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275 result(s) for "Richardson, Jonathan L."
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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
ObjectivesGlucagon-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.DesignThis 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.SettingData were collected from the databases of six Teratology Information Services.ParticipantsThis 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.ResultsExposure 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.ConclusionsThis 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.
Road ecology: shifting gears toward evolutionary perspectives
Recent advances in understanding the often rapid pace of evolution are reshaping our view of organisms and their capacity to cope with environmental change. Though evolutionary perspectives have gained traction in many fields of conservation, road ecology is not among them. This is surprising because roads are pervasive landscape features that generate intense natural selection. The biological outcomes from these selection pressures – whether adaptive or maladaptive – can have profound consequences for population persistence. We argue that studying evolutionary responses is critical to accurately understand the impacts of roads. Toward that end, we describe the basic tenets and relevance of contemporary evolution and showcase the few examples where it has been documented in road ecology. We outline practical ways that road ecologists can estimate and interpret evolutionary responses in their research. Finally, we suggest priority research topics and discuss how evolutionary insights can inform conservation in landscapes traversed by roads.
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.
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.
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.
Pregabalin Safety in Pregnancy: A Disproportionality Analysis of VigiBase Spontaneous Reporting System
Background/Objectives: Some product information on pregabalin suggests a potential risk for congenital anomalies (CAs), although evidence remains inconsistent and lacks clear patterns. This study aimed to provide additional safety information on pregabalin use in pregnancy by analyzing VigiBase, the World Health Organization’s global pharmacovigilance database of individual case safety reports (ICSRs). Methods: The analysis included de-duplicated ICSRs related to pregabalin exposure in pregnancy, collected up to 16 January 2024. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for CA categories reported in at least 10 ICSRs, with a statistical threshold defined as a 95% CI lower bound > 1. Results: Among 410 ICSRs, the majority originated from Europe (64.8%) and North America (26.5%). Of these, 59 (14.4%) ICSRs documented only pregabalin exposure in pregnancy, while 351 (85.6%) also reported adverse events in pregnancy. CAs occurred in 82 ICSRs (23.3%), most commonly involving heart defects (30), nervous system anomalies (18), and limb anomalies (12). No signals of disproportionate reporting were identified for these categories compared to the full database (heart defects: ROR 0.587, 95% CI 0.410–0.839; nervous system anomalies: ROR 0.588, 95% CI 0.370–0.933; limb anomalies: ROR 0.671, 95% CI 0.381–1.183). Conclusions: Future disproportionality analyses, along with pharmacovigilance and pharmacoepidemiological studies using patient registries and large-scale collaborative projects, are essential for the ongoing monitoring of pregabalin safety in pregnancy.
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.
Using fine‐scale spatial genetics of Norway rats to improve control efforts and reduce leptospirosis risk in urban slum environments
The Norway rat (Rattus norvegicus) is a key pest species globally and responsible for seasonal outbreaks of the zoonotic bacterial disease leptospirosis in the tropics. The city of Salvador, Brazil, has seen recent and dramatic increases in human population residing in slums, where conditions foster high rat density and increasing leptospirosis infection rates. Intervention campaigns have been used to drastically reduce rat numbers. In planning these interventions, it is important to define the eradication units ‐ the spatial scale at which rats constitute continuous populations and from where rats are likely recolonizing, post‐intervention. To provide this information, we applied spatial genetic analyses to 706 rats collected across Salvador and genotyped at 16 microsatellite loci. We performed spatially explicit analyses and estimated migration levels to identify distinct genetic units and landscape features associated with genetic divergence at different spatial scales, ranging from valleys within a slum community to city‐wide analyses. Clear genetic breaks exist between rats not only across Salvador but also between valleys of slums separated by <100 m—well within the dispersal capacity of rats. The genetic data indicate that valleys may be considered separate units and identified high‐traffic roads as strong impediments to rat movement. Migration data suggest that most (71–90%) movement is contained within valleys, with no clear source population contributing to migrant rats. We use these data to recommend eradication units and discuss the importance of carrying out individual‐based analyses at different spatial scales in urban landscapes.
Rats and the COVID-19 pandemic: considering the influence of social distancing on a global commensal pest
Rats contaminate foods and spread pathogens. Thus, changes in rat populations have consequences for society, especially in densely-populated cities. Following widespread social distancing and lockdown measures to curtail SARS-CoV-2, worldwide media outlets reported increased sightings of rats. To document possible changes in rat populations, we: (i) examined public service requests in the 6 years before, and during, ‘lockdown’ in New York City; (ii) used spatial analyses to identify calls in proximity to food service establishments (FSE); and (iii) surveyed pest-management companies. Over 6 years prior to the pandemic, we found a consistent moderate spatial association (r = 0.35) between FSE and rat-related calls. During the early stages of the pandemic, the association between rat reports and food services did not decrease as would be expected by restaurant closures, but instead modestly increased (r = 0.45). There was a 29.5% decrease in rat reports, overall. However, hotspot analysis showed that new reports were highly localized, yet absent in several industrial areas they were previously observed in, potentially masking a higher proportion of calls in neighborhoods near closed restaurants. Additionally, 37% of pest management companies surveyed reported that, unlike previous years, 50–100% of requests were from new clients and addresses. The finding that hotspots remained nearby dense clusters of restaurants does not support the common narrative that rats moved long distances. Rather, our results are consistent with rats finding nearby alternative food resources. Tracking these dynamics as the COVID-19 pandemic abates will be an important step to identifying how rats respond to society returning to normal activity patterns.
Plasticity and genetic adaptation mediate amphibian and reptile responses to climate change
Phenotypic plasticity and genetic adaptation are predicted to mitigate some of the negative biotic consequences of climate change. Here, we evaluate evidence for plastic and evolutionary responses to climate variation in amphibians and reptiles via a literature review and meta‐analysis. We included studies that either document phenotypic changes through time or space. Plasticity had a clear and ubiquitous role in promoting phenotypic changes in response to climate variation. For adaptive evolution, we found no direct evidence for evolution of amphibians or reptiles in response to climate change over time. However, we found many studies that documented adaptive responses to climate along spatial gradients. Plasticity provided a mixture of adaptive and maladaptive responses to climate change, highlighting that plasticity frequently, but not always, could ameliorate climate change. Based on our review, we advocate for more experiments that survey genetic changes through time in response to climate change. Overall, plastic and genetic variation in amphibians and reptiles could buffer some of the formidable threats from climate change, but large uncertainties remain owing to limited data.