Hybrid speciation driven by multilocus introgression of ecological traits.

Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific traits to examine a case of hybrid speciation in Heliconius butterflies. We show that Heliconius elevatus is a hybrid species that is sympatric with both parents and has persisted as an independently evolving lineage for at least 180,000 years. This is despite pervasive and ongoing gene flow with one parent, Heliconius pardalinus, which homogenizes 99% of their genomes. The remaining 1% introgressed from the other parent, Heliconius melpomene, and is scattered widely across the H. elevatus genome in islands of divergence from H. pardalinus. These islands contain multiple traits that are under disruptive selection, including colour pattern, wing shape, host plant preference, sex pheromones and mate choice. Collectively, these traits place H. elevatus on its own adaptive peak and permit coexistence with both parents. Our results show that speciation was driven by introgression of ecological traits, and that speciation with gene flow is possible with a multilocus genetic architecture.

The burden of skin and soft tissue, bone and joint infections in an Australian cohort of people who inject drugs.

INTRODUCTION: There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID). METHODS: Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies. RESULTS: A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2-51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission. CONCLUSION: Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.

Improving psychological well-being among healthcare workers during the COVID-19 pandemic with an online mindfulness intervention: A randomised waitlist-controlled trial.

The high prevalence of psychological problems observed among healthcare workers (HCWs) during the COVID-19 pandemic called for interventions to safeguard their mental health. We assessed the effectiveness of a 6-week online mindfulness-based intervention in improving well-being and reducing stress among HCWs in Sri Lanka. Eighty HCWs were recruited and randomised into two groups: waitlist-control (WLC) and intervention groups. In the intervention, 1-hour online sessions were conducted at weekly intervals and participants were encouraged to do daily home practice. Stress and well-being were measured pre- and post-intervention using the Perceived Stress Scale and WHO-5 Well-being Index, respectively. One-way analysis of covariance was used to evaluate the effectiveness, in both intention-to-treat (ITT) and complete-case (CC) analyses. A significantly greater improvement in well-being occurred in the intervention arm compared to WLC on both ITT (p = .002) and CC analyses (p < .001), with medium-to-large effect sizes (partial η2 = .117-.278). However, the reduction in stress following the intervention was not significant compared to the WLC group on both ITT (p = .636) and CC analyses (p = .262). In the intervention arm, the median number of sessions attended by participants was 3. Low adherence to the intervention may have contributed to the apparent non-significant effect on stress.

Multivalent Targeting of the Asialoglycoprotein Receptor by Virus-Like Particles.

The asialoglycoprotein receptor (ASGPR) is expressed in high density on hepatocytes. Multivalent variants of galactosyl carbohydrates bind ASGPR with high affinity, enabling hepatic delivery of ligand-bound cargo. Virus-like particle (VLP) conjugates of a relatively high-affinity ligand were efficiently endocytosed by ASGPR-expressing cells in a manner strongly dependent on the nature and density of ligand display, with the best formulation using a nanomolar-, but not a picomolar-level, binder. Optimized particles were taken up by HepG2 cells with greater efficiency than competing small molecules or the natural multigalactosylated ligand, asialoorosomucoid. Upon systemic injection in mice, these VLPs were rapidly cleared to the liver and were found in association with sinusoidal endothelial cells, Kupffer cells, hepatocytes, dendritic cells, and other immune cells. Both ASGPR-targeted and nontargeted particles were distributed similarly to endothelial and Kupffer cells, but targeted particles were distributed to a greater number and fraction of hepatocytes. Thus, selective cellular trafficking in the liver is difficult to achieve: even with the most potent ASGPR targeting available, barrier cells take up much of the injected particles and hepatocytes are accessed only approximately twice as efficiently in the best case.

Spatiotemporal dynamics in butterfly hybrid zones.

Evaluating whether hybrid zones are stable or mobile can provide novel insights for evolution and conservation biology. Butterflies exhibit high sensitivity to environmental changes and represent an important model system for the study of hybrid zone origins and maintenance. Here, we review the literature exploring butterfly hybrid zones, with a special focus on their spatiotemporal dynamics and the potential mechanisms that could lead to their movement or stability. We then compare different lines of evidence used to investigate hybrid zone dynamics and discuss the strengths and weaknesses of each approach. Our goal with this review is to reveal general conditions associated with the stability or mobility of butterfly hybrid zones by synthesizing evidence obtained using different types of data sampled across multiple regions and spatial scales. Finally, we discuss spatiotemporal dynamics in the context of a speciation/divergence continuum, the relevance of hybrid zones for conservation biology, and recommend key topics for future investigation.

Scale-dependent environmental effects on phenotypic distributions in Heliconius butterflies.

Identifying the relative importance of different mechanisms responsible for the emergence and maintenance of phenotypic diversity can be challenging, as multiple selective pressures and stochastic events are involved in these processes. Therefore, testing how environmental conditions shape the distribution of phenotypes can offer important insights on local adaptation, divergence, and speciation. The red-yellow Müllerian mimicry ring of Heliconius butterflies exhibits a wide diversity of color patterns across the Neotropics and is involved in multiple hybrid zones, making it a powerful system to investigate environmental drivers of phenotypic distributions. Using the distantly related Heliconius erato and Heliconius melpomene co-mimics and a multiscale distribution approach, we investigated whether distinct phenotypes of these species are associated with different environmental conditions. We show that Heliconius red-yellow phenotypic distribution is strongly driven by environmental gradients (especially thermal and precipitation variables), but that phenotype and environment associations vary with spatial scale. While co-mimics are usually predicted to occur in similar environments at large spatial scales, patterns at local scales are not always consistent (i.e., different variables are best predictors of phenotypic occurrence in different locations) or congruent (i.e., co-mimics show distinct associations with environment). We suggest that large-scale analyses are important for identifying how environmental factors shape broad mimetic phenotypic distributions, but that local studies are essential to understand the context-dependent biotic, abiotic, and historical mechanisms driving finer-scale phenotypic transitions.

The iHealth-T2D study: a cluster randomised trial for the prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes-a statistical analysis plan.

BACKGROUND: South Asians are at high risk of type 2 diabetes (T2D). Lifestyle modification is effective at preventing T2D amongst South Asians, but the approaches to screening and intervention are limited by high costs, poor scalability and thus low impact on T2D burden. An intensive family-based lifestyle modification programme for the prevention of T2D was developed. The aim of the iHealth-T2D trial is to compare the effectiveness of this programme with usual care. METHODS: The iHealth-T2D trial is designed as a cluster randomised controlled trial (RCT) conducted at 120 sites across India, Pakistan, Sri Lanka and the UK. A total of 3682 South Asian men and women with age between 40 and 70 years without T2D but at elevated risk for T2D [defined by central obesity (waist circumference ≥ 95 cm in Sri Lanka or ≥ 100 cm in India, Pakistan and the UK) and/or prediabetes (HbA1c ≥ 6.0%)] were included in the trial. Here, we describe in detail the statistical analysis plan (SAP), which was finalised before outcomes were available to the investigators. The primary outcome will be evaluated after 3 years of follow-up after enrolment to the study and is defined as T2D incidence in the intervention arm compared to usual care. Secondary outcomes are evaluated both after 1 and 3 years of follow-up and include biochemical measurements, anthropometric measurements, behavioural components and treatment compliance. DISCUSSION: The iHealth-T2D trial will provide evidence of whether an intensive family-based lifestyle modification programme for South Asians who are at high risk for T2D is effective in the prevention of T2D. The data from the trial will be analysed according to this pre-specified SAP. ETHICS AND DISSEMINATION: The trial was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and in conference presentations. TRIAL REGISTRATION: EudraCT 2016-001,350-18 . Registered on 14 April 2016. CLINICALTRIALS: gov NCT02949739 . Registered on 31 October 2016.

Reference equations for evaluation of spirometry function tests in South Asia, and among South Asians living in other countries.

BACKGROUND: There are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease. METHOD: We measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore. RESULTS: The Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sd z-score: FEV1 -0.94±1.05, FVC -0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p<0.001), and sex-specific reference equations using these three variables were highly accurate in both internal validation (z-scores: FEV1 0.03±0.99, FVC 0.04±0.97, FEV1/FVC -0.03±0.99) and external validation (z-scores: FEV1 0.31±0.99, FVC 0.24±0.97, FEV1/FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia. CONCLUSION: We present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population.

Genomics-based higher classification of the species-rich Hairstreaks (Lepidoptera: Lycaenidae: Eumaeini).

We propose a higher classification of the lycaenid hairstreak tribe Eumaeini - one of the youngest and most species-rich butterfly tribes - based on autosome, Lepidopteran Z sex chromosome, and mitochondrial protein-coding genes. The subtribe Neolycaenina Korb is a synonym of Callophryidina Tutt, and subtribe Tmolusina Bálint is a synonym of Strephonotina K. Johnson, Austin, Le Crom, & Salazar. Proposed names are Rhammina Prieto & Busby, new subtribe; Timaetina Busby & Prieto, new subtribe; Atlidina Martins & Duarte, new subtribe; Evenina Faynel & Grishin, new subtribe; Jantheclina Robbins & Faynel, new subtribe; Paiwarriina Lamas & Robbins, new subtribe; Cupatheclina Lamas & Grishin, new subtribe; Parrhasiina Busby & Robbins, new subtribe; Ipideclina Martins & Grishin, new subtribe; and Trichonidina Duarte & Faynel, new subtribe. Phylogenetic results from the autosome and Z sex chromosome analyses are similar. Future analyses of datasets with hundreds of terminal taxa may be more practical time-wise by focussing on the smaller number of sex chromosome sequences (2.6% of nuclear protein-coding sequences). The phylogenetic classification and biological summaries for each subtribe suggest that a variety of factors affected Eumaeini diversification. About a dozen kinds of male secondary sexual organs with frequent evolutionary gains and losses occur in Atlidina, Evenina, and Jantheclina (141 species combined). Females have been shown to use these organs to discriminate between conspecific and non-conspecific males, facilitating sympatry among close relatives. Eumaeina, Rhammina, and Timaetina (140 species combined) are overwhelmingly montane with some evidence for a higher incidence of sympatric diversification. Seven Neotropical lineages in five subtribes invaded the temperate parts of the Nearctic Region with a diversification increase in the Callophryidina (262 species). North American Satyrium and Callophrys then invaded the Palearctic at least once each, with a major species-richness increase in Satyrium. The evolution of litter feeding detritivores within Calycopidina (172 species) resulted in an increase in diversification rate compared with its flower-feeding sister lineage. Atlidina, Strephonotina, Parrhasiina, and Strymonina (562 species combined) each contain a mixture of genera that specialize on one or two caterpillar food plant families and genera that are polyphagous. These would be appropriate subtribes to assess how the breadth of caterpillar food plants and the frequency of host shifts affected diversification.

Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.

South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

Preventive Health Service Coverage Among Infants and Children at Six Maternal-Child Health Clinics in Western Kenya: A Cross-Sectional Assessment.

OBJECTIVES: Despite the substantial reduction of child mortality in recent decades, Kenya still strives to provide universal healthcare access and to meet other international benchmarks for child health. This study aimed to describe child health service coverage among children visiting six maternal and child health (MCH) clinics in western Kenya. METHODS: In a cross-sectional study of Kenyan children who are under the age of 5 years presenting to MCH clinics, child health records were reviewed to determine coverage of immunizations, growth monitoring, vitamin A supplementation, and deworming. Among 78 children and their caregivers, nearly 70% of children were fully vaccinated for their age. RESULTS: We found a significant disparity in full vaccination coverage by gender (p = 0.017), as males had 3.5 × higher odds of being fully vaccinated compared to females. Further, full vaccination coverage also varied across MCH clinic sites ranging from 43.8 to 92.9%. CONCLUSIONS FOR PRACTICE: Health service coverage for Kenyan children in this study is consistent with national and sub-national findings; however, our study found a significant gender equity gap in coverage at these six clinics that warrants further investigation to ensure that all children receive critical preventative services.

The iHealth-T2D study, prevention of type 2 diabetes amongst South Asians with central obesity and prediabetes: study protocol for a randomised controlled trial.

BACKGROUND: People from South Asia are at increased risk of type 2 diabetes (T2D). There is an urgent need to develop approaches for the prevention of T2D in South Asians that are cost-effective, generalisable and scalable across settings. HYPOTHESIS: Compared to usual care, the risk of T2D can be reduced amongst South Asians with central obesity or raised HbA1c, through a 12-month lifestyle modification programme delivered by community health workers. DESIGN: Cluster randomised clinical trial (1:1 allocation to intervention or usual care), carried out in India, Pakistan, Sri Lanka and the UK, with 30 sites per country (120 sites total). Target recruitment 3600 (30 participants per site) with annual follow-up for 3 years. ENTRY CRITERIA: South Asian, men or women, age 40-70 years with (i) central obesity (waist circumference ≥ 100 cm in India and Pakistan; ≥90 cm in Sri Lanka) and/or (ii) prediabetes (HbA1c 6.0-6.4% inclusive). EXCLUSION CRITERIA: known type 1 or 2 diabetes, normal or underweight (body mass index < 22 kg/m2); pregnant or planning pregnancy; unstable residence or planning to leave the area; and serious illness. ENDPOINTS: The primary endpoint is new-onset T2D at 3 years, defined as (i) HbA1c ≥ 6.5% or (ii) physician diagnosis and on treatment for T2D. Secondary endpoints at 1 and 3 years are the following: (i) physical measures: waist circumference, weight and blood pressure; (ii) lifestyle measures: smoking status, alcohol intake, physical activity and dietary intake; (iii) biochemical measures: fasting glucose, insulin and lipids (total and HDL cholesterol, triglycerides); and (iv) treatment compliance. INTERVENTION: Lifestyle intervention (60 sites) or usual care (60 sites). Lifestyle intervention was delivered by a trained community health worker over 12 months (5 one-one sessions, 4 group sessions, 13 telephone sessions) with the goal of the participants achieving a 7% reduction in body mass index and a 10-cm reduction in waist circumference through (i) improved diet and (ii) increased physical activity. Usual care comprised a single 30-min session of lifestyle modification advice from the community health worker. RESULTS: We screened 33,212 people for inclusion into the study. We identified 10,930 people who met study entry criteria, amongst whom 3682 agreed to take part in the intervention. Study participants are 49.2% female and aged 52.8 (SD 8.2) years. Clinical characteristics are well balanced between intervention and usual care sites. More than 90% of follow-up visits are scheduled to be complete in December 2020. Based on the follow-up to end 2019, the observed incidence of T2D in the study population is in line with expectations (6.1% per annum). CONCLUSION: The iHealth-T2D study will advance understanding of strategies for the prevention of diabetes amongst South Asians, use approaches for screening and intervention that are adapted for low-resource settings. Our study will thus inform the implementation of strategies for improving the health and well-being of this major global ethnic group. IRB APPROVAL: 16/WM/0171 TRIAL REGISTRATION: EudraCT 2016-001350-18 . Registered on 14 April 2016. ClinicalTrials.gov NCT02949739 . Registered on 31 October 2016, First posted on 31/10/2016.

Neurodevelopmental Outcomes of Young Children Born to HIV-Infected Mothers: A Pilot Study.

Introduction: Over 15 million children who were exposed to HIV perinatally but uninfected (HEU) are alive globally, and they are faced with multiple risk factors for poor neurodevelopment. While children who are HIV-infected (HIV+) appear to have worse neurodevelopmental scores compared to children unexposed and uninfected with HIV (HUU), the evidence is mixed in children who are HEU. This small descriptive pilot study aimed to compare neurodevelopmental scores of children who are HIV+, HEU, and HUU in Kenya. Methods: This cross-sectional pilot study included children ages 18-36 months who were HIV+, HEU, or HUU. Neurodevelopment was assessed, along with sociodemographic, lab, and growth data. Statistical analysis included descriptive statistics, one-way ANOVA, chi-squared, and adjusted linear regression models. Results: One hundred seventy two were included (n = 24 HIV+; n = 74 HEU; n = 74 HUU). Mothers of children who were HEU experienced more depressive symptoms (p < 0.001). The only neurodevelopmental differences were found among groups was that children who were HIV+ had higher receptive language scores (p = 0.007). Lower height-for-age z-scores and being left home alone were associated with worse neurodevelopmental scores. Conclusions: Being stunted, left completely alone for at least an hour within the last week, and having higher sociodemographic status were associated with worse neurodevelopmental scores. The higher levels of depressive symptoms within mothers of children who are HEU warrants further investigation.

Child Development Monitoring in Well-baby Clinics in Kenya.

BACKGROUND: Maternal and child health (MCH) clinics represent an integrated approach for providing healthcare to pregnant women and children 0-59 months of age. Although MCH clinics are also charged with monitoring child development, which involves tracking developmental milestones, it is unclear how these services are provided or perceived within the clinic. This study aimed to describe self-reported knowledge, perceptions, and practice of developmental monitoring in selected MCH clinics in western Kenya. METHODS: This cross-sectional descriptive study was conducted within six clinics. We administered a descriptive survey to measure caregiver and healthcare staff attitudes towards and awareness of developmental monitoring; we also reviewed MCH booklets to identify services received at the clinic. Data collection occurred over a period of one day at each of the six clinic sites. The data were analyzed using descriptive statistics. RESULTS: During the study period, 78 caregiver-child pairs presented to the clinics and had their MCH booklets reviewed. The median child age was three months (interquartile range [IQR]: 1-8 months). Most caregivers were aware of weight monitoring and immunization services; however, when asked specifically about developmental monitoring, only 2.6% of caregivers were aware this service was available at the clinics. Nearly 80% of caregivers reported that they would be very interested in developmental monitoring services. Thirty-three MCH healthcare staff were interviewed about services provided and goals of clinical care. Fewer healthcare staff (60.6%) identified their roles in developmental monitoring compared to their roles in growth (90.9%) and nutritional monitoring (84.8%). Developmental milestones had not been recorded in any of the 78 MCH booklets. However, 78.1% of healthcare staff indicated support for developmental screening. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: While developmental monitoring was valued by healthcare providers, it was not consistently performed at the six clinics in our study. We recommend further work to raise awareness about developmental monitoring and to measure the implications of increased caregiver knowledge and perceptions on developmental monitoring practice.

Anemia and Iron-Deficiency Anemia in Children Born to Mothers with HIV in Western Kenya.

The objective of this study was to determine and compare anemia and iron-deficiency anemia (IDA) rates in young Kenyan children who are HIV infected (HI), HIV exposed, uninfected (HEU), and HIV unexposed (HU). Questionnaires, anthropometrics, and blood samples were collected from HI, HEU, and HU aged 18 to 36 months. Descriptive statistics, Fisher's exact tests, and linear regression were used for analysis. Of 137 total participants, HI (n = 18), HEU (n = 70), and HU (n = 49), 61.1%, 53.6%, and 36.7%, respectively, were anemic, with mean hemoglobin levels highest in HU (P = .006). After adjusting for covariates, HI (ß = -9.6, 95% CI:-17.3 to -2.0) and HEU (ß = -7.4, 95% CI: -12.9 to -1.9) had lower hemoglobin levels compared with HU. The proportion of children with IDA did not differ significantly across groups (P = .08). HEU have rates of anemia and IDA similar to HI. Anemia risk is generally higher in HEU than HU, even after adjusting for covariates.

Cultural adaptation of the Bayley Scales of Infant and Toddler Development, 3rd Edition for use in Kenyan children aged 18-36 months: A psychometric study.

BACKGROUND: The Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) is frequently used in international child development research. No studies examine its psychometric properties when culturally adapted within the Kenyan context. AIMS: To culturally adapt the Bayley-III for use in Kenya and evaluate its validity and reliability. METHODS AND PROCEDURES: Forward and backward translation, cognitive interviews, and a brief pilot of culturally adapted items were performed. This psychometric study was part of another study on children born to mothers with HIV in Eldoret, Kenya. One hundred seventy-two children aged 18-36 months were assessed for cognition, receptive/expressive communication, and fine/gross motor domains using the Bayley-III. Confirmatory factor analysis (CFA), inter-scale Pearson correlations, internal consistency, t-tests, and test-retest reliability were performed. OUTCOMES AND RESULTS: The mean age of children was 22.8 (SD 4.5) months old; 52.7 % (n = 89) were male. CFA revealed that both two- and three-factor indices had good and comparable fit. Pearson correlations were high between fine motor and receptive communication (r >0.70). Internal consistency was very strong for all of the subtests, with Cronbach coefficient alpha scores ranging from 0.88 to 0.96. Known groups/convergent validity was confirmed with stunting and parental concern for delays. Test-retest reliability was good and did not differ substantially across groups. CONCLUSIONS AND IMPLICATIONS: The Kenyan adapted Bayley-III is a psychometrically acceptable tool to assess child development. The scaled and composite scores should not be used to define Kenyan developmental norms, but it can be useful for comparing groups within research settings.

Optimal vaccination strategy for dengue transmission in Kupang city, Indonesia.

Dengue is a public health problem with around 390 million cases annually and is caused by four distinct serotypes. Infection by one of the serotypes provides lifelong immunity to that serotype but have a higher chance of attracting the more dangerous forms of dengue in subsequent infections. Therefore, a perfect strategy against dengue is required. Dengue vaccine with 42-80% efficacy level has been licensed for the use in reducing disease transmission. However, this may increase the likelihood of obtaining the dangerous forms of dengue. In this paper, we have developed single and two-serotype dengue mathematical models to investigate the effects of vaccination on dengue transmission dynamics. The model is validated against dengue data from Kupang city, Indonesia. We investigate the effects of vaccination on seronegative and seropositive individuals and perform a global sensitivity analysis to determine the most influential parameters of the model. A sensitivity analysis suggests that the vaccination rate, the transmission probability and the biting rate have greater effects on the reduction of the proportion of dengue cases. Interestingly, with vaccine implementation, the mosquito-related parameters do not have significant impact on the reduction in the proportion of dengue cases. If the vaccination is implemented on seronegative individuals only, it may increase the likelihood of obtaining the severe dengue. To reduce the proportion of severe dengue cases, it is better to vaccinate seropositive individuals. In the context of Kupang City where the majority of individuals have been infected by at least one dengue serotype, the implementation of vaccination strategy is possible. However, understanding the serotype-specific differences is required to optimise the delivery of the intervention.