RESUMO
Understanding how interactions among microevolutionary forces generate genetic population structure of exploited species is vital to the implementation of management policies that facilitate persistence. Philopatry displayed by many coastal shark species can impact gene flow and facilitate selection, and has direct implications for the spatial scales of management. Here, genetic structure of the blacktip shark (Carcharhinus limbatus) was examined using a mixed-marker approach employing mitochondrial control region sequences and 4339 SNP-containing loci generated using ddRAD-Seq. Genetic variation was assessed among young-of-the-year sampled in 11 sites in waters of the United States in the western North Atlantic Ocean, including the Gulf of Mexico. Spatial and environmental analyses detected 68 nuclear loci putatively under selection, enabling separate assessments of neutral and adaptive genetic structure. Both mitochondrial and neutral SNP data indicated three genetically distinct units-the Atlantic, eastern Gulf, and western Gulf-that align with regional stocks and suggest regional philopatry by males and females. Heterogeneity at loci putatively under selection, associated with temperature and salinity, was observed among sites within Gulf units, suggesting local adaptation. Furthermore, five pairs of siblings were identified in the same site across timescales corresponding with female reproductive cycles. This indicates that females re-used a site for parturition, which has the potential to facilitate the sorting of adaptive variation among neighbouring sites. The results demonstrate differential impacts of microevolutionary forces at varying spatial scales and highlight the importance of conserving essential habitats to maintain sources of adaptive variation that may buffer species against environmental change.
Assuntos
Genética Populacional , Tubarões , Animais , Masculino , Feminino , Haplótipos/genética , Oceano Atlântico , Tubarões/genética , Estruturas GenéticasRESUMO
Colonization of the New World by marine taxa has been hypothesized to have occurred through the Tethys Sea or by crossing the East Pacific Barrier. To better understand patterns and timing of diversification, geological events can be coupled with time calibrated phylogenetic hypotheses to infer major drivers of diversification. Phylogenetic relationships among members of Sphoeroides, a genus of four toothed pufferfishes (Tetraodontiformes: Tetraodontidae) which are found nearly exclusively in the New World (eastern Pacific and western Atlantic), were reconstructed using sequences from ultra-conserved DNA elements, nuclear markers with clear homology among many vertebrate taxa. Hypotheses derived from concatenated maximum-likelihood and species tree summary methods support a paraphyletic Sphoeroides, with Colomesus deeply nested within the genus. Analyses also revealed S. pachygaster, a pelagic species with a cosmopolitan distribution, as the sister taxon to the remainder of Sphoeroides and recovered distinct lineages within S. pachygaster, indicating that this cosmopolitan species may represent a species complex. Ancestral range reconstruction may suggest the genus colonized the New World through the eastern Pacific before diversifying in the western Atlantic, though date estimates for these events are uncertain due to the lack of reliable fossil record for the genus.
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Tetraodontiformes , Animais , Filogenia , Tetraodontiformes/genética , DNA , Análise de Sequência de DNA , FósseisRESUMO
The genomic landscape of divergence-the distribution of differences among populations or species across the genome-is increasingly characterized to understand the role that microevolutionary forces such as natural selection and recombination play in causing and maintaining genetic divergence. This line of inquiry has also revealed chromosome structure variation to be an important factor shaping the landscape of adaptive genetic variation. Owing to a high prevalence of chromosome structure variation and the strong pressure for local adaptation necessitated by their sessile nature, bivalve molluscs are an ideal taxon for exploring the relationship between chromosome structure variation and local adaptation. Here, we report a population genomic survey of king scallop (Pecten maximus) across its natural range in the northeastern Atlantic Ocean, using a recent chromosome-level genome assembly. We report the presence of at least three large (12-22 Mb), putative chromosomal inversions associated with sea surface temperature and whose frequencies are in contrast to neutral population structure. These results highlight a potentially large role for recombination-suppressing chromosomal inversions in local adaptation and suggest a hypothesis to explain the maintenance of differences in reproductive timing found at relatively small spatial scales across king scallop populations.
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Inversão Cromossômica , Pecten , Adaptação Fisiológica/genética , Animais , Seleção Genética , TemperaturaRESUMO
BACKGROUND AND OBJECTIVES: Visceral angiosarcoma is rare and aggressive, accounting for 2% of soft tissue sarcomas. Using a national data set, we examine determinants of outcomes for patients presenting with this rare disease. METHODS: The 2004-2015 National Cancer Database was queried for patients with visceral angiosarcoma. Trends in treatment and outcomes were examined. Factors affecting overall survival (OS) were assessed with log-rank and Cox regression. RESULTS: Eight hundred and ninety-three patients with visceral angiosarcoma were identified (median age 65 years, male [63%], Charlson comorbidity index <1 [86%]). Tumor size was <5 cm in 20.7%, and 34.2% were moderate/high grade. Median OS was 3.8 months (95% CI: 3.4-4.4). By multivariate analysis, increased tumor grade and size, and liver/biliary origin demonstrated worse OS while surgery, radiation, and systemic chemotherapy demonstrated improved OS (all p < 0.001). Survival was similar between patients achieving R0 resection and those with R1/2 resection receiving chemotherapy by Kaplan-Meier analysis. CONCLUSIONS: Visceral angiosarcomas are rare tumors with poor outcomes. Liver/biliary origin, higher tumor grade, and larger tumor size demonstrate worse outcomes. While R0 resection remains the mainstay of treatment, patients with R1/R2 resection have improved survival with addition of chemotherapy. Consideration should be made for multimodal therapy in these patients.
Assuntos
Hemangiossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Idoso , Hemangiossarcoma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estudos Retrospectivos , Sarcoma/patologiaRESUMO
Neonates of hammerhead sharks (Sphyrnidae), Sphyrna lewini (Griffith and Smith, 1834), the sympatric cryptic species, Sphyrna gilberti Quattro et al., 2013, and their hybrids were captured in the western North Atlantic, along the coast of South Carolina, USA, between 2018 and 2019 and examined for gill monogenoids. Parasites were identified and redescribed from the gills of 79 neonates, and DNA sequences from partial fragments of the nuclear 28S ribosomal RNA (rDNA) and cytochrome c oxidase I mitochondrial DNA (COI) genes were generated to confirm species identifications. Three species of monogenoids from Hexabothriidae Price, 1942 and Monocotylidae Taschenberg, 1879 were determined and redescribed. Two species of Hexabothriidae, Erpocotyle microstoma (Brooks, 1934) and Erpocotyle sphyrnae (MacCallum, 1931), infecting both species of Sphyrna and hybrids; and 1 species of Monocotylidae, Loimosina wilsoni Manter, 1944, infecting only S. lewini and hybrids. Loimosina wilsoni 28S rDNA sequences matched those of Loimosina sp. from the southern coast of Brazil. Based on limited morphological analysis, Loimosina parawilsoni is likely a junior synonym of L. wilsoni. This is the first taxonomic study of monogenoids infecting S. gilberti and hybrids of S. gilberti and S. lewini.
Assuntos
Tubarões , Trematódeos , Animais , Tubarões/anatomia & histologia , Tubarões/parasitologia , Brânquias , Oceano Atlântico , Aves , DNA Ribossômico/genéticaRESUMO
INTRODUCTION: Studies largely focus on nicotine-containing e-cigarettes (NiCE) though non-nicotine-containing e-cigarettes (NoCE) exist; NoCE prevalence and patterns of use are largely unknown. This study examines self-reported prevalence and patterns of NiCE/NoCE use. METHODS: We analyzed adult (18+ years) data from the Population Assessment of Tobacco and Health (PATH) study from Wave 1 (2013-2014, n = 32,320), Wave 2 (2014-2015, n = 28,632), and Wave 3 (2015-2016, n = 28,148). We test associations between Wave 1 self-reported current NoCE/NiCE use status and demographic characteristics and assess the proportion of self-reported current NoCE/NiCE users at Wave 1 or Wave 2 who continue to use NoCE or NiCE, switch to NiCE or NoCE, discontinue e-cigarette use, switch to use other nicotine products (ONP), or add ONP use 1 year later (i.e., at Wave 2 or 3). RESULTS: Maintaining the same self-reported NiCE/NoCE and ONP use status 1 year later was the most common use pattern between waves. However, 15.65% of exclusive NoCE users in Wave 2 transitioned to NoCE plus nicotine product use in Wave 3. Also, some exclusive NoCE users transitioned to exclusive NiCE use (17.77% Waves 1-2; 11.55% Waves 2-3). DISCUSSION: Some exclusive NoCE users transitioned to NiCE or added nicotine product use, suggesting there may be other factors (e.g., familiarity with using an aerosolizing device) in addition to the presence of nicotine in influencing initiation or sustained use of nicotine products. IMPLICATIONS: Studies largely focus on nicotine-containing e-cigarettes (NiCE) though non-nicotine-containing e-cigarettes (NoCE) exist; this study adds to the literature by describing demographic characteristics and tobacco use of adult self-reported NoCE users. In addition, the study examines transitions in self-reported NoCE/NiCE use, revealing that some exclusive NoCE users transition to other nicotine product use 1 year later.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Autorrelato , Produtos do Tabaco/estatística & dados numéricos , Tabagismo/epidemiologia , Vaping/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Projetos de Pesquisa , Produtos do Tabaco/classificação , Estados Unidos/epidemiologia , Adulto JovemRESUMO
INTRODUCTION: Pursuant to the Tobacco Control Act (TCA), the US Food and Drug Administration (FDA) is developing new cigarette health warnings to convey the negative health consequences of cigarette smoking. AIMS AND METHODS: This study assessed which of 15 revised warning statements (10 on topics similar to TCA statements and 5 on other topics) promoted greater understanding of cigarette smoking risks relative to TCA statements. In February 2018, adolescent and adult smokers and adolescents susceptible to smoking (n = 2505) completed an online experiment. Control condition participants viewed TCA statements; treatment condition participants viewed combinations of TCA and revised statements. Analyses compared revised statements to TCA statements on the same health topic or to randomly selected TCA statements if there were no statements on the same topic. RESULTS: Relative to TCA statements, 12 of 15 revised statements were more likely to be considered new information, and 12 resulted in more self-reported learning. Three revised statements made participants think more about health risks than TCA statements; the reverse was true for one revised statement. Participants rated most TCA and revised statements as moderately believable and informative. Seven revised statements were found to be less believable and factual, and one revised statement more believable and factual. Treatment condition participants correctly selected more smoking-related health conditions than control condition participants (13.79 versus 12.42 of 25). CONCLUSIONS: Findings suggest that revised statements can promote greater understanding of cigarette smoking risks. Results informed FDA's selection of warning text that was paired with images for testing in a follow-up study. IMPLICATIONS: The US FDA may adjust the text of the cigarette warning statements provided in the TCA if the revised statements promote greater public understanding of the negative health consequences of cigarette smoking. Most of the revised warning statements tested were more likely to be considered new information and resulted in more self-reported learning compared with paired TCA statements, providing support for using revised statements as part of cigarette health warnings. These results informed the development of pictorial cigarette warnings by FDA that were tested in a follow-up study and included in a proposed rule.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Rotulagem de Produtos , Produtos do Tabaco , Educação em Saúde , Humanos , Estados Unidos , United States Food and Drug AdministrationRESUMO
INTRODUCTION: The Family Smoking Prevention and Tobacco Control Act requires cigarette packages and advertisements to bear health warnings with "color graphics depicting the negative health consequences of smoking." AIMS AND METHODS: This study assessed whether new US Food and Drug Administration developed pictorial cigarette warnings (PCW) increased understanding of smoking-related risks relative to the current Surgeon General's (SG) warnings. In March-May 2019, adolescent and adult smokers and nonsmokers participated in an online experiment with three sessions completed over approximately 2 weeks. Participants viewed 1 of 16 PCW (treatment conditions) or an SG warning (control) on mock cigarette packages and advertisements. Measures assessed whether warnings provided new information, induced thinking about risks, changed smoking-related health beliefs, and were accurately recalled, among other outcomes. RESULTS: The majority of PCW (≥13 conditions) resulted in greater learning of new information, higher self-reported learning, and greater reports of thinking about smoking risks; they were viewed as more informative, understandable, and attention-drawing compared with the control condition. Most participants believed the warning were factual, although 8 PCW were perceived as less factual than the control. There were changes toward more agreement with health beliefs for 11 PCW between Sessions 1 and 2 and 7 PCW between Sessions 1 and 3. Participants in all treatment conditions were more likely than control condition participants to correctly recall the warning. Across outcomes, PCW related to addiction, death, and quitting did not perform as well as other PCW. CONCLUSIONS: Many of the PCW tested increased understanding of the risks associated with cigarette smoking relative to current SG warnings. IMPLICATIONS: The Tobacco Control Act requires cigarette packages and advertisements to bear PCW depicting the negative health consequences of smoking. This study tested whether any of 16 newly proposed PCW increased understanding of smoking-related risks relative to existing SG warnings. Results suggest that most PCW tested, particularly those related to less widely known health effects, resulted in greater learning of new information, higher self-reported learning, and greater reports of thinking about smoking risks compared with SG warnings. These results, along with other factors, informed the US Food and Drug Administration's selection of proposed PCW.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Rotulagem de Produtos , Produtos do Tabaco , Adolescente , Adulto , Humanos , Adulto JovemRESUMO
The almaco jack, Seriola rivoliana, is a circumtropical pelagic fish of importance both in commercial fisheries and in aquaculture. To understand levels of genetic diversity within and among populations in the wild, population genetic structure and the relative magnitude of migration were assessed using mtDNA sequence data and single nucleotide polymorphisms (SNPs) from individuals sampled from locations in the Pacific and Atlantic Oceans. A total of 25 variable sites of cytochrome c oxidase subunit 1 and 3678 neutral SNPs were recovered. Three genetic groups were identified, with both marker types distributed in different oceanic regions: Pacific-1 in central Pacific, Pacific-2 in eastern Pacific and Atlantic in western Atlantic. Nonetheless, the analysis of SNP identified a fourth population in the Pacific coast of Baja California Sur, Mexico (Pacific-3), whereas that of mtDNA did not. This mito-nuclear discordance is likely explained by a recently diverged Pacific-3 population. In addition, two mtDNA haplogroups were found within the western Atlantic, likely indicating that the species came into the Atlantic from the Indian Ocean with historical gene flow from the eastern Pacific. Relative gene flow among ocean basins was low with r m < 0.2, whereas in the eastern Pacific it was asymmetric and higher from south to north (r m > 0.79). The results reflect the importance of assessing genetic structure and gene flow of natural populations for the purposes of sustainable management.
Assuntos
Conservação dos Recursos Naturais , Pesqueiros , Variação Genética , Perciformes/genética , Animais , DNA Mitocondrial/genética , Fluxo Gênico , Genética Populacional , México , Oceanos e Mares , Perciformes/classificação , Clima TropicalRESUMO
Hybridization between closely related species has been documented across a wide range of taxa but has not been well studied in elasmobranchs. Hammerhead sharks have drawn global conservation concern because they experience some of the highest mortality rates among sharks when interacting with fisheries. Here we report on the detection of hybrids between the globally distributed scalloped hammerhead ( Sphyrna lewini) and recently described Carolina hammerhead ( S. gilberti) which are only known from the western Atlantic Ocean. Using a genomics approach, 10 first-generation hybrids and 15-17 backcrosses were detected from 554 individuals. The identification of backcrosses demonstrates hybrids are viable, and all backcrosses but one involved a scalloped hammerhead. All hybrids but one possessed Carolina hammerhead mtDNA, indicating sex-biased gene flow between species. Repeated hybridization and backcrossing with scalloped hammerheads could lead to the loss of endemic Carolina hammerheads.
Assuntos
Tubarões , Animais , Oceano Atlântico , Pesqueiros , Hibridização Genética , SimpatriaRESUMO
INTRODUCTION: Emerging tobacco products have become increasingly popular, and the US Food and Drug Administration extended its authority to all products meeting the definition of a tobacco product in 2016. These changes may lead to shifts in public perceptions about tobacco products and regulation, and national surveys are attempting to assess these perceptions at the population level. This article describes the item development and cognitive interviewing of the tobacco product and regulation perception items included in two tobacco-focused cycles of the Health Information National Trends Survey (HINTS-FDA), referred to as HINTS-FDA. METHODS: Cognitive interviewing was used to investigate how respondents comprehended and responded to tobacco product and regulation perception items. Adult participants (n = 20) were selected purposively to oversample current tobacco users and were interviewed in two iterative rounds. Weighted descriptive statistics from the fielded HINTS-FDA surveys (N = 5474) were also calculated. RESULTS: Items were generally interpreted as intended, and participants meaningfully discriminated between tobacco products when assessing addiction perceptions. Response selection issues involved inconsistent reporting among participants with little knowledge or ambivalent opinions about either government regulation or tobacco products and ingredients, which resolved when a "don't know" response option was included in the survey. The fielded survey found that a non-negligible proportion of the population do not have clear perceptions of emerging tobacco products or government regulation. CONCLUSIONS: A "don't know" response option is helpful for items assessing many emerging tobacco products but presents several analytic challenges that should be carefully considered. Multiple items assessing specific tobacco product and regulation perception items are warranted in future surveys. IMPLICATIONS: The findings from this study can serve as a foundation for future surveys that assess constructs related to emerging tobacco products, harm perceptions across multiple tobacco products, and tobacco-related government regulatory activities. The data provide unique insight into item-specific motivation for selecting a "don't know" response option for tobacco survey items.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários , Produtos do Tabaco/legislação & jurisprudência , Tabagismo/prevenção & controle , Regulamentação Governamental , Humanos , Estados UnidosRESUMO
BACKGROUND: Southern flounder, Paralichthys lethostigma, historically support a substantial fishery along the Atlantic and Gulf coasts of the southern United States. Low year-class strengths over the past few years in the western Gulf of Mexico have raised concern that spawning stocks may be overfished. Current management of the resource includes releasing hatchery-raised juveniles to restock bays and estuaries; additionally, there is a growing interest in the potential for commercial aquaculture of the species. Currently, genomic resources for southern flounder do not exist. Here, we used two hatchery-reared families and double-digest, restriction-site-associated DNA (ddRAD) sequencing to create a reduced-representation genomic library consisting of several thousand single nucleotide polymorphisms (SNPs) located throughout the genome. RESULTS: The relative position of each SNP-containing locus was determined to create a high-density genetic map spanning the 24 linkage groups of the southern flounder genome. The consensus map was used to identify regions of shared synteny between southern flounder and seven other fish species for which genome assemblies are available. Finally, syntenic blocks were used to localize genes identified from transcripts in European flounder as potentially being involved in ecotoxicological and osmoregulatory responses, as well as QTLs associated with growth and disease resistance in Japanese flounder, on the southern flounder linkage map. CONCLUSIONS: The information provided by the linkage map will enrich restoration efforts by providing a foundation for interpreting spatial genetic variation within the species, ultimately furthering an understanding of the adaptive potential and resilience of southern flounder to future changes in local environmental conditions. Further, the map will facilitate the use of genetic markers to enhance restoration and commercial aquaculture.
Assuntos
Mapeamento Cromossômico/métodos , Linguado/genética , Genômica/métodos , Polimorfismo de Nucleotídeo Único , Animais , Meio Ambiente , Ligação Genética , Marcadores Genéticos , Variação Genética , Genoma , Locos de Características Quantitativas , Análise de Sequência de DNA , SinteniaRESUMO
Sequencing reduced-representation libraries of restriction site-associated DNA (RADseq) to identify single nucleotide polymorphisms (SNPs) is quickly becoming a standard methodology for molecular ecologists. Because of the scale of RADseq data sets, putative loci cannot be assessed individually, making the process of filtering noise and correctly identifying biologically meaningful signal more difficult. Artefacts introduced during library preparation and/or bioinformatic processing of SNP data can create patterns that are incorrectly interpreted as indicative of population structure or natural selection. Therefore, it is crucial to carefully consider types of errors that may be introduced during laboratory work and data processing, and how to minimize, detect and remove these errors. Here, we discuss issues inherent to RADseq methodologies that can result in artefacts during library preparation and locus reconstruction resulting in erroneous SNP calls and, ultimately, genotyping error. Further, we describe steps that can be implemented to create a rigorously filtered data set consisting of markers accurately representing independent loci and compare the effect of different combinations of filters on four RAD data sets. At last, we stress the importance of publishing raw sequence data along with final filtered data sets in addition to detailed documentation of filtering steps and quality control measures.
RESUMO
The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For the 2018 update, new sections were added on "Signs and Symptoms of SCLC" and "Principles of Pathologic Review."
Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Pulmonares/terapia , Oncologia/normas , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Quimiorradioterapia/métodos , Quimiorradioterapia/normas , Irradiação Craniana/métodos , Irradiação Craniana/normas , Relação Dose-Resposta à Radiação , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Oncologia/métodos , Estadiamento de Neoplasias , Pneumonectomia/métodos , Pneumonectomia/normas , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/secundário , Sociedades Médicas/normas , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
Understanding factors associated with youth e-cigarette openness and curiosity are important for assessing probability of future use. We examined how e-cigarette harm perceptions and advertising exposure are associated with openness and curiosity among tobacco naive youth. Findings from the 2015 National Youth Tobacco Survey (NYTS) were analyzed. The 2015 NYTS is a nationally representative survey of 17,711 U.S. middle and high school students. We calculated weighted prevalence estimates of never users of tobacco products (cigarettes, cigars/cigarillos/little cigars, waterpipe/hookah, smokeless tobacco, bidis, pipes, dissolvables, e-cigarettes) who were open to or curious about e-cigarette use, by demographics. Weighted regression models examined how e-cigarette harm perceptions and advertising exposure were associated with openness using e-cigarettes and curiosity about trying e-cigarettes. Among respondents who never used tobacco products, 23.8% were open to using e-cigarettes and 25.4% were curious. Respondents that perceived e-cigarettes cause a lot of harm had lower odds of both openness (ORâ¯=â¯0.10, 95% CIâ¯=â¯0.07, 0.15) and curiosity about e-cigarettes (ORâ¯=â¯0.10, 95% CIâ¯=â¯0.07, 0.13) compared to those with lower harm perception. Respondents who reported high exposure to e-cigarette advertising in stores had greater odds of being open to e-cigarette use (ORâ¯=â¯1.22, 95% CIâ¯=â¯1.03, 1.44) and highly curious (ORâ¯=â¯1.25, 95% CIâ¯=â¯1.01, 1.53) compared to those not highly exposed. These findings demonstrate that youth exposed to e-cigarette advertising are open and curious to e-cigarette use. These findings could help public health practitioners better understand the interplay of advertising exposure and harm perceptions with curiosity and openness to e-cigarette use in a rapidly changing marketplace.
Assuntos
Publicidade , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Comportamento Exploratório , Percepção , Estudantes/estatística & dados numéricos , Vaping/efeitos adversos , Adolescente , Criança , Feminino , Humanos , Masculino , Prevalência , Instituições Acadêmicas , Fumar , Estudantes/psicologia , Inquéritos e Questionários , Vaping/psicologia , Adulto JovemRESUMO
BACKGROUND: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma. METHODS: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12). RESULTS: Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy. CONCLUSIONS: The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640-4647. © 2017 American Cancer Society.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Lipossarcoma/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Indazóis , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: This multicentre, open-label study evaluated the efficacy and safety of SPI-1620, an analogue of endothelin-1, administered in combination with docetaxel as second-line treatment for patients with advanced biliary tract cancer (ABTC). METHODS: Eligible patients received continuous cycles of combination therapy with SPI-1620 (11 µg m-2) and docetaxel (75 mg m-2) intravenously every 3 weeks until disease progression (PD) or intolerable toxicity. Tumour response was evaluated using computed tomography or magnetic resonance imaging every 2 cycles (6 weeks). The primary efficacy end point was progression-free survival (PFS); secondary end points included overall response rate (ORR), duration of response, and overall survival (OS) that were estimated using the Kaplan-Meier method. RESULTS: Of the 30 enrolled patients, 25 patients had qualifying events (PD or death), 1 patient was nonevaluable, and 4 patients were censored at the time of their last tumour assessment. Our primary end point of PFS ⩾5 months was not reached. Median PFS was 2.6 months (95% confidence interval (CI): 1.4-2.8), ranging from 0.7 to 8.4 months. The ORR was 10.3% (95% CI: 0.02-0.27). Eleven additional patients achieved stable disease. The OS was 4.87 months. The most common grade 3-4 toxicities were febrile neutropenia and neutropenia. CONCLUSIONS: The addition of docetaxel to SPI-1620 in second-line ABTC did not meet the pre-specified primary end point of PFS ⩾5 months in unselected patient population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Biliar/tratamento farmacológico , Endotelinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Intervalo Livre de Doença , Docetaxel , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Endotelinas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Fragmentos de Peptídeos/efeitos adversos , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
Phylogenetic relationships among members of the New World searobin genera Bellator and Prionotus (Family Triglidae, Subfamily Prionotinae) and among other searobins in the families Triglidae and Peristediidae were investigated using both mitochondrial and nuclear DNA sequences. Phylogenetic hypotheses derived from maximum likelihood and Bayesian methodologies supported a monophyletic Prionotinae that included four well resolved clades of uncertain relationship; three contained species in the genus Prionotus and one contained species in the genus Bellator. Bellator was always recovered within the genus Prionotus, a result supported by post hoc model testing. Two nominal species of Prionotus (P. alatus and P. paralatus) were not recovered as exclusive lineages, suggesting the two may comprise a single species. Phylogenetic hypotheses also supported a monophyletic Triglidae but only if armored searobins (Family Peristediidae) were included. A robust morphological assessment is needed to further characterize relationships and suggest classification of clades within Prionotinae; for the time being we recommend that Bellator be considered a synonym of Prionotus. Relationships between armored searobins (Family Peristediidae) and searobins (Family Triglidae) and relationships within Triglidae also warrant further study.
Assuntos
Perciformes/classificação , Perciformes/genética , Filogenia , Animais , Teorema de Bayes , Núcleo Celular/genética , DNA Mitocondrial/genética , Funções Verossimilhança , Cadeias de Markov , Método de Monte Carlo , Especificidade da EspécieRESUMO
The purpose of this study was to investigate susceptibility and ever use of tobacco products among adolescents and young adults in the US. Cross-sectional analysis of Wave 1(2013-2014) adolescent (12-17year-olds; n=13,651) and young adult (18-24year-olds; n=9112) data from the nationally-representative Population Assessment of Tobacco and Health (PATH) Study was conducted. At 12years, 5% were ever tobacco users and 36% were susceptible to use. Seventy percent were susceptible at age 17years, and the same proportion were ever users at age 22years. Susceptibility levels were comparable for cigarettes and e-cigarette (28.6% and 27.4%, respectively), followed by hookah (22.0%), pipes (17.5%), cigars (15.2%), and smokeless tobacco (9.7%). Non-Hispanic (NH) Black (Adjusted Odds Ratio [ORadj]=1.36; 95% Confidence Limit [CL], 1.18-1.56) and Hispanic (ORadj=1.34: 95% CL,1.19-1.49) adolescent never- users were more likely to be susceptible to future use of a tobacco product than NH Whites. Susceptibility was higher with age (15-17yrs. vs 12-14yrs.: ORadj=1.69; 95% CL, 1.55-1.85) and parental education (college graduates vs less than HS education: ORadj=1.22, 95% CL, 1.08-1.39). Compared to exclusive users of hookah, cigars, or smokeless products, larger proportions of exclusive e-cigarette ever users were also susceptible to cigarette use. Among adolescents, lower levels of ever use of tobacco products are often counterbalanced by higher levels of susceptibility for future use, which may suggest delayed initiation in some groups. Ever users of a given tobacco product were more susceptible to use other tobacco products, putting them at risk for future multiple tobacco product use.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Fumar/epidemiologia , Produtos do Tabaco/estatística & dados numéricos , Adolescente , Comportamento do Adolescente , Criança , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Fumar/etnologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
The National Cancer Institute (NCI) developed the Health Information National Trends Survey (HINTS) to monitor population trends in cancer communication practices, information preferences, health risk behaviors, attitudes, and cancer knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a unique data resource for informing its health communication endeavors and partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self-administered paper instrument sent by mail May 29 to September 8, 2015, using a random probability-based sample of U.S. postal addresses stratified by county-level smoking rates, with an oversampling of high and medium-high smoking strata to increase the yield of current smokers responding to the survey. The response rate for HINTS-FDA 2015 was 33% (N = 3,738). The yield of current smokers (n = 495) was lower than expected, but the sampling strategy achieved the goal of obtaining more former smokers (n = 1,132). Public-use HINTS-FDA 2015 data and supporting documentation have been available for download and secondary data analyses since June 2016 at http://hints.cancer.gov . NCI and FDA encourage the use of HINTS-FDA for health communication research and practice related to tobacco-related communications, public knowledge, and behaviors as well as beliefs and actions related to medical products and dietary supplements.