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The National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) are studying how samples might be brought back to Earth from Mars safely. Backward planetary protection is key in this complex endeavour, as it is required to prevent potential adverse effects from returning materials to Earth's biosphere. As the question of whether or not life exists on Mars today or whether it ever did in the past is still unanswered, the effort to return samples from Mars is expected to be categorized as a ‘Restricted Earth Return’ mission, for which NASA policy requires the containment of any unsterilized material returned to Earth. NASA is investigating several solutions to contain Mars samples and sterilize any uncontained Martian particles. This effort has significant implications for both NASA's scientific mission, and the Earth's environment; and so special care and vigilance are needed in planning and execution in order to assure acceptance of safety to Earth's biosphere. To generate a technically acceptable sterilization process across a wide array of scientific and other stakeholders, on 30–31 January 2019, 10–11 June 2019 and 19–20 February 2020, NASA informally convened a Sterilization Working Group (SWG) composed of experts from industry, academia and government to assess methods for sterilization and inactivation, to identify future work needed to verify these methods against biological challenges, and to determine their feasibility for implementation on robotic spacecraft in deep space. The goals of the SWG were:
(1) Understand what it means to sterilize and/or inactivate Martian materials and how that understanding can be applied to the Mars Sample Return (MSR) mission.
(2) Assess methods for sterilization and inactivation, and identify future work needed to verify these methods.
(3) Provide an effective plan for communicating with other agencies and the public.
This paper provides a summary of the discussions and conclusions of the SWG over these three workshops. It reflects a consensus position based on qualitative discussion of how agencies might approach the problem of sterilization of Mars material. The SWG reached a consensus that sterilization options can be considered on the basis of biology as we know it, and that sterilization modalities that are effective on terrestrial materials and organisms should be part of the MSR planetary protection strategy. Conclusions pointed to several industry standards for sterilization to include heat, chemical, UV radiation and low-heat plasma. Technical trade-offs for each sterilization modality were discussed while simultaneously considering the engineering challenges and limitations for spaceflight. Future work includes more in-depth discussions on technical trade-offs of sterilization modalities, identifying and testing Earth analogue challenge organisms and proteinaceous molecules against chosen modalities, and executing collaborative agreements between NASA and external working group partners to help close data gaps, and to establish strong, scientifically grounded sterilization and inactivation standards for MSR.
An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.
Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).
BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy.
The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
F17464 is a new dopamine receptor antagonist that recently demonstrated antipsychotic activity in a proof of concept study in schizophrenic patients under acute exacerbation. The compound has a unique profile with high affinity for hD3 receptors (Ki = 0.17 nM) and lower affinity for hD2L (Ki = 12.1 nM) and hD2S (Ki = 6.5 nM). F17464 exhibits also high affinity for h5-HT1A receptors (Ki = 0.16 nM). F17464 is a hD3 antagonist (pKB = 9.13), hD2S very week partial agonist (pKB = 7.87, emax 8% of DA stimulated in ERK assay) and a 5-HT1A partial agonist (pEC50 = 7.99). F17464 exhibits consistent affinities for rat striatal D2 (Ki = 4.8 nM) and for rat hippocampal 5-HT1A receptors (Ki = 1.14 nM). Neurochemical studies show that F17464 ip (1 h post-dose) produces a significant dose–dependent increase in the levels of DOPAC and HVA in the frontal cortex, caudate-putamen and limbic forebrain and an increase in 3-MT levels in the latter two regions with no changes in total DA content. The effect is significant at the doses of 0.63–2.5 mg/kg ip (PK/PD data will be provided). This pattern of DA metabolite changes is similar to that described for several antipsychotic drugs in rodents and it is indicative of a cortical effect of F17464. F17464 has a very low cataleptogenic activity in rats and mice and does not induce serotoninergic signs typical of 5-HT1A. F17464 is therefore a novel a D3 preferential antipsychotic with a unique mechanism of action and receptor affinity profile and a consistent effect in neurochemistry studies in rodents.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Weaning is known to induce important nutritional and energetic stress in piglets. Low-birthweight (LBW) piglets, now frequently observed in swine production, are more likely to be affected. The weaning period is also associated with dysfunctional immune responses, uncontrolled inflammation and oxidative stress conditions that are recognized risk factors for infections and diseases. Mounting evidence indicates that mitochondria, the main cellular sources of energy in the form of adenosine 5′ triphosphate (ATP) and primary sites of reactive oxygen species production, are related to immunity, inflammation and bacterial pathogenesis. However, no information is currently available regarding the link between mitochondrial energy production and oxidative stress in weaned piglets. The objective of this study was to characterize markers of cellular and mitochondrial energy metabolism and oxidative status in both normal-birthweight (NBW) and LBW piglets throughout the peri-weaning period. To conduct the study, 30 multiparous sows were inseminated and litters were standardized to 12 piglets. All the piglets were weighted at day 1 and 120 piglets were selected and assigned to 1 of 2 experimental groups: NBW (n = 60, mean weight of 1.73 ± 0.01 kg) and LBW piglets weighing less than 1.2 kg (n = 60, 1.01 ± 0.01 kg). Then, 10 piglets from each group were selected at 14, 21 (weaning), 23, 25, 29 and 35 days of age to collect plasma and organ (liver, intestine and kidney) samples. Analysis revealed that ATP concentrations were lower in liver of piglets after weaning than during lactation (P < 0.05) thus suggesting a significant impact of weaning stress on mitochondrial energy production. Oxidative damage to DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and proteins (carbonyls) measured in plasma increased after weaning and this coincides with a rise in enzymatic antioxidant activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) (P < 0.05). Mitochondrial activities of both GPx and SOD are also significantly higher (P < 0.05) in kidney of piglets after weaning. Additionally, oxidative damage to macromolecules is more important in LBW piglets as measured concentrations of 8-OHdG and protein carbonyls are significantly higher (P < 0.05) in plasma and liver samples, respectively, than for NBW piglets. These results provide novel information about the nature, intensity and duration of weaning stress by revealing that weaning induces mitochondrial dysfunction and cellular oxidative stress conditions which last for at least 2 weeks and more severely impact smaller piglets.
Plasma radiative properties play a pivotal role both in nuclear fusion and astrophysics. They are essential to analyze and explain experiments or observations and also in radiative-hydrodynamics simulations. Their computation requires the generation of large atomic databases and the calculation, by solving a set of rate equations, of a huge number of atomic level populations in wide ranges of plasma conditions. These facts make that, for example, radiative-hydrodynamics in-line simulations be almost infeasible. This has lead to develop analytical expressions based on the parametrization of radiative properties. However, most of them are accurate only for coronal or local thermodynamic equilibrium. In this work we present a code for the parametrization of plasma radiative properties of mono-component plasmas, in terms of plasma density and temperature, such as radiative power loss, the Planck and Rosseland mean opacities and the average ionization, which is valid for steady-state optically thin plasmas in wide ranges of plasma densities and temperatures. Furthermore, we also present some applications of this parametrization such as the analysis of the optical depth and radiative character of plasmas, the use to perform diagnostics of the electron temperature, the determination of mean radiative properties for multicomponent plasmas and the analysis of radiative cooling instabilities in some kind of experiments on high-energy density laboratory astrophysics. Finally, to ease the use of the code for the parametrization, this one has been integrated in a user interface and brief comments about it are presented.
A cross-sectional study on 32 different Belgian broiler farms was performed in 2007 and 2008 to identify risk factors for ceftiofur resistance in Escherichia coli. On each farm, one E. coli colony was isolated from 30 random birds. Following susceptibility testing of 14 antimicrobials, an on-farm questionnaire was used to obtain information on risk factors. Using a multilevel logistic regression model two factors were identified at the animal level: resistance to amoxicillin and to trimethoprim–sulfonamide. On the farm level, besides antimicrobial use, seven management factors were found to be associated with the occurrence of ceftiofur resistance in E. coli from broilers: poor hygienic condition of the medicinal treatment reservoir, no acidification of drinking water, more than three feed changes during the production cycle, hatchery of origin, breed, litter material used, and treatment with amoxicillin. This study confirms that not only on-farm antimicrobial therapy, but also management- and hatchery-related factors influence the occurrence of antimicrobial resistance.
Direct numerical simulations (DNSs) are used to investigate the drag-reducing performance of superhydrophobic surfaces (SHSs) in turbulent channel flow. SHSs combine surface roughness with hydrophobicity and can, in some cases, support a shear-free air–water interface. Slip velocities, wall shear stresses and Reynolds stresses are considered for a variety of SHS microfeature geometry configurations at a friction Reynolds number of Reτ ≈ 180. For the largest microfeature spacing studied, an average slip velocity over 75% of the bulk velocity is obtained, and the wall shear stress reduction is found to be nearly 40%. The simulation results suggest that the mean velocity profile near the superhydrophobic wall continues to scale with the wall shear stress but is offset by a slip velocity that increases with increasing microfeature spacing.
Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Multidrug resistance gene-deficient (mdr1a− / − ) mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet–gene interactions and potential effects of foods on remission or development of IBD. The present study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a− / − mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets (control (AIN-76A), control +0·2 % curcumin or control +0·1 % rutin) and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a− / − mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways, probably mediated by pregnane X receptor (Pxr) and peroxisome proliferator-activated receptor α (Ppara) activation of retinoid X receptor (Rxr). These results indicate the potential of global gene expression and pathway analyses to study and better understand the effect of foods in modulating colonic inflammation.
Radiative properties are fundamental for plasma diagnostics and hydro-simulations. For this reason, there is a high interest in their determination and they are a current topic of investigation both in astrophysics and inertial fusion confinement research. In this work a flexible computation package for calculating radiative properties for low and high Z optically thin and thick plasmas, both under local thermodynamic equilibrium and non-local thermodynamic equilibrium conditions, named RAPCAL is presented. This code has been developed with the aim of providing accurate radiative properties for low and medium Z plasmas within the context of detailed level accounting approach and for heavy elements under the detailed configuration accounting approach. In order to show the capabilities of the code, there are presented calculations of some radiative properties for carbon, aluminum, krypton and xenon plasmas under local thermodynamic and non-local thermodynamic equilibrium conditions.
In this work is accomplished the determination of the corona, local and non-local thermodynamic equilibrium regimes for optically thin carbon plasmas in steady state, in terms of the plasma density and temperature using the ABAKO code. The determination is made through the analysis of the plasma average ionization and ion and level populations. The results are compared whit those obtained applying Griem's criterion. Finally, it is made a brief analysis of the effects of the calculation of level populations assuming different plasma regimes in radiative properties, such as emissivities and opacities.
We describe a method of working on publicly available data to estimate disease prevalence in small geographic areas using Helicobacter pylori as a model infection. Using data from the Third National Health and Nutrition Examination Survey, risk parameters for H. pylori infection were obtained by logistic regression and validated by predicting 737·5 infections in an independent cohort with 736 observed infections. The prevalence of H. pylori infection in the San Francisco Bay Area was estimated with the probabilities obtained from a predictive logistic model, using risk parameters with individual-level 1990 U.S. Census data as input. Predicted H. pylori prevalence was also compared to gastric cancer incidence obtained from the Northern California Cancer Center and showed a positive correlation with gastric cancer incidence (P<0·001, R2=0·87), and no statistically significant association with other malignancies. By exclusively using publicly available data, these methods may be applied to selected conditions with strong demographic predictors.
In this work, we first presents a review of the work that research
teams have developed in collaboration in order to determine the optical
properties of plasmas during the recent years, and showing the
achievements reached. The second part of this paper is devoted to one of
these improvements, which is to include reabsorption of the radiation in
the calculations of dense optically thick plasmas in non-LTE conditions.
Two models recently developed for this purpose are presented. The
quantitative study was focused on aluminum plasmas, which was obtained
recently at LULI experiments.
We previously reported that 25% (108/441) of consecutive patients presenting to the emergency department (ED) of the Montreal Heart Institute with a chief complaint of chest pain suffered from panic disorder (PD). The purpose of the present study was to re-examine these patients (with and without PD) 2 years after their initial ED visit to determine their psychiatric and psychosocial status.
An interviewer, who was kept blind to patients’ initial medical and psychiatric diagnoses, attempted to contact all patients who participated in the initial study by phone. Patients who completed the phone interview were sent a battery of psychological questionnaires by mail.
A total of 301 (70%) patients completed the phone interview, and 228 (52%) patients completed the self-report questionnaires. Participants and non-participants did not differ with respect to age, gender, initial self-report scores, or initial cardiac or psychiatric diagnoses. At follow-up, significantly (p < 0.05) more PD+ than non-PD (PD–) patients reported: 1) chest pains in the last month (57% vs. 31%); 2) one or more ED consultations in the past year for chest pain (40% vs. 14%); 3) one or more hospitalizations in the past year (31% vs. 11%); and 4) perceiving their general health as “poor” (22% vs. 9%). PD+ patients displayed a significant (p < 0.05) worsening of their panic symptoms, agoraphobic avoidance, depression, and trait anxiety, and reported significantly (p < 0.05) greater suicidal ideation compared to PD– patients (32% vs. 9%). Of all PD+ patients, only 22% (18/82) reported receiving some form of mental health treatment for their symptoms.
Unrecognized and untreated PD has a chronic and disabling course. Greater efforts should be made to screen for PD in patients complaining of chest pain in EDs.
In this work, a new analytical potential for studying ions
in excited configurations is presented, which is built up from
a parametric potential for ions in a ground state. It is used
to calculate atomic magnitudes of special importance in plasmas
such as total energies, energy levels, and transition energies,
for ions in excited configurations. The results are successfully
compared with those obtained with both self-consistent or
In this work, the Saha equation is solved using atomic data
provided by means of a new relativistic-screened hydrogenic
model based on analytical potentials to calculate the ionization
state and ion abundance for LTE iron plasmas. The plasma effects
on the atomic structure are taken into account by including
the classical continuum lowering correction of Stewart and Pyatt.
For high density, the Saha equation is modified to consider
the degeneration of free electrons using the Fermi–Dirac
statistics instead of the Maxwellian distribution commonly used.
The results are compared with more sophisticated self-consistent
Thermally grown Si3N4 films in NH3 are known to have a higher dielectric constant and a higher N concentration than silicon oxynitrides, although they incorporate hydrogen atoms that induce hot electron carriers during subsequent high temperature processing. Further, a silicon nitride is difficult to grow over about 6 nm thick, due to self-limiting growth. One alternative is SiOxNy post-nitrided with NH3.
In this work, we study the scope of improvement of Ar annealed nitrided oxynitrides as a function of annealing temperature and duration. Secondary ion mass spectroscopy (SIMS) studies of the nitrogen and hydrogen profiles suggest increasing N and H removal with increasing annealing time and temperature. Electrical characterizations have been performed to determine the total charge (Qox) and interface trap (Dit) densities at different processing conditions, before and after the annealing step. Post-annealing steps are not found to yield improvements of the electrical properties of these dielectric films. Instead, sometimes Qox is even seen to increase (e.g., after a 30 min Ar anneal at 1000 °C). Therefore, an optimization of such annealing steps is essential in designing nanodielectrics with desired nitrogen amounts and N concentration profiles as well as in understanding related process-structure-function relationships.