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Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society. Key observations and findings include:
– high escape rates of early Mars' atmosphere, including loss of water, impact present-day habitability;
– putative fossils on Mars will likely be ambiguous biomarkers for life;
– microbial contamination resulting from human habitation is unavoidable; and
– based on Mars' current planetary protection category, robotic payload(s) should characterize the local martian environment for any life-forms prior to human habitation.
Some of the outstanding questions are:
– which interpretation of the hemispheric dichotomy of the planet is correct;
– to what degree did deep-penetrating faults transport subsurface liquids to Mars' surface;
– in what abundance are carbonates formed by atmospheric processes;
– what properties of martian meteorites could be used to constrain their source locations;
– the origin(s) of organic macromolecules;
– was/is Mars inhabited;
– how can missions designed to uncover microbial activity in the subsurface eliminate potential false positives caused by microbial contaminants from Earth;
– how can we ensure that humans and microbes form a stable and benign biosphere; and
– should humans relate to putative extraterrestrial life from a biocentric viewpoint (preservation of all biology), or anthropocentric viewpoint of expanding habitation of space?
Studies of Mars' evolution can shed light on the habitability of extrasolar planets. In addition, Mars exploration can drive future policy developments and confirm (or put into question) the feasibility and/or extent of human habitability of space.
The pandemic caused by severe acute respiratory coronavirus virus 2 (SARS-CoV-2) has dramatically increased cheshospitalizations, and it is often difficult to determine whether there is a bacterial or fungal coinfection at time of presentation. In this study, we sought to determine the rates of coinfection and utilization of antibiotics in SARS-CoV-2 disease.
Retrospective chart review of patients hospitalized with COVID-19 pneumonia from April 13, 2020, to July 14, 2020.
In total, 277 patients were hospitalized for COVID-19 pneumonia during this period. Patients that received antibiotics within 48 hours of presentation were more likely to be febrile (59.3% vs 41.2%; P = .01) and to have leukocytosis (23.9% vs 5.9%; P < .01) and were less likely to have a procalcitonin level <0.25 ng/mL (58.8% vs 74.5%; P = .04). In total, 45 patients had positive blood cultures collected during hospitalization, 16 of which were clinically significant. Of the clinically significant blood cultures, 5 were collected <48 hours of admission. Moreover, 18 sputum cultures were clinically significant, 2 of which were collected within 48 hours of admission.
Bacterial and fungal coinfections in COVID-19 appear to be rare on presentation; thus, this factor may be a good target for enhanced antibiotic stewardship.
Motivated by the industrial manufacture of organic light-emitting-diode displays, we formulate and analyse a mathematical model for the evolution of a thin droplet in a shallow axisymmetric well of rather general shape both before and after touchdown that accounts for the spatially non-uniform evaporation of the fluid, perform physical experiments using three cylindrical wells with different small aspect ratios, and validate the mathematical model by comparing the present experimental results with the corresponding theoretical predictions for a cylindrical well.
Nucleated red blood cells (NRBCs) are immature red cells that under normal conditions are not present in the peripheral circulation. Several studies have suggested an association between elevated NRBC and poor outcome in critically ill adults and neonates. We sought to determine if elevations in NRBC value following cardiac surgery and following clinical events during the hospital stay can be used as a biomarker to monitor for mortality risk in neonates post-cardiac surgery.
Materials and methods:
We constructed a retrospective study of 264 neonates who underwent cardiac surgery at Children’s Hospital, New Orleans between 2011 and 2020. Variables included mortality and NRBC value were recorded following cardiac surgery and following peri-operative clinical events. The study was approved by LSU Health IRB. Sensitivity, specificity, receiver operating characteristic (ROC) curves with area under the curve (AUC) and logistic regression analysis were performed.
Thirty-six patients (13.6%) died, of which 32 had an NRBC value ≥10/100 white blood cell (WBC) during hospitalisation. Multi-variable analysis found extracorporeal membrane oxygenation use (OR 10, 95% CI 2.9–33, p=<0.001), NRBC ≥10/100 WBC (OR 16.1, CI 4.1–62.5, p ≤ 0.001) and peak NRBC in the 14-day period post-cardiac surgery (continuous variable, OR 1.05, 95% CI 1.0–1.09, p = 0.03), to be independently associated with mortality. Using a cut-off NRBC value of 10/100 WBC, there was an 88.9% sensitivity and a 90.8% specificity, with ROC curve showing an AUC of 0.9 and 0.914 for peak NRBC value in 14 days post-surgery and entire hospitalisation, respectively.
NRBC ≥10/100 WBC post-cardiac surgery is strongly associated with mortality. Additionally, NRBC trend appears to show promise as an accurate biomarker for mortality.
Prior investigation of adult patients with obsessive compulsive disorder (OCD) has found greater functional connectivity within orbitofrontal–striatal–thalamic (OST) circuitry, as well as altered connectivity within and between large-scale brain networks such as the cingulo-opercular network (CON) and default mode network (DMN), relative to controls. However, as adult OCD patients often have high rates of co-morbid anxiety and long durations of illness, little is known about the functional connectivity of these networks in relation to OCD specifically, or in young patients near illness onset.
In this study, unmedicated female patients with OCD (ages 8–21 years, n = 23) were compared to age-matched female patients with anxiety disorders (n = 26), and healthy female youth (n = 44). Resting-state functional connectivity was used to determine the strength of functional connectivity within and between OST, CON, and DMN.
Functional connectivity within the CON was significantly greater in the OCD group as compared to the anxiety and healthy control groups. Additionally, the OCD group displayed greater functional connectivity between OST and CON compared to the other two groups, which did not differ significantly from each other.
Our findings indicate that previously noted network connectivity differences in pediatric patients with OCD were likely not attributable to co-morbid anxiety disorders. Moreover, these results suggest that specific patterns of hyperconnectivity within CON and between CON and OST circuitry may characterize OCD relative to non-OCD anxiety disorders in youth. This study improves understanding of network dysfunction underlying pediatric OCD as compared to pediatric anxiety.
Sarcopenic obesity is regarded as a risk factor for the progression and development of non-alcoholic fatty liver disease (NAFLD). Since male sex is a risk factor for NAFLD and skeletal muscle mass markedly varies between the sexes, we examined whether sex influences the association between appendicular skeletal muscle mass to visceral fat area ratio (SVR), that is, an index of skeletal muscle mass combined with abdominal obesity, and the histological severity of NAFLD. The SVR was measured by bioelectrical impedance in a cohort of 613 (M/F = 443/170) Chinese middle-aged individuals with biopsy-proven NAFLD. Multivariable logistic regression and subgroup analyses were used to test the association between SVR and the severity of NAFLD (i.e. non-alcoholic steatohepatitis (NASH) or NASH with the presence of any stage of liver fibrosis). NASH was identified by a NAFLD activity score ≥5, with a minimum score of 1 for each of its categories. The presence of fibrosis was classified as having a histological stage ≥1. The SVR was inversely associated with NASH in men (adjusted OR 0·62; 95 % CI 0·42, 0·92, P = 0·017 for NASH, adjusted OR 0·65; 95 % CI 0·43, 0·99, P = 0·043 for NASH with the presence of fibrosis), but not in women (1·47 (95 % CI 0·76, 2·83), P = 0·25 for NASH, and 1·45 (95 % CI 0·74, 2·83), P = 0·28 for NASH with the presence of fibrosis). There was a significant interaction for sex and SVR (Pinteraction = 0·017 for NASH and Pinteraction = 0·033 for NASH with the presence of fibrosis). Our findings show that lower skeletal muscle mass combined with abdominal obesity is strongly associated with the presence of NASH only in men.
Ventriculo-ventricular interactions are known to exist, though not well quantified. We hypothesised that the ventricular–vascular coupling ratio assessed by cardiovascular MRI would provide insight into this relationship. We also sought to compare MRI-derived ventricular–vascular coupling ratio to echocardiography and patient outcomes.
Children with cardiac disease and biventricular physiology were included. Sanz’s and Bullet methods were used to calculate ventricular–vascular coupling ratio by MRI and echocardiography, respectively. Subgroup analysis was performed for right and left heart diseases. Univariate and multivariate regressions were performed to determine associations with outcomes.
A total of 55 patients (age 14.3 ± 2.5 years) were included. Biventricular ventricular–vascular coupling ratio by MRI correlated with each other (r = 0.41; p = 0.003), with respect to ventricle’s ejection fraction (r = −0.76 to −0.88; p < 0.001) and other ventricle’s ejection fraction (r = −0.42 to −0.47; p < 0.01). However, biventricular ejection fraction had only weak correlation with each other (r = 0.31; p = 0.02). Echo underestimated ventricular–vascular coupling ratio for the left ventricle (p < 0.001) with modest correlation to MRI-derived ventricular–vascular coupling ratio (r = 0.43; p = 0.002). There seems to be a weak correlation between uncoupled right ventricular–vascular coupling ratio with the need for intervention and performance on exercise testing (r = 0.33; p = 0.02).
MRI-derived biventricular ventricular–vascular coupling ratio provides a better estimate of ventriculo-ventricular interaction in children and adolescents with CHD. These associations are stronger than traditional parameters and applicable to right and left heart conditions.
Adults who were born preterm are at increased risk of hypertension and cardiovascular disease in later life. Infants born late preterm are the majority of preterm births; however, the effect of late preterm on risk of cardiovascular disease is unclear. The objective of this study was to assess whether vascular health and cardiac autonomic control differ in a group of late preterm newborn infants compared to a group of term-born infants.
A total of 35 healthy late preterm newborn infants, with normal growth (34–36 completed weeks’ gestation) and 139 term-born infants (37–42 weeks’ gestation) were compared in this study. Aortic wall thickening, assessed as aortic intima–media thickness (IMT) by high-resolution ultrasound, and cardiac autonomic control, assessed by heart rate variability, were measured during the first week of life. Postnatal age of full-term and late preterm infants at the time of the study was 5 days (standard deviation [SD] 5) and 4 days (SD 3), respectively.
Infants born late preterm show reduced aortic IMT (574 μm [SD 51] vs. 612 μm [SD 73]) and reduced heart rate variability [log total power 622.3 (606.5) ms2 vs. 1180. 6 (1114.3) ms2], compared to term infants. These associations remained even after adjustment for sex and birth weight.
Infants born late preterm show selective differences in markers of cardiovascular risk, with potentially beneficial differences in aortic wall thickness in contrast to potentially detrimental differences in autonomic control, when compared with term-born control infants. These findings provide pathophysiologic evidence to support an increased risk of hypertension and sudden cardiac death in individuals born late preterm.
The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels.
We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI −0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = −0.01(binding ratio); 95% CI −0.01 to −0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
To evaluate broad-spectrum intravenous antibiotic use before and after the implementation of a revised febrile neutropenia management algorithm in a population of adults with hematologic malignancies.
Setting and population:
Patients admitted between 2014 and 2018 to the Adult Malignant Hematology service of an acute-care hospital in the United States.
Aggregate data for adult malignant hematology service were obtained for population-level antibiotic use: days of therapy (DOT), C. difficile infections, bacterial bloodstream infections, intensive care unit (ICU) length of stay, and in-hospital mortality. All rates are reported per 1,000 patient days before the implementation of an febrile neutropenia management algorithm (July 2014–May 2016) and after the intervention (June 2016–December 2018). These data were compared using interrupted time series analysis.
In total, 2,014 patients comprised 6,788 encounters and 89,612 patient days during the study period. Broad-spectrum intravenous (IV) antibiotic use decreased by 5.7% with immediate reductions in meropenem and vancomycin use by 22 (P = .02) and 15 (P = .001) DOT per 1,000 patient days, respectively. Bacterial bloodstream infection rates significantly increased following algorithm implementation. No differences were observed in the use of other antibiotics or safety outcomes including C. difficile infection, ICU length of stay, and in-hospital mortality.
Reductions in vancomycin and meropenem were observed following the implementation of a more stringent febrile neutropenia management algorithm, without evidence of adverse outcomes. Successful implementation occurred through a collaborative effort and continues to be a core reinforcement strategy at our institution. Future studies evaluating patient-level data may identify further stewardship opportunities in this population.
This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03–1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08–1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05–0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19–1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.
Few studies provide clear rationale for and the reception of adaptations of evidence-based interventions. To address this gap, we describe the context-dependent adaptations in critical time intervention-task shifting (CTI-TS), a manualized recovery program for individuals with psychosis in Rio de Janeiro, Brazil and Santiago, Chile. Implications of the adaptations – incorporating a task-shifting approach and modifying the mode of community-based service delivery – are examined from users' perspectives.
A secondary analysis of in-depth interviews with CTI-TS users (n = 9 in Brazil; n = 15 in Chile) was conducted. Using the framework method, we thematically compared how participants from each site perceived the main adapted components of CTI-TS.
Users of both sites appreciated the task-shifting worker pair to provide personalized, flexible, and relatable support. They wanted CTI-TS to be longer and experienced difficulty maintaining intervention benefits in the long-term. In Chile, stigma and a perceived professional hierarchy toward the task-shifting providers were more profound than in Brazil. Engagement with community-based services delivery in homes and neighborhoods (Chile), and at community mental health centers (Brazil) were influenced by various personal, familial, financial, and social factors. Uniquely, community violence was a significant barrier to engagement in Brazil.
CTI-TS’ major adaptations were informed by the distinct mental health systems and social context of Santiago and Rio. Evaluation of user experiences with these adaptations provides insights into implementing and scaling-up task-shifting and community-oriented interventions in the region through the creation of specialized roles for the worker pair, targeting sustained intervention effects, and addressing socio-cultural barriers.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
To improve the endurance performance of long-endurance Unmanned Aerial Vehicles (UAVs), a smart morphing method to adjust the UAV and flight mode continuously during flight is proposed. Using this method as a starting point, a smart morphing long-endurance UAV design is conducted and the resulting improvement in the endurance performance studied. Firstly, the initial overall design of the smart morphing long-endurance UAV is carried out, then the morphing form is designed and various control parameters are selected. Secondly, based on multi-agent theory, an architecture for the smart morphing control system is built and the workflow of the smart morphing control system is planned. The morphing decision method is designed in detail based on the particle swarm optimisation algorithm. Finally, a simulation of the smart morphing approach in the climb and cruise stages is carried out to quantitatively verify the improvement in the endurance performance. The simulation results show that the smart morphing method can improve the cruise time by 4.1% with the same fuel consumption.
To determine the association between livestock ownership and Hb concentration of women of child-bearing age (WCBA) and preschool-aged children in Sub-Saharan Africa (SSA).
A prospective analysis of publicly available cross-sectional data, using linear and logistic regressions controlling for potential confounders.
Twenty-eight countries in SSA.
162 305 WCBA and 118 607 children aged 6–59 months.
More than half of WCBA (62·5 %) and children (58 %) belonged to households that owned livestock. The average altitude-adjusted blood Hb concentration for WCBA and children was 12.23 and 10·24 g/dL, respectively. In adjusted models, higher number of livestock owned was associated with lower Hb concentration for children but not for WCBA. The magnitude of the association for children was small, with one additional unit of livestock owned reducing Hb concentration by 0·001 g/dL. Higher numbers of cattle, cows and bulls, sheep, and goats were associated with lower Hb concentration for both groups. The number of certain categories of livestock owned was associated with the consumption of relevant foods by children. There was no association between the consumption of animal-source foods and Hb concentration or between livestock ownership and diarrhoeal diseases or fever among children.
Livestock ownership in SSA had a net negative association with the Hb concentration of children and no association with that of WCBA. The results highlight the need for research aimed at clarifying the mechanisms linking livestock ownership and nutritional status, and identifying entry points for leveraging livestock ownership to improve the health of women and children in SSA.