The ancestry and geographical origins of St Helena's liberated Africans.

The island of St Helena played a crucial role in the suppression of the transatlantic slave trade. Strategically located in the middle of the South Atlantic, it served as a staging post for the Royal Navy and reception point for enslaved Africans who had been "liberated" from slave ships intercepted by the British. In total, St Helena received approximately 27,000 liberated Africans between 1840 and 1867. Written sources suggest that the majority of these individuals came from West Central Africa, but their precise origins are unknown. Here, we report the results of ancient DNA analyses that we conducted as part of a wider effort to commemorate St Helena's liberated Africans and to restore knowledge of their lives and experiences. We generated partial genomes (0.1-0.5×) for 20 individuals whose remains had been recovered during archaeological excavations on the island. We compared their genomes with genotype data for over 3,000 present-day individuals from 90 populations across sub-Saharan Africa and conclude that the individuals most likely originated from different source populations within the general area between northern Angola and Gabon. We also find that the majority (17/20) of the individuals were male, supporting a well-documented sex bias in the latter phase of the transatlantic slave trade. The study expands our understanding of St Helena's liberated African community and illustrates how ancient DNA analyses can be used to investigate the origins and identities of individuals whose lives were bound up in the story of slavery and its abolition.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Craniofacial and dental features in children aged 3-5 years with congenital Zika syndrome.

OBJECTIVE: Zika virus infection has been associated to congenital zika syndrome (CZS) in newborns and is characterized by microcephaly, central/axial motor and sensory dysfunction, dysphagia among other previously described severe health complications. CZS is usually diagnosed postpartum by evident/apparent neural development problems. Although there are some reports of craniofacial/dentition development in CZS, several clinical oral aspects are still unknown. This study describes some structural and functional characteristics of facial and cranial growth and deciduous dentition in CZS-affected children. MATERIAL AND METHODS: Some cranial, facial and dental characteristics were determined in 14 children with CZS aged 3-5 years and compared them against 12 apparently healthy children paired by age and gender. RESULTS: Fourteen CZS cases presented microcephaly, maxillary prognathism, altered facial thirds, asymmetric pupillary line, bruxism (p = 0.006), deep and anterior open bite and distal step decidual molar relationship (p = 0.031). CZS children cannot feed by themselves and most cannot walk and have not develop coordinated and intelligible language according to their chronological age. In contrast, controls presented normal skull features, have autonomous locomotion skills, speak intelligible language, feed by themselves, presented a harmonic intermaxillary relationship and have symmetrical facial thirds. CONCLUSION: Microcephaly, dysphagia, bruxism, mandibular retrognathia, altered facial proportions and malocclusion are the main craniofacial and oral features at CZS. CLINICAL RELEVANCE: The complications of CZS including those related with the face and the oral cavity are still being identified. This study revealed some cranial, facial and oral features in children affected by CSZ. Interdisciplinary rehabilitation protocols must address these syndromic features that could improve children and parents living conditions.

Imputation of ancient human genomes.

Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel's rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.

Device-associated infections in neonatal care units in a middle-income country, 2016-2018.

OBJECTIVE: Describe the device-associated infections in the NICUs in Cali - Colombia, a middle-income country, between August 2016 to December 2018. METHODS: Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR CI95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. RESULTS: 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53-8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33-7.06, p = 0.008). CONCLUSIONS: These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.

Mapache: a flexible pipeline to map ancient DNA.

SUMMARY: We introduce mapache, a flexible, robust and scalable pipeline to map, quantify and impute ancient and present-day DNA in a reproducible way. Mapache is implemented in the workflow manager Snakemake and is optimized for low-space consumption, allowing to efficiently (re)map large datasets-such as reference panels and multiple extracts and libraries per sample - to one or several genomes. Mapache can easily be customized or combined with other Snakemake tools. AVAILABILITY AND IMPLEMENTATION: Mapache is freely available on GitHub (https://github.com/sneuensc/mapache). An extensive manual is provided at https://github.com/sneuensc/mapache/wiki. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Device-associated infections in neonatal care units in a middle-income country, 2016-2018

Abstract Objective: Describe the device-associated infections in the NICUs in Cali - Colombia, a middle-income country, between August 2016 to December 2018. Methods: Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR Cl95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16. Results: 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53-8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33-7.06, p = 0.008). Conclusions: These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used.

Use of polymyxins for carbapenem-resistant infections in children and adolescents.

Background: Polymyxins are still used in children in some regions due to limited availability of newer antibiotics. Objectives: To describe our experience in a cohort of children who received polymyxins for suspected or confirmed carbapenem-resistant bacterial infections (CRI), and explore potential factors associated with therapeutic success. Methods: Retrospective, observational study in children and adolescents <18 years who received IV polymyxin B or colistin therapy for suspected or culture-documented CRI and were admitted to a high complexity clinic in Cali, Colombia between 1 September 2016 and 22 June 2020. Patients' demographic, clinical and microbiological characteristics were collected and analysed; associations with therapeutic success were explored using univariate and multivariate models. Results: There were 40 episodes of polymyxin use (polymyxin B, n = 34; colistin, n = 6) in 34 patients with a median age of 10 years (IQR 7-15); 65% were male. There were 17 adverse events: 3 (17.6%) neurotoxic and 14 (82.4%) nephrotoxic. Therapeutic success was achieved in 28 episodes (70%), of which 32% (9/28) had adverse events. Therapeutic success decreased by 35% with each additional year of age (OR 0.65; 95% CI 0.49-0.80) and by 7% for every hour that elapsed between the onset of fever and the start of appropriate antibiotic therapy (OR 0.93; 95% CI 0.8-0.97) and increased with concomitant non-carbapenem treatment (OR 6.87; 95% CI 1.04-71.01) and the use of adequate empirical therapy (OR 121.36; 95% CI 2.90-1147.95). Conclusions: Several factors were associated with the therapeutic success of polymyxins, however, more than half of episodes had therapeutic failure or adverse events. Antibiotics with greater efficacy and safety are needed in regions with high rates of CRI.

Etiology and Risk Factors for Admission to the Pediatric Intensive Care Unit in Children With Encephalitis in a Developing Country.

OBJECTIVE: To describe a cohort of pediatric patients with encephalitis and their risk factors for admission to the pediatric intensive care unit (PICU). STUDY DESIGN: Children (<18 years old), with encephalitis evaluated by conventional microbiology and syndromic, multiplex test in cerebrospinal fluid (CSF) between July 2017 and July 2020, were recruited from 14 hospitals that comprise the Colombian Network of Encephalitis in Pediatrics. Multivariate analyses were used to evaluate risk factors associated with the need for PICU admission. RESULTS: Two hundred two children were included, of which 134 (66.3%) were male. The median age was 23 months (IQR 5.7-73.2). The main etiologies were bacteria (n = 55, 27%), unspecified viral encephalitis (n = 44, 22%) and enteroviruses (n = 27, 13%), with variations according to age group. Seventy-eight patients (38.6%) required management in the PICU. In multivariate analysis, factors associated with admission to the PICU were the presence of generalized seizures (OR 2.73; 95% CI: 1.82-4.11), status epilepticus (OR 3.28; 95% CI: 2.32-4.62) and low leukocyte counts in the CSF (OR 2.86; 95% CI: 1.47-5.57). Compared with enterovirus, bacterial etiology (OR 7.50; 95% CI: 1.0-56.72), herpes simplex encephalitis (OR 11.81; 95% CI: 1.44-96.64), autoimmune encephalitis (OR 22.55; 95% CI: 3.68-138.16) and other viral infections (OR 5.83; 95% CI: 1.09-31.20) increased the risk of PICU admission. CONCLUSIONS: Data from this national collaborative network of pediatric patients with encephalitis allow early identification of children at risk of needing advanced care and can guide the risk stratification of admission to the PICU.

Factors Associated With Hospitalization or Intensive Care Admission in Children With COVID-19 in Latin America.

Background: Limited data is available from low-middle and upper-middle income countries of the factors associated with hospitalization or admission to pediatric intensive care unit (PICU) for children with COVID-19. Objective: To describe the factors associated with hospitalization or PICU admission of children with COVID-19 in Latin America. Method: Multicenter, analytical, retrospective study of children reported from 10 different Latin American countries to the Latin-American Society of Pediatric Infectious Diseases (SLIPE-COVID) research network from June 1, 2020, and February 28, 2021. Outpatient or hospitalized children <18 years of age with COVID-19 confirmed by polymerase chain reaction or antigen detection from the nasopharynx were included. Children with multisystem inflammatory syndrome in children (MIS-C) were excluded. Associations were assessed using univariate and multivariable logistic regression models. Results: A total of 1063 children with COVID-19 were included; 500 (47%) hospitalized, with 419 (84%) to the pediatric wards and 81 (16%) to the ICU. In multivariable analyses, age <1 year (Odds Ratio [OR] 1.78; 95% CI 1.08-2.94), native race (OR 5.40; 95% CI 2.13-13.69) and having a co-morbid condition (OR 5.3; 95% CI 3.10-9.15), were associated with hospitalization. Children with metabolic or endocrine disorders (OR 4.22; 95% CI 1.76-10.11), immune deficiency (1.91; 95% CI 1.05-3.49), preterm birth (OR 2.52; 95% CI 1.41-4.49), anemia at presentation (OR 2.34; 95% CI 1.28-4.27), radiological peribronchial wall thickening (OR 2.59; 95% CI 1.15-5.84) and hypoxia, altered mental status, seizures, or shock were more likely to require PICU admission. The presence of pharyngitis (OR 0.34; 95% CI 0.25-0.48); myalgia (OR 0.47; 95% CI 0.28-0.79) or diarrhea (OR 0.38; 95% CI 0.21-0.67) were inversely associated with hospital admission. Conclusions: In this data analysis reported to the SLIPE research network in Latin America, infants, social inequalities, comorbidities, anemia, bronchial wall thickening and specific clinical findings on presentation were associated with higher rates of hospitalization or PICU admission. This evidence provides data for prioritization prevention and treatment strategies for children suffering from COVID-19.

The genomic history of the Aegean palatial civilizations.

The Cycladic, the Minoan, and the Helladic (Mycenaean) cultures define the Bronze Age (BA) of Greece. Urbanism, complex social structures, craft and agricultural specialization, and the earliest forms of writing characterize this iconic period. We sequenced six Early to Middle BA whole genomes, along with 11 mitochondrial genomes, sampled from the three BA cultures of the Aegean Sea. The Early BA (EBA) genomes are homogeneous and derive most of their ancestry from Neolithic Aegeans, contrary to earlier hypotheses that the Neolithic-EBA cultural transition was due to massive population turnover. EBA Aegeans were shaped by relatively small-scale migration from East of the Aegean, as evidenced by the Caucasus-related ancestry also detected in Anatolians. In contrast, Middle BA (MBA) individuals of northern Greece differ from EBA populations in showing ∼50% Pontic-Caspian Steppe-related ancestry, dated at ca. 2,600-2,000 BCE. Such gene flow events during the MBA contributed toward shaping present-day Greek genomes.

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial.

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.

Methylation Status of GLP2R, LEP and IRS2 in Small for Gestational Age Children with and without Catch-up Growth

Objective: In small for gestational age (SGA) children, catch-up growth could be influenced by methylation of several genes involved in metabolism. Epigenetics may influence the development of metabolic diseases in adulthood. To compare the methylation of leptin (LEP), glucagon-like peptide-2 receptor (GLP2R), insulin receptor substrate-2 (IRS2) in SGA patients with and without catch-up growth. Methods: Observational prospective study of SGA children. Demographical and clinical variables were collected from clinical records and parents' questionnaire. Methylation status of LEP, IRS2, and GLP2R promoters was evaluated in DNA extracted from patient and one parent saliva samples. Results: Forty-eight SGA patients were included. Twenty-six (54.2%) had catch-up growth phenotype and 22 (45.8%) did not. The median age was 5.2 years [RIC 4.1-6.8] without difference between groups (p=0.306). The catch-up group had increased appetite (42.3% vs 9.1%, p=0.008), family history of dyslipidemia (42.3% vs 27.3%) and diabetes (34.6% vs 22.7%) compared to non-catch-up group. Catch-up patients had significantly larger waist circumference compared to non-catch-up group (median 55 cm [RIC 52-58] versus median 49.5 cm [RIC46-52]; p<0.001). LEP and GLP2R were methylated in all samples. IRS2 was methylated in 60% of SGA patients without difference between groups (p=0.520). Conclusion: There is no association between IRS2 methylation and catch-up growth among SGA patients. LEP and GLP2R were methylated in all SGA patients. Gene methylation may be implicated in metabolic disease later in life. More studies should be performed to confirm this hypothesis.

Risks of Adverse Childhood Outcomes According to Prenatal Time of Exposure to Zika Virus: Assessment in a Cohort Exposed to Zika During an Outbreak in Colombia.

Late gestational exposure to Zika increases the odds of delay in the Bayley-II mental developmental index (MDI) in children with normal baseline neurologic assessments; 9-fold when comparing third and first trimester exposure. Risk of MDI developmental delay increases by 8% for each week of gestational age at time of exposure.

Structural variant calling: the long and the short of it.

Recent research into structural variants (SVs) has established their importance to medicine and molecular biology, elucidating their role in various diseases, regulation of gene expression, ethnic diversity, and large-scale chromosome evolution-giving rise to the differences within populations and among species. Nevertheless, characterizing SVs and determining the optimal approach for a given experimental design remains a computational and scientific challenge. Multiple approaches have emerged to target various SV classes, zygosities, and size ranges. Here, we review these approaches with respect to their ability to infer SVs across the full spectrum of large, complex variations and present computational methods for each approach.

Outcomes of Congenital Zika Virus Infection During an Outbreak in Valle del Cauca, Colombia.

BACKGROUND: Despite increasing information in the literature regarding congenital Zika infection, gaps remain in our knowledge of its clinical manifestations. METHODS: We did a prospective observational study of exposed fetuses and infants whose mothers developed symptomatic and confirmed Zika infection during pregnancy in Valle del Cauca, Colombia. We performed neurological, ophthalmologic and audiologic evaluations, and classified outcomes as possibly or uncertainly related to Zika. Frequencies of outcomes were compared according to the trimester of pregnancy when infection occurred. RESULTS: We evaluated 171 products of gestation including 17 pregnancy losses and 154 patients evaluated postnatally. Ninety (52.6%) pregnancies presented an adverse outcome, 36% possibly related with Zika and the remaining 64% of uncertain relation. Infection in the first trimester had the highest frequencies of adverse outcomes possibly related with Zika compared with the second and third trimesters (39% vs. 12.5% vs. 12%) with risk ratios of adverse outcomes possibly related to Zika in pregnancies infected in the first versus second or third trimester of 3.1 (95% CI: 2.4-4.1) and 3.3 (95% CI: 2.5-4.2), respectively. The frequencies of pregnancy loss and microcephaly were 9.4% and 4.5%, respectively. Auditory and ophthalmic abnormalities possibly related with Zika were present in 3% and 6% of the patients evaluated, respectively. CONCLUSIONS: We observed a high frequency of gestational and neonatal complications in pregnant women who acquired Zika infection, especially in early pregnancy, resulting in a broad spectrum of clinical manifestations. Preventive measures are urgently needed to reduce the clinical burden during future Zika outbreaks.

Interventions to treat cutaneous leishmaniasis in children: A systematic review.

BACKGROUND: Case management in children with cutaneous leishmaniasis (CL) is mainly based on studies performed in adults. We aimed to determine the efficacy and harms of interventions to treat CL in children. METHODS: We conducted a systematic review of clinical trials and cohort studies, assessing treatments of CL in children (≤12 years old). We performed structured searches in PubMed, CENTRAL, LILACS, SciELO, Scopus, the International Clinical Trials Registry Platform (ICTRP), clinicaltrials.gov and Google Scholar. No restrictions regarding ethnicity, country, sex or year of publication were applied. Languages were limited to English, Spanish and Portuguese. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A qualitative summary of the included studies was performed. RESULTS: We identified 1092 records, and included 8 manuscripts (6 Randomized Clinical Trials [RCT] and 2 non-randomized studies). Most of the articles excluded in full-text review did not report outcomes separately for children. In American CL (ACL), 5 studies evaluated miltefosine and/or meglumine antimoniate (MA). Their efficacy varied from 68-83% and 17-69%, respectively. In Old-World CL (OWCL), two studies evaluated systemic therapies: rifampicin and MA; and one study assessed efficacy of cryotherapy (42%, Per Protocol [PP]) vs intralesional MA (72%, PP). Few studies (4) provided information on adverse events (AEs) for children, and no serious AEs were reported in participants. Risk of bias was generally low to unclear in ACL studies, and unclear to high in OWCL studies. CONCLUSION: Information on efficacy of treatment for CL in children is scarce. There is an unmet need to develop specific formulations, surveillance of AEs, and guidelines both for the management of CL and clinical trials involving the pediatric population. REGISTRATION: The protocol of this review was registered in the PROSPERO International register of systematic reviews, number CRD42017062164.

Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016.

Arboviruses are responsible for a large burden of disease globally and are thus subject to intense epidemiological scrutiny. However, a variable notably absent from most epidemiological analyses has been the impact of violence on arboviral transmission and surveillance. Violence impedes surveillance and delivery of health and preventative services and affects an individual's health-related behaviors when survival takes priority. Moreover, low and middle-income countries bear a disproportionately high burden of violence and related health outcomes, including vector borne diseases. To better understand the epidemiology of arboviral outbreaks in Cali, Colombia, we georeferenced chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viral cases from The National System of Surveillance in Public Health between October 2014 and April 2016. We extracted homicide data from the municipal monthly reports and kernel density of homicide distribution from IdeasPaz. Crucially, an overall higher risk of homicide is associated with increased risk of reported DENV, lower rates of acute testing, and higher rates of lab versus clinical discordance. In the context of high violence as a potential barrier to access to preventive health services, a community approach to improve health and peace should be considered.

In-solution Y-chromosome capture-enrichment on ancient DNA libraries.

BACKGROUND: As most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach-in-solution capture-enrichment-retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre-capture) libraries. RESULTS: The six samples show different levels of initial endogenous content, with very low (< 0.05%, 4 samples) or low (0.1-1.54%, 2 samples) percentages of sequenced reads mapping to the human genome. We recover 12-9549 times more targeted unique Y-chromosome sequences after capture, where 0.0-6.2% (WGC + YCC) and 0.0-23.5% (YCC) of the sequence reads were on-target, compared to 0.0-0.00003% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC + YCC) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, the libraries' initial low complexity leads to minor proportions of Y-chromosome reads. Finally, increasing recovery of informative sites enabled us to assign Y-chromosome haplogroups to some of the archeological remains and gain insights about their paternal lineages and origins. CONCLUSIONS: We present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC + YCC enrichments lead to an increase in the amount of Y-DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our probe design effectively recovers regions of the Y-chromosome bearing phylogenetically informative sites, allowing us to identify paternal lineages with less sequencing than needed for pre-capture libraries. Finally, we recommend considering the endogenous content in the experimental design and avoiding consecutive rounds of capture, as clonality increases considerably with each round.