Artificial maturation of iron- and sulfur-rich Mars analogues: Implications for the diagenetic stability of biopolymers and their detection with pyrolysis gas chromatography–mass spectrometry

Acidic iron- and sulfur-rich streams are appropriate analogues for the late Noachian and early Hesperian periods of martian history, when Mars exhibited extensive habitable environments. Any past life on Mars may have left behind diagnostic evidence of life that could be detected at the present day. For effective preservation, these remains must have avoided the harsh radiation flux at the martian surface, survived geological storage for billions of years, and remained detectable within their geochemical environment by analytical instrument suites used on Mars today, such as thermal extraction techniques. We investigated the detectability of organic matter within sulfur stream sediments that had been subjected to artificial maturation by hydrous pyrolysis. After maturation, the samples were analyzed by pyrolysis–gas chromatography–mass spectrometry (py-GC-MS) to determine whether organic matter could be detected with this commonly used technique. We find that macromolecular organic matter can survive the artificial maturation process in the presence of iron- and sulfur-rich minerals but cannot be unambiguously distinguished from abiotic organic matter. However, if jarosite and goethite are present in the sulfur stream environment, they interfere with the py-GC-MS detection of organic compounds in these samples. Clay reduces the obfuscating effect of the oxidizing minerals by providing nondeleterious adsorption sites. We also find that after a simple alkali and acid leaching process that removes oxidizing minerals such as iron sulfates, oxides, and oxyhydroxides, the sulfur stream samples exhibit much greater organic responses during py-GC-MS in terms of both abundance and diversity of organic compounds, such as the detection of hopanes in all leached samples. Our results suggest that insoluble organic matter can be preserved over billions of years of geological storage while still retaining diagnostic organic information, but sample selection strategies must either avoid jarosite- and goethite-rich outcrops or conduct preparative chemistry steps to remove these oxidants prior to analysis by thermal extraction techniques

Solid Phase Micro Extraction: Potential for Organic Contamination Control for Planetary Protection of Life-Detection Missions to the Icy Moons of the Outer Solar System

Conclusively detecting, or ruling out the possibility of, life on the icy moons of the outer solar system will require spacecraft missions to undergo rigorous planetary protection and contamination control procedures to achieve extremely low levels of organic terrestrial contamination. Contamination control is necessary to avoid forward contamination of the body of interest and to avoid the detection of false positive signals which could either mask indigenous organic chemistry of interest or cause an astrobiological false alarm. Here we test a new method for rapidly and inexpensively assessing the organic cleanliness of spaceflight hardware surfaces using solid phase micro extraction (SPME) fibres to directly swab surfaces. The results suggest that the method is both time and cost efficient. The SPME-gas chromatography mass spectrometry (GC-MS) method is sensitive to common mid-weight, non-polar contaminant compounds, e.g. aliphatic and aromatic hydrocarbons, which are common contaminants in laboratory settings. While we demonstrate the potential of SPME for surface sampling, the GC-MS instrumentation restricts the SPME-GC-MS technique’s sensitivity to larger polar and non-volatile compounds. Although not used in this study, to increase the potential range of detectable compounds, SPME can also be used in conjunction with high performance liquid chromatography/liquid chromatography-mass spectrometry systems suitable for polar analytes [Kataoka et al., 2000]. Thus, our SPME method presents an opportunity to monitor organic contamination in a relatively rapid and routine way that produces information-rich data sets

Solid phase micro extraction for organic contamination control throughout assembly and operational phases of space missions

Space missions concerned with life detection contain highly sensitive instruments for the detection of organics. Terrestrial contamination can interfere with signals of indigenous organics in samples and has the potential to cause false positive biosignature detections, which may lead to incorrect suggestions of the presence of life elsewhere in the Solar System. This study assessed the capability of solid phase micro extraction (SPME) as a method for monitoring organic contamination encountered by spacecraft hardware during assembly and operation. SPME-gas chromatography-mass spectrometry (SPME-GC-MS) analysis was performed on potential contaminant source materials, which are commonly used in spacecraft construction. The sensitivity of SPME-GC-MS to organics was assessed in the context of contaminants identified in molecular wipes taken from hardware surfaces on the ExoMars Rosalind Franklin rover. SPME was found to be effective at detecting a wide range of common organic contaminants that include aromatic hydrocarbons, non-aromatic hydrocarbons, nitrogen-containing compounds, alcohols and carbonyls. A notable example of correlation of contaminant with source material was the detection of benzenamine compounds in an epoxy adhesive analyzed by SPME-GC-MS and in the ExoMars rover surface wipe samples. The current form of SPME-GC-MS does not enable quantitative evaluation of contaminants, nor is it suitable for the detection of every group of organic molecules relevant to astrobiological contamination concerns, namely, large and/or polar molecules such as amino acids. However, it nonetheless represents an effective new monitoring method for rapid, easy identification of organic contaminants commonly present on spacecraft hardware and could thus be utilized in future space missions as part of their contamination control and mitigation protocols

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy : a systematic review and economic evaluation

Peer reviewedPublisher PD

Bayesian inference in camera trapping studies for a class of spatial capture-recapture models

We develop a class of models for inference about abundance or density using spatial capture-recapture data from studies based on camera trapping and related methods. The model is a hierarchical model composed of two components: a point process model describing the distribution of individuals in space (or their home range centers) and a model describing the observation of individuals in traps. We suppose that trap- and individual-specific capture probabilities are a function of distance between individual home range centers and trap locations. We show that the models can be regarded as generalized linear mixed models, where the individual home range centers are random effects. We adopt a Bayesian framework for inference under these models using a formulation based on data augmentation. We apply the models to camera trapping data on tigers from the Nagarahole Reserve, India, collected over 48 nights in 2006. For this study, 120 camera locations were used, but cameras were only operational at 30 locations during any given sample occasion. Movement of traps is common in many camera-trapping studies and represents an important feature of the observation model that we address explicitly in our application

Offspring social network structure predicts fitness in families.

addresses: Centre for Ecology and Conservation, Biosciences, College of Life and Environmental Sciences, University of Exeter, Cornwall Campus, Penryn, Cornwall TR10 9EZ, UK. [email protected]: PMCID: PMC3497231types: Journal Article; Research Support, Non-U.S. Gov'tSocial structures such as families emerge as outcomes of behavioural interactions among individuals, and can evolve over time if families with particular types of social structures tend to leave more individuals in subsequent generations. The social behaviour of interacting individuals is typically analysed as a series of multiple dyadic (pair-wise) interactions, rather than a network of interactions among multiple individuals. However, in species where parents feed dependant young, interactions within families nearly always involve more than two individuals simultaneously. Such social networks of interactions at least partly reflect conflicts of interest over the provision of costly parental investment. Consequently, variation in family network structure reflects variation in how conflicts of interest are resolved among family members. Despite its importance in understanding the evolution of emergent properties of social organization such as family life and cooperation, nothing is currently known about how selection acts on the structure of social networks. Here, we show that the social network structure of broods of begging nestling great tits Parus major predicts fitness in families. Although selection at the level of the individual favours large nestlings, selection at the level of the kin-group primarily favours families that resolve conflicts most effectively

A tree-decomposed transfer matrix for computing exact Potts model partition functions for arbitrary graphs, with applications to planar graph colourings

Combining tree decomposition and transfer matrix techniques provides a very general algorithm for computing exact partition functions of statistical models defined on arbitrary graphs. The algorithm is particularly efficient in the case of planar graphs. We illustrate it by computing the Potts model partition functions and chromatic polynomials (the number of proper vertex colourings using Q colours) for large samples of random planar graphs with up to N=100 vertices. In the latter case, our algorithm yields a sub-exponential average running time of ~ exp(1.516 sqrt(N)), a substantial improvement over the exponential running time ~ exp(0.245 N) provided by the hitherto best known algorithm. We study the statistics of chromatic roots of random planar graphs in some detail, comparing the findings with results for finite pieces of a regular lattice.Comment: 5 pages, 3 figures. Version 2 has been substantially expanded. Version 3 shows that the worst-case running time is sub-exponential in the number of vertice

Habitat‐dependent occupancy and movement in a migrant songbird highlights the importance of mangroves and forested lagoons in Panama and Colombia

Climate change is predicted to impact tropical mangrove forests due to decreased rainfall, sea‐level rise, and increased seasonality of flooding. Such changes are likely to influence habitat quality for migratory songbirds occupying mangrove wetlands during the tropical dry season. Overwintering habitat quality is known to be associated with fitness in migratory songbirds, yet studies have focused primarily on territorial species. Little is known about the ecology of nonterritorial species that may display more complex movement patterns within and among habitats of differing quality. In this study, we assess within‐season survival and movement at two spatio‐temporal scales of a nonterritorial overwintering bird, the prothonotary warbler (Protonotaria citrea), that depends on mangroves and tropical lowland forests. Specifically, we (a) estimated within‐patch survival and persistence over a six‐week period using radio‐tagged birds in central Panama and (b) modeled abundance and occupancy dynamics at survey points throughout eastern Panama and northern Colombia as the dry season progressed. We found that site persistence was highest in mangroves; however, the probability of survival did not differ among habitats. The probability of warbler occupancy increased with canopy cover, and wet habitats were least likely to experience local extinction as the dry season progressed. We also found that warbler abundance is highest in forests with the tallest canopies. This study is one of the first to demonstrate habitat‐dependent occupancy and movement in a nonterritorial overwintering migrant songbird, and our findings highlight the need to conserve intact, mature mangrove, and lowland forests

Cone-Beam Computed Tomography and Deformable Registration-Based “Dose of the Day” Calculations for Adaptive Proton Therapy

Purpose: The aim of this work was to evaluate the feasibility of cone-beam computed tomography (CBCT) and deformable image registration (DIR)–based ‘‘dose of the day’’ calculations for adaptive proton therapy. Methods: Intensity-modulated radiation therapy (IMRT) and proton therapy plans were designed for 3 head and neck patients that required replanning, and hence had a replan computed tomography (CT). Proton plans were generated for different beam arrangements and optimizations: intensity modulated proton therapy and single-field uniform dose. We used an in-house DIR software implemented at our institution to generate a deformed CT, by warping the planning CT onto the daily CBCT. This CBCT had a similar patient geometry to the replanned CT. Dose distributions on the replanned CT were considered the gold standard for ‘‘dose of the day’’ calculations, and were compared with doses on deformed CT (our method) and directly on the calibrated CBCT and rigidly aligned planning CT (alternative methods) in terms of dose difference (DD), by calculating the percentage of voxels whose DD was smaller than 2% of the prescribed dose (DD2%-pp) and the root mean square of the DD distribution (DDRMS). Results: Using a deformed CT, the DD2%-pp within the CBCT imaging volume was 93.2% 6 0.7% for IMRT, and 87% 6 3% for proton plans. In a region of higher dose gradient, we found that although DD2%-pp was 94.3% 6 0.2% for IMRT, in proton plans, it dropped to 74% 6 4%. A larger number of treatment beams and single-field uniform dose optimization appear to make the proton plans less sensitive to DIR errors. For example, within the treated volume, the DDRMS was reduced from 2.6% 6 0.6% of the prescribed doseto 1.0% 6 1.3% ofthe prescribed dose when using single-field uniform dose optimization. Conclusions: Promising results were found for DIR- and CBCT-based proton dose calculations. Proton dose calculations were, however, more sensitive to registration errors than IMRT doses were, particularly in high dose gradient regions

Ixazomib for relapsed or refractory multiple myeloma : review from an evidence review group on a NICE single technology appraisal

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer’s first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified according to one previous treatment and two or more previous treatments. A further deficiency was considered to be the manufacturer’s use of interim survival data rather than the most mature data available. A second submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or fourth-line treatment (the two or more previous lines population) and a new patient access scheme was introduced. Covariate modeling of survival outcomes was proposed using the most mature survival data. The Evidence Review Group’s main criticisms of the new evidence included: the utility associated with the pre-progression health state was overestimated, treatment costs of ixazomib were underestimated, survival models were still associated with great uncertainty, leading to clinically implausible anomalies and highly variable incremental cost-effectiveness ratio estimates, and the company had not explored a strong assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully maintained for a further 22 years beyond the observed data, which encompassed only approximately 2.5 years of observation. The appraisal committee remained unconvinced that ixazomib represented a cost-effective use of National Health Service resources. Takeda’s third submission offered new base-case parametric models for survival outcomes, a new analysis of utilities, and proposed a commercial access agreement. In a brief critique of the third submission, the Evidence Review Group agreed that the selection of appropriate survival models was problematic and at the request of the National Institute for Health Care and Excellence investigated external sources of evidence regarding survival outcomes. The Evidence Review Group considered that some cost and utility estimates in the submission may have remained biased in favor of ixazomib. As a result of their third appraisal meeting, the committee judged that for the two to three prior therapies population, and at the price agreed in a commercial access agreement, ixazomib had the potential to be cost effective. It was referred to the Cancer Drugs Fund so that further data could accrue with the aim of diminishing the clinical uncertainties