Dimethylformamide dimethyl acetal reagent for in situ chiral analyses of organic molecules on Titan with the Dragonfly mass spectrometer space instrument (Dragonfly mission).

Thanks to the Cassini-Huygens space mission between 2004 and 2017, a lot was learned about Titan, the biggest satellite of Saturn, and its intriguing atmosphere, surface, and organic chemistry complexity. However, key questions about the potential for the atmosphere and surface chemistry to produce organic molecules of direct interest for prebiotic chemistry and life did not find an answer. Due to Titan potential as a habitable world, NASA selected the Dragonfly space mission to be launched in 2027 to Titan's surface and explore the Shangri-La surface region for minimum 3 years. One of the main goals of this mission will be to understand the past and actual abundant prebiotic chemistry on Titan, especially using the Dragonfly Mass Spectrometer (DraMS). Two recently used sample pre-treatments for Gas Chromatography - Mass Spectrometry (GC-MS mode of DraMS) analyses are planned prior analysis to extract refractory organic molecules of interest for prebiotic chemistry and astrobiology. The dimethylformamide dimethylacetal (DMF-DMA) derivatization reaction offers undoubtedly an opportunity to detect biosignatures by volatilizing refractory biological or prebiotic molecules and conserving the chiral carbons' conformation while an enantiomeric excess indicates a chemical feature induced primarily by life (and may be aided on the primitive systems by light polarization). The goal of this study is to investigate the ageing of DMF-DMA in DraMS (and likely MOMA) capsules prior to in situ analysis on Titan (or Mars). The main results highlighted by our work on DMF-DMA are first its satisfactory stability for space requirements through time (no significant degradation over a year of storage and less than 30 % of lost under thermal stress) to a wide range of temperature (0 °C to 250 °C), or the presence of water and oxidants during the derivatization reaction (between 0 and 10 % of DMF-DMA degradation). Moreover, this reagent derivatized very well amines and carboxylic acids in high or trace amounts (ppt to hundreds of ppm), conserving their molecular conformation during the heat at 145 °C for 3 min (0 to 4% in the enantiomeric form change).

Evaluation of the interference of Tenax®TA adsorbent with dimethylformamide dimethyl acetal reagent for gas chromatography-Dragonfly mass spectrometry and future gas chromatography-mass spectrometry in situ analysis.

Among future space missions, national aeronautics and space administration (NASA) selected two of them to analyze the diversity in organic content within Martian and Titan soil samples using a gas chromatograph - mass spectrometer (GC-MS) instrument. The Dragonfly space mission is planned to be launched in 2027 to Titan's surface and explore the Shangri-La surface region for years. One of the main goals of this mission is to understand the past and actual abundant prebiotic chemistry on Titan, which is not well characterized yet. The ExoMars space mission is planned to be launched in 2028 to Mars' surface and explore the Oxia Planum and Mawrth Vallis region for years. The main objectives focus on the exploration of the subsurface soil samples, potentially richer in organics, that might be relevant for the search of past life traces on Mars where irradiation does not impact the matrices and organics. One recently used sample pre-treatment for gas chromatography - mass spectrometry analysis is planned on both space missions to detect refractory organic molecules of interest for astrobiology. This pre-treatment is called derivatization and uses a chemical reagent - called dimethylformamide dimethyl acetal (DMF-DMA) - to sublimate organic compounds keeping them safe from thermal degradation and conserving the chirality of the molecules extracted from Titan or Mars' matrices. Indeed, the detection of building blocks of life or enantiomeric excess of some organics (e.g. amino acids) after DMF-DMA pre-treatment and GC-MS analyses would be both bioindicators. The main results highlighted by our work on DMF-DMA and Tenax®TA interaction and efficiency to detect organic compounds at ppb levels in a fast and single preparation are first that Tenax®TA did not show the onset of degradation until after 150 experiments - a 120 h at 300 °C experiment - which greatly exceeds the experimental lifetimes for the DraMS and GC-space in situ investigations. Tenax®TA polymer and DMF-DMA produce many by-products (about 70 and 46, respectively, depending on the activation temperature). Further, the interaction between the two leads to the production of 22 additional by-products from DMF-DMA degradation, but these listed by-products do not prevent the detection of trace-level organic molecules after their efficient derivatization and volatilization by DMF-DMA in the oven ahead the GC-MS trap and column.

Influence of pH and salts on DMF-DMA derivatization for future Space Applications.

For gas chromatography - mass spectrometry (GC-MS) analyses performed in situ, pH and salts (e.g., chlorides, sulfates) may enhance or inhibit the detection of targeted molecules of interest for astrobiology (e.g. amino acids, fatty acids, nucleobases). Obviously, salts influence the ionic strength of the solutions, the pH value, and the salting effect. But the presence of salts may also produce complexes or mask ions in the sample (masking effect on hydroxide ion, ammonia, etc.). For future space missions, wet chemistry will be conducted before GC-MS analyses to detect the full organic content of a sample. The defined organic targets for space GC-MS instrument requirements are generally strongly polar or refractory organic compounds, such as amino acids playing a role in the protein production and metabolism regulations for life on Earth, nucleobases essential for DNA and RNA formation and mutation, and fatty acids that composed most of the eukaryote and prokaryote membranes on Earth and resist to environmental stress long enough to still be observed on Mars or ocean worlds in geological well-preserved records. The wet-chemistry chemical treatment consists of reacting an organic reagent with the sample to extract and volatilize polar or refractory organic molecules (i.e. dimethylformamide dimethyl acetal (DMF-DMA) in this study). DMF-DMA derivatizes functional groups with labile H in organics, without modifying their chiral conformation. The influence of pH and salt concentration of extraterrestrial materials on the DMF-DMA derivatization remains understudied. In this research, we studied the influence of different salts and pHs on the derivatization of organic molecules of astrobiological interest with DMF-DMA, such as amino acids, carboxylic acids, and nucleobases. Results show that salts and pH influence the derivatization yield, and that their effect depend on the nature of the organics and the salts studied. Second, monovalent salts lead to a higher or similar organic recovery compared to divalent salts regardless of pH below 8. However, a pH above 8 inhibits the DMF-DMA derivatization influencing the carboxylic acid function to become an anionic group without labile H. Overall, considering the negative effect of the salts on the detection of organic molecules, future space missions may have to consider a desalting step prior to derivatization and GC-MS analyses.

Comparison of tetramethylammonium hydroxide (TMAH), trimethylsulfonium hydroxide (TMSH), and trimethylphenylammonium hydroxide (TMPAH) thermochemolysis for in situ space analysis of organic molecules in planetary environments.

One of the main objectives of present and future space exploration missions dedicated to astrobiology is the detection of organic molecules of interest for life (e.g. amino and fatty acids). With this aim, a sample preparation and a gas chromatograph (connected to a mass spectrometer) are generally used. To date, tetramethylammonium hydroxide (TMAH) has been the first and only thermochemolysis reagent to be used for in situ sample preparation and chemical analysis of planetary environments. Although TMAH is widely used in terrestrial laboratories, numerous applications also leverage other thermochemolysis reagents that may be more relevant than TMAH to meet both scientific and technical objectives of space instrumentation. The present study compares the performance of tetramethylammonium hydroxide (TMAH), trimethylsulfonium hydroxide (TMSH), and trimethylphenylammonium hydroxide (TMPAH) reagents on molecules of interest to astrobiology. The study focuses on the analyses of 13 carboxylic acids (C7-C30), 17 proteinic amino acids, and the 5 nucleobases. Here we report the derivatization yield without stirring or adding solvents, the detection sensitivity with mass spectrometry, and the nature of the degradation products from the reagents produced during pyrolysis. We conclude that TMSH and TMAH are the best reagents for analyzing carboxylic acids and nucleobases. Amino acids are not relevant targets for a thermochemolysis over 300 °C as they are degraded and showed high limits of detection. As TMAH, and probably TMSH, meet the space instrumentation requirements, this study informs sample treatment approaches prior to GC-MS analysis in in situ space studies. The thermochemolysis reaction using TMAH or TMSH is also recommended for space return missions to extract organics from a macromolecular matrix, derivatize polar or refractory organic targets, and volatilize with the fewest organic degradations.

Thermal stability of adsorbents used for gas chromatography in space exploration.

For analytical purpose, thermal desorption is now used in gas chromatographs developed to analyse the chemical composition of planetary environments. Due to technical constraints, the thermal desorption cannot be as finely controlled as in the laboratory resulting in possible thermal alteration of the adsorbents used. For these reasons, the influence of heat on physical and chemical properties of various adsorbents, either used or that could be used in gas chromatographs for space exploration, is studied. If the adsorbents made of carbon molecular sieves and graphitised carbon black that were tested show a very high thermal stability up to 800°C, the porous polymers tested are highly degraded from a minimum temperature that depends on the nature of the polymer. Poly-2,6-diphenylphenylene oxide is shown to be the more thermally robust as it is degraded at higher temperatures, confirming it is currently the best choice for analysing organic molecules with a space instrument. Finally, the products of degradation of the porous polymers tested were analysed after heating the porous polymers at 400 °C and 800 °C. They were identified and listed as potential contaminants of analyses performed with this type of adsorbent. If the exposure to the higher temperature produces numerous organic compounds, mainly aromatic ones, a few ones are also detected at the lower temperature tested, meaning they should be considered as potential contaminants. Again poly-2,6-diphenylphenylene oxide should be preferred because it releases less organic compounds, the structure of which is completely specific to the adsorbent composition.

Application of TMAH thermochemolysis to the detection of nucleobases: Application to the MOMA and SAM space experiment.

Thermochemolysis of seven nucleobases-adenine, thymine, uracil, cytosine, guanine, xanthine, and hypoxanthine-in tetramethylammonium hydroxide (TMAH) was studied individually by pyrolysis gas chromatography mass spectrometry in the frame of the Mars surface exploration. The analyses were performed under conditions relevant to the Sample Analysis at Mars (SAM) instrument of the Mars Curiosity Rover and the Mars Organic Molecule Analyzer (MOMA) instrument of the ExoMars Rover. The thermochemolysis products of each nucleobase were identified and the reaction mechanisms studied. The thermochemolysis temperature was optimized and the limit of detection and quantification of each nucleobase were also investigated. Results indicate that 600°C is the optimal thermochemolysis temperature for all seven nucleobases. The methylated products trimethyl-adenine, 1, 3-dimethyl-thymine, 1, 3-dimethyl-uracil, trimethyl-cytosine, 1, 3, 7-trimethyl-xanthine (caffeine), and dimethyl-hypoxanthine, respectively, are the most stable forms of adenine, thymine, uracil, cytosine, guanine, and xanthine, and hypoxanthine in TMAH solutions. The limits of detection for adenine, thymine, and uracil were 0.075 nmol; the limits of detection for guanine, cytosine, and hypoxanthine were higher, at 0.40, 0.55, and 0.75 nmol, respectively. These experiments allowed to well constrain the analytical capabilities of the thermochemolysis experiments that will be performed on Mars to detect nucleobases.

Performance of the SAM gas chromatographic columns under simulated flight operating conditions for the analysis of chlorohydrocarbons on Mars.

The Sample Analysis at Mars (SAM) instrument is a gas chromatograph-mass spectrometer onboard the NASA Curiosity rover, currently operating on the surface of Mars. Organic compounds are of major importance with regard to questions of habitability and the potential presence of life on Mars, and one of the mission's main objectives is to analyze the organic content of soil and rock samples. In SAM's first chromatographic measurements, however, unexpected chlorine-bearing organic molecules were detected. These molecules have different origins but the presence of perchlorates and chlorates detected at the surface of Mars suggests that reactivity between organic molecules and thermal decomposition products from oxychlorines is one of the major sources of the chlorinated organic molecules. Here we perform a comprehensive and systematic study of the separation of volatile chlorohydrocarbons with the chromatographic columns used in the SAM instrument. Despite the constrained operating conditions of the flight instrument, we demonstrate that SAM's capillary chromatographic columns allow for effective separation and identification of a wide range of chlorine-bearing species. We also show that instrumental limitations prevent the detection of certain molecules, obscuring our ability to make definitive conclusions about the origin of these organic materials.

[Cognitive impairment in patients with metabolic syndrome. The current treatment possibilities]. / Vozmozhnosti terapii kognitivnykh narushenii u patsientov s metabolicheskim sindromom.

AIM: To study the effect of therapy with cytoflavin on cognitive function in patients with metabolic syndrome (MS). MATERIAL AND METHODS: The randomized controlled open study included 156 patients with MS. The mean age was 41.27±5.16 years. The duration of observation was 16 weeks. The main group of patients (n=78) received cytoflavin in the dose of 2 tablets 2 times a day. Patients in the control group (n=78) received basic therapy. All patients underwent neuropsychological testing at baseline, after 2 months and at the end of the study. Cognitive evoked potentials (Р300) were recorded to assess cognitive functions. The levels of plasma glucose and lipid profile were measured. RESULTS: Cytoflavin improved cognitive functions. Two months after treatment, the results of neuropsychological testing and electrophysiological study were better in the main group compared to the control group.

Probiotics administration following sleeve gastrectomy surgery: a randomized double-blind trial.

BACKGROUND: Probiotics are commonly used after bariatric surgery; however, uncertainty remains regarding their efficacy. Our aim was to compare the effect of probiotics vs placebo on hepatic, inflammatory and clinical outcomes following laparoscopic sleeve gastrectomy (LSG). METHODS: This randomized, double-blind, placebo-controlled, trial of 6-month treatment with probiotics (Bio-25; Supherb) vs placebo and 6 months of additional follow-up was conducted among 100 morbidly obese nonalcoholic fatty liver disease (NAFLD) patients who underwent LSG surgery. The primary outcome was a reduction in liver fat content, measured by abdominal ultrasound, and secondary outcomes were improvement of fibrosis, measured by shear-wave elastography, metabolic and inflammatory parameters, anthropometrics and quality of life (QOL). Fecal samples were collected and analyzed for microbial composition. RESULTS: One hundred patients (60% women, mean age of 41.9±9.8 years and body mass index of 42.3±4.7 kg m-2) were randomized, 80% attended the 6-month visit and 77% completed the 12-month follow-up. Fat content and NAFLD remission rate were similarly reduced in the probiotics and placebo groups at 6 months postsurgery (-0.9±0.5 vs -0.7±0.4 score; P=0.059 and 52.5 vs 40%; P=0.262, respectively) and at 12 months postsurgery. Fibrosis, liver-enzymes, C-reactive protein (CRP), leptin and cytokeratin-18 levels were significantly reduced and QOL significantly improved within groups (P⩽0.014 for all), but not between groups (P⩾0.173 for all) at 6 and 12 months postsurgery. Within-sample microbiota diversity (alpha-diversity) increased at 6-month postsurgery compared with baseline in both study arms (P⩽0.008) and decreased again at 12 months postsurgery compared with 6 months postsurgery (P⩽0.004) but did not reach baseline values. CONCLUSIONS: Probiotics administration does not improve hepatic, inflammatory and clinical outcomes 6- and 12 months post-LSG.

Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale crater, Mars.

H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.

Volatile, isotope, and organic analysis of martian fines with the Mars Curiosity rover.

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity's Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

Enantiomeric separation of volatile organics by gas chromatography for the in situ analysis of extraterrestrial materials: kinetics and thermodynamics investigation of various chiral stationary phases.

The performances of several commercial chiral capillary columns have been evaluated with the aim of determining the one most suitable for enantiomeric separation in a gas chromatograph onboard a space probe. We compared the GC-MS response of three capillary columns coated with different chiral stationary phases (CSP) using volatile chiral organic molecules which are potential markers of a prebiotic organic chemistry. The three different chiral capillary columns are Chirasil-Val, with an amino acid derivative CSP, ChiralDex-ß-PM, with a CSP composed of dissolved permethylated ß-cyclodextrins in polysiloxane, and Chirasil-Dex, with a CSP made of modified cyclodextrins chemically bonded to the polysiloxane backbone. Both kinetics and thermodynamics studies have been carried out to evaluate the chiral recognition potential in these different types of columns. The thermodynamic parameters also allow a better understanding of the driving forces affecting the retention and separation of the enantiomers. The Chirasil-Dex-CSP displays the best characteristics for an optimal resolution of the chiral compounds, without preliminary derivatization. This CSP had been chosen to be the only chiral column in the Sample Analysis at Mars (SAM) experiment onboard the current Mars Science Laboratory (MSL) mission, and is also part of the Mars Organic Molecules Analyzer (MOMA) gas chromatograph onboard the next Martian mission ExoMars. The use of this column could also be extended to all space missions aimed at studying chirality in space.

Formation of amino acids and nucleotide bases in a Titan atmosphere simulation experiment.

The discovery of large (>100 u) molecules in Titan's upper atmosphere has heightened astrobiological interest in this unique satellite. In particular, complex organic aerosols produced in atmospheres containing C, N, O, and H, like that of Titan, could be a source of prebiotic molecules. In this work, aerosols produced in a Titan atmosphere simulation experiment with enhanced CO (N(2)/CH(4)/CO gas mixtures of 96.2%/2.0%/1.8% and 93.2%/5.0%/1.8%) were found to contain 18 molecules with molecular formulae that correspond to biological amino acids and nucleotide bases. Very high-resolution mass spectrometry of isotopically labeled samples confirmed that C(4)H(5)N(3)O, C(4)H(4)N(2)O(2), C(5)H(6)N(2)O(2), C(5)H(5)N(5), and C(6)H(9)N(3)O(2) are produced by chemistry in the simulation chamber. Gas chromatography-mass spectrometry (GC-MS) analyses of the non-isotopic samples confirmed the presence of cytosine (C(4)H(5)N(3)O), uracil (C(5)H(4)N(2)O(2)), thymine (C(5)H(6)N(2)O(2)), guanine (C(5)H(5)N(5)O), glycine (C(2)H(5)NO(2)), and alanine (C(3)H(7)NO(2)). Adenine (C(5)H(5)N(5)) was detected by GC-MS in isotopically labeled samples. The remaining prebiotic molecules were detected in unlabeled samples only and may have been affected by contamination in the chamber. These results demonstrate that prebiotic molecules can be formed by the high-energy chemistry similar to that which occurs in planetary upper atmospheres and therefore identifies a new source of prebiotic material, potentially increasing the range of planets where life could begin.

Gas chromatography-mass spectrometry of hexafluoroacetone derivatives: First time utilization of a gaseous phase derivatizing agent for analysis of extraterrestrial amino acids.

Within the perspective of the current and next space missions to Mars (MSL 2011 and Exomars 2016-2018), the detection and enantioselective separation of building blocks such as the amino acids are important subjects which are becoming fundamental for the search for traces of life on the surface and subsurface of Mars. In this work, we have developed and optimized a method adapted to space experimentation to derivatize and analyze amino acids, using hexafluoroacetone as the derivatizing agent. The temperature, duration of the derivative transfer to the analyser, and chromatographic separation parameters have been optimized to meet the instrument design constraints imposed on devices for extraterrestrial experiments. The work presented in this rationale has established that hexafluoroacetone, in addition to its intrinsic qualities, such as the production of light-weight derivatives (no racemization) and great resistance to the drastic operating conditions, has indeed facilitated simple and fast derivatization that appears to be suitable for in situ analysis in space. By using hexafluoroacetone as the derivatizing agent, we successfully identified, 21 amino acids including 12 of the 20 proteinic amino acids without stirring or extraction steps. Ten of these derivatized amino acids were enantioselectively separated. The precision and accuracy measurements for the D/L ratio showed that the proposed method was also suitable for the determination of both enantioselective forms of most of the tested amino acids. The limits of detection obtained were lower than the ppb level of organic molecules detected in Martian meteorites.

Fine needle aspiration cytology in breast tuberculosis: diagnostic difficulties--study of eleven cases.

BACKGROUND: Incidence of extra-pulmonary tuberculosis is on the rise. Tuberculosis of breast is rare and have multifaceted clinical presentation, often mimicking carcinoma and pyogenic breast abscess. AIM: To study morphologic variations and diagnostic difficulties of breast tuberculosis on fine needle aspiration cytology (FNAC). METHODS: FNAC smears of breast tuberculosis were studied by Leishman's Stain and categorized into four groups. Cytology smears were also studied for presence of Acid Fast Bacilli (AFB) by Ziehl Neelsen (ZN) stain. Histology of excised tissue was studied by Hematoxylin and Eosin stain (H& E). RESULTS: Out of 11 cases, 10 were females and 1 was male. Group 1 (n = 2) showed epithelioid granulomas with necrosis. Group 2 (n = 2) showed epithelioid granulomas without necrosis. Group 3 (n = 3) showed necrosis with a few scattered epithelioid histiocytes. Group 4 (n = 4) showed necrosis with numerous neutrophilic inflammatory cells. In four cases, caseous necrosis could be identified on cytology smears. AFB were found in five cases on FNAC smears. Histology confirmed diagnosis of tuberculosis in all cases. CONCLUSION: In developing countries like India, based on clinical history and other features, FNAC smears showing epithelioid granulomas with or without necrosis should be considered as breast tuberculosis as demonstration of AFB is not mandatory. Identification of caseous necrosis alone is diagnostic of breast tuberculosis in cytology smears.

[Early onset psychosis: rationale and concept of a cognitive-behavioral intervention]. / Jugendliche mit psychotischen Störungen: Rationale und Konzept einer kognitiv-verhaltenstherapeutischen Intervention.

Early onset psychoses (EOP, age of onset between age 14 and 18 years) are known to be associated with a poorer outcome than adult onset psychoses, both in terms of psychotic symptoms and social remission. For adult patients with psychosis, numerous cognitive-behavioral interventions have proven their effectiveness in recent years. This contrasts with a dearth of findings for EOP, even though it can be considered as a variant of adult onset psychosis. Thus, we have developed a cognitive-behavioral therapy intervention that was specifically adapted to the characteristics and needs of young people suffering from psychosis. The concept of the intervention is outlined in the present article. Acceptability and feasibility of the intervention are currently undergoing evaluation in a randomised, controlled pilot study.

The fate of aerosols on the surface of Titan.

A laboratory study based on the chemical transformation that Titan's aerosol analogues suffer when placed under putative surface conditions of the satellite was performed. In order to understand the role that aqueous ammonia may play on the chemical transformation of atmospheric aerosols once they reach the surface, we synthesized laboratory analogues of Titan's aerosols from an N2 : CH4 (98 : 2) mixture irradiated at low temperatures under a continuous flow regime by a cold plasma discharge of 180 W. The analogues were recovered, partitioned in several 10.0 mg samples and placed inside different ammonia concentrations during 10 weeks at temperatures as low as those reported for Titan's surface. After a derivatization process performed to the aerosols' refractory phase with MTBSTFA in DMF, the products were identified and quantified using a GC-MS system. We found derived residues related to amino acids as well as urea. The simplest amino acids aminoethanoic acid (glycine) and 2-aminopropanoic acid (alanine) as well as diaminomethanal (urea), are found regardless of the ammonia concentration and temperature value to which the aerosol analogues were exposed. Our results have important astrobiological implications to Titan's environment particularly if the existence of the suggested subsurface water-ammonia mixture and its deposition on the satellite's surface is validated.

Search for evidence of life in space: analysis of enantiomeric organic molecules by N,N-dimethylformamide dimethylacetal derivative dependant Gas Chromatography-Mass Spectrometry.

Within the context of the future space missions to Mars (MSL 2011 and Exomars 2016), which aim at searching for traces of life at the surface, the detection and quantitation of enantiomeric organic molecules is of major importance. In this work, we have developed and optimized a method to derivatize and analyze chiral organic molecules suitable for space experiments, using N,N-dimethylformamide dimethylacetal (DMF-DMA) as the derivatization agent. The temperature, duration of the derivatization reaction, and chromatographic separation parameters have been optimized to meet instrument design constraints imposed upon space experiment devices. This work demonstrates that, in addition to its intrinsic qualities, such as production of light-weight derivatives and a great resistance to drastic operating conditions, DMF-DMA facilitates simple and fast derivatization of organic compounds (three minutes at 140 degrees C in a single-step) that is suitable for an in situ analysis in space. By using DMF-DMA as the derivatization agent, we have successfully identified 19 of the 20 proteinic amino acids and been able to enantiomerically separate ten of the potential 19 (glycine being non-chiral). Additionally, we have minimized the percentage of racemized amino acid compounds produced by optimizing the conditions of the derivatization reaction itself. Quantitative linearity studies and the determination of the limit of detection show that the proposed method is also suitable for the quantitative determination of both enantiomeric forms of most of the tested amino acids, as limits of detection obtained are lower than the ppb level of organic molecules already detected in Martian meteorites.

Chemical characterization of Titan's tholins: solubility, morphology and molecular structure revisited.

In this work Titan's atmospheric chemistry is simulated using a capacitively coupled plasma radio frequency discharge in a N(2)-CH(4) stationnary flux. Samples of Titan's tholins are produced in gaseous mixtures containing either 2 or 10% methane before the plasma discharge, covering the methane concentration range measured in Titan's atmosphere. We study their solubility and associated morphology, their infrared spectroscopy signature and the mass distribution of the soluble fraction by mass spectrometry. An important result is to highlight that the previous Titan's tholin solubility studies are inappropriate to fully characterize such a heterogeneous organic matter and we develop a new protocol to evaluate quantitatively tholins solubility. We find that tholins contain up to 35% in mass of molecules soluble in methanol, attached to a hardly insoluble fraction. Methanol is then chosen as a discriminating solvent to characterize the differences between soluble and insoluble species constituting the bulk tholins. No significant morphological change of shape or surface feature is derived from scanning electron microscopy after the extraction of the soluble fraction. This observation suggests a solid structure despite an important porosity of the grains. Infrared spectroscopy is recorded for both fractions. The IR spectra of the bulk, soluble, and insoluble tholins fractions are found to be very similar and reveal identical chemical signatures of nitrogen bearing functions and aliphatic groups. This result confirms that the chemical information collected when analyzing only the soluble fraction provides a valuable insight representative of the bulk material. The soluble fraction is ionized with an atmospheric pressure photoionization source and analyzed by a hybrid mass spectrometer. The congested mass spectra with one peak at every mass unit between 50 and 800 u confirm that the soluble fraction contains a complex mixture of organic molecules. The broad distribution, however, exhibits a regular pattern of mass clusters. Tandem collision induced dissociation analysis is performed in the negative ion mode to retrieve structural information. It reveals that (i) the molecules are ended by methyl, amine and cyanide groups, (ii) a 27 u neutral moiety (most probably HCN) is often released in the fragmentation of tholin anions, and (iii) an ubiquitous ionic fragment at m/z 66 is found in all tandem spectra. A tentative structure is proposed for this negative ion.