A two-galectin network establishes mesenchymal condensation phenotype in limb development.

Previous work showed that Gal-1A and Gal-8, two proteins belonging to the galactoside-binding galectin family, are the earliest determinants of the patterning of the skeletal elements of embryonic chicken limbs, and further, that their experimentally determined interactions in the embryonic limb bud can be interpreted via a reaction-diffusion-adhesion (2GL: two galectin plus ligands) model. Here, we use an ordinary differential equation-based approach to analyze the intrinsic switching modality of the 2GL network and characterize the network behavior independent of the diffusive and adhesive arms of the patterning mechanism. We identify two states: where the concentrations of both the galectins are respectively, negligible, and very high. This bistable switch-like system arises via a saddle-node bifurcation from a monostable state. For the case of mass-action production terms, we provide an explicit Lyapunov function for the system, which shows that it has no periodic solutions. Our model therefore predicts that the galectin network may exist in low expression and high expression states separated in space or time, without any intermediate states. We test these predictions in experiments performed with high density cultures of chick limb mesenchymal cells and observe that cells inside precartilage protocondensations express Gal-1A at a much higher rate than those outside, for which it was negligible. The Gal-1A and -8-based patterning network is therefore sufficient to partition the mesenchymal cell population into two discrete cell states with different developmental (chondrogenic vs. non-chondrogenic) fates. When incorporated into an adhesion and diffusion-enabled framework this system can generate a spatially patterned limb skeleton.

Potential of in-plant intramuscular fat predictions to enable sheep breeders to incorporate consumer preferences in breeding programmes.

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers.

In-home dementia caregiving is associated with greater psychological burden and poorer mental health than out-of-home caregiving: a cross-sectional study.

INTRODUCTION: Caregivers who live with a person with dementia who receives care, compared with those who live elsewhere, are often considered to experience greater levels of psychological and affective burden. The evidence for this is, however, only limited to studies employing small sample sizes and that failed to examine caregivers' psychological wellbeing. We address these issues in a large cohort of dementia caregivers. METHODS: We conducted a cross-sectional study comparing caregivers living with a dementia care recipient (n = 240) to caregivers living elsewhere (n = 255) on caregivers' burden, anxiety, and depression. RESULTS: We found that caregivers living with the care recipient relative to those living elsewhere showed significantly greater burden and depression, but we found no group difference in anxiety. CONCLUSIONS: Our study adds to the evidence by showing that cohabiting with a care recipient with dementia is associated with greater burden and poorer psychological wellbeing. Strategies aiming to improve caregivers' burden and psychological wellbeing should take account of caregivers' living arrangements.

Strength of interference screw fixation of meniscus prosthesis matches native meniscus attachments.

PURPOSE: Meniscal surgery is one of the most common orthopaedic surgical interventions. Total meniscus replacements have been proposed as a solution for patients with irreparable meniscal injuries. Reliable fixation is crucial for the success and functionality of such implants. The aim of this study was to characterise an interference screw fixation system developed for a novel fibre-matrix-reinforced synthetic total meniscus replacement in an ovine cadaveric model. METHODS: Textile straps were tested in tension to failure (n = 15) and in cyclic tension (70-220 N) for 1000 cycles (n = 5). The textile strap-interference screw fixation system was tested in 4.5 mm-diameter single anterior and double posterior tunnels in North of England Mule ovine tibias aged > 2 years using titanium alloy (Ti6Al4Va) and polyether-ether-ketone (PEEK) screws (n ≥ 5). Straps were preconditioned, dynamically loaded for 1000 cycles in tension (70-220 N), the fixation slippage under cyclic loading was measured, and then pulled to failure. RESULTS: Strap stiffness was at least 12 times that recorded for human meniscal roots. Strap creep strain at the maximum load (220 N) was 0.005 following 1000 cycles. For all tunnels, pull-out failure resulted from textile strap slippage or bone fracture rather than strap rupture, which demonstrated that the textile strap was comparatively stronger than the interference screw fixation system. Pull-out load (anterior 544 ± 119 N; posterior 889 ± 157 N) was comparable to human meniscal root strength. Fixation slippage was within the acceptable range for anterior cruciate ligament graft reconstruction (anterior 1.9 ± 0.7 mm; posterior 1.9 ± 0.5 mm). CONCLUSION: These findings show that the textile attachment-interference screw fixation system provides reliable fixation for a novel ovine meniscus implant, supporting progression to in vivo testing. This research provides a baseline for future development of novel human meniscus replacements, in relation to attachment design and fixation methods. The data suggest that surgical techniques familiar from ligament reconstruction may be used for the fixation of clinical meniscal prostheses.

Unmet supportive care needs in prostate cancer survivors with advanced disease: A mixed-methods exploration.

Purpose: Men with advanced prostate cancer experience a wide range of side effects from the cancer and its therapies, which have a negative effect on their quality of life (QOL). Few studies have evaluated supportive care needs in these individuals. The purpose of this study was to conduct a holistic supportive care needs assessment among these survivors guided by the Supportive Care Framework for Cancer Care. Methods: Using a convergent parallel mixed-methods approach, prostate cancer survivors with advanced disease (n = 188) completed a cross-sectional survey. A subset of these survivors (n = 20) participated in an interview to further explore their experience of unmet needs. Results: Survivors reported unmet supportive care needs in every domain of the framework. Up to 95.2% of the survivors had at least one unmet need, with a mean of 14.9 (range: 0-42). Several areas of convergence among the quantitative and qualitative data (fatigue, sexual dysfunction, practical, and emotional/psychological domains), as well as divergence (informational and spiritual domains, depression, urinary dysfunction) were found through the integration process. Conclusions: This study confirms that prostate cancer survivors with advanced disease experience high rates of unmet supportive care needs. The findings also highlight the diversity of those unmet needs. These results may assist with future development of patient-centered supportive care interventions that better meet the specific needs of this vulnerable group of cancer survivors.

Glutamate levels in the medial prefrontal cortex of healthy pregnant women compared to non-pregnant controls.

Very little is known about maternal cerebral changes during pregnancy. Since there is an increased risk for major depression during pregnancy and postpartum, it is important to understand the structural and neurochemical changes that occur in the brain during pregnancy. Using proton magnetic resonance spectroscopy (1H-MRS) (3 T field strength), glutamate (Glu) levels were measured in the medial prefrontal cortex (MPFC) of 21 healthy gravid subjects 2-3 weeks before their due date (6.74 ± 1.39), and in 14 non-pregnant healthy controls during their follicular phase (8.53 ± 1.55). Water quantified MPFC Glu levels were decreased in pregnant women (p < 0.01). We also observed a 13.9% decrease in percentage grey matter (%GM) (p < 0.01) in our MPFC voxel. As Glu is mostly found in GM, we repeated the statistical analysis after adjustment for %GM and found that the difference in Glu levels was no longer statistically significant when adjusted for %GM (p = 0.10). This investigation is the only systematic direct investigation of brain tissue composition and Glu levels in pregnant women. The main finding of this investigation is the decreased %GM in healthy pregnant women compared to non-pregnant women. These findings of decreased %GM in pregnancy may be responsible for the frequent complaints by pregnant women of cognitive difficulties also described as pregnesia.

Offshore pelagic subsidies dominate carbon inputs to coral reef predators.

Coral reefs were traditionally perceived as productive hot spots in oligotrophic waters. While modern evidence indicates that many coral reef food webs are heavily subsidized by planktonic production, the pathways through which this occurs remain unresolved. We used the analytical power of carbon isotope analysis of essential amino acids to distinguish between alternative carbon pathways supporting four key reef predators across an oceanic atoll. This technique separates benthic versus planktonic inputs, further identifying two distinct planktonic pathways (nearshore reef-associated plankton and offshore pelagic plankton), and revealing that these reef predators are overwhelmingly sustained by offshore pelagic sources rather than by reef sources (including reef-associated plankton). Notably, pelagic reliance did not vary between species or reef habitats, emphasizing that allochthonous energetic subsidies may have system-wide importance. These results help explain how coral reefs maintain exceptional productivity in apparently nutrient-poor tropical settings, but also emphasize their susceptibility to future ocean productivity fluctuations.

Safety footwear: A survey of end-users.

This paper presents the results of an extensive survey concerning the experience of safety footwear end-users. Safety footwear has been in widespread use across many industries worldwide since the 1970s, and has become an essential part of industrial Personal Protective Equipment. The number of women entering predominantly male industrial environments, and requiring safety footwear is rising, and this is accompanied by anecdotal reports of ill-fitting and uncomfortable footwear. This research proactively compares the opinions of women and men regarding their experience of safety footwear. A systematically designed survey aims to substantiate previously anecdotal knowledge around safety footwear, including key drivers for end-user purchases, wear habits and comfort issues (establishing any differences between women and men). Chi-squared testing was used to assess statistical significance and ensure robustness of findings. The responses and resulting analysis confirmed that comfort and fit were key drivers for all end users; women and men have different wear habits (women wear their safety footwear less frequently and for shorter periods of time than men - likely due to the reported comfort issues); a significant proportion of women (60%) found their safety footwear less comfortable than their regular footwear, however, 45% of men also reported the same, which has not been reported anecdotally. In general, the users of safety footwear accepted a level of discomfort in at least one area of the foot before deeming footwear 'uncomfortable'. The significant analysis performed on the captured data has, to the authors knowledge, never before been undertaken for this breadth of industry, age and gender with 632 responses received. This makes it the largest study of this field to date.

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis.

AIMS: At diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11-21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease. MATERIALS AND METHODS: This retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan-Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors. RESULTS: Forty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34-76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30-59). At 3 and 5 years, OS was 45% (95% confidence interval 32-63) and 30% (95% confidence interval 18-51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18-63). The 3- and 5-year PFS was 8% (95% confidence interval 3-22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11-0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15-0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13-2.15, P = 0.007) were associated with longer PFS. CONCLUSIONS: Definitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

Diagnosis of death using neurological criteria in adult patients on extracorporeal membrane oxygenation: Development of UK guidance.

The diagnosis of death using neurological criteria is an important legal method of establishing death in the UK. The safety of the diagnosis lies in the exclusion of conditions which may mask the diagnosis and the testing of the fundamental reflexes of the brainstem including the apnoea reflex. Extracorporeal membrane oxygenation for cardiac or respiratory support can impact upon these tests, both through drug sequestration in the circuit and also through the ability to undertake the apnoea test. Until recently, there has been no nationally accepted guidance regarding the conduct of the tests to undertake the diagnosis of death using neurological criteria for a patient on extracorporeal membrane oxygenation. This article considers both the background to and the process of guideline development.

Case Report: Cutaneous Leishmaniasis due to Leishmania (Viannia) panamensis in Two Travelers Successfully Treated with Miltefosine.

We present two cases of Leishmania (V) panamensis in returning travelers from Central America successfully treated with miltefosine. The couple presented with ulcerative skin lesions nonresponsive to antibiotics. Skin biopsy with polymerase chain reaction (PCR) revealed L. (V) panamensis. To prevent the development of mucosal disease and avoid the inconvenience of parental therapy, we treated both patients with oral miltefosine. We suggest that miltefosine represents an important therapeutic alternative in the treatment of cutaneous lesions caused by L. panamensis and in preventing mucosal involvement.

One Health collaborations for zoonotic disease control in Ethiopia.

Zoonotic diseases require a One Health approach for successful control and elimination due to the nature of their transmission between animals and humans. One Health recognises that the health of humans, animals, and the environment are all interconnected. Ethiopia has committed itself to controlling five prioritised zoonotic diseases (rabies, anthrax, brucellosis, leptospirosis and echinococcosis), using a One Health approach. The National One Health Steering Committee (NOHSC) provides a framework for national stakeholders to address gaps in multisectoral communication, coordination and collaboration. In addition, the NOHSC oversees the formation of several specialised disease-focused groups, referred to as 'Technical Working Groups' (TWGs). These TWGs are responsible for developing disease prevention and control strategies, as well as implementing disease-focused public health activities and providing recommendations to the NOHSC. Ethiopia's success using the One Health approach and its efficient control of zoonotic diseases will depend on the commitment of all member Ministries to support the NOHSC and TWGs, as well as to build capacity in Ethiopia's workforce and laboratories, a task supported by its many international partners.

Les zoonoses étant par nature des maladies transmissibles entre les animaux et l'homme, l'approche Une seule santé est la seule qui permette de les contrôler efficacement en vue de les éliminer. Le concept Une seule santé repose sur la prise en compte de l'interconnexion entre la santé humaine, celle des animaux et celle de l'environnement. L'Éthiopie s'est fixé pour objectif de lutter contre cinq maladies zoonotiques classées comme prioritaires (rage, fièvre charbonneuse, brucellose, leptospirose et échinococcose) en suivant une approche Une seule santé. Le comité de pilotage national Une seule santé (NOHSC) apporte un cadre permettant aux parties prenantes du pays de résoudre les problèmes de communication, de coordination et de collaboration intersectorielles. En outre, le NOHSC supervise la création de plusieurs groupes de travail techniques dédiés à des maladies spécifiques. Ces groupes de travail sont chargés d'élaborer des stratégies de prévention et de contrôle, de mettre en oeuvre des activités de santé publique axées sur ces maladies et de formuler des recommandations à l'intention du NOHSC. La réussite des efforts déployés par l'Éthiopie pour appliquer les principes Une seule santé et l'efficacité de la lutte contre les maladies zoonotiques dépendront de l'engagement des ministères concernés à soutenir le NOHSC et les groupes de travail techniques et à renforcer les capacités des ressources humaines et des laboratoires éthiopiens, tâche qui bénéficie de l'appui de nombreux partenaires internationaux.

Toda labor eficaz de control y eliminación de las enfermedades zoonóticas, por la propia naturaleza de su transmisión entre animales y personas, pasa por abordar estas patologías desde los planteamientos de Una sola salud, noción esta que parte del reconocimiento de que salud humana, animal y ambiental están siempre interconectadas. Etiopía está embarcada en el innegociable empeño de combatir cinco enfermedades zoonóticas consideradas prioritarias (rabia, carbunco bacteridiano, brucelosis, leptospirosis y equinococosis) trabajando desde la óptica de Una sola salud. El Comité Directivo Nacional de Una sola salud proporciona a los interlocutores del país un marco de referencia que sirve para subsanar las lagunas existentes en cuanto a comunicación, coordinación y colaboración entre los diversos sectores. Ese órgano, además, supervisa la formación de varios grupos especializados y centrados en una u otra enfermedad, denominados grupos de trabajo técnicos, que tienen por cometido elaborar estrategias de prevención y control de una enfermedad concreta, llevar adelante acciones de salud pública dirigidas contra ella y formular recomendaciones para el Comité Directivo. El éxito de Etiopía a la hora de aplicar los postulados de Una sola salud y de combatir eficazmente las enfermedades zoonóticas dependerá del nivel de compromiso con que todos los ministerios copartícipes presten apoyo al Comité Directivo y los grupos de trabajo técnicos y ayuden a instaurar en el país un tejido lo bastante solvente de laboratorios y recursos humanos, empresa esta en la que Etiopía cuenta con el respaldo de sus numerosos asociados internacionales.

Does using anatomical models improve patient satisfaction in orthopaedic consenting? Single-blinded randomised controlled trial.

BACKGROUND: Patient satisfaction in consenting is a major pillar of clinical governance and healthcare quality assessment. The purpose was to observe the effect of using 3D anatomical models of knee and shoulder joints on patient satisfaction during informed consent in the largest single-blinded randomised controlled trial in this field. METHODS: 52 patients undergoing elective knee or shoulder surgery were randomised into two groups when being consented. The intervention group (n = 26) was shown an anatomical model of the knee/shoulder joint while the control group (n = 26) was given only a verbal explanation without a model. Patients rated their satisfaction on the validated Medical Interview Satisfaction Scale (MISS-26) questionnaire. Semi-structured interviews were analysed for specific themes to determine key factors that influenced patient satisfaction. The mean score ±SD were calculated with significance set at p < 0.05. RESULTS: There was a significant difference in the overall satisfaction between the control and intervention cohorts (MISS-26 score 4.33 [86.6%] ± 0.646 vs 4.70 [94.0%] ± 0.335 respectively, 7.4% improvement, 8.5% difference, p = 0.01). Behavioural criteria showed a 13% increase in satisfaction (p = 0.02). Semi-structured interviews determined that the factors influencing satisfaction included the surgeon's interpersonal manner, the use of the visual aid and seeing the consultant surgeon in clinic. All patients in the intervention cohort identified factors contributing to their satisfaction, whereas a fifth of the control cohort claimed nothing at all made them feel satisfied. CONCLUSION: Anatomical models as visual aids significantly increased patient satisfaction during the consenting process and played an integral part of the surgeon's explanation. Patients exposed to anatomical models also claimed to be more satisfied with the surgeon's inter-personal skills. This study recommends the use of anatomical models, which are both cost-effective and easily implementable, during explanation and consent for orthopaedic procedures.

The combined diabetes and renal control trial (C-DIRECT) - a feasibility randomised controlled trial to evaluate outcomes in multi-morbid patients with diabetes and on dialysis using a mixed methods approach.

BACKGROUND: This cluster randomised controlled trial set out to investigate the feasibility and acceptability of the "Combined Diabetes and Renal Control Trial" (C-DIRECT) intervention, a nurse-led intervention based on motivational interviewing and self-management in patients with coexisting end stage renal diseases and diabetes mellitus (DM ESRD). Its efficacy to improve glycaemic control, as well as psychosocial and self-care outcomes were also evaluated as secondary outcomes. METHODS: An assessor-blinded, clustered randomised-controlled trial was conducted with 44 haemodialysis patients with DM ESRD and ≥ 8% glycated haemoglobin (HbA1c), in dialysis centres across Singapore. Patients were randomised according to dialysis shifts. 20 patients were assigned to intervention and 24 were in usual care. The C-DIRECT intervention consisted of three weekly chair-side sessions delivered by diabetes specialist nurses. Data on recruitment, randomisation, and retention, and secondary outcomes such as clinical endpoints, emotional distress, adherence, and self-management skills measures were obtained at baseline and at 12 weeks follow-up. A qualitative evaluation using interviews was conducted at the end of the trial. RESULTS: Of the 44 recruited at baseline, 42 patients were evaluated at follow-up. One patient died, and one discontinued the study due to deteriorating health. Recruitment, retention, and acceptability rates of C-DIRECT were generally satisfactory HbA1c levels decreased in both groups, but C-DIRECT had more participants with HbA1c < 8% at follow up compared to usual care. Significant improvements in role limitations due to physical health were noted for C-DIRECT whereas levels remained stable in usual care. No statistically significant differences between groups were observed for other clinical markers and other patient-reported outcomes. There were no adverse effects. CONCLUSIONS: The trial demonstrated satisfactory feasibility. A brief intervention delivered on bedside as part of routine dialysis care showed some benefits in glycaemic control and on QOL domain compared with usual care, although no effect was observed in other secondary outcomes. Further research is needed to design and assess interventions to promote diabetes self-management in socially vulnerable patients. TRIAL REGISTRATION NUMBER: Trial registered with the International Standard Randomised Controlled Trial (ISRCTN10546597). Registered 12 September 2016 (Retrospectively registered).

Genetic (co)variation in skin pigmentation patterns and growth in rainbow trout.

From a physiological-behavioral perspective, it has been shown that fish with a higher density of black eumelanin spots are more dominant, less sensitive to stress, have higher feed intake, better feed efficiency and therefore are larger in size. Thus, we hypothesized that genetic (co)variation between skin pigmentation patterns and growth exists and it is advantageous in rainbow trout. The objective of this study was to determine the genetic relationships between skin pigmentation patterns and BW in a breeding population of rainbow trout. We performed a genetic analysis of pigmentation traits including dorsal color (DC), lateral band (LB) intensity, amount of spotting above (SA) and below (SB) the lateral line, and BW at harvest (HW). Variance components were estimated using a multi-trait linear animal model fitted by restricted maximum likelihood. Estimated heritabilities were 0.08±0.02, 0.17±0.03, 0.44±0.04, 0.17±0.04 and 0.23±0.04 for DC, LB, SA, SB and HW, respectively. Genetic correlations between HW and skin color traits were 0.42±0.13, 0.32±0.14 and 0.25±0.11 for LB, SA and SB, respectively. These results indicate positive, but low to moderate genetic relationships between the amount of spotting and BW in rainbow trout. Thus, higher levels of spotting are genetically associated with better growth performance in this population.

Validation of the cognitive recovery assessments with the Postoperative Quality of Recovery Scale in patients with low-baseline cognition.

Patients with pre-surgery cognitive impairment cannot currently be assessed for cognitive recovery after surgery using the Postoperative Quality of Recovery Scale (PostopQRS), as they would mathematically be scored as recovered. We aimed to validate a novel method to score cognitive recovery in patients with low-baseline cognition, using the number of low-score tests rather than their numerical values. Face validity was demonstrated in 86 participants in whom both the Postoperative Quality of Recovery Scale and an 11-item neuropsychological battery were performed. The Postoperative Quality of Recovery Scale agreed with neuropsychological categorisation of low vs. normal cognition 74% of the time, with all but five incorrectly coded participants deviating by only one neurocognitive test. Cognitive recovery over time was comparable for groups with differing baseline cognitive function, irrespective of whether the Postoperative Quality of Recovery Scale or neuropsychological methods were used. Discriminant validation was demonstrated in a post-hoc analysis of the steroids in cardiac surgery substudy by allocating groups to normal (n = 246) or low-baseline cognition (n = 231) stratified by cognitive recovery on day 1. Recovery was similar for participants with low and normal baseline cognition. Postoperative length of stay was longer in patients with failed cognitive recovery whether they had normal mean (SD) (10.4 (10.0) vs. 8.0 (5.9) days, p = 0.02) or low-baseline cognition (12.0 (11.1) vs. 8.2 (4.7) days, p < 0.01). Overall quality, as well as cognitive, emotive and physiological recovery was independent of baseline cognition. The modified scoring method for the Postoperative Quality of Recovery Scale cognitive domain demonstrates acceptable face and discriminant validity.

A Field Guide to Finding Fossils on Mars.

The Martian surface is cold, dry, exposed to biologically harmful radiation and apparently barren today. Nevertheless, there is clear geological evidence for warmer, wetter intervals in the past that could have supported life at or near the surface. This evidence has motivated National Aeronautics and Space Administration and European Space Agency to prioritize the search for any remains or traces of organisms from early Mars in forthcoming missions. Informed by (1) stratigraphic, mineralogical and geochemical data collected by previous and current missions, (2) Earth's fossil record, and (3) experimental studies of organic decay and preservation, we here consider whether, how, and where fossils and isotopic biosignatures could have been preserved in the depositional environments and mineralizing media thought to have been present in habitable settings on early Mars. We conclude that Noachian-Hesperian Fe-bearing clay-rich fluvio-lacustrine siliciclastic deposits, especially where enriched in silica, currently represent the most promising and best understood astropaleontological targets. Siliceous sinters would also be an excellent target, but their presence on Mars awaits confirmation. More work is needed to improve our understanding of fossil preservation in the context of other environments specific to Mars, particularly within evaporative salts and pore/fracture-filling subsurface minerals.

Chiral auxiliary recycling in continuous flow: automated recovery and reuse of Oppolzer's sultam.

The telescoping of a three-stage, chiral auxiliary-mediated transformation in flow is described, including continuous separation of the product and auxiliary. The auxiliary can either be collected for later reuse, or directly fed back to the beginning of the process for recycling in real time, enabling each molecule of auxiliary to make multiple equivalents of chiral product and thus minimizing the step- and atom-economy issues associated with auxiliary-mediated synthesis. This concept is demonstrated for the asymmetric hydrogenation of olefins using Oppolzer's sultam, shortening the total reaction time >100 fold compared to batch, and demonstrating formal sub-stoichiometric auxiliary loading with respect to the process by automating auxiliary recycling within a closed loop.