexes. Conclusions Understanding sex-specific differences in cardiovascular ageing is important for public health and biomedical research, given increasingly larger older populations and the need to prevent and treat cardiovascular disease