Analysis of the Chagas disease situation in Japan: a cross sectional study and cost-effectiveness analysis of a Chagas disease screening program.

Background: Japan is estimated to host 3000 cases of Chagas disease (CD). However, there are no epidemiological data and policies for prevention and care. We aimed to analyze the current situation of CD in Japan and identify possible barriers to seeking care. Methods: This cross-sectional study included Latin American (LA) migrants living in Japan from March 2019 to October 2020. We obtained blood samples to identify participants infected with Trypanosoma cruzi, and data about sociodemographic information, CD risk factors, and barriers to access to the Japanese national health care system (JNHS). We used the observed prevalence to calculate the cost-effectiveness analysis of the screening of CD in the JNHS. Findings: The study included 428 participants, most of them were from Brazil, Bolivia and Peru. The observed prevalence was 1.6% (expected prevalence= 0.75%) and 5.3% among Bolivians. Factors associated with seropositivity were being born in Bolivia, having previously taken a CD test, witnessing the triatome bug at home, and having a relative with CD. The screening model was more cost-effective than the non-screening model from a health care perspective (ICER=200,320 JPY). Factors associated with access to JNHS were being female, length of stay in Japan, Japanese communication skills, source of information, and satisfaction about the JNHS. Interpretation: Screening of asymptomatic adults at risk of CD may be a cost-effective strategy in Japan. However, its implementation should consider the barriers that affect LA migrants in access to the JNHS. Funding: Nagasaki University and Infectious Diseases Japanese Association.

Incidence of SARS-CoV-2 over four epidemic waves in a low-resource community in Rio de Janeiro, Brazil: A prospective cohort study.

Background: Incidence rates of SARS-CoV-2 infections in low-resource communities can inform vaccination strategies and non-pharmaceutical interventions (NPIs). Our objective was to estimate incidence over four epidemic waves in a slum in Rio de Janeiro, a proxy for economically deprived areas in the Global South. Methods: Prospective cohort of children and household contacts screened for SARS-CoV-2 by PCR and serology (IgG). The incidence density of PCR positive infections estimated for each wave - the first wave, Zeta, Gamma and Delta - was compared to an index combining NPIs and vaccination coverage. Findings: 718 families and 2501 individuals were enrolled, from May 2020 to November 2021. The incidence density of SARS-CoV-2 infection due to the first wave was 2, 3 times that of the other waves. The incidence among children was lower than that of older participants, except in later waves, when vaccination of the elderly reached 90%. Household agglomeration was significantly associated with incidence only during the first wave. Interpretation: The incidence of infection greatly exceeded rates reported in similar cohorts. The observed reduction in incidence in the elderly during the Delta variant wave, in spite of the rollback of NPIs, can be attributed to increased vaccine coverage. The high incidence in young people reinforces the importance of vaccination in this age group, a policy that has yet to receive the full support of some sectors of society. Funding: UK Medical Research Council, Foundation for the Advancement of Science of the State of Rio de Janeiro, National Council for Scientific and Technological Development.

Ecosystem service benefits and costs of deep-sea ecosystem restoration.

Deep-sea ecosystems are facing degradation which could have severe consequences for biodiversity and the livelihoods of coastal populations. Ecosystem restoration as a natural based solution has been regarded as a useful means to recover ecosystems. The study provides a social cost-benefit analysis for a proposed project to restore the Dohrn Canyon cold water corals and the deep-sea ecosystem in the Bay of Naples, Italy. By incorporating ecosystem service benefits and uncertainties related to a complex natural-technological-social system surrounding restoration activities, the study demonstrated how to evaluate large-scale ecosystem restoration activities. The results indicate that an ecosystem restoration project can be economic (in terms of welfare improvement) even if the restoration costs are high. Our study shows the uncertainty associated with restoration success rate significantly affects the probability distribution of the expected net present values. Identifying and controlling the underlying factors to improve the restoration successful rate is thus crucial.

Costing analysis of field implementation of hepatitis C case detection in rural Maung Russey operational district, Cambodia.

BACKGROUND: When a new health programme is introduced, it is crucial to estimate the costs for rational health policy decision-making. The aim of this study was to determine the costs of implementing two strategies for hepatitis C virus (HCV) screening in rural Cambodia. METHODS: We retrospectively analysed clinical and cost data that were collected routinely for a demonstration project for scaling up HCV screening and testing in Cambodia. The programme data were collected between March and December 2018 in Maung Russey operational district in Battambang Province, Cambodia. FINDINGS: During the study period, 24 230 people were screened; 1194 (5%) were HCV seropositive, of whom 793 (66%) were confirmed to be viraemic. During the study period, 18% of the estimated population of the operational district were screened, of whom 45% were estimated to be seropositive and 41% to be viraemic. With passive screening alone, 8% of the estimated population were screened, of whom 29% were estimated to be seropositive and 28% viraemic. The cost per detected viraemic case was US$ 194 for passive screening alone and US$ 283 for passive and active screening combined. Labour costs (31%) and tests and materials (29%) comprised the largest proportions of the cost. CONCLUSION: Combined active and passive screening per viraemic case detected was US$ 89 more expensive than passive screening alone but provided a higher yield (41% versus 28%) of viraemic cases. Therefore, adding active screening to passive screening is beneficial. Selective active screening strategies, such as targeting people over 45 years and other higher-risk groups, added value for HCV diagnosis.

Economic burden of the persistent morbidity of nodding syndrome on caregivers in affected households in Northern Uganda.

BACKGROUND: Nodding syndrome (NS), is an unexplained form of epilepsy which leads to stunted growth, cognitive decline, and a characteristic nodding of the head. Current data about its impact on households in Uganda is scarce. Therefore, this study aims to assess the economic burden of the persistent morbidity of NS on caregivers in affected households in Northern Uganda. METHODS: A cross-sectional cost-of-care study was conducted from January 2019 to February 2019 in Lakwela village-Northern Uganda in 14 households, who are members of a community-based organization (CBO) established in the village with the support of a Japanese research team, (Uganda-Japan Nodding Syndrome Network). Data was collected through questionnaires. Both direct (medical and non-medical) and indirect (informal care) costs of caregiving were assessed. Indirect costs were valued using the human-capital method as loss of production. RESULTS: Direct costs constituted a higher proportion of costs for NS households, accounting for on average 7.7% of household expenditure. The annual weighted mean cost per NS patient was estimated at 27.6 USD (26.4 USD direct costs, 96.2% and 1.2 USD indirect cost, 3.8%). Average time spent on informal caregiving was 4.4 ±1.7 (standard deviation) hours/week with an estimated annual informal caregiving cost of 24.85 USD and gross domestic product (GDP) loss of 412.40 USD. CONCLUSION: Direct costs due to NS are still high among households in this study. More studies are needed to investigate measures that could help bring down these costs and equally reduce the day-to-day disruption of caregiver's activities; consequently, improving the lives of these affected households and communities.

A Mobile Phone-Based Support Intervention to Increase Use of Postabortion Family Planning in Cambodia: Cost-Effectiveness Evaluation.

BACKGROUND: Despite progress over the last decade, there is a continuing unmet need for contraception in Cambodia. Interventions delivered by mobile phone could help increase uptake and continuation of contraception, particularly among hard-to-reach populations, by providing interactive personalized support inexpensively wherever the person is located and whenever needed. OBJECTIVE: The objective of this study was to evaluate the cost-effectiveness of mobile phone-based support added to standard postabortion family planning care in Cambodia, according to the results of the MOTIF (MObile Technology for Improved Family planning) trial. METHODS: A model was created to estimate the costs and effects of the intervention versus standard care. We adopted a societal perspective when estimating costs, including direct and indirect costs for users. The incremental cost-effectiveness ratio was calculated for the base case, as well as a deterministic and probabilistic sensitivity analysis, which we compared against a range of likely cost-effectiveness thresholds. RESULTS: The incremental cost of mobile phone-based support was estimated to be an additional US $8160.49 per 1000 clients, leading to an estimated 518 couple-years of protection (CYPs) gained per 1000 clients and 99 disability-adjusted life-years (DALYs) averted. The incremental cost-effectiveness ratio was US $15.75 per additional CYP and US $82.57 per DALY averted. The model was most sensitive to personnel and mobile service costs. Assuming a range of cost-effectiveness thresholds from US $58 to US $176 for Cambodia, the probability of the intervention being cost-effective ranged from 11% to 95%. CONCLUSIONS: This study demonstrates that the cost-effectiveness of the intervention delivered by mobile phone assessed in the MOTIF trial lies within the estimated range of the cost-effectiveness threshold for Cambodia. When assessing value in interventions to improve the uptake and adherence of family planning services, the use of interactive mobile phone messaging and counselling for women who have had an abortion should be considered as an option by policy makers. TRIAL REGISTRATION: ClinicalTrials.gov NCT01823861; https://clinicaltrials.gov/ct2/show/NCT01823861.

Reasons for Increased Caesarean Section Rate in Vietnam: A Qualitative Study among Vietnamese Mothers and Health Care Professionals.

The Caesarean section rate in urban Vietnam is 43% in 2014, which is more than twice the recommended rate (10%-15%) by the World Health Organization. This qualitative study aims to identify the perceptions of pregnant mothers and health care professionals on the medical and social factors related to the increased Caesarean section rate in Vietnam. A qualitative descriptive study was conducted among pregnant mothers and healthcare professionals at two public hospitals in Nha Trang city. A content analysis was adopted in order to identify social and medical factors. As a result, 29 pregnant women and 19 health care professionals were invited to participate in the qualitative interviews. Private interviews were conducted with 10 women who wished to have a Caesarean section, and the others participated in focus group interviews. The main themes of the social factors were 'request for Caesarean section,' 'mental strain of obstetricians,' and 'decision-making process.' To conclude, this qualitative study suggests that there were unnecessary caesarean sections without a clear medical indication, which were requested by women and family members. Psychological fear occurred among women and family, and doctors were the main determinants for driving the requests for Caesarean section, which implies that education and emotional encouragement is necessary by midwives. In addition, a multi-faced approach including a mandatory reporting system in clinical fields and involving family members in antenatal education is important.

Prevalence and burden of dengue infection in Europe: A systematic review and meta-analysis.

Imported dengue cases are thought to be important source for transmission of autochthonous dengue in Europe. We aimed to investigate the prevalence of dengue in Europe, its severity, and factors associated with it. Out of 5287 reports resulting from the search of nine electronic search engines, we included 174 reports. Meta-analysis was performed by pooling the event rate and 95% confidence interval (CI). Subgroup meta-analyses were performed to test the effect of the covariates. Among 20 284 reported cases, 130 autochthonous dengue cases were reported in eight countries with the highest number of cases reported in Israel (n = 41). The highest number of imported dengue cases was in Germany (n = 6638) then France (n = 6610). Most cases were imported from Southeast Asia (n = 2533) especially Thailand. Dengue infection cases increased with time, with 4157 cases reported in 2010. Second dengue infection and dengue serotype 2 were positively associated with dengue severity. The proportion of autochthonous dengue infection increased with time to reach 14.8% (95% CI, 7.6-26.9) in 2015. The pooled proportion of severe dengue was 6.18% (95% CI, 2.7-13.3). The United Kingdom and France had the highest rate of severe dengue (25%; 95% CI, 6.3-62.3, and 21.4%; 95% CI, 24.5-18.7, respectively). This change may be due to the surveillance efforts instead of true biological phenomenon; thus, the lack of surveillance is an obvious limitation. In conclusion, imported and autochthonous dengue has been increasing in Europe. Severe dengue began to increase recently in Europe. European health authorities should pay more attention for the diagnosis and control of dengue infection among returning travelers, especially the travelers with fever of unknown origin.

Liaison psychiatry-measurement and evaluation of service types, referral patterns and outcomes (LP-MAESTRO): a protocol.

INTRODUCTION: We describe the protocol for a project that will use linkage of routinely collected NHS data to answer a question about the nature and effectiveness of liaison psychiatry services in acute hospitals in England. METHODS AND ANALYSIS: The project will use three data sources: (1) Hospital Episode Statistics (HES), a database controlled by NHS Digital that contains patient data relating to emergency department (ED), inpatient and outpatient episodes at hospitals in England; (2) ResearchOne, a research database controlled by The Phoenix Partnership (TPP) that contains patient data relating to primary care provided by organisations using the SystmOne clinical information system and (3) clinical databases controlled by mental health trusts that contain patient data relating to care provided by liaison psychiatry services. We will link patient data from these sources to construct care pathways for patients who have been admitted to a particular hospital and determine those patients who have been seen by a liaison psychiatry service during their admission.Patient care pathways will form the basis of a matched cohort design to test the effectiveness of liaison intervention. We will combine healthcare utilisation within care pathways using cost figures from national databases. We will compare the cost of each care pathway and the impact of a broad set of health-related outcomes to obtain preliminary estimates of cost-effectiveness for liaison psychiatry services. We will carry out an exploratory incremental cost-effectiveness analysis from a whole system perspective. ETHICS AND DISSEMINATION: Individual patient consent will not be feasible for this study. Favourable ethical opinion has been obtained from the NHS Research Ethics Committee (North of Scotland) (REF: 16/NS/0025) for Work Stream 2 (phase 1) of the Liaison psychiatry-measurement and evaluation of service types, referral patterns and outcomes study. The Confidentiality Advisory Group at the Health Research Authority determined that Section 251 approval under Regulation 5 of the Health Service (Control of Patient Information) Regulations 2002 was not required for the study 'on the basis that there is no disclosure of patient identifiable data without consent' (REF: 16/CAG/0037).Results of the study will be published in academic journals in health services research and mental health. Details of the study methodology will also be published in an academic journal. Discussion papers will be authored for health service commissioners.

Unintended Consequences of mHealth Interactive Voice Messages Promoting Contraceptive Use After Menstrual Regulation in Bangladesh: Intimate Partner Violence Results From a Randomized Controlled Trial.

BACKGROUND: Mobile phones for health (mHealth) hold promise for delivering behavioral interventions. We evaluated the effect of automated interactive voice messages promoting contraceptive use with a focus on long-acting reversible contraceptives (LARCs) among women in Bangladesh who had undergone menstrual regulation (MR), a procedure to "regulate the menstrual cycle when menstruation is absent for a short duration." METHODS: We recruited MR clients from 41 public- and private-sector clinics immediately after MR. Eligibility criteria included having a personal mobile phone and consenting to receive messages about family planning by phone. We randomized participants remotely to an intervention group that received at least 11 voice messages about contraception over 4 months or to a control group (no messages). The primary outcome was LARC use at 4 months. Adverse events measured included experience of intimate partner violence (IPV). Researchers recruiting participants and 1 analyst were blinded to allocation groups. All analyses were intention to treat. The trial is registered with ClinicalTrials.gov (NCT02579785). RESULTS: Between December 2015 and March 2016, 485 women were allocated to the intervention group and 484 to the control group. We completed follow-up on 389 intervention and 383 control participants. Forty-eight (12%) participants in the intervention group and 59 (15%) in the control group reported using a LARC method at 4 months (adjusted odds ratio [aOR] using multiple imputation=0.95; 95% confidence interval [CI]=0.49 to 1.83; P=.22). Reported physical IPV was higher in the intervention group: 42 (11%) intervention versus 25 (7%) control (aOR=1.97; 95% CI=1.12 to 3.46; P=.03) when measured using a closed question naming acts of violence. No violence was reported in response to an open question about effects of being in the study. CONCLUSIONS: The intervention did not increase LARC use but had an unintended consequence of increasing self-reported IPV. Researchers and health program designers should consider possible negative impacts when designing and evaluating mHealth and other reproductive health interventions. IPV must be measured using closed questions naming acts of violence.

Addressing the dichotomy between individual and societal approaches to personalised medicine in oncology.

Academic, industry, regulatory leaders and patient advocates in cancer clinical research met in November 2018 at the Innovation and Biomarkers in Cancer Drug Development meeting in Brussels to address the existing dichotomy between increasing calls for personalised oncology approaches based on individual molecular profiles and the need to make resource and regulatory decisions at the societal level in differing health-care delivery systems around the globe. Novel clinical trial designs, the utility and limitations of real-world evidence (RWE) and emerging technologies for profiling patient tumours and tumour-derived DNA in plasma were discussed. While randomised clinical trials remain the gold standard approach to defining clinical utility of local and systemic therapeutic interventions, the broader adoption of comprehensive tumour profiling and novel trial designs coupled with RWE may allow patient and physician autonomy to be appropriately balanced with broader assessments of safety and overall societal benefit.

Assessing loss to follow-up in the MObile Technology for Improved Family Planning (MOTIF) randomised controlled trial.

BACKGROUND: Loss to follow-up (LTFU) in clinical trials is an important source of bias that can affect statistical power and generalisability of findings. The aim of this paper is to assess factors associated with LTFU in the MObile Technology for Improved Family Planning (MOTIF) trial in Cambodia and compare how the result might have varied using different analytical methods. METHODS: Follow-up in the MOTIF trial was 86% at 4 months and 66% at 12 months. For the primary analysis, we undertook a complete case analysis, similar to the approach used in similar trials of interventions delivered by mobile phone to increase contraception use. We conducted an exploratory analysis and found that factors associated with LTFU were young age, lower socio-economic status, not planning to use post-abortion contraception, availability of phone credit and not providing additional contact numbers. We then undertook two analyses to estimate the effect of the intervention on the primary outcome at 4 and 12 months for comparison with the complete case analysis. First, we undertook multiple imputation, and second we conducted an analysis treating all participants' LTFU as non-users of contraception. RESULTS: Using multiple imputation, we found that the risk ratio was slightly increased at 4 months and slightly decreased at 12 months compared with the complete case analysis. When counting all participants' LTFU as non-users of contraception, we observed that, compared with the complete case analysis, the risk ratio was slightly decreased at 4 months and slightly increased at 12 months. Despite the changes in the risk ratio, use of the different analytical methods did not result in an effect using the complete case analysis becoming statistically significant or vice versa. CONCLUSION: Future studies assessing contraception use might anticipate increased attrition amongst younger participants, those of lower socio-economic status or those who do not provide additional contact details. Attrition could be reduced by collecting as many contact details as possible, by providing incentives and possibly by enhanced counselling to groups at higher risk of LTFU on recruitment. Multiple imputation should be considered in addition to complete case analysis if LTFU not missing at random is expected or observed. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01823861 . Registered on 30 March 2013.

The usefulness and costs of routine contrast studies after laparoscopic sleeve gastrectomy for detecting staple line leaks.

BACKGROUND: Although laparoscopic sleeve gastrectomy (LSG) has been shown to be a safe and effective treatment for severe obesity (body mass index ≥ 35), staple line leaks remain a major complication and account for a substantial portion of the procedure's morbidity and mortality. Many centres performing LSG routinely obtain contrast studies on postoperative day 1 for early detection of staple line leaks. We examined the usefulness of Gastrografin swallow as an early detection test for staple line leaks on postoperative day 1 after LSG as well as the associated costs. METHODS: We conducted a retrospective review of a prospectively collected database that included 200 patients who underwent LSG for severe obesity between 2011 and 2014. Primary outcome measures were the incidence of staple line leaks and the results of Gastrografin swallow tests. We obtained imaging costs from appropriate hospital departments. RESULTS: Gastrografin swallow was obtained on postoperative day 1 for all 200 patients who underwent LSG. Three patients (1.5%) were found to have staple line leaks. Gastrograffin swallows yielded 1 true positive result and 2 false negatives. The false negatives were subsequently diagnosed on computed tomography (CT) scan. The sensitivity of Gastrografin swallow in this study was 33%. For 200 patients, the total direct cost of the Gastrografin swallows was $35 000. CONCLUSION: The use of routine upper gastrointestinal contrast studies for early detection of staple line leaks has low sensitivity and is costly. We recommend selective use of CT instead.

CONTEXTE: Même si la gastrectomie longitudinale par laparoscopie (GLL) s'est révélée sûre et efficace pour le traitement de l'obésité sévère (indice de masse corporelle ≥ 35), les fuites survenant à la ligne d'agrafes demeurent une complication majeure et sont responsables d'une bonne partie des complications et des décès associés à cette chirurgie. Plusieurs des centres effectuant des GLL procèdent au dépistage systématique des fuites à la ligne d'agrafes en réalisant des tests avec des agents de contraste le jour suivant la chirurgie. Nous avons évalué l'utilité du test à la gastrografine comme méthode de dépistage précoce des fuites à la ligne d'agrafes au jour 1, ainsi que les coûts qui y sont associés. MÉTHODES: Nous avons mené une étude rétrospective à partir d'une base de données créée de façon prospective qui portait sur 200 patients ayant subi une GLL entre 2011 et 2014 en raison d'une obésité sévère. Les principaux indicateurs de résultats étaient l'incidence de fuites à la ligne d'agrafes et les résultats obtenus aux tests à la gastrografine. Les renseignements sur le coût des tests d'imagerie nous ont été fournis par les départements appropriés des hôpitaux. RÉSULTATS: Selon les résultats des tests à la gastrografine au jour 1 obtenus pour les 200 patients ayant subi une GLL, 3 patients (1,5 %) présentaient des fuites à la ligne d'agrafes. Il s'agissait en réalité d'un vrai positif et 2 faux négatifs. Le diagnostic des faux négatifs a ensuite été effectué par tomographie par ordinateur. La sensibilité du test à la gastrografine était donc de 33 % au cours de cette étude. Le coût total de ce test, pour les 200 patients, était de 35 000 $. CONCLUSION: Le recours à des examens systématiques du tractus gastro-intestinal supérieur au moyen d'agents de contraste pour le dépistage précoce des fuites à la ligne d'agrafes a une faible sensibilité et est associé à des coûts élevés. Nous recommandons plutôt l'utilisation sélective de la tomographie par ordinateur.

BCFtools/RoH: a hidden Markov model approach for detecting autozygosity from next-generation sequencing data.

UNLABELLED: Runs of homozygosity (RoHs) are genomic stretches of a diploid genome that show identical alleles on both chromosomes. Longer RoHs are unlikely to have arisen by chance but are likely to denote autozygosity, whereby both copies of the genome descend from the same recent ancestor. Early tools to detect RoH used genotype array data, but substantially more information is available from sequencing data. Here, we present and evaluate BCFtools/RoH, an extension to the BCFtools software package, that detects regions of autozygosity in sequencing data, in particular exome data, using a hidden Markov model. By applying it to simulated data and real data from the 1000 Genomes Project we estimate its accuracy and show that it has higher sensitivity and specificity than existing methods under a range of sequencing error rates and levels of autozygosity. AVAILABILITY AND IMPLEMENTATION: BCFtools/RoH and its associated binary/source files are freely available from https://github.com/samtools/BCFtools CONTACT: vn2@sanger.ac.uk or pd3@sanger.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Community-Driven Research Agenda to Reduce Health Disparities.

This paper describes how a new regional campus of an academic health center engaged in a community-based participatory research (CBPR) process to set a community-driven research agenda to address health disparities. The campus is situated among growing Marshallese and Hispanic populations that face significant health disparities. In 2013, with support from the Translational Research Institute, the University of Arkansas for Medical Sciences Northwest began building its research capacity in the region with the goal of developing a community-driven research agenda for the campus. While many researchers engage in some form of community-engaged research, using a CBPR process to set the research agenda for an entire campus is unique. Utilizing multiple levels of engagement, three research areas were chosen by the community: (1) chronic disease management and prevention; (2) obesity and physical activity; and (3) access to culturally appropriate healthcare. In only 18 months, the CBPR collaboration had dramatic results. Ten grants and five scholarly articles were collaboratively written and 25 community publications and presentations were disseminated. Nine research projects and health programs were initiated. In addition, many interprofessional educational and service learning objectives were aligned with the community-driven agenda resulting in practical action to address the needs identified.

Tracing the route of modern humans out of Africa by using 225 human genome sequences from Ethiopians and Egyptians.

The predominantly African origin of all modern human populations is well established, but the route taken out of Africa is still unclear. Two alternative routes, via Egypt and Sinai or across the Bab el Mandeb strait into Arabia, have traditionally been proposed as feasible gateways in light of geographic, paleoclimatic, archaeological, and genetic evidence. Distinguishing among these alternatives has been difficult. We generated 225 whole-genome sequences (225 at 8× depth, of which 8 were increased to 30×; Illumina HiSeq 2000) from six modern Northeast African populations (100 Egyptians and five Ethiopian populations each represented by 25 individuals). West Eurasian components were masked out, and the remaining African haplotypes were compared with a panel of sub-Saharan African and non-African genomes. We showed that masked Northeast African haplotypes overall were more similar to non-African haplotypes and more frequently present outside Africa than were any sets of haplotypes derived from a West African population. Furthermore, the masked Egyptian haplotypes showed these properties more markedly than the masked Ethiopian haplotypes, pointing to Egypt as the more likely gateway in the exodus to the rest of the world. Using five Ethiopian and three Egyptian high-coverage masked genomes and the multiple sequentially Markovian coalescent (MSMC) approach, we estimated the genetic split times of Egyptians and Ethiopians from non-African populations at 55,000 and 65,000 years ago, respectively, whereas that of West Africans was estimated to be 75,000 years ago. Both the haplotype and MSMC analyses thus suggest a predominant northern route out of Africa via Egypt.

Social supergenes of superorganisms: do supergenes play important roles in social evolution?

We suggest that supergenes, groups of co-inherited loci, may be involved in a range of intriguing genetic and evolutionary phenomena in insect societies, and may play broad roles in the evolution of cooperation and conflict. Supergenes are central in the evolution of an array of traits including self-incompatibility, mimicry, and sex chromosomes. Recently, researchers identified a large supergene, described as a social chromosome, which controls social organization in the fire ant. This system was previously considered to be a remarkable example of a single gene affecting a complex social trait. We describe how selection may commonly favor reduced recombination and the formation of supergenes for social traits, and once formed, supergenes may strongly influence further evolutionary dynamics within and between lineages. The evolution of supergenes, and even wholly non-recombining genomes, may be particularly common in systems in which genetically distinct lineages can form mutually reinforcing socially parasitic relationships.

Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality.

Genomes of eusocial insects code for dramatic examples of phenotypic plasticity and social organization. We compared the genomes of seven ants, the honeybee, and various solitary insects to examine whether eusocial lineages share distinct features of genomic organization. Each ant lineage contains ∼4000 novel genes, but only 64 of these genes are conserved among all seven ants. Many gene families have been expanded in ants, notably those involved in chemical communication (e.g., desaturases and odorant receptors). Alignment of the ant genomes revealed reduced purifying selection compared with Drosophila without significantly reduced synteny. Correspondingly, ant genomes exhibit dramatic divergence of noncoding regulatory elements; however, extant conserved regions are enriched for novel noncoding RNAs and transcription factor-binding sites. Comparison of orthologous gene promoters between eusocial and solitary species revealed significant regulatory evolution in both cis (e.g., Creb) and trans (e.g., fork head) for nearly 2000 genes, many of which exhibit phenotypic plasticity. Our results emphasize that genomic changes can occur remarkably fast in ants, because two recently diverged leaf-cutter ant species exhibit faster accumulation of species-specific genes and greater divergence in regulatory elements compared with other ants or Drosophila. Thus, while the "socio-genomes" of ants and the honeybee are broadly characterized by a pervasive pattern of divergence in gene composition and regulation, they preserve lineage-specific regulatory features linked to eusociality. We propose that changes in gene regulation played a key role in the origins of insect eusociality, whereas changes in gene composition were more relevant for lineage-specific eusocial adaptations.