No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations.

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today1. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations2-5. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere6,7, which-given methane's lifetime of several centuries-predicts an even, well mixed distribution of methane1,6,8. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections2,4. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater4 would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally.

Publisher Correction: No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations.

The surname of author Cathy Quantin-Nataf was misspelled 'Quantin-Nata', authors Ehouarn Millour and Roland Young were missing from the ACS and NOMAD Science Teams list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.

Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.

Publisher Correction: Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.

The surname of author Cathy Quantin-Nataf was misspelled 'Quantin-Nata' , authors Ehouarn Millour and Roland Young were missing from the ACS Science Team list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

Optimal outbreeding is shaped during larval life-history in the splash pool copepod Tigriopus californicus.

Inbreeding and outbreeding depression are dynamic forms of selection critical to mating system evolution and the efficacy of conservation biology. Most evidence on how the relative severity and timing of these forces are shaped is confined to self-fertilization, distant outcrossing, and intermediate 'optimal outcrossing' in hermaphrodites. We tested the notion that closed population demographics may reduce and delay the costs of inbreeding relative to distant outbreeding in an intertidal copepod with separate sexes and a biphasic larval / post-metamorphic life-history (Tigriopus californicus). At three lifecycle stages (fecundity, metamorphosis, and post-metamorphosis), we quantified the effects of inbreeding and outbreeding in crosses with varying degrees of recent common ancestry. Although inbreeding and outbreeding depression have distinct genetic mechanisms, both manifested the same stage-specific consequences for fitness. Inbreeding and outbreeding depression were not apparent for fecundity, post-metamorphic survival, sex ratio, or the ability to acquire mates, but inbreeding between full siblings and outbreeding between interpopulation hybrids reduced the fraction of offspring that completed metamorphosis by 32% and 47%, respectively. On average, the effects of inbreeding on metamorphic rate were weaker and nearly twice as variable among families than those of outbreeding, suggesting genetic load was less pervasive than the incompatibilities accrued between divergent populations. Overall, our results indicate the transition from larval to juvenile life stages is markedly susceptible to both inbreeding and outbreeding depression in T. californicus. We suggest stage-specific selection acting concurrently with the timing of metamorphosis may be an instrumental factor shaping reproductive optima in species with complex life-histories.

Interpopulation variation in inbreeding is primarily driven by tolerance of mating with relatives in a spermcasting invertebrate.

The degree to which individuals inbreed is a fundamental aspect of population biology shaped by both passive and active processes. Yet, the relative influences of random and non-random mating on the overall magnitude of inbreeding are not well characterized for many taxa. We quantified variation in inbreeding among qualitatively accessible and isolated populations of a sessile marine invertebrate (the colonial ascidian Lissoclinum verrilli) in which hermaphroditic colonies cast sperm into the water column for subsequent uptake and internal fertilization. We compared estimates of inbreeding to simulations predicting random mating within sites to evaluate if levels of inbreeding were (1) less than expected because of active attempts to limit inbreeding, (2) as predicted by genetic subdivision and passive inbreeding tolerance, or (3) greater than simulations due to active attempts to promote inbreeding via self-fertilization or a preference for related mates. We found evidence of restricted gene flow and significant differences in the genetic diversity of L. verrilli colonies among sites, indicating that on average colonies were weakly related in accessible locations, but their levels of relatedness matched that of first cousins or half-siblings on isolated substrates. Irrespective of population size, progeny arrays revealed variation in the magnitude of inbreeding across sites that tracked with the mean relatedness of conspecifics. Biparental reproduction was confirmed in most offspring (86%) and estimates of total inbreeding largely overlapped with simulations of random mating, suggesting that interpopulation variation in mother-offspring resemblance was primarily due to genetic subdivision and passive tolerance of related mates. Our results highlight the influence of demographic isolation on the genetic composition of populations, and support theory predicting that tolerance of biparental inbreeding, even when mates are closely related, may be favoured under a broad set of ecological and evolutionary conditions.

Effects of N-terminus modified Hx-amides on DNA binding affinity, sequence specificity, cellular uptake, and gene expression.

Five X-HxIP (Hx-amides) 6a-e, in which the N-terminus p-anisyl moiety is modified, were designed and synthesised with the purpose of optimising DNA binding, improving cellular uptake/nuclear penetration, and enhancing the modulation of the topoisomerase IIα (TOP2A) gene expression. The modifications include a fluorophenyl group and other heterocycles bearing different molecular shapes, size, and polarity. Like their parent compound HxIP 3, all five X-HxIP analogues bind preferentially to their cognate sequence 5'-TACGAT-3', which is found embedded on the 5' flank of the inverted CCAAT box-2 (ICB2) site in the TOP2A gene promoter, and inhibit protein complex binding. Interestingly, the 4-pyridyl analog 6a exhibits greater binding affinity for the target DNA sequence and abolishes the protein:ICB2 interaction in vitro, at a lower concentration, compared to the prototypical compound HxIP 3. Analogues 6b-e, display improved DNA sequence specificity, but reduced binding affinity for the cognate sequence, relative to the unmodified HxIP 3, with polyamides 6b and 6e being the most sequence selective. However, unlike 3 and 6b, 6a was unable to enter cells, access the nucleus and thereby affect TOP2A gene expression in confluent human lung cancer cells. These results show that while DNA binding affinity and sequence selectivity are important, consideration of cellular uptake and concentration in the nucleus are critical when exerting biological activity is the desired outcome. By characterising the DNA binding, cellular uptake and gene regulatory properties of these small molecules, we can elucidate the determinants of the elicited biological activity, which can be impacted by even small structural modifications in the polyamide molecular design.

Postoperative surgical trainee opioid prescribing practices (POST OPP): an institutional study.

BACKGROUND: Increasing mortality from opioid overdoses has prompted increased focus on prescribing practices of physicians. Unfortunately, resident physicians rarely receive formal education in effective opioid prescribing practices or postoperative pain management. Data to inform surgical training programs regarding the utility and feasibility of formal training are lacking. METHODS: Following Institutional Review Board approval, a single institution's resident physicians who had completed at least one surgical rotation were surveyed to assess knowledge of pain management and evaluate opioid prescribing practices. RESULTS: Fifty-three respondents (68% males and 32% females) completed the survey. Most respondents denied receiving formal instruction in opioid pain medication prescribing practices during either medical school (62.3%) or residency (56.6%); however, nearly all respondents stated they were aware of the side effects of opioid pain medications, and a majority felt confident in their knowledge of opioid pharmacokinetics and pharmacodynamics. Of the respondents, 47% either "agreed" or "strongly agreed" that they prescribed more opioid medications than necessary to patients being discharged following a surgical procedure. Individual case scenario responses demonstrated variability in the number of morphine milligram equivalents prescribed across scenarios (P < 0.001). Male and nonsurgical specialty respondents reported prescribing significantly fewer overall morphine milligram equivalents in these scenarios. CONCLUSIONS: This pilot study shows wide variability in opioid prescribing practices and attitudes toward pain management among surgical trainees, illustrating the potential utility of formal education in pain management and effective prescribing of these medications. A broader assessment of surgical trainees' knowledge and perception of opioid prescribing practices is warranted to facilitate the development of such a program.

Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

Improvement in Detection of Wrong-Patient Errors When Radiologists Include Patient Photographs in Their Interpretation of Portable Chest Radiographs.

This study was conducted to determine whether facial photographs obtained simultaneously with radiographs improve radiologists' detection rate of wrong-patient errors, when they are explicitly asked to include the photographs in their evaluation. Radiograph-photograph combinations were obtained from 28 patients at the time of portable chest radiography imaging. From these, pairs of radiographs were generated. Each unique pair consisted of one new and one old (comparison) radiograph. Twelve pairs of mismatched radiographs (i.e., pairs containing radiographs of different patients) were also generated. In phase 1 of the study, 5 blinded radiologist observers were asked to interpret 20 pairs of radiographs without the photographs. In phase 2, each radiologist interpreted another 20 pairs of radiographs with the photographs. Radiologist observers were not instructed about the purpose of the photographs but were asked to include the photographs in their review. The detection rate of mismatched errors was recorded along with the interpretation time for each session for each observer. The two-tailed Fisher exact test was used to evaluate differences in mismatch detection rates between the two phases. A p value of <0.05 was considered significant. The error detection rates without (0/20 = 0%) and with (17/18 = 94.4%) photographs were different (p = 0.0001). The average interpretation times for the set of 20 radiographs were 26.45 (SD 8.69) and 20.55 (SD 3.40) min, for phase 1 and phase 2, respectively (two-tailed Student t test, p = 0.1911). When radiologists include simultaneously obtained photographs in their review of portable chest radiographs, there is a significant improvement in the detection of labeling errors. No statistically significant difference in interpretation time was observed. This may lead to improved patient safety without affecting radiologists' throughput.

Retained arterial catheter following patient self-discontinuation-a case report.

A patient self-discontinues arterial line resulting in retention of arterial catheter. The retained catheter was identified on bedside ultrasound and the patient required radial artery exploration and removal of catheter under general anesthesia. We describe potential contributing factors and solutions to catheter design and placement as well as next steps once a retained catheter has been identified.

Images in Anesthesiology: Carotid Sinus Reflex From Neck Mass and Opioids.

Surgery on head and neck masses presents unique challenges to overcome, especially in relation to preoperative anesthesia induction. Tumor proximity to the carotid sinus can result in extreme hemodynamic depression, by way of compression or direct invasion of the node. Neck hyperextension required for endotracheal intubation can worsen the underlying compression. Additionally, many anesthetic agents have sympatholytic properties that can exacerbate this imbalance further toward the parasympathetic response. We present a case of a patient with non-Hodgkin lymphoma whose tumor compression of the carotid sinus precipitated an exaggerated vagal reflex response following fentanyl administration.

Genomic Architecture of Hybrid Male Sterility in a Species Without Sex Chromosomes (Tigriopus californicus, Copepoda: Harpacticoida).

Sterility among hybrids is one of the most prevalent forms of reproductive isolation delineating species boundaries and is expressed disproportionately in heterogametic XY males. While hybrid male sterility (HMS) due to the "large X effect" is a well-recognized mechanism of reproductive isolation, it is less clear how HMS manifests in species that lack heteromorphic sex chromosomes. We evaluated differences in allele frequencies at approximately 460,000 SNPs between fertile and sterile F2 interpopulation male hybrids to characterize the genomic architecture of HMS in a species without sex chromosomes (Tigriopus californicus). We tested associations between HMS and mitochondrial-nuclear and/or nuclear-nuclear signatures of incompatibility. Genomic regions associated with HMS were concentrated on a single chromosome with the same primary 2-Mbp regions identified in one pair of reciprocal crosses. Gene Ontology analysis revealed that annotations associated with spermatogenesis were the most overrepresented within the implicated region, with nine protein-coding genes connected with this process found in the quantitative trait locus of chromosome 2. Our results indicate that a narrow genomic region was associated with the sterility of male hybrids in T. californicus and suggest that incompatibilities among select nuclear loci may replace the large X effect when sex chromosomes are absent.

Transient HCl in the atmosphere of Mars.

A major quest in Mars' exploration has been the hunt for atmospheric gases, potentially unveiling ongoing activity of geophysical or biological origin. Here, we report the first detection of a halogen gas, HCl, which could, in theory, originate from contemporary volcanic degassing or chlorine released from gas-solid reactions. Our detections made at ~3.2 to 3.8 µm with the Atmospheric Chemistry Suite and confirmed with Nadir and Occultation for Mars Discovery instruments onboard the ExoMars Trace Gas Orbiter, reveal widely distributed HCl in the 1- to 4-ppbv range, 20 times greater than previously reported upper limits. HCl increased during the 2018 global dust storm and declined soon after its end, pointing to the exchange between the dust and the atmosphere. Understanding the origin and variability of HCl shall constitute a major advance in our appraisal of martian geo- and photochemistry.

Volatile anaesthetic for treatment of respiratory failure from status asthmaticus requiring extracorporeal membrane oxygenation.

A 37-year-old male smoker with asthma presented with status asthmaticus refractory to terbutaline, intravenous magnesium, continuous bronchodilators, steroids, heliox and theophylline infusion. He was intubated on hospital day 2 and cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) on hospital day 3 for refractory respiratory acidosis secondary to hypercapnia and hypoxemia despite maximum medical management over 4 days. He was started on inhaled isoflurane with improvement in peak airway pressures and respiratory acidosis, allowing for prompt weaning from V-V ECMO and extubation. Inhaled volatile anaesthetics exert a direct action on bronchiole smooth muscle causing relaxation with significant effect despite severely impaired pulmonary function. This treatment in patients on ECMO may allow for earlier decannulation and decreased risk of coagulopathy, ECMO circuit failure, infection, renal failure, pulmonary haemorrhage and central nervous system haemorrhage. However, major limitations exist in delivering volatile anaesthetics, which may make use inefficient and costly despite efficacy.

Pterygopalatine Ganglion Block as a Rescue Technique for Failed Epidural Blood Patch.

Placement of an epidural blood patch is the gold standard treatment for a postdural puncture headache when conservative measures have failed. If unsuccessful in relieving the symptoms, a second epidural blood patch may be warranted. However, when the accepted gold standard treatment has failed, alternative therapies may be pursued. A pterygopalatine ganglion block has been shown to be effective as an alternative to epidural blood patch placement. This case demonstrates the use of a suprazygomatic pterygopalatine ganglion block as a rescue technique for failed repeated epidural blood patch, with complete and permanent resolution of the headache.

Inbreeding shapes the evolution of marine invertebrates.

Inbreeding is a potent evolutionary force shaping the distribution of genetic variation within and among populations of plants and animals. Yet, our understanding of the forces shaping the expression and evolution of nonrandom mating in general, and inbreeding in particular, remains remarkably incomplete. Most research on plant mating systems focuses on self-fertilization and its consequences for automatic selection, inbreeding depression, purging, and reproductive assurance, whereas studies of animal mating systems have often assumed that inbreeding is rare, and that natural selection favors traits that promote outbreeding. Given that many sessile and sedentary marine invertebrates and marine macroalgae share key life history features with seed plants (e.g., low mobility, modular construction, and the release of gametes into the environment), their mating systems may be similar. Here, we show that published estimates of inbreeding coefficients (FIS ) for sessile and sedentary marine organisms are similar and at least as high as noted in terrestrial seed plants. We also found that variation in FIS within invertebrates is related to the potential to self-fertilize, disperse, and choose mates. The similarity of FIS for these organismal groups suggests that inbreeding could play a larger role in the evolution of sessile and sedentary marine organisms than is currently recognized. Specifically, associations between traits of marine invertebrates and FIS suggest that inbreeding could drive evolutionary transitions between hermaphroditism and separate sexes, direct development and multiphasic life cycles, and external and internal fertilization.

Stormy water on Mars: The distribution and saturation of atmospheric water during the dusty season.

The loss of water from Mars to space is thought to result from the transport of water to the upper atmosphere, where it is dissociated to hydrogen and escapes the planet. Recent observations have suggested large, rapid seasonal intrusions of water into the upper atmosphere, boosting the hydrogen abundance. We use the Atmospheric Chemistry Suite on the ExoMars Trace Gas Orbiter to characterize the water distribution by altitude. Water profiles during the 2018-2019 southern spring and summer stormy seasons show that high-altitude water is preferentially supplied close to perihelion, and supersaturation occurs even when clouds are present. This implies that the potential for water to escape from Mars is higher than previously thought.

Somatic Mutation Is a Function of Clone Size and Depth in Orbicella Reef-Building Corals.

In modular organisms, the propagation of genetic variability within a clonal unit can alter the scale at which ecological and evolutionary processes operate. Genetic variation within an individual primarily arises through the accretion of somatic mutations over time, leading to genetic mosaicism. Here, we assess the prevalence of intraorganismal genetic variation and potential mechanisms influencing the degree of genetic mosaicism in the reef corals Orbicella franksi and Orbicella annularis. Colonies of both species, encompassing a range of coral sizes and depths, were sampled multiple times and genotyped at the same microsatellite loci to detect intraorganismal genetic variation. Genetic mosaicism was detected in 38% of corals evaluated, and mutation frequency was found to be positively related with clonal size and negatively associated with coral depth. We suggest that larger clones experience a greater number of somatic cell divisions and consequently have an elevated potential to accumulate mutations. Furthermore, corals at shallower depths may be exposed to abiotic conditions such as elevated thermal regimes, which promote increased mutation rates. The results highlight the pervasiveness of intraorganismal genetic variation in reef-building corals and emphasize potential mechanisms generating somatic mutations in modular organisms.

Postoperative surgical trainee opioid prescribing practices (POST-OPP): A national survey.

BACKGROUND: Increasing opioid-related deaths have heightened focus on combating the opioid epidemic. The impact of surgical trainees on opioid-related deaths is unclear, and there is little data examining the association between trainee pain management education and opioid prescribing practices. METHODS: An anonymous, online survey was distributed to members of the Resident and Associate Society of the American College of Surgeons. The survey covered five themes: education and knowledge, prescribing practices, clinical case scenarios, policy, and beliefs and attitudes. Linear mixed models were used to evaluate the influence of respondent characteristics on reported morphine milligram equivalents (MME) prescribed for common general surgery clinical scenarios. RESULTS: Of 427 respondents, 54 percent indicated receiving training in postoperative pain management during medical school and 66 percent during residency. Only 35 percent agreed that they had received adequate training in prescribing opioids. There was a significant association between undergoing formal pain management training in medical school and prescribing fewer MME for common outpatient general surgery scenarios (94 ± 15.2 vs 108 ± 15.0; p = 0.003). Similarly, formal pain management training in residency was associated with prescribing fewer MME in the survey scenarios (92.6 ± 15.2 vs 109 ± 15.2; p = 0.002). CONCLUSION: In this survey, nearly two-thirds of surgical residents felt that they were inadequately trained in opioid pre-scribing. Our findings additionally suggest that improving education may result in increased resident comfort with man-aging surgical pain, potentially leading to more responsible opioid prescribing. Further work will facilitate residency pro-grams' development of educational curricula for opioid prescribing best practices.