A protocol for the safe recruitment of Indigenous and Black women experiencing intimate partner violence during the COVID-19 pandemic into a large mixed methods study: The Sisters by Choice Study.

Intimate partner violence (IPV) is a complex and pervasive public health problem disproportionately affecting Indigenous and Black women. During the COVID-19 pandemic, IPV became more complicated for advocates because social distancing, quarantine, and isolation measures further endangered women experiencing IPV. This manuscript is based on an ongoing community-engaged study in an upper Midwestern state. Our primary goal for this study is to generate urgently needed knowledge on the impact of the COVID-19 pandemic on Indigenous and Black women's help-seeking behaviours following IPV by systematically documenting barriers women faced during the pandemic. Engaging women in a large study that seeks to garner information about their experiences of violence is complex and challenging and requires significant planning, especially for ensuring participants' safety. In this write-up, we detail the safety planning protocol developed for the purposes of recruiting and engaging women in rural and urban areas in an upper Midwestern state in the United States. Our goal is to provide scholars conducting research in the area of violence with practical considerations for safely conducting a study of this nature.

Using Computational Simulations to Model Deleterious Variation and Genetic Load in Natural Populations.

AbstractDeleterious genetic variation is abundant in wild populations, and understanding the ecological and conservation implications of such variation is an area of active research. Genomic methods are increasingly used to quantify the impacts of deleterious variation in natural populations; however, these approaches remain limited by an inability to accurately predict the selective and dominance effects of mutations. Computational simulations of deleterious variation offer a complementary tool that can help overcome these limitations, although such approaches have yet to be widely employed. In this perspective article, we aim to encourage ecological and conservation genomics researchers to adopt greater use of computational simulations to aid in deepening our understanding of deleterious variation in natural populations. We first provide an overview of the components of a simulation of deleterious variation, describing the key parameters involved in such models. Next, we discuss several approaches for validating simulation models. Finally, we compare and validate several recently proposed deleterious mutation models, demonstrating that models based on estimates of selection parameters from experimental systems are biased toward highly deleterious mutations. We describe a new model that is supported by multiple orthogonal lines of evidence and provide example scripts for implementing this model (https://github.com/ckyriazis/simulations_review).

Evolution of the Mutation Spectrum Across a Mammalian Phylogeny.

Although evolutionary biologists have long theorized that variation in DNA repair efficacy might explain some of the diversity of lifespan and cancer incidence across species, we have little data on the variability of normal germline mutagenesis outside of humans. Here, we shed light on the spectrum and etiology of mutagenesis across mammals by quantifying mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility and k-mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clock-like mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these signatures to fit each species' 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the 1-mer spectrum's phylogenetic signal in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.

The genomic footprint of whaling and isolation in fin whale populations.

Twentieth century industrial whaling pushed several species to the brink of extinction, with fin whales being the most impacted. However, a small, resident population in the Gulf of California was not targeted by whaling. Here, we analyzed 50 whole-genomes from the Eastern North Pacific (ENP) and Gulf of California (GOC) fin whale populations to investigate their demographic history and the genomic effects of natural and human-induced bottlenecks. We show that the two populations diverged ~16,000 years ago, after which the ENP population expanded and then suffered a 99% reduction in effective size during the whaling period. In contrast, the GOC population remained small and isolated, receiving less than one migrant per generation. However, this low level of migration has been crucial for maintaining its viability. Our study exposes the severity of whaling, emphasizes the importance of migration, and demonstrates the use of genome-based analyses and simulations to inform conservation strategies.

"Evolution of the mutation spectrum across a mammalian phylogeny".

Little is known about how the spectrum and etiology of germline mutagenesis might vary among mammalian species. To shed light on this mystery, we quantify variation in mutational sequence context biases using polymorphism data from thirteen species of mice, apes, bears, wolves, and cetaceans. After normalizing the mutation spectrum for reference genome accessibility and k -mer content, we use the Mantel test to deduce that mutation spectrum divergence is highly correlated with genetic divergence between species, whereas life history traits like reproductive age are weaker predictors of mutation spectrum divergence. Potential bioinformatic confounders are only weakly related to a small set of mutation spectrum features. We find that clocklike mutational signatures previously inferred from human cancers cannot explain the phylogenetic signal exhibited by the mammalian mutation spectrum, despite the ability of these clocklike signatures to fit each species' 3-mer spectrum with high cosine similarity. In contrast, parental aging signatures inferred from human de novo mutation data appear to explain much of the mutation spectrum's phylogenetic signal when fit to non-context-dependent mutation spectrum data in combination with a novel mutational signature. We posit that future models purporting to explain the etiology of mammalian mutagenesis need to capture the fact that more closely related species have more similar mutation spectra; a model that fits each marginal spectrum with high cosine similarity is not guaranteed to capture this hierarchy of mutation spectrum variation among species.

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Deleterious Variation in Natural Populations and Implications for Conservation Genetics.

Deleterious mutations decrease reproductive fitness and are ubiquitous in genomes. Given that many organisms face ongoing threats of extinction, there is interest in elucidating the impact of deleterious variation on extinction risk and optimizing management strategies accounting for such mutations. Quantifying deleterious variation and understanding the effects of population history on deleterious variation are complex endeavors because we do not know the strength of selection acting on each mutation. Further, the effect of demographic history on deleterious mutations depends on the strength of selection against the mutation and the degree of dominance. Here we clarify how deleterious variation can be quantified and studied in natural populations. We then discuss how different demographic factors, such as small population size, nonequilibrium population size changes, inbreeding, and gene flow, affect deleterious variation. Lastly, we provide guidance on studying deleterious variation in nonmodel populations of conservation concern.

Effect of the Cyberattack Targeting the Irish Health System in May 2021 on Radiation Treatment at St. Luke's Radiation Oncology Network.

On May 14, 2021, the Health Service Executive (HSE) of Ireland experienced a major ransomware cyberattack. The HSE initially took down all of its information technology systems to protect its core systems. All Internet connections within the HSE were unavailable from 7 am for approximetely three weeks which had a major effect on the radiation oncology service nationally within the public service. St. Luke's Radiation Oncology Network (SLRON) is a complex, 3-center radiation oncology service, and it is the largest in the country; with 14 linear accelerators, it is one of the largest radiation centers in Europe. This article details the response of SLRON to the outage resultant from the cyberattack. Although the outage affected all patient services, including laboratory, diagnostic imaging, and inpatient care, the article primarily focuses on our response to get the radiation oncology service restarted as quickly as possible and details the steps we took to reinstate our systems safely, how we prioritized patient treatments, and how we communicated with patients, staff, and the public without having access to standard communication pathways. All decisions were risk assessed and were made with the best resources available to us at the time to maximize the outcome for our patients and mitigate significant delays. The risk remains ongoing, and the onerous task of uploading backlogs and reconciling patient records is a continuing risk.

Selection against admixture and gene regulatory divergence in a long-term primate field study.

Genetic admixture is central to primate evolution. We combined 50 years of field observations of immigration and group demography with genomic data from ~9 generations of hybrid baboons to investigate the consequences of admixture in the wild. Despite no obvious fitness costs to hybrids, we found signatures of selection against admixture similar to those described for archaic hominins. These patterns were concentrated near genes where ancestry is strongly associated with gene expression. Our analyses also show that introgression is partially predictable across the genome. This study demonstrates the value of integrating genomic and field data for revealing how "genomic signatures of selection" (e.g., reduced introgression in low-recombination regions) manifest in nature; moreover, it underscores the importance of other primates as living models for human evolution.

The critically endangered vaquita is not doomed to extinction by inbreeding depression.

In cases of severe wildlife population decline, a key question is whether recovery efforts will be impeded by genetic factors, such as inbreeding depression. Decades of excess mortality from gillnet fishing have driven Mexico's vaquita porpoise (Phocoena sinus) to ~10 remaining individuals. We analyzed whole-genome sequences from 20 vaquitas and integrated genomic and demographic information into stochastic, individual-based simulations to quantify the species' recovery potential. Our analysis suggests that the vaquita's historical rarity has resulted in a low burden of segregating deleterious variation, reducing the risk of inbreeding depression. Similarly, genome-informed simulations suggest that the vaquita can recover if bycatch mortality is immediately halted. This study provides hope for vaquitas and other naturally rare endangered species and highlights the utility of genomics in predicting extinction risk.

Response to Bakker et al.

Robinson and colleagues respond to the points raised about their paper by Bakker et al.

High-Resolution Estimates of Crossover and Noncrossover Recombination from a Captive Baboon Colony.

Homologous recombination has been extensively studied in humans and a handful of model organisms. Much less is known about recombination in other species, including nonhuman primates. Here, we present a study of crossovers (COs) and noncrossover (NCO) recombination in olive baboons (Papio anubis) from two pedigrees containing a total of 20 paternal and 17 maternal meioses, and compare these results to linkage disequilibrium (LD) based recombination estimates from 36 unrelated olive baboons. We demonstrate how COs, combined with LD-based recombination estimates, can be used to identify genome assembly errors. We also quantify sex-specific differences in recombination rates, including elevated male CO and reduced female CO rates near telomeres. Finally, we add to the increasing body of evidence suggesting that while most NCO recombination tracts in mammals are short (e.g., <500 bp), there is a non-negligible fraction of longer (e.g., >1 kb) NCO tracts. For NCO tracts shorter than 10 kb, we fit a mixture of two (truncated) geometric distributions model to the NCO tract length distribution and estimate that >99% of all NCO tracts are very short (mean 24 bp), but the remaining tracts can be quite long (mean 4.3 kb). A single geometric distribution model for NCO tract lengths is incompatible with the data, suggesting that LD-based methods for estimating NCO recombination rates that make this assumption may need to be modified.

Genome-wide diversity in the California condor tracks its prehistoric abundance and decline.

Due to their small population sizes, threatened and endangered species frequently suffer from a lack of genetic diversity, potentially leading to inbreeding depression and reduced adaptability.1 During the latter half of the twentieth century, North America's largest soaring bird,2 the California condor (Gymnogyps californianus; Critically Endangered3), briefly went extinct in the wild. Though condors once ranged throughout North America, by 1982 only 22 individuals remained. Following decades of captive breeding and release efforts, there are now >300 free-flying wild condors and ∼200 in captivity. The condor's recent near-extinction from lead poisoning, poaching, and loss of habitat is well documented,4 but much about its history remains obscure. To fill this gap and aid future management of the species, we produced a high-quality chromosome-length genome assembly for the California condor and analyzed its genome-wide diversity. For comparison, we also examined the genomes of two close relatives: the Andean condor (Vultur gryphus; Vulnerable3) and the turkey vulture (Cathartes aura; Least Concern3). The genomes of all three species show evidence of historic population declines. Interestingly, the California condor genome retains a high degree of variation, which our analyses reveal is a legacy of its historically high abundance. Correlations between genome-wide diversity and recombination rate further suggest a history of purifying selection against linked deleterious alleles, boding well for future restoration. We show how both long-term evolutionary forces and recent inbreeding have shaped the genome of the California condor, and provide crucial genomic resources to enable future research and conservation.

Reference genome and demographic history of the most endangered marine mammal, the vaquita.

The vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline for more than 20 years resulting from inadvertent deaths due to the increasing use of large-mesh gillnets. To understand the evolutionary and demographic history of the vaquita, we used combined long-read sequencing and long-range scaffolding methods with long- and short-read RNA sequencing to generate a near error-free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome-length autosome scaffolds and the X-chromosome scaffold, with a scaffold N50 of 115 Mb. Genome-wide heterozygosity is the lowest (0.01%) of any mammalian species analysed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long-term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long-term population stability at less than 5,000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health.

Yes and! Actor Improvisation Enhances Psychiatric-Mental Health Nursing Education.

ABSTRACT: Based on a comparative dearth of simulation products to support the attainment of key skills in psychiatric-mental health nursing, the authors developed scripted scenarios to provide students with exposure to low-incidence/high-risk simulated clinical scenarios in the classroom setting. Acting students from the university's theater school were provided with character sketches and information on psychopathology-psychopharmacology to add a sense of authenticity to the performances. In turn, students questioned the actor-patients in character. The actor-patients employed the improvisational technique of "yes…and" to further develop their characters and provide deeper opportunities for faculty-student engagement and psychiatric-mental health nursing skills development.

Accurate assembly of the olive baboon (Papio anubis) genome using long-read and Hi-C data.

BACKGROUND: Baboons are a widely used nonhuman primate model for biomedical, evolutionary, and basic genetics research. Despite this importance, the genomic resources for baboons are limited. In particular, the current baboon reference genome Panu_3.0 is a highly fragmented, reference-guided (i.e., not fully de novo) assembly, and its poor quality inhibits our ability to conduct downstream genomic analyses. FINDINGS: Here we present a de novo genome assembly of the olive baboon (Papio anubis) that uses data from several recently developed single-molecule technologies. Our assembly, Panubis1.0, has an N50 contig size of ∼1.46 Mb (as opposed to 139 kb for Panu_3.0) and has single scaffolds that span each of the 20 autosomes and the X chromosome. CONCLUSIONS: We highlight multiple lines of evidence (including Bionano Genomics data, pedigree linkage information, and linkage disequilibrium data) suggesting that there are several large assembly errors in Panu_3.0, which have been corrected in Panubis1.0.

A Genome-Wide Perspective on the Persistence of Red Wolf Ancestry in Southeastern Canids.

The red wolf (Canis rufus), a legally recognized and critically endangered wolf, is known to interbreed with coyotes (Canis latrans). Declared extirpated in the wild in 1980, red wolves were reintroduced to northeastern North Carolina nearly a decade later. Interbreeding with coyotes was thought to be restricted to a narrow geographic region adjacent to the reintroduced population and largely believed to threaten red wolf recovery. However, red wolf ancestry was recently discovered in canids along the American Gulf Coast, igniting a broader survey of ancestry in southeastern canid populations. Here, we examine geographic and temporal patterns of genome-wide red wolf ancestry in 260 canids across the southeastern United States at over 164 000 SNP loci. We found that red wolf ancestry was most prevalent in canids sampled from Texas in the mid-1970s, although non-trivial amounts of red wolf ancestry persist in this region today. Further, red wolf ancestry was also observed in a subset of coyotes inhabiting North Carolina, despite management efforts to limit the occurrence of hybridization events. Lastly, we found no evidence of substantial red wolf ancestry in southeastern canids outside of these 2 admixture zones. Overall, this study provides a genome-wide survey of red wolf ancestry in canids across the southeastern United States, which may ultimately inform future red wolf restoration efforts.