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1.
Cell ; 169(4): 597-609.e11, 2017 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-28475892

RESUMO

Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with pre-existing reactivity to DENV1 in humans.


Assuntos
Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Infecção por Zika virus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Brasil , Feminino , Humanos , Memória Imunológica , Leucócitos Mononucleares/imunologia , Masculino , México , Camundongos , Infecção por Zika virus/sangue
2.
Nature ; 630(8018): 912-919, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867041

RESUMO

The ancient city of Chichén Itzá in Yucatán, Mexico, was one of the largest and most influential Maya settlements during the Late and Terminal Classic periods (AD 600-1000) and it remains one of the most intensively studied archaeological sites in Mesoamerica1-4. However, many questions about the social and cultural use of its ceremonial spaces, as well as its population's genetic ties to other Mesoamerican groups, remain unanswered2. Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes5, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period.


Assuntos
Comportamento Ritualístico , DNA Antigo , Genoma Humano , Humanos , México , Genoma Humano/genética , Masculino , DNA Antigo/análise , História Antiga , Feminino , Sepultamento/história , Arqueologia , Gêmeos/genética , História Medieval
3.
Nature ; 622(7984): 784-793, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37821707

RESUMO

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.


Assuntos
Sequenciamento do Exoma , Genoma Humano , Genótipo , Hispânico ou Latino , Adulto , Humanos , África/etnologia , América/etnologia , Europa (Continente)/etnologia , Frequência do Gene/genética , Genética Populacional , Genoma Humano/genética , Técnicas de Genotipagem , Hispânico ou Latino/genética , Homozigoto , Mutação com Perda de Função/genética , México , Estudos Prospectivos
4.
Nature ; 622(7984): 775-783, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37821706

RESUMO

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.


Assuntos
Bancos de Espécimes Biológicos , Genética Médica , Genoma Humano , Genômica , Hispânico ou Latino , Humanos , Glicemia/genética , Glicemia/metabolismo , Estatura/genética , Índice de Massa Corporal , Interação Gene-Ambiente , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/classificação , Hispânico ou Latino/genética , Homozigoto , México , Fenótipo , Triglicerídeos/sangue , Triglicerídeos/genética , Reino Unido , Genoma Humano/genética
5.
Nature ; 624(7990): 122-129, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37993721

RESUMO

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.


Assuntos
Variação Genética , Povos Indígenas , Humanos , Agricultura/história , California/etnologia , Região do Caribe/etnologia , Etnicidade/genética , Etnicidade/história , Europa (Continente)/etnologia , Variação Genética/genética , História do Século XV , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História Antiga , História Medieval , Migração Humana/história , Povos Indígenas/genética , Povos Indígenas/história , Ilhas , Idioma/história , México/etnologia , Zea mays , Genoma Humano/genética , Genômica , Alelos
6.
N Engl J Med ; 390(6): 522-529, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38324485

RESUMO

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.


Assuntos
Surtos de Doenças , Fusariose , Fusarium , Doença Iatrogênica , Meningite Fúngica , Humanos , Antifúngicos/uso terapêutico , Fusariose/epidemiologia , Fusariose/etiologia , Fusarium/isolamento & purificação , Doença Iatrogênica/epidemiologia , Meningite Fúngica/epidemiologia , Meningite Fúngica/etiologia , México/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Internacionalidade , Imunocompetência , Farmacorresistência Fúngica , Analgesia Epidural/efeitos adversos
8.
Nature ; 599(7886): 611-615, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34819681

RESUMO

A band of intense rainfall extends more than 1,000 km along Mexico's west coast during Northern Hemisphere summer, constituting the core of the North American monsoon1,2. As in other tropical monsoons, this rainfall maximum is commonly thought to be thermally forced by emission of heat from land and elevated terrain into the overlying atmosphere3-5, but a clear understanding of the fundamental mechanism governing this monsoon is lacking. Here we show that the core North American monsoon is generated when Mexico's Sierra Madre mountains deflect the extratropical jet stream towards the Equator, mechanically forcing eastward, upslope flow that lifts warm and moist air to produce convective rainfall. These findings are based on analyses of dynamic and thermodynamic structures in observations, global climate model integrations and adiabatic stationary wave solutions. Land surface heat fluxes do precondition the atmosphere for convection, particularly in summer afternoons, but these heat fluxes alone are insufficient for producing the observed rainfall maximum. Our results indicate that the core North American monsoon should be understood as convectively enhanced orographic rainfall in a mechanically forced stationary wave, not as a classic, thermally forced tropical monsoon. This has implications for the response of the North American monsoon to past and future global climate change, making trends in jet stream interactions with orography of central importance.


Assuntos
Altitude , Atmosfera , Temperatura Alta , Chuva , Estações do Ano , Clima Tropical , México , Vento
9.
Nature ; 594(7862): 234-239, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33981035

RESUMO

Loss of gut microbial diversity1-6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.


Assuntos
Bactérias/isolamento & purificação , Biodiversidade , Evolução Biológica , Fezes/microbiologia , Microbioma Gastrointestinal , Genoma Bacteriano/genética , Interações entre Hospedeiro e Microrganismos , Antibacterianos/administração & dosagem , Bactérias/classificação , Bactérias/genética , Doença Crônica , Países Desenvolvidos , Países em Desenvolvimento , Dieta Ocidental , História Antiga , Humanos , Desenvolvimento Industrial/tendências , Methanobrevibacter/classificação , Methanobrevibacter/genética , Methanobrevibacter/isolamento & purificação , México , Comportamento Sedentário , Sudoeste dos Estados Unidos , Especificidade da Espécie , Simbiose
10.
Proc Natl Acad Sci U S A ; 121(23): e2311425121, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38814865

RESUMO

Theories of language development-informed largely by studies of Western, middleclass infants-have highlighted the language that caregivers direct to children as a key driver of language learning. However, some have argued that language development unfolds similarly across environmental contexts, including those in which childdirected language is scarce. This raises the possibility that children are able to learn from other sources of language in their environments, particularly the language directed to others in their environment. We explore this hypothesis with infants in an indigenous Tseltal-speaking community in Southern Mexico who are rarely spoken to, yet have the opportunity to overhear a great deal of other-directed language by virtue of being carried on their mothers' backs. Adapting a previously established gaze-tracking method for detecting early word knowledge to our field setting, we find that Tseltal infants exhibit implicit knowledge of common nouns (Exp. 1), analogous to their US peers who are frequently spoken to. Moreover, they exhibit comprehension of Tseltal honorific terms that are exclusively used to greet adults in the community (Exp. 2), representing language that could only have been learned through overhearing. In so doing, Tseltal infants demonstrate an ability to discriminate words with similar meanings and perceptually similar referents at an earlier age than has been shown among Western children. Together, these results suggest that for some infants, learning from overhearing may be an important path toward developing language.


Assuntos
Compreensão , Desenvolvimento da Linguagem , Humanos , Lactente , Feminino , Masculino , Compreensão/fisiologia , México , Idioma , Vocabulário
11.
Proc Natl Acad Sci U S A ; 121(43): e2410410121, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39405357

RESUMO

The conservation status of monarch butterflies in North America is a topic of intense scrutiny and debate. It is clear that winter colonies in Mexico are declining, yet some recent studies suggest that summer breeding populations are relatively stable and similar to historical abundances. One possible explanation for these discordant patterns is that fall migration success has been recently disrupted. Here, we use a relatively unexplored citizen-scientist dataset on the size of monarch "roosts," which are resting aggregations on vegetation, to infer changes in monarch abundance along the fall migration route over the last 17 y. We found that the timing of migration remained relatively unchanged while the flyway has generally become warmer and greener. Warmer and greener conditions were associated with larger roosts, yet we found steady, dramatic declines in roost sizes through time that were independent of climate and landscape factors. Roost sizes have declined as much as 80%, with losses increasing from north to south along the migration route. These findings suggest that failure during the fall migration could explain the apparent drop in monarch numbers from summer breeding to overwintering populations. This in turn suggests that conservation efforts that support fall migration success are most needed, such as providing high quality nectar plants along the migration route or limiting the planting of nonnative milkweeds that enhance monarch parasite loads. Overall, it appears the fall migration of monarch butterflies is under imminent threat, even if the species' overall survival is not.


Assuntos
Migração Animal , Borboletas , Estações do Ano , Animais , Borboletas/fisiologia , Migração Animal/fisiologia , México , Dinâmica Populacional
12.
Nature ; 582(7813): 530-533, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32494009

RESUMO

Archaeologists have traditionally thought that the development of Maya civilization was gradual, assuming that small villages began to emerge during the Middle Preclassic period (1000-350 BC; dates are calibrated throughout) along with the use of ceramics and the adoption of sedentism1. Recent finds of early ceremonial complexes are beginning to challenge this model. Here we describe an airborne lidar survey and excavations of the previously unknown site of Aguada Fénix (Tabasco, Mexico) with an artificial plateau, which measures 1,400 m in length and 10 to 15 m in height and has 9 causeways radiating out from it. We dated this construction to between 1000 and 800 BC using a Bayesian analysis of radiocarbon dates. To our knowledge, this is the oldest monumental construction ever found in the Maya area and the largest in the entire pre-Hispanic history of the region. Although the site exhibits some similarities to the earlier Olmec centre of San Lorenzo, the community of Aguada Fénix probably did not have marked social inequality comparable to that of San Lorenzo. Aguada Fénix and other ceremonial complexes of the same period suggest the importance of communal work in the initial development of Maya civilization.


Assuntos
Arquitetura/história , Civilização/história , Arqueologia , Teorema de Bayes , História Antiga , México , Datação Radiométrica
13.
Nature ; 584(7819): 87-92, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32699412

RESUMO

The initial colonization of the Americas remains a highly debated topic1, and the exact timing of the first arrivals is unknown. The earliest archaeological record of Mexico-which holds a key geographical position in the Americas-is poorly known and understudied. Historically, the region has remained on the periphery of research focused on the first American populations2. However, recent investigations provide reliable evidence of a human presence in the northwest region of Mexico3,4, the Chiapas Highlands5, Central Mexico6 and the Caribbean coast7-9 during the Late Pleistocene and Early Holocene epochs. Here we present results of recent excavations at Chiquihuite Cave-a high-altitude site in central-northern Mexico-that corroborate previous findings in the Americas10-17of cultural evidence that dates to the Last Glacial Maximum (26,500-19,000 years ago)18, and which push back dates for human dispersal to the region possibly as early as 33,000-31,000 years ago. The site yielded about 1,900 stone artefacts within a 3-m-deep stratified sequence, revealing a previously unknown lithic industry that underwent only minor changes over millennia. More than 50 radiocarbon and luminescence dates provide chronological control, and genetic, palaeoenvironmental and chemical data document the changing environments in which the occupants lived. Our results provide new evidence for the antiquity of humans in the Americas, illustrate the cultural diversity of the earliest dispersal groups (which predate those of the Clovis culture) and open new directions of research.


Assuntos
Migração Humana/história , Camada de Gelo , Altitude , Arqueologia , Teorema de Bayes , Cavernas , Diversidade Cultural , DNA Antigo/análise , História Antiga , Humanos , México
14.
Proc Natl Acad Sci U S A ; 120(5): e2204427120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36693105

RESUMO

Physical inactivity is a scourge to human health, promoting metabolic disease and muscle wasting. Interestingly, multiple ecological niches have relaxed investment into physical activity, providing an evolutionary perspective into the effect of adaptive physical inactivity on tissue homeostasis. One such example, the Mexican cavefish Astyanax mexicanus, has lost moderate-to-vigorous activity following cave colonization, reaching basal swim speeds ~3.7-fold slower than their river-dwelling counterpart. This change in behavior is accompanied by a marked shift in body composition, decreasing total muscle mass and increasing fat mass. This shift persisted at the single muscle fiber level via increased lipid and sugar accumulation at the expense of myofibrillar volume. Transcriptomic analysis of laboratory-reared and wild-caught cavefish indicated that this shift is driven by increased expression of pparγ-the master regulator of adipogenesis-with a simultaneous decrease in fast myosin heavy chain expression. Ex vivo and in vivo analysis confirmed that these investment strategies come with a functional trade-off, decreasing cavefish muscle fiber shortening velocity, time to maximal force, and ultimately maximal swimming speed. Despite this, cavefish displayed a striking degree of muscular endurance, reaching maximal swim speeds ~3.5-fold faster than their basal swim speeds. Multi-omic analysis suggested metabolic reprogramming, specifically phosphorylation of Pgm1-Threonine 19, as a key component enhancing cavefish glycogen metabolism and sustained muscle contraction. Collectively, we reveal broad skeletal muscle changes following cave colonization, displaying an adaptive skeletal muscle phenotype reminiscent to mammalian disuse and high-fat models while simultaneously maintaining a unique capacity for sustained muscle contraction via enhanced glycogen metabolism.


Assuntos
Characidae , Animais , Humanos , Characidae/genética , Evolução Biológica , Glicogênio , Músculos , México , Cavernas , Mamíferos
15.
Proc Natl Acad Sci U S A ; 120(9): e2212184120, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36802415

RESUMO

This study examines changes in the sociodemographic patterns of deportation and voluntary return of undocumented immigrants from the United States to Mexico during three US presidential administrations (2001 to 2019) with different immigration policies. Most previous studies examining these migration flows for the United States as a whole have relied exclusively on counts of deportees and returnees, thereby ignoring changes over the past 20 y in the characteristics of the undocumented population itself, i.e., the population at risk of deportation or voluntary return. We estimate Poisson models based on two data sources that permit us to compare changes in the sex, age, education, and marital status distributions of both deportees and voluntary return migrants with the corresponding changes in the undocumented population during the Bush, Obama, and Trump administrations: the Migration Survey on the Borders of Mexico-North (Encuesta sobre Migración en las Fronteras de México-Norte) for counts of deportees and voluntary return migrants and the Current Population Survey's Annual Social and Economic Supplement for estimated counts of the undocumented population living in the United States. We find that whereas disparities by sociodemographic characteristics in the likelihood of deportation generally increased beginning in Obama's first term, sociodemographic disparities in the likelihood of voluntary return generally decreased over this period. Despite heightened antiimmigrant rhetoric during the Trump administration, the changes in deportation and voluntary return migration to Mexico among the undocumented during Trump's term were part of a trend that began early in the Obama administration.


Assuntos
Migrantes , Imigrantes Indocumentados , Estados Unidos , Humanos , Emigração e Imigração , México/epidemiologia , Deportação
16.
Lancet ; 404(10462): 1525-1535, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39419054

RESUMO

BACKGROUND: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. METHODS: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0-50·4 Gy external beam radiotherapy delivered in 20-28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78-86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. FINDINGS: Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46-0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40-0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. INTERPRETATION: Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. FUNDING: Cancer Research UK and University College London-University College London Hospitals Biomedical Research Centre.


Assuntos
Carboplatina , Quimiorradioterapia , Cisplatino , Quimioterapia de Indução , Paclitaxel , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/tratamento farmacológico , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Adulto , Paclitaxel/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Índia , Braquiterapia/métodos , México
17.
N Engl J Med ; 386(6): 531-543, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34910859

RESUMO

BACKGROUND: NVX-CoV2373 is an adjuvanted, recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019 (Covid-19) in phase 2b-3 trials in the United Kingdom and South Africa, but its efficacy had not yet been tested in North America. METHODS: We conducted a phase 3, randomized, observer-blinded, placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults (≥18 years of age) who had not had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose. Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed. RESULTS: Of the 29,949 participants who underwent randomization between December 27, 2020, and February 18, 2021, a total of 29,582 (median age, 47 years; 12.6% ≥65 years of age) received at least one dose: 19,714 received vaccine and 9868 placebo. Over a period of 3 months, 77 cases of Covid-19 were noted - 14 among vaccine recipients and 63 among placebo recipients (vaccine efficacy, 90.4%; 95% confidence interval [CI], 82.9 to 94.6; P<0.001). Ten moderate and 4 severe cases occurred, all in placebo recipients, yielding vaccine efficacy against moderate-to-severe disease of 100% (95% CI, 87.0 to 100). Most sequenced viral genomes (48 of 61, 79%) were variants of concern or interest - largely B.1.1.7 (alpha) (31 of the 35 genomes for variants of concern, 89%). Vaccine efficacy against any variant of concern or interest was 92.6% (95% CI, 83.6 to 96.7). Reactogenicity was mostly mild to moderate and transient but was more frequent among NVX-CoV2373 recipients than among placebo recipients and was more frequent after the second dose than after the first dose. CONCLUSIONS: NVX-CoV2373 was safe and effective for the prevention of Covid-19. Most breakthrough cases were caused by contemporary variant strains. (Funded by Novavax and others; PREVENT-19 ClinicalTrials.gov number, NCT04611802.).


Assuntos
Vacinas contra COVID-19 , COVID-19/prevenção & controle , Eficácia de Vacinas , Adolescente , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Vacinas contra COVID-19/efeitos adversos , Humanos , Incidência , Masculino , México , Pessoa de Meia-Idade , SARS-CoV-2 , Método Simples-Cego , Estados Unidos
18.
Syst Biol ; 73(2): 323-342, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-38190300

RESUMO

The opposing forces of gene flow and isolation are two major processes shaping genetic diversity. Understanding how these vary across space and time is necessary to identify the environmental features that promote diversification. The detection of considerable geographic structure in taxa from the arid Nearctic has prompted research into the drivers of isolation in the region. Several geographic features have been proposed as barriers to gene flow, including the Colorado River, Western Continental Divide (WCD), and a hypothetical Mid-Peninsular Seaway in Baja California. However, recent studies suggest that the role of barriers in genetic differentiation may have been overestimated when compared to other mechanisms of divergence. In this study, we infer historical and spatial patterns of connectivity and isolation in Desert Spiny Lizards (Sceloporus magister) and Baja Spiny Lizards (Sceloporus zosteromus), which together form a species complex composed of parapatric lineages with wide distributions in arid western North America. Our analyses incorporate mitochondrial sequences, genomic-scale data, and past and present climatic data to evaluate the nature and strength of barriers to gene flow in the region. Our approach relies on estimates of migration under the multispecies coalescent to understand the history of lineage divergence in the face of gene flow. Results show that the S. magister complex is geographically structured, but we also detect instances of gene flow. The WCD is a strong barrier to gene flow, while the Colorado River is more permeable. Analyses yield conflicting results for the catalyst of differentiation of peninsular lineages in S. zosteromus. Our study shows how large-scale genomic data for thoroughly sampled species can shed new light on biogeography. Furthermore, our approach highlights the need for the combined analysis of multiple sources of evidence to adequately characterize the drivers of divergence.


Assuntos
Fluxo Gênico , Lagartos , Animais , Lagartos/genética , Lagartos/classificação , Clima Desértico , Filogenia , México , Genômica
20.
Proc Natl Acad Sci U S A ; 119(51): e2215615119, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36508656

RESUMO

In the hot dry spring of monsoon-driven environments, keeping an accurate calendar to regulate the annual planting of crops is of critical importance. Before the Spanish conquest, the Basin of Mexico had a highly productive farming system able to feed its very large population. However, how they managed to keep their farming dates in synchrony with the solar year is not known. In this paper, we show that the observation of sunrise against the Basin's eastern horizon could have provided an accurate solar calendar and that some important sunrise landmarks coincide well with the themes of seasonal festivities described in early codices. We also show that a long stone causeway in the summit of Mount Tlaloc aligns perfectly with the rising sun on February 23 to 24, in coincidence with the Basin's new year in the Mexica calendar. Third, we demonstrate that, when viewed from the sacred Mount Tepeyac in the bottom of the Basin, sunrise aligns with Mount Tlaloc also on February 24. The importance of Mount Tlaloc as a calendric landmark seems to be corroborated by illustrations and texts in ancient Mexica codices. Our findings demonstrate that by using carefully developed alignments with the rugged eastern horizon, the inhabitants of the Basin of Mexico were able to adjust their calendar to keep in synchrony with the solar year and successfully plan their corn harvests.


Assuntos
Agricultura , Produtos Agrícolas , Luz Solar , México
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