Signatures of Convergent Evolution and Natural Selection at the Alcohol Dehydrogenase Gene Region are Correlated with Agriculture in Ethnically Diverse Africans.

The alcohol dehydrogenase (ADH) family of genes encodes enzymes that catalyze the metabolism of ethanol into acetaldehyde. Nucleotide variation in ADH genes can affect the catalytic properties of these enzymes and is associated with a variety of traits, including alcoholism and cancer. Some ADH variants, including the ADH1B*48His (rs1229984) mutation in the ADH1B gene, reduce the risk of alcoholism and are under positive selection in multiple human populations. The advent of Neolithic agriculture and associated increase in fermented foods and beverages is hypothesized to have been a selective force acting on such variants. However, this hypothesis has not been tested in populations outside of Asia. Here, we use genome-wide selection scans to show that the ADH gene region is enriched for variants showing strong signals of positive selection in multiple Afroasiatic-speaking, agriculturalist populations from Ethiopia, and that this signal is unique among sub-Saharan Africans. We also observe strong selection signals at putatively functional variants in nearby lipid metabolism genes, which may influence evolutionary dynamics at the ADH region. Finally, we show that haplotypes carrying these selected variants were introduced into Northeast Africa from a West-Eurasian source within the last ∼2,000 years and experienced positive selection following admixture. These selection signals are not evident in nearby, genetically similar populations that practice hunting/gathering or pastoralist subsistence lifestyles, supporting the hypothesis that the emergence of agriculture shapes patterns of selection at ADH genes. Together, these results enhance our understanding of how adaptations to diverse environments and diets have influenced the African genomic landscape.

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes.

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Near doubling of Brazil's intensive row crop area since 2000.

Brazil has become a global leader in the production of commodity row crops such as soybean, sugarcane, cotton, and corn. Here, we report an increase in Brazilian cropland extent from 26.0 Mha in 2000 to 46.1 Mha in 2014. The states of Maranhão, Tocantins, Piauí, Bahia (collectively MATOPIBA), Mato Grosso, Mato Grosso do Sul, and Pará all more than doubled in cropland extent. The states of Goiás, Minas Gerais, and São Paulo each experienced >50% increases. The vast majority of expansion, 79%, occurred on repurposed pasture lands, and 20% was from the conversion of natural vegetation. Area of converted Cerrado savannas was nearly 2.5 times that of Amazon forests, and accounted for more than half of new cropland in MATOPIBA. Spatiotemporal dynamics of cropland expansion reflect market conditions, land use policies, and other factors. Continued extensification of cropland across Brazil is possible and may be likely under current conditions, with attendant benefits for and challenges to development.

Establishing the Key Outcomes for Pediatric Emergency Medical Services Research.

The evidence supporting best practices when treating children in the prehospital setting or even the effect emergency medical services (EMS) has on patient outcomes is limited. Standardizing the critical outcomes for EMS research will allow for focused and comparable effort among the small but growing group of pediatric EMS investigators on specific topics. Standardized outcomes will also provide the opportunity to collectively advance the science of EMS for children and demonstrate the effect of EMS on patient outcomes. This article describes a consensus process among stakeholders in the pediatric emergency medicine and EMS community that identified the critical outcomes for EMS care in five clinical areas (traumatic brain injury, general injury, respiratory disease/failure, sepsis, and seizures). These areas were selected based on both their known public health importance and their commonality in EMS encounters. Key research outcomes identified by participating stakeholders using a modified nominal group technique for consensus building, which included small group brainstorming and independent voting for ranking outcomes that were feasible and/or important for the field.

Types and rates of forest disturbance in Brazilian Legal Amazon, 2000-2013.

Deforestation rates in primary humid tropical forests of the Brazilian Legal Amazon (BLA) have declined significantly since the early 2000s. Brazil's national forest monitoring system provides extensive information for the BLA but lacks independent validation and systematic coverage outside of primary forests. We use a sample-based approach to consistently quantify 2000-2013 tree cover loss in all forest types of the region and characterize the types of forest disturbance. Our results provide unbiased forest loss area estimates, which confirm the reduction of primary forest clearing (deforestation) documented by official maps. By the end of the study period, nonprimary forest clearing, together with primary forest degradation within the BLA, became comparable in area to deforestation, accounting for an estimated 53% of gross tree cover loss area and 26 to 35% of gross aboveground carbon loss. The main type of tree cover loss in all forest types was agroindustrial clearing for pasture (63% of total loss area), followed by small-scale forest clearing (12%) and agroindustrial clearing for cropland (9%), with natural woodlands being directly converted into croplands more often than primary forests. Fire accounted for 9% of the 2000-2013 primary forest disturbance area, with peak disturbances corresponding to droughts in 2005, 2007, and 2010. The rate of selective logging exploitation remained constant throughout the study period, contributing to forest fire vulnerability and degradation pressures. As the forest land use transition advances within the BLA, comprehensive tracking of forest transitions beyond primary forest loss is required to achieve accurate carbon accounting and other monitoring objectives.

Patient Safety Perceptions in Pediatric Out-of-Hospital Emergency Care: Children's Safety Initiative.

OBJECTIVE: To characterize emergency medical service (EMS) providers' perceptions of the factors that contribute to safety events and errors in the out-of-hospital emergency care of children. STUDY DESIGN: We used a Delphi process to achieve consensus in a national sample of 753 emergency medicine physicians and EMS professionals. Convergence and stability were achieved in 3 rounds, and findings were reviewed and interpreted by a national expert panel. RESULTS: Forty-four (88%) states were represented, and 66% of participants were retained through all 3 rounds. From an initial set of 150 potential contributing factors derived from focus groups and literature, participants achieved consensus on the following leading contributors: airway management, heightened anxiety caring for children, lack of pediatric skill proficiency, lack of experience with pediatric equipment, and family members leading to delays or interference with care. Somewhat unexpectedly, medications and communication were low-ranking concerns. After thematic analysis, the overarching domains were ranked by their relative importance: (1) clinical assessment; (2) training; (3) clinical decision-making; (4) equipment; (5) medications; (6) scene characteristics; and (7) EMS cultural norms. CONCLUSIONS: These findings raise considerations for quality improvement and suggest important roles for pediatricians and pediatric emergency physicians in training, medical oversight, and policy development.

Annual Carbon Emissions from Deforestation in the Amazon Basin between 2000 and 2010.

Reducing emissions from deforestation and forest degradation (REDD+) is considered one of the most cost-effective strategies for mitigating climate change. However, historical deforestation and emission rates-critical inputs for setting reference emission levels for REDD+-are poorly understood. Here we use multi-source, time-series satellite data to quantify carbon emissions from deforestation in the Amazon basin on a year-to-year basis between 2000 and 2010. We first derive annual deforestation indicators by using the Moderate Resolution Imaging Spectroradiometer Vegetation Continuous Fields (MODIS VCF) product. MODIS indicators are calibrated by using a large sample of Landsat data to generate accurate deforestation rates, which are subsequently combined with a spatially explicit biomass dataset to calculate committed annual carbon emissions. Across the study area, the average deforestation and associated carbon emissions were estimated to be 1.59 ± 0.25 M ha•yr(-1) and 0.18 ± 0.07 Pg C•yr(-1) respectively, with substantially different trends and inter-annual variability in different regions. Deforestation in the Brazilian Amazon increased between 2001 and 2004 and declined substantially afterwards, whereas deforestation in the Bolivian Amazon, the Colombian Amazon, and the Peruvian Amazon increased over the study period. The average carbon density of lost forests after 2005 was 130 Mg C•ha(-1), ~11% lower than the average carbon density of remaining forests in year 2010 (144 Mg C•ha(-1)). Moreover, the average carbon density of cleared forests increased at a rate of 7 Mg C•ha(-1)•yr(-1) from 2005 to 2010, suggesting that deforestation has been progressively encroaching into high-biomass lands in the Amazon basin. Spatially explicit, annual deforestation and emission estimates like the ones derived in this study are useful for setting baselines for REDD+ and other emission mitigation programs, and for evaluating the performance of such efforts.

Diagnostic testing and treatment of pediatric headache in the emergency department.

OBJECTIVE: To describe the variability in diagnostic testing and treatment of headaches in children presenting to the emergency department (ED) with use of a nationally representative sample. STUDY DESIGN: This was a retrospective cohort study using the National Hospital Ambulatory Medical Care Survey during 2005-2009. To assess the use of evidence-based treatment, we analyzed all patients <18 years old in 2 groups: (1) primary discharge diagnosis of headache and (2) discharge diagnosis of migraine. RESULTS: Four hundred forty-eight sampled ED visits from 2005-2009 represented a national estimate of 1.7 million visits with a discharge diagnosis of headache. A total of 95 visits represented a national estimate of 340 000 visits with a discharge diagnosis of migraine. Median age was 13.1 years and 60% were female with a primary diagnosis of headache. In this group, neuroimaging was performed in 37% of patients and 39% underwent blood tests. Nonsteroidal anti-inflammatory drugs and opioids were most commonly used for treatment. For children with a discharge diagnosis of migraine, approximately 40% of patients received non-evidence-based treatment, most commonly with opioid medications, and >20% of patients underwent computed tomography scanning. CONCLUSIONS: There is significant variability in the evaluation and treatment of pediatric headache in the ED. Despite evidence-based clinical guidelines for migraine headache, a large number of children continue to receive opioids and ionizing radiation in the ED.