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1.
Cell ; 186(5): 923-939.e14, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36868214

RESUMO

We conduct high coverage (>30×) whole-genome sequencing of 180 individuals from 12 indigenous African populations. We identify millions of unreported variants, many predicted to be functionally important. We observe that the ancestors of southern African San and central African rainforest hunter-gatherers (RHG) diverged from other populations >200 kya and maintained a large effective population size. We observe evidence for ancient population structure in Africa and for multiple introgression events from "ghost" populations with highly diverged genetic lineages. Although currently geographically isolated, we observe evidence for gene flow between eastern and southern Khoesan-speaking hunter-gatherer populations lasting until ∼12 kya. We identify signatures of local adaptation for traits related to skin color, immune response, height, and metabolic processes. We identify a positively selected variant in the lightly pigmented San that influences pigmentation in vitro by regulating the enhancer activity and gene expression of PDPK1.


Assuntos
Aclimatação , Pigmentação da Pele , Humanos , Sequenciamento Completo do Genoma , Densidade Demográfica , África , Proteínas Quinases Dependentes de 3-Fosfoinositídeo
2.
Am J Hum Genet ; 111(5): 927-938, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38701745

RESUMO

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.


Assuntos
Malária Falciparum , Telômero , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , África Subsaariana/epidemiologia , População Negra/etnologia , População Negra/genética , Doenças Endêmicas , Leucócitos/metabolismo , Malária Falciparum/genética , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidade , População da África Subsaariana , Telômero/genética , Homeostase do Telômero/genética , Botsuana , Tanzânia , Camarões , População da África Austral
3.
Proc Natl Acad Sci U S A ; 121(28): e2318029121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38950360

RESUMO

Indonesia has experienced rapid primary forest loss, second only to Brazil in modern history. We examined the fates of Indonesian deforested areas, immediately after clearing and over time, to quantify deforestation drivers in Indonesia. Using time-series satellite data, we tracked degradation and clearing events in intact and degraded natural forests from 1991 to 2020, as well as land use trajectories after forest loss. While an estimated 7.8 Mha (SE = 0.4) of forest cleared during this period had been planted with oil palms by 2020, another 8.8 Mha (SE = 0.4) remained unused. Of the 28.4 Mha (SE = 0.7) deforested, over half were either initially left idle or experienced crop failure before a land use could be detected, and 44% remained unused for 5 y or more. A majority (54%) of these areas were cleared mechanically (not by escaped fires), and in cases where idle lands were eventually converted to productive uses, oil palm plantations were by far the most common outcome. The apparent deliberate creation of idle deforested land in Indonesia and subsequent conversion of idle areas to oil palm plantations indicates that speculation and land banking for palm oil substantially contribute to forest loss, although failed plantations could also contribute to this dynamic. We also found that in Sumatra, few lowland forests remained, suggesting that a lack of remaining forest appropriate for palm oil production, together with an extensive area of banked deforested land, may partially explain slowing forest loss in Indonesia in recent years.


Assuntos
Conservação dos Recursos Naturais , Florestas , Indonésia , Árvores/crescimento & desenvolvimento , Agricultura
4.
Trends Genet ; 38(2): 152-168, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34740451

RESUMO

There has been a rapid increase in human genome sequencing in the past two decades, resulting in the identification of millions of previously unknown genetic variants. However, African populations are under-represented in sequencing efforts. Additional sequencing from diverse African populations and the construction of African-specific reference genomes is needed to better characterize the full spectrum of variation in humans. However, sequencing alone is insufficient to address the molecular and cellular mechanisms underlying variable phenotypes and disease risks. Determining functional consequences of genetic variation using multi-omics approaches is a fundamental post-genomic challenge. We discuss approaches to close the knowledge gaps about African genomic diversity and review advances in African integrative genomic studies and their implications for precision medicine.


Assuntos
Genoma Humano , Genômica , Genoma Humano/genética , Humanos , Medicina de Precisão
5.
Proc Natl Acad Sci U S A ; 119(12): e2116267119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35294280

RESUMO

Hydrophobic interactions have long been established as essential for stabilizing struc-tured proteins as well as drivers of aggregation, but the impact of hydrophobicity on thefunctional significance of sequence variants has rarely been considered in a genome-wide context. Here we test the role of hydrophobicity on functional impact across70,000 disease- and non­disease-associated single-nucleotide polymorphisms (SNPs),using enrichment of disease association as an indicator of functionality. We find thatfunctional impact is uncorrelated with hydrophobicity of the SNP itself and only weaklycorrelated with the average local hydrophobicity, but is strongly correlated with boththe size and minimum hydrophobicity of the contiguously hydrophobic sequence (or"blob") that contains the SNP. Disease association is found to vary by more than sixfoldas a function of contiguous hydrophobicity parameters, suggesting utility as a prior foridentifying causal variation. We further find signatures of differential selective constrainton hydrophobic blobs and that SNPs splitting a long hydrophobic blob or joiningtwo short hydrophobic blobs are particularly likely to be disease associated. Trends arepreserved for both aggregating and nonaggregating proteins, indicating that the role ofcontiguous hydrophobicity extends well beyond aggregation risk.


Assuntos
Exoma , Genoma Humano , Aminoácidos/química , Exoma/genética , Genoma Humano/genética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Proteínas/química
6.
Proc Natl Acad Sci U S A ; 119(21): e2123000119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35580180

RESUMO

Human genomic diversity has been shaped by both ancient and ongoing challenges from viruses. The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a devastating impact on population health. However, genetic diversity and evolutionary forces impacting host genes related to SARS-CoV-2 infection are not well understood. We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection (angiotensin converting enzyme 2 [ACE2], transmembrane protease serine 2 [TMPRSS2], dipeptidyl peptidase 4 [DPP4], and lymphocyte antigen 6 complex locus E [LY6E]). We analyzed data from 2,012 ethnically diverse Africans and 15,977 individuals of European and African ancestry with electronic health records and integrated with global data from the 1000 Genomes Project. At ACE2, we identified 41 nonsynonymous variants that were rare in most populations, several of which impact protein function. However, three nonsynonymous variants (rs138390800, rs147311723, and rs145437639) were common among central African hunter-gatherers from Cameroon (minor allele frequency 0.083 to 0.164) and are on haplotypes that exhibit signatures of positive selection. We identify signatures of selection impacting variation at regulatory regions influencing ACE2 expression in multiple African populations. At TMPRSS2, we identified 13 amino acid changes that are adaptive and specific to the human lineage compared with the chimpanzee genome. Genetic variants that are targets of natural selection are associated with clinical phenotypes common in patients with COVID-19. Our study provides insights into global variation at host genes related to SARS-CoV-2 infection, which have been shaped by natural selection in some populations, possibly due to prior viral infections.


Assuntos
COVID-19 , África , Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Variação Genética , Humanos , Fenótipo , SARS-CoV-2/genética , Seleção Genética
7.
Nat Chem Biol ; 18(3): 305-312, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34969973

RESUMO

The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.


Assuntos
Ceramidas , Esfingolipídeos , Bactérias/genética , Bactérias/metabolismo , Vias Biossintéticas , Ceramidas/química , Ceramidas/metabolismo , Humanos , Filogenia , Esfingolipídeos/química , Esfingolipídeos/metabolismo
8.
Nature ; 563(7732): E26, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30275480

RESUMO

In this Letter, errors in Supplementary Table 1 have been corrected.

9.
Nature ; 560(7720): 639-643, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089903

RESUMO

Land change is a cause and consequence of global environmental change1,2. Changes in land use and land cover considerably alter the Earth's energy balance and biogeochemical cycles, which contributes to climate change and-in turn-affects land surface properties and the provision of ecosystem services1-4. However, quantification of global land change is lacking. Here we analyse 35 years' worth of satellite data and provide a comprehensive record of global land-change dynamics during the period 1982-2016. We show that-contrary to the prevailing view that forest area has declined globally5-tree cover has increased by 2.24 million km2 (+7.1% relative to the 1982 level). This overall net gain is the result of a net loss in the tropics being outweighed by a net gain in the extratropics. Global bare ground cover has decreased by 1.16 million km2 (-3.1%), most notably in agricultural regions in Asia. Of all land changes, 60% are associated with direct human activities and 40% with indirect drivers such as climate change. Land-use change exhibits regional dominance, including tropical deforestation and agricultural expansion, temperate reforestation or afforestation, cropland intensification and urbanization. Consistently across all climate domains, montane systems have gained tree cover and many arid and semi-arid ecosystems have lost vegetation cover. The mapped land changes and the driver attributions reflect a human-dominated Earth system. The dataset we developed may be used to improve the modelling of land-use changes, biogeochemical cycles and vegetation-climate interactions to advance our understanding of global environmental change1-4,6.


Assuntos
Planeta Terra , Ecossistema , Monitoramento Ambiental , Atividades Humanas/estatística & dados numéricos , Agricultura/estatística & dados numéricos , Agricultura/tendências , Mudança Climática/estatística & dados numéricos , Agricultura Florestal/estatística & dados numéricos , Agricultura Florestal/tendências , Atividades Humanas/tendências , Imagens de Satélites , Árvores/crescimento & desenvolvimento
10.
J Fish Biol ; 104(3): 713-722, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987173

RESUMO

Billfish rostra potentially have several functions; however, their role in feeding is unequivocal in some species. Recent work linked morphological variation in rostral micro-teeth to differences in feeding behavior in two billfish species, the striped marlin (Kajikia audax) and the sailfish (Istiophorus platypterus). Here, we present the rostral micro-tooth morphology for a third billfish species, the blue marlin (Makaira nigricans), for which the use of the rostrum in feeding behavior is still undocumented from systematic observations in the wild. We measured the micro-teeth on rostrum tips of blue marlin, striped marlin, and sailfish using a micro-computed tomography approach and compared the tooth morphology among the three species. This was done after an analysis of video-recorded hunting behavior of striped marlin and sailfish revealed that both species strike prey predominantly with the first third of the rostrum, which provided the justification to focus our analysis on the rostrum tips. In blue marlin, intact micro-teeth were longer compared to striped marlin but not to sailfish. Blue marlin had a higher fraction of broken teeth than both striped marlin and sailfish, and broken teeth were distributed more evenly on the rostrum. Micro-tooth regrowth was equally low in both marlin species but higher in sailfish. Based on the differences and similarities in the micro-tooth morphology between the billfish species, we discuss potential feeding-related rostrum use in blue marlin. We put forward the hypothesis that blue marlin might use their rostra in high-speed dashes as observed in striped marlin, rather than in the high-precision rostral strikes described for sailfish, possibly focusing on larger prey organisms.


Assuntos
Perciformes , Animais , Microtomografia por Raio-X , Perciformes/anatomia & histologia , Comportamento Alimentar
11.
Mol Biol Evol ; 39(10)2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36026493

RESUMO

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.


Assuntos
Álcool Desidrogenase , Alcoolismo , Acetaldeído , Agricultura , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Alcoolismo/genética , Etanol/metabolismo , Etiópia , Humanos , Nucleotídeos , Seleção Genética
12.
Prehosp Emerg Care ; 27(2): 252-262, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35394855

RESUMO

OBJECTIVE: Whether ambulance transport patterns are optimized to match children to high-readiness emergency departments (EDs) and the resulting effect on survival are unknown. We quantified the number of children transported by 9-1-1 emergency medical services (EMS) to high-readiness EDs, additional children within 30 minutes of a high-readiness ED, and the estimated effect on survival. METHODS: This was a cross-sectional study using data from the National EMS Information System for 5,461 EMS agencies in 28 states from 1/1/2012 through 12/31/2019, matched to the 2013 National Pediatric Readiness Project assessment of ED pediatric readiness. We performed a geospatial analysis of children 0 to 17 years requiring 9-1-1 EMS transport to acute care hospitals, including day-, time-, and traffic-adjusted estimates for driving times to all EDs within 30 minutes of the scene. We categorized receiving hospitals by quartile of ED pediatric readiness using the weighted Pediatric Readiness Score (wPRS, range 0-100) and defined a high-risk subgroup of children as a proxy for admission. We used published estimates for the survival benefit of high readiness EDs to estimate the number of lives saved. RESULTS: There were 808,536 children transported by EMS, of whom 253,541 (31.4%) were high-risk. Among the 2,261 receiving hospitals, the median wPRS was 70 (IQR 57-85, range 26-100) and the median number of receiving hospitals within 30 minutes was 4 per child (IQR 2-11, range 1 to 53). Among all children, 411,685 (50.9%) were taken to EDs in the highest quartile of pediatric readiness, and 180,547 (22.3%) children transported to lower readiness EDs were within 30 minutes of a high readiness ED. Findings were similar among high-risk children. Based on high-risk children, we estimated that 3,050 pediatric lives were saved by transport to high-readiness EDs and an additional 1,719 lives could have been saved by shifting transports to high readiness EDs within 30 minutes. CONCLUSIONS: Approximately half of children transported by EMS were taken to high-readiness EDs and an additional one quarter could have been transported to such an ED, with measurable effect on survival.


Assuntos
Serviços Médicos de Emergência , Criança , Humanos , Ambulâncias , Estudos Transversais , Serviço Hospitalar de Emergência , Coleta de Dados
13.
Am J Emerg Med ; 70: 61-65, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37201452

RESUMO

OBJECTIVE: To evaluate the association between capillary refill time (CRT) measured by a medical device and sepsis among patients presenting to the Emergency Department (ED). METHODS: This prospective observational study enrolled adult and pediatric patients during ED triage when sepsis was considered a potential diagnosis by the triage nurse. Patients were enrolled at an academic medical center between December 2020 and June 2022. CRT was measured by a research assistant using an investigational medical device. The outcomes included sepsis and septic shock defined using sep-3 criteria, septic shock defined as IV antibiotics and a vasopressor requirement, ICU admission, and hospital mortality. Other measures included patient demographics and vital signs at ED triage. We evaluated univariate associations between CRT and sepsis outcomes. RESULTS: We enrolled 563 patients in the study, 48 met Sep-3 criteria, 5 met Sep-3 shock criteria, and 11 met prior septic shock criteria (IV antibiotics and vasopressors to maintain mean arterial pressure of 65). Sixteen patients were admitted to the ICU. The mean age was 49.1 years, and 51% of the cohort was female. The device measured CRT was significantly associated with the diagnosis of sepsis by sep-3 criteria (OR 1.23, 95% CI 1.06-1-43), septic shock by sep-3 criteria (OR 1.57, 95% CI 1.02-2.40), and septic shock defined as receipt of IV antibiotics and a vasopressor requirement (OR 1.37, 95% CI 1.03-1.82). Patients with CRT >3.5 s measured by the DCR device had an odds ratio of 4.67 (95%CI 1.31-16.1) of septic shock (prior definition), and an odds ratio of 3.97 (95% CI 1.99-7.92) of ICU admission, supporting the potential for the 3.5-s cutoff of the DCR measurement. CONCLUSIONS: CRT measured by a medical device at ED triage was associated with the diagnosis of sepsis. Objective CRT measurement using a medical device may be a relatively simple way to improve sepsis diagnosis during ED triage.


Assuntos
Sepse , Choque Séptico , Adulto , Humanos , Feminino , Criança , Pessoa de Meia-Idade , Triagem , Estudos Retrospectivos , Serviço Hospitalar de Emergência , Vasoconstritores/uso terapêutico , Mortalidade Hospitalar , Antibacterianos
14.
Pediatr Emerg Care ; 39(8): 569-573, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252055

RESUMO

OBJECTIVE: Dehydration is a commonly encountered problem worldwide. Current clinical assessment is limited by subjectivity and limited provider training with children. The objective of this study is to investigate a new noninvasive, point-of-care technology that measures capillary refill combined with patient factors to accurately diagnose dehydration. METHODS: This is a prospective observational study at a tertiary care children's hospital in Buenos Aires, Argentina. Patients were eligible if younger than 10 years who presented to the emergency department with vomiting and/or diarrhea whom the triage nurse deems to be potentially dehydrated. Patients had the digital capillary refill device done on presentation in addition to standard of care vital signs and weight. Patients had serial weights measured on hospital scales throughout their stay. The primary outcome was dehydration, which was calculated as a percent change in weight from admission to discharge. RESULTS: Seventy-six children were enrolled in the study with 56 included in the final analysis. A stepwise forward method selection chose malnutrition, temperature, and systolic blood pressure for the multivariable model. The area under the curve for the final model was fair (0.7431). To further look into the utility of such a device in the home setting where blood pressure is not available often, we reran the model without systolic blood pressure. The area under the curve for the final model was 0.7269. CONCLUSIONS: The digital capillary refill point-of-care device combined with readily available patient-specific factors may improve the ability to detect pediatric dehydration and facilitate earlier treatment or transfer to higher levels of care.


Assuntos
Desidratação , Sistemas Automatizados de Assistência Junto ao Leito , Criança , Humanos , Lactente , Desidratação/diagnóstico , Desidratação/terapia , Estudos Prospectivos , Diarreia , Tecnologia
15.
Hum Mol Genet ; 29(18): 3014-3020, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32821950

RESUMO

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of LTL variance versus 27% in AAms and 34% in EAms. Adjustment for genetic variation removed the LTL differences among SSAs. LTL genetic variation among SSAs, with the longest LTL in the San, supports the hypothesis that longer LTL was ancestral in humans. Identifying factors driving LTL variation in Africa may have important ramifications for LTL-associated diseases.


Assuntos
Doenças Cardiovasculares/genética , Neoplasias/genética , Homeostase do Telômero/genética , Telômero/genética , Adulto , África Subsaariana/epidemiologia , Negro ou Afro-Americano/genética , População Negra/genética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/epidemiologia , Filogeografia , População Branca/genética
16.
Ann Emerg Med ; 79(2): 118-131, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34538500

RESUMO

STUDY OBJECTIVE: While often prioritized in the resuscitation of patients with out-of-hospital cardiac arrest, the optimal timing of advanced airway insertion is unknown. We evaluated the association between the timing of advanced airway (laryngeal tube and endotracheal intubation) insertion attempt and survival to hospital discharge in adult out-of-hospital cardiac arrest. METHODS: We performed a secondary analysis of the Pragmatic Airway Resuscitation Trial (PART), a clinical trial comparing the effects of laryngeal tube and endotracheal intubation on outcomes after adult out-of-hospital cardiac arrest. We stratified the cohort by randomized airway strategy (laryngeal tube or endotracheal intubation). Within each subset, we defined a time-dependent propensity score using patients, arrest, and emergency medical services systems characteristics. Using the propensity score, we matched each patient receiving an initial attempt of laryngeal tube or endotracheal intubation with a patient at risk of receiving laryngeal tube or endotracheal intubation attempt within the same minute. RESULTS: Of 2,146 eligible patients, 1,091 (50.8%) and 1,055 (49.2%) were assigned to initial laryngeal tube and endotracheal intubation strategies, respectively. In the propensity score-matched cohort, timing of laryngeal tube insertion attempt was not associated with survival to hospital discharge: 0 to lesser than 5 minutes (risk ratio [RR]=1.35, 95% confidence interval [CI] 0.53 to 3.44); 5 to lesser than10 minutes (RR=1.07, 95% CI 0.66 to 1.73); 10 to lesser than 15 minutes (RR=1.17, 95% CI 0.60 to 2.31); or 15 to lesser than 20 minutes (RR=2.09, 95% CI 0.35 to 12.47) after advanced life support arrival. Timing of endotracheal intubation attempt was also not associated with survival: 0 to lesser than 5 minutes (RR=0.50, 95% CI 0.05 to 4.87); 5 to lesser than10 minutes (RR=1.20, 95% CI 0.51 to 2.81); 10 to lesser than15 minutes (RR=1.03, 95% CI 0.49 to 2.14); 15 to lesser than 20 minutes (RR=0.85, 95% CI 0.30 to 2.42); or more than/equal to 20 minutes (RR=0.71, 95% CI 0.07 to 7.14). CONCLUSION: In the PART, timing of advanced airway insertion attempt was not associated with survival to hospital discharge.


Assuntos
Intubação Intratraqueal/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Ressuscitação/métodos , Tempo para o Tratamento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/mortalidade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
J Intensive Care Med ; 37(9): 1159-1164, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35306923

RESUMO

Background: Monitoring of capillary refill time (CRT) is a common bedside assessment used to ascertain peripheral perfusion in a patient for a vast array of conditions. The literature has shown that a change in CRT can be used to recognize life-threatening conditions that cause decreased perfusion, such as sepsis, and aid in resuscitation. The current practice for calculating CRT invites subjectivity and produces a highly variable result. Innovative technology may be able to standardize this process and provide a reliable and accurate value for use in diagnostics and treatment. This study aimed to assess a new technology (DCR by ProMedix Inc.) for rapid, bedside, and noninvasive detection of CRT. Methods: This was a secondary analysis of a prospective observational study evaluating the accuracy of new technology towards CRT-guided diagnosis of sepsis. It was carried out in the adult emergency departments (ED) of an academic tertiary care medical center. Patients seeking care in the ED were determined eligible if they were > 18 years in age and exhibited chief complaints suggestive of possible sepsis. The CRT produced by the technology was compared to the gold standard manual waveform assessment. Results: 218 consecutive subject enrollments were included and multiple measurements were made on each patient. Data with irregular waveforms were excluded. A total of 692 waveforms were evaluated for CRT values by a pair of trained PhD biomedical engineers. The average age of the cohort was 50.62 and 51.4% female. Results showed a Pearson correlation coefficient of 0.91 for the device CRT compared to the CRT gold standard. The Pearson correlation coefficient for the two independent engineering review of the waveform data was 0.98. This device produces accurate, consistent results and eliminates the subjectivity of CRT measurements that is in practice currently.


Assuntos
Sepse , Adulto , Feminino , Hemodinâmica , Humanos , Masculino , Microcirculação , Perfusão , Sepse/diagnóstico , Sepse/terapia , Tecnologia
18.
Clin Trials ; 19(1): 62-70, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34875893

RESUMO

Emergency Medical Services personnel are often the first to intervene in the care of critically ill children. Airway management is a fundamental step in prehospital resuscitation, yet there is significant variation in current prehospital airway management practices. Our objective is to present a methodologic approach to determine the optimal strategy for prehospital pediatric airway management. We describe the conceptual premise for the Pediatric Prehospital Airway Resuscitation Trial, a novel Bayesian adaptive sequential platform trial. We developed an innovative design to enable comparison of the three predominant prehospital pediatric airway techniques (bag-mask-ventilation, supraglottic airway insertion, and endotracheal intubation) in three distinct disease groups (cardiac arrest, major trauma, and other respiratory failure). We used a Bayesian statistical approach to provide flexible modeling that can adapt based on prespecified rules according to accumulating trial data with patient enrollment continuing until stopping rules are met. The approach also allows the comparison of multiple interventions in sequence across the different disease states. This Bayesian hierarchical model will be the primary analysis method for the Pediatric Prehospital Airway Resuscitation Trial. The model integrates information across subgroups, a technique known as "borrowing" to generate accurate global and subgroup-specific estimates of treatment effects and enables comparisons of airway intervention arms within the overarching trial. We will use this Bayesian hierarchical linear model that adjusts for subgroup to estimate treatment effects within each subgroup. The model will predict a patient-centered score of 30-day intensive care unit-free survival using arm, subgroup, and emergency medical services agency as predictors. The novel approach of Pediatric Prehospital Airway Resuscitation Trial will provide a feasible method to determine the optimal strategy for prehospital pediatric airway management and may transform the design of future prehospital resuscitation trials.


Assuntos
Manuseio das Vias Aéreas , Ensaios Clínicos como Assunto , Projetos de Pesquisa , Teorema de Bayes , Reanimação Cardiopulmonar , Criança , Serviços Médicos de Emergência/métodos , Humanos , Intubação Intratraqueal/métodos , Insuficiência Respiratória/terapia
19.
Proc Natl Acad Sci U S A ; 116(2): 428-435, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30559198

RESUMO

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.


Assuntos
Conservação dos Recursos Naturais , Produção Agrícola , Floresta Úmida , Brasil , Humanos
20.
J Fish Biol ; 100(5): 1205-1213, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35194781

RESUMO

Recent comparative studies of billfishes (Istiophoridae and Xiphiidae) have provided evidence of differences in the form and function of the rostra (bill) among species. Here, we report the discovery of a new structure, lacuna rostralis, on the rostra of sailfish Istiophorus platypterus, which is absent on the rostra of swordfish Xiphias gladius, striped marlin Kajikia audax and blue marlin Makaira nigricans. The lacunae rostralis are small cavities that contain teeth. They were found on the ventral rostrum surface of all I. platypterus specimens examined and dorsally in half of them. Ventrally, the lacunae rostralis were most prominent in the mid-section of the rostrum. Dorsally, they occurred closer to the tip. The density of lacunae rostralis increased towards the rostrum tip but, because they are smaller in size, the percentage of rostrum coverage decreased. The teeth located within the lacunae rostralis were found to be different in size, location and orientation from the previously identified micro-teeth of billfish. We propose two potential functions of the lacunae rostralis that both relate to the use of the bill in feeding: mechanoreception of prey before tapping it with the bill and more efficient prey handling via the creation of suction, or physical grip.


Assuntos
Perciformes , Animais , Peixes
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