Constraints on Evolutionary Timescales for M Dwarf Planets from Dynamical Stability Arguments

The diversity of dynamical conditions among exoplanets is now well established. Yet, the relevance of orbital dynamical timescales to biological evolutionary timescales is poorly understood. Given that even minor orbital changes may place significant pressure on any organisms living on a planet, dynamical sculpting has important implications for the putative evolution of life. In this manuscript, we employ a Monte Carlo framework to investigate how a range of exoplanetary dynamical sculpting timescales affects timescales for biological evolution. We proceed with minimal assumptions for how dynamical sculpting proceeds and the emergence and persistence of life. We focus our investigation on M dwarf stars, the most common exoplanetary hosts in the Milky Way. We assign dynamical statuses, dependent on stellar age, to a suite of planetary systems, varying the rate of dynamical disruption within limits that are consistent with present-day planet demographics. We then simulate the observed yield of planets according to the completeness of NASA's Kepler and TESS missions, and investigate the properties of these samples. With this simplified approach, we find that systems hosting multiple transiting planets ought to have, on average, shorter dynamically-uninterrupted intervals than single-transiting systems. However, depending upon the rate of dynamical sculpting, planets orbiting older stars will exhibit the opposite trend. Even modest constraints on stellar age would help identify "older" stars for which this holds. The degree of these effects varies, dependent upon both the intrinsic dynamical demographics of exoplanets and whether we consider planets detected by NASA's Kepler or TESS missions.Comment: 17 pages, 15 figures, 1 table, submitted to Ap

The carbon-deficient evolution of TRAPPIST-1c

Transiting planets orbiting M dwarfs provide the best opportunity to study the atmospheres of rocky planets with current facilities. As JWST enters its second year of science operations, an important initial endeavor is to determine whether these rocky planets have atmospheres at all. M dwarf host stars are thought to pose a major threat to planetary atmospheres due to their high magnetic activity over several billion-year timescales, and might completely strip atmospheres. Several Cycle 1 and 2 GO and GTO programs are testing this hypothesis, observing a series of rocky planets to determine whether they retained their atmospheres. A key case-study is TRAPPIST-1c, which receives almost the same bolometric flux as Venus. We might, therefore, expect TRAPPIST-1c to possess a thick, CO₂-dominated atmosphere. Instead, Zieba et al. (2023) show that TRAPPIST-1c has little to no CO₂ in its atmosphere. To interpret these results, we run coupled time-dependent simulations of planetary outgassing and atmospheric escape to model the evolution of TRAPPIST-1c’s atmosphere. We find that the stellar wind stripping that is expected to occur on TRAPPIST-1c over its lifetime can only remove up to ~ 16 bar of CO₂, less than the modern CO₂ inventory of either Earth or Venus. Therefore, we infer that TRAPPIST-1c either formed volatile-poor, as compared to Earth and Venus, or lost a substantial amount of CO₂ during an early phase of hydrodynamic hydrogen escape. Finally, we scale our results for the other TRAPPIST-1 planets, finding that the more distant TRAPPIST-1 planets may readily retain atmospheres.Astronom

A Review of Validation Methods for the Intracranial Response of FEHM to Blunt Impacts

The following is a review of the processes currently employed when validating the intracranial response of Finite Element Head Models (FEHM) against blunt impacts. The authors aim to collate existing validation tools, their applications and findings on their effectiveness to aid researchers in the validation of future FEHM and potential efforts in improving procedures. In this vain, publications providing experimental data on the intracranial pressure, relative brain displacement and brain strain responses to impacts in human subjects are surveyed and key data are summarised. This includes cases that have previously been used in FEHM validation and alternatives with similar potential uses. The processes employed to replicate impact conditions and the resulting head motion are reviewed, as are the analytical techniques used to judge the validity of the models. Finally, publications exploring the validation process and factors affecting it are critically discussed. Reviewing FEHM validation in this way highlights the lack of a single best practice, or an obvious solution to create one using the tools currently available. There is clear scope to improve the validation process of FEHM, and the data available to achieve this. By collecting information from existing publications, it is hoped this review can help guide such developments and provide a point of reference for researchers looking to validate or investigate FEHM in the future, enabling them to make informed choices about the simulation of impacts, how they are generated numerically and the factors considered during output assessment, whilst being aware of potential limitations in the process

The Carbon-Deficient Evolution of TRAPPIST-1c

Transiting planets orbiting M dwarfs provide the best opportunity to study the atmospheres of rocky planets with current facilities. As JWST enters its second year of science operations, an important initial endeavor is to determine whether these rocky planets have atmospheres at all. M dwarf host stars are thought to pose a major threat to planetary atmospheres due to their high magnetic activity over several billion-year timescales, and might completely strip atmospheres. Several Cycle 1 and 2 GO and GTO programs are testing this hypothesis, observing a series of rocky planets to determine whether they retained their atmospheres. A key case-study is TRAPPIST-1c, which receives almost the same bolometric flux as Venus. We might, therefore, expect TRAPPIST-1c to possess a thick, $\mathrm{CO}_2$-dominated atmosphere. Instead, Zieba et al. (2023) show that TRAPPIST-1c has little to no CO$_2$ in its atmosphere. To interpret these results, we run coupled time-dependent simulations of planetary outgassing and atmospheric escape to model the evolution of TRAPPIST-1c's atmosphere. We find that the stellar wind stripping that is expected to occur on TRAPPIST-1c over its lifetime can only remove up to $\sim 16$ bar of $\mathrm{CO}_2$, less than the modern $\mathrm{CO}_2$ inventory of either Earth or Venus. Therefore, we infer that TRAPPIST-1c either formed volatile-poor, as compared to Earth and Venus, or lost a substantial amount of $\mathrm{CO}_2$ during an early phase of hydrodynamic hydrogen escape. Finally, we scale our results for the other TRAPPIST-1 planets, finding that the more distant TRAPPIST-1 planets may readily retain atmospheres.Comment: 16 pages, 11 figures, 1 table, accepted to Ap

Dengue in pregnancy and maternal mortality: a cohort analysis using routine data.

Dengue is a mosquito-borne disease with major public health importance due to its growing incidence and geographical spread. There is a lack of knowledge on its contribution to maternal death. We conducted a population-based cohort study to investigate the association between symptomatic dengue during pregnancy and deaths in Brazil from 2007 to 2012. We did this by linking routine records of confirmed dengue cases to records of deaths of women who had a live birth. Using the Firth method, we estimated odds ratios for maternal deaths associated with dengue during pregnancy. Dengue increased the risk of maternal death by 3 times (95%CI,1.5-5.8) and dengue haemorrhagic fever increased the risk of maternal death by 450 times (95%CI,186.9-1088.4) when compared to mortality of pregnant women without dengue. The increase in risk occurred mostly during acute dengue 71.5 (95%CI,32.8-155.8), compared with no dengue cases. This study showed an increased risk of adverse outcomes in pregnant women with dengue. Therefore in areas where dengue is circulating, the health of pregnant women should be not only a public health priority, but health professionals attending pregnant women with dengue should more closely observe these patients to be able to intervene in a timely way and avoid deaths

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

BACKGROUND: Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. METHODS: We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. CONCLUSION: Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes

Symptomatic dengue infection during pregnancy and the risk of stillbirth in Brazil, 2006-12: a matched case-control study.

BACKGROUND: Maternal infections during pregnancy can increase the risk of fetal death. Dengue infection is common, but little is known about its role in fetal mortality. We aimed to investigate the association between symptomatic dengue infection during pregnancy and fetal death. METHODS: We did a nested case-control study using obstetrician-collected data from the Brazilian livebirth information system (SINASC), the mortality information system (SIM), and the national reportable disease information system (SINAN). We identified all pregnancies ending in stillbirth and a random sample of livebirths between Jan 1, 2006, and Dec 31, 2012. We did linkage to determine which mothers were diagnosed with dengue infection during pregnancy. By use of stillbirths as cases and a sample of matched livebirths as a control, we calculated matched odds ratios (mORs) using conditional logistic regression adjusted for maternal age and education. FINDINGS: 275 (0·2%) of 162 188 women who had stillbirths and 1507 (0·1%) of 1 586 105 women who had livebirths were diagnosed with dengue infection during pregnancy. Symptomatic dengue infection during pregnancy almost doubled the odds of fetal death (mOR 1·9, 95% CI 1·6-2·2). The increase in risk was similar when analyses were restricted to laboratory-confirmed cases of dengue infection (1·8, 1·4-2·4). Severe dengue infection increased the risk of fetal death by about five times (4·9, 2·3-10·2). INTERPRETATION: Symptomatic dengue infection during pregnancy is associated with an increased risk of fetal death. We recommend further epidemiological and biological studies of the association between dengue and poor birth outcomes to measure the burden of subclinical infections and elucidate pathological mechanisms. FUNDING: Brazilian National Council for Scientific and Technological Development, Horizon 2020

Validating linkage of multiple population-based administrative databases in Brazil.

BACKGROUND: Linking routinely-collected data provides an opportunity to measure the effects of exposures that occur before birth on maternal, fetal and infant outcomes. High quality linkage is a prerequisite for producing reliable results, and there are specific challenges in mother-baby linkage. Using population-based administrative databases from Brazil, this study aimed to estimate the accuracy of linkage between maternal deaths and birth outcomes and dengue notifications, and to identify potential sources of bias when assessing the risk of maternal death due to dengue in pregnancy. METHODS: We identified women with dengue during pregnancy in a previously linked dataset of dengue notifications in women who had experienced a live birth or stillbirth during 2007-2012. We then linked this dataset with maternal death records probabilistically using maternal name, age and municipality. We estimated the accuracy of the linkage, and examined the characteristics of false-matches and missed-matches to identify any sources of bias. RESULTS: Of the 10,259 maternal deaths recorded in 2007-2012, 6717 were linked: 5444 to a live birth record, 1306 to a stillbirth record, and 33 to both a live and stillbirth record. After identifying 2620 missed-matches and 124 false-matches, our estimated sensitivity was 72%, specificity was 88%, and positive predictive value was 98%. Linkage errors were associated with maternal education and self-identified race; women with more than 7 years of education or who self-declared as Caucasian were more likely to link. Dengue status was not associated with linkage error. CONCLUSION: Despite not having unique identifiers to link mothers and birth outcomes, we demonstrated a high standard of linkage, with sensitivity and specificity values comparable to previous literature. Although there were no differences in the characteristics of dengue cases missed or included in our linked dataset, linkage error occurred disproportionally by some social-demographic characteristics, which should be taken into account in future analyses

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression