Population genomic structure of a widespread, urban-dwelling mammal: The eastern grey squirrel (Sciurus carolinensis).

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.

A critical appraisal of controlled studies investigating malformation risks following pregabalin use in early pregnancy.

In March 2022, the Summary of Product Characteristics for the Lyrica brand of pregabalin was updated with warnings regarding malformation risks. This literature review and critical appraisal aims to explore whether these Summary of Product Characteristics updates are justified and provide clarity on the risk-benefit balance for pregabalin use in early pregnancy. A literature review was conducted in May 2022 to identify English language comparative studies of any design providing data about first trimester maternal pregabalin use and malformation risk. Five observational comparative cohort studies using data from 9 distinct datasets were located. Collectively these studies described at least 5300 unique pregabalin exposed pregnancies, with 4900 exposed in at least the first trimester. Three studies investigated overall major malformation risks, and 4 investigated specific malformation risks. The available evidence was found to be conflicting and generally of low quality, probably influenced by bias and data confounding, with no clear pattern of specific malformations observed. Findings from the largest study suggested absolute risks of major malformation of 4.8-5.6%, relative to a background risk of approximately 4%. Due to study methodology limitations, the available data were judged to only provide low quality evidence suggestive of a possible and unconfirmed small increased risk that cannot be solely attributed to foetal pregabalin exposure. This literature review and critical appraisal indicates that the Lyrica product literature updates are insufficiently substantiated and could result in confusion and misinformed clinical risk-benefit decision making.

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

OBJECTIVE: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. METHOD: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. RESULTS: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. CONCLUSION: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.

Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic-A multinational cross-sectional study.

INTRODUCTION: Evidence on perinatal mental health during the coronavirus disease 2019 (COVID-19) pandemic and its potential determinants is limited. Therefore, this multinational study aimed to assess the mental health status of pregnant and breastfeeding women during the pandemic, and to explore potential associations between depressive symptoms, anxiety, and stress and women's sociodemographic, health, and reproductive characteristics. MATERIAL AND METHODS: A cross-sectional, web-based study was performed in Ireland, Norway, Switzerland, the Netherlands, and the UK between 16 June and 14 July 2020. Pregnant and breastfeeding women up to 3 months postpartum who were older than 18 years of age were eligible. The online, anonymous survey was promoted through social media and hospital websites. The Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder seven-item scale (GAD-7), and the Perceived Stress Scale (PSS) were used to assess mental health status. Regression model analysis was used to identify factors associated with poor mental health status. RESULTS: In total, 9041 women participated (including 3907 pregnant and 5134 breastfeeding women). The prevalence of major depressive symptoms (EDS ≥ 13) was 15% in the pregnancy cohort and and 13% the breastfeeding cohort. Moderate to severe generalized anxiety symptoms (GAD ≥ 10) were found among 11% and 10% of the pregnant and breastfeeding women. The mean (±SD) PSS scores for pregnant and breastfeeding women were 14.1 ± 6.6 and 13.7 ± 6.6, respectively. Risk factors associated with poor mental health included having a chronic mental illness, a chronic somatic illness in the postpartum period, smoking, having an unplanned pregnancy, professional status, and living in the UK or Ireland. CONCLUSIONS: This multinational study found high levels of depressive symptoms and generalized anxiety among pregnant and breastfeeding women during the COVID-19 outbreak. The study findings underline the importance of monitoring perinatal mental health during pandemics and other societal crises to safeguard maternal and infant mental health.

Microgeographic divergence of functional responses among salamanders under antagonistic selection from apex predators.

A predator's functional response determines predator-prey interactions by describing the relationship between the number of prey available and the number eaten. Its shape and parameters fundamentally govern the dynamic equilibrium of predator-prey interactions and their joint abundances. Yet, estimates of these key parameters generally assume stasis in space and time and ignore the potential for local adaptation to alter feeding responses and the stability of trophic dynamics. Here, we evaluate if functional responses diverge among populations of spotted salamander (Ambystoma maculatum) larvae that face antagonistic selection on feeding strategies based on their own risk of predation. Common garden experiments revealed that spotted salamander from ponds with varying predation risks differed in their functional responses, suggesting an evolutionary response. Applying mechanistic equations, we discovered that the combined changes in attack rates, handling times and shape of the functional response enhanced feeding rate in environments with high densities of gape-limited predators. We suggest how these parameter changes could alter community equilibria and other emergent properties of food webs. Community ecologists might often need to consider how local evolution at fine scales alters key relationships in ways that alter local diversity patterns, food web dynamics, resource gradients and community responses to disturbance.

Peromyscus transcriptomics: Understanding adaptation and gene expression plasticity within and between species of deer mice.

Deer mice in the genus Peromyscus occupy nearly every terrestrial habitat in North America, and have a long history as subjects of behavioral, ecological, evolutionary, and physiological study. Recent advances in transcriptomics, the study of the complete set of RNA transcripts produced by certain cell types or under certain conditions, have contributed to the development of Peromyscus as a model system. We review the recent use of transcriptomics to investigate how natural selection and gene expression plasticity contribute to the existence of deer mice in challenging environments such as highlands, deserts, and cities across North America. Transcriptomics also holds great promise for elucidating the genetic basis of mating systems and other behaviors in Peromyscus, but has to date been underutilized for developmental biology and disease studies. Future Peromyscus studies should apply robust comparative frameworks to analyze the transcriptomics of multiple populations of the same species across varying environmental conditions, as well as multiple species that vary in traits of interest.

Urban rat races: spatial population genomics of brown rats (Rattus norvegicus) compared across multiple cities.

Urbanization often substantially influences animal movement and gene flow. However, few studies to date have examined gene flow of the same species across multiple cities. In this study, we examine brown rats (Rattus norvegicus) to test hypotheses about the repeatability of neutral evolution across four cities: Salvador, Brazil; New Orleans, USA; Vancouver, Canada; and New York City, USA. At least 150 rats were sampled from each city and genotyped for a minimum of 15 000 genome-wide single nucleotide polymorphisms. Levels of genome-wide diversity were similar across cities, but varied across neighbourhoods within cities. All four populations exhibited high spatial autocorrelation at the shortest distance classes (less than 500 m) owing to limited dispersal. Coancestry and evolutionary clustering analyses identified genetic discontinuities within each city that coincided with a resource desert in New York City, major waterways in New Orleans, and roads in Salvador and Vancouver. Such replicated studies are crucial to assessing the generality of predictions from urban evolution, and have practical applications for pest management and public health. Future studies should include a range of global cities in different biomes, incorporate multiple species, and examine the impact of specific characteristics of the built environment and human socioeconomics on gene flow.

Range position and climate sensitivity: The structure of among-population demographic responses to climatic variation.

Species' distributions will respond to climate change based on the relationship between local demographic processes and climate and how this relationship varies based on range position. A rarely tested demographic prediction is that populations at the extremes of a species' climate envelope (e.g., populations in areas with the highest mean annual temperature) will be most sensitive to local shifts in climate (i.e., warming). We tested this prediction using a dynamic species distribution model linking demographic rates to variation in temperature and precipitation for wood frogs (Lithobates sylvaticus) in North America. Using long-term monitoring data from 746 populations in 27 study areas, we determined how climatic variation affected population growth rates and how these relationships varied with respect to long-term climate. Some models supported the predicted pattern, with negative effects of extreme summer temperatures in hotter areas and positive effects on recruitment for summer water availability in drier areas. We also found evidence of interacting temperature and precipitation influencing population size, such as extreme heat having less of a negative effect in wetter areas. Other results were contrary to predictions, such as positive effects of summer water availability in wetter parts of the range and positive responses to winter warming especially in milder areas. In general, we found wood frogs were more sensitive to changes in temperature or temperature interacting with precipitation than to changes in precipitation alone. Our results suggest that sensitivity to changes in climate cannot be predicted simply by knowing locations within the species' climate envelope. Many climate processes did not affect population growth rates in the predicted direction based on range position. Processes such as species-interactions, local adaptation, and interactions with the physical landscape likely affect the responses we observed. Our work highlights the need to measure demographic responses to changing climate.

Navigating the pitfalls and promise of landscape genetics.

The field of landscape genetics has been evolving rapidly since its emergence in the early 2000s. New applications, techniques and criticisms of techniques appear like clockwork with each new journal issue. The developments are an encouraging, and at times bewildering, sign of progress in an exciting new field of study. However, we suggest that the rapid expansion of landscape genetics has belied important flaws in the development of the field, and we add an air of caution to this breakneck pace of expansion. Specifically, landscape genetic studies often lose sight of the fundamental principles and complex consequences of gene flow, instead favouring simplistic interpretations and broad inferences not necessarily warranted by the data. Here, we describe common pitfalls that characterize such studies, and provide practical guidance to improve landscape genetic investigation, with careful consideration of inferential limits, scale, replication, and the ecological and evolutionary context of spatial genetic patterns. Ultimately, the utility of landscape genetics will depend on translating the relationship between gene flow and landscape features into an understanding of long-term population outcomes. We hope the perspective presented here will steer landscape genetics down a more scientifically sound and productive path, garnering a field that is as informative in the future as it is popular now.

Multiple Paternity in the Norway Rat, Rattus norvegicus, from Urban Slums in Salvador, Brazil.

The Norway rat, Rattus norvegicus, is one of the most important pest species globally and the main reservoir of leptospires causing human leptospirosis in the urban slums of tropical regions. Rodent control is a frequent strategy in those settings to prevent the disease but rapid growth from residual populations and immigration limit the long-term effectiveness of interventions. To characterize the breeding ecology of R. norvegicus and provide needed information for the level of genetic mixing, which can help identify inter-connected eradication units, we estimated the occurrence of multiple paternity, distances between mothers and sires, and inbreeding in rats from urban slum habitat in Salvador, Brazil. We genotyped 9 pregnant females, their 66 offspring, and 371 males at 16 microsatellite loci. Multiple paternity was observed in 22% (2/9) of the study litters. Of the 12 sires that contributed to the 9 litters, we identified 5 (42%) of those sires among our genotyped males. Related males were captured in close proximity to pregnant females (the mean inter-parent trapping distance per litter was 70 m, ±58 m SD). Levels of relatedness between mother-sire pairs were higher than expected and significantly higher than relatedness between all females and non-sire males. Our findings indicate multiple paternity is common, inbreeding is apparent, and that mother-sire dyads occur in close proximity within the study area. This information is relevant to improve the spatial definition of the eradication units that may enhance the effectiveness of rodent management programs aimed at preventing human leptospirosis. High levels of inbreeding may also be a sign that eradication efforts are successful.

The evolution of foraging rate across local and geographic gradients in predation risk and competition.

Multiple theories predict the evolution of foraging rates in response to environmental variation in predation risk, intraspecific competition, time constraints, and temperature. We tested six hypotheses for the evolution of foraging rate in 24 spotted salamander (Ambystoma maculatum) populations from three latitudinally divergent sites using structural equation models derived from theory and applied to our system. We raised salamander larvae in a common-garden experiment and then assayed foraging rate under controlled conditions. Gape-limited predation risk from marbled salamanders solely explained foraging rate variation among populations at the southern site, which was dominated by this form of selection. However, at the middle and northern sites, populations evolved different foraging rates depending on their unique responses to local intraspecific density. The coupling of gape-limited predation risk from marbled salamanders and high intraspecific density at the middle site jointly contributed to selection for rapid foraging rate. At the northernmost site, intraspecific density alone explained 97% of the interpopulation variation in foraging rate. These results suggest that foraging rate has evolved multiple times in response to varying contributions from predation risk and intraspecific competition. Predation risk often varies along environmental gradients, and, thus, organisms might often shift evolutionary responses from minimizing predation risk to maximizing intraspecific competitive performance.

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study.

AIMS: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. METHODS: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. RESULTS: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. CONCLUSIONS: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING: Data were collected from the databases of six Teratology Information Services. PARTICIPANTS: This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS: Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS: This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. METHODS: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. RESULTS: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). CONCLUSIONS: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible.

First survey for the amphibian chytrid fungus Batrachochytrium dendrobatidis in Connecticut (USA) finds widespread prevalence.

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is an emerging infectious fungal pathogen of amphibians and is linked to global population declines. Until now, there has only been 1 survey for the fungus in the northeastern USA, which focused primarily on northern New England. We tested for Bd in a large number of samples (916 individuals from 116 sites) collected throughout the state of Connecticut, representing 18 native amphibian species. In addition, 239 preserved wood frog Lithobates sylvaticus tadpoles from throughout the state were screened for the fungus. Bd presence was assessed in both the fresh field swabs and the preserved samples using a sensitive quantitative PCR assay. Our contemporary survey found widespread Bd prevalence throughout Connecticut, occurring in 14 species and in 28% of all sampled animals. No preserved L. sylvaticus specimens tested positive for the fungus. Two common species, bullfrogs R. catesbeiana and green frogs R. clamitans had particularly high infection rates (0.21-0.39 and 0.33-0.42, respectively), and given their wide distribution throughout the state, we suggest they may serve as sentinels for Bd occurrence in this region. Further analyses found that several other factors increase the likelihood of infection, including life stage, host sex, and host family. Within sites, ponds with ranids, especially green frogs, increased the likelihood of Bd prevalence. By studying Bd in populations not facing mass declines, the results from this study are an important contribution to our understanding of how some amphibian species and populations remain infected yet exhibit no signs of chytridiomycosis even when Bd is widely distributed.

Monitoring the safety of COVID-19 vaccination in pregnancy in the UK: A national study using the UK Obstetric Surveillance System (UKOSS), UK Teratology Information Service (UKTIS) and Vaccination in Pregnancy (VIP) safety monitoring systems.

Background: COVID-19 vaccines are protective against disease. Pregnant women benefit from vaccination as they are at higher risk of poor maternal and neonatal outcomes following infection. Methods: Following regulatory approval of two COVID-19 vaccines in the United Kingdom, a rapid national study of vaccination in pregnancy was instituted using three existing safety surveillance platforms: UKOSS, UKTIS and VIP. This preliminary report describes the data collected up to the 15th June 2021. Results: There were 971 reports of COVID-19 vaccination in the UKOSS/UKTIS (n = 493) and VIP (n = 478) monitoring systems describing 908 individual pregnancies. Pfizer-BioNTech mRNA vaccination was most common (n = 501, 55.2%), most women were vaccinated in their second or third trimester (n = 566, 62.3%), and were mainly vaccinated due to occupational infection risk (n = 577, 63.5%). Conclusion: Obstetric outcome data will be obtained by December 2021. However, women should not delay vaccination whilst awaiting further safety data to emerge.

Core Data Elements for Pregnancy Pharmacovigilance Studies Using Primary Source Data Collection Methods: Recommendations from the IMI ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The risks and benefits of medication use in pregnancy are typically established through post-marketing observational studies. As there is currently no standardised or systematic approach to the post-marketing assessment of medication safety in pregnancy, data generated through pregnancy pharmacovigilance (PregPV) research can be heterogenous and difficult to interpret. The aim of this article is to describe the development of a reference framework of core data elements (CDEs) for collection in primary source PregPV studies that can be used to standardise data collection procedures and, thereby, improve data harmonisation and evidence synthesis capabilities. METHODS: This CDE reference framework was developed within the Innovative Medicines Initiative (IMI) ConcePTION project by experts in pharmacovigilance, pharmacoepidemiology, medical statistics, risk-benefit communication, clinical teratology, reproductive toxicology, genetics, obstetrics, paediatrics, and child psychology. The framework was produced through a scoping review of data collection systems used by established PregPV datasets, followed by extensive discussion and debate around the value, definition, and derivation of each data item identified from these systems. RESULTS: The finalised listing of CDEs comprises 98 individual data elements, arranged into 14 tables of related fields. These data elements are openly available on the European Network of Teratology Information Services (ENTIS) website ( http://www.entis-org.eu/cde ). DISCUSSION: With this set of recommendations, we aim to standardise PregPV primary source data collection processes to improve the speed at which high-quality evidence-based statements can be provided about the safety of medication use in pregnancy.

Divergent landscape effects on population connectivity in two co-occurring amphibian species.

The physical and environmental attributes of landscapes often shape patterns of population connectivity by influencing dispersal and gene flow. Landscape effects on movement are typically evaluated for single species. However, inferences from multiple species are required for multi-species management strategies increasingly being applied in conservation. In this study, I compared the spatial genetic patterns of two amphibian species across the northeastern United States and estimated the influence of specific landscape features on the observed genetic structure. The spotted salamander (Ambystoma maculatum) and wood frog (Rana sylvatica) share many ecological attributes related to habitat use, phenology and site fidelity. However, I hypothesized that important differences in their movement patterns and life history would create distinct genetic patterns for each species. Using 14 microsatellite loci, I tested for differences in the level of genetic differentiation between the two species across 22 breeding ponds. The effects of eight landscape features were also estimated by evaluating 32 landscape resistance models. Spotted salamanders exhibited significantly higher genetic differentiation than wood frogs. Different landscape features were also identified as potential drivers of the genetic patterns in each species, with little overlap in model support between species. Collectively, these results provide strong evidence that these two amphibian species interact with the landscape in measurably different ways. The distinct genetic patterns observed are consistent with key differences in movement ability and life history between A. maculatum and R. sylvatica. These results highlight the importance of considering more than one species when assessing the impacts of the landscape matrix on population connectivity, even for ecologically similar species within the same habitats.

Asynchrony, density dependence, and persistence in an amphibian.

Understanding drivers of metapopulation dynamics remains a critical challenge for ecology and conservation. In particular, the degree of synchrony in metapopulation dynamics determines how resilient a metapopulation is to a widespread disturbance. In this study, we used 21 years of egg mass count data across 64 nonpermanent freshwater ponds in Connecticut, USA to evaluate patterns of abundance and growth and to assess regional as well as local factors in shaping the population dynamics of wood frogs (Rana sylvatica = Lithobates sylvaticus). In particular, we asked whether a species known to undergo metapopulation dynamics exhibited spatial synchrony in abundances. With the exception of a single year when breeding took place during severe drought conditions, our analyses revealed no evidence of synchrony despite close proximity (mean minimum distance < 300 m) of breeding ponds across the 3213-ha study area. Instead, local, pond-scale conditions best predicted patterns of abundance and population growth rate. We found negative density dependence on population growth rate within ponds as well as evidence that larger neighboring pond populations had a negative effect on focal ponds. Beyond density, pond depth was a critical predictor; deeper ponds supported larger populations. Drought conditions and warm winters negatively affected populations. Overall, breeding ponds vary in critical ways that either support larger, more persistent populations or smaller populations that are not represented by breeding pairs in some years. The infrequency of spatial synchrony in this system is surprising and suggests greater resilience to stressors than would have been expected if dynamics were strongly synchronized. More generally, understanding the characteristics of systems that determine synchronous population dynamics will be critical to predicting which species are more or less resilient to widespread disturbances like land conversion or climate change.

Dispersal ability predicts spatial genetic structure in native mammals persisting across an urbanization gradient.

As the rate of urbanization continues to increase globally, a growing body of research is emerging that investigates how urbanization shapes the movement-and consequent gene flow-of species in cities. Of particular interest are native species that persist in cities, either as small relict populations or as larger populations of synanthropic species that thrive alongside humans in new urban environments. In this study, we used genomic sequence data (SNPs) and spatially explicit individual-based analyses to directly compare the genetic structure and patterns of gene flow in two small mammals with different dispersal abilities that occupy the same urbanized landscape to evaluate how mobility impacts genetic connectivity. We collected 215 white-footed mice (Peromyscus leucopus) and 380 big brown bats (Eptesicus fuscus) across an urban-to-rural gradient within the Providence, Rhode Island (U.S.A.) metropolitan area (population =1,600,000 people). We found that mice and bats exhibit clear differences in their spatial genetic structure that are consistent with their dispersal abilities, with urbanization having a stronger effect on Peromyscus mice. There were sharp breaks in the genetic structure of mice within the Providence urban core, as well as reduced rates of migration and an increase in inbreeding with more urbanization. In contrast, bats showed very weak genetic structuring across the entire study area, suggesting a near-panmictic gene pool likely due to the ability to disperse by flight. Genetic diversity remained stable for both species across the study region. Mice also exhibited a stronger reduction in gene flow between island and mainland populations than bats. This study represents one of the first to directly compare multiple species within the same urban-to-rural landscape gradient, an important gap to fill for urban ecology and evolution. Moreover, here we document the impacts of dispersal capacity on connectivity for native species that have persisted as the urban landscape matrix expands.