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MOTIVATION: This paper presents Parkour, a software package for sample processing and quality management of next generation sequencing data and samples. RESULTS: Starting with user requests, Parkour allows tracking and assessing samples based on predefined quality criteria through different stages of the sample preparation workflow. Ideally suited for academic core laboratories, the software aims to maximize efficiency and reduce turnaround time by intelligent sample grouping and a clear assignment of staff to work units. Tools for automated invoicing, interactive statistics on facility usage and simple report generation minimize administrative tasks. Provided as a web application, Parkour is a convenient tool for both deep sequencing service users and laboratory personal. A set of web APIs allow coordinated information sharing with local and remote bioinformaticians. The flexible structure allows workflow customization and simple addition of new features as well as the expansion to other domains. AVAILABILITY AND IMPLEMENTATION: The code and documentation are available at https://github.com/maxplanck-ie/parkour. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Sequenciamento de Nucleotídeos em Larga Escala , Software , Humanos , Laboratórios , Fluxo de TrabalhoRESUMO
BACKGROUND: Hospitalized patients with cancer experience a high symptom burden, which is associated with poor health outcomes and increased health care utilization. However, studies investigating symptom monitoring interventions in this population are lacking. We conducted a pilot randomized trial to assess the feasibility and preliminary efficacy of a symptom monitoring intervention to improve symptom management in hospitalized patients with advanced cancer. PATIENTS AND METHODS: We randomly assigned patients with advanced cancer who were admitted to the inpatient oncology service to a symptom monitoring intervention or usual care. Patients in both arms self-reported their symptoms daily (Edmonton Symptom Assessment System and Patient Health Questionnaire-4). Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily team rounds. The primary end point of the study was feasibility. We defined the intervention as feasible if >75% of participants hospitalized >2 days completed >2 symptom reports. We observed daily rounds to determine whether clinicians discussed and developed a plan to address patients' symptoms. We used regression models to assess intervention effects on patients' symptoms throughout their hospitalization, readmission risk, and hospital length of stay (LOS). RESULTS: Among 150 enrolled patients (81.1% enrollment), 94.2% completed >2 symptom reports. Clinicians discussed 60.4% of the symptom reports and developed a plan to address the symptoms highlighted by the symptom reports 20.8% of the time. Compared with usual care, intervention patients had a greater proportion of days with lower psychological distress (B = 0.12, P = 0.008), but no significant difference in the proportion of days with improved Edmonton Symptom Assessment System-physical symptoms (B = 0.07, P = 0.138). Intervention patients had lower readmission risk (hazard ratio = 0.68, P = 0.224), although this difference was not significant. We found no significant intervention effects on hospital LOS (B = 0.16, P = 0.862). CONCLUSIONS: This symptom monitoring intervention is feasible and demonstrates encouraging preliminary efficacy for improving patients' symptoms and readmission risk.ClinicalTrials.gov identifier NCT02891993.
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Hospitalização/estatística & dados numéricos , Monitorização Ambulatorial/métodos , Neoplasias/psicologia , Neoplasias/terapia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Avaliação de Sintomas/métodos , Telemedicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Psicometria , Qualidade de Vida , Autorrelato , Índice de Gravidade de Doença , Adulto JovemRESUMO
Dietary intake of methyl donors, such as folic acid and methionine, shows considerable intra-individual variation in human populations. While it is recognized that maternal departures from the optimum of dietary methyl donor intake can increase the risk for mental health issues and neurological disorders in offspring, it has not been explored whether paternal dietary methyl donor intake influences behavioral and cognitive functions in the next generation. Here, we report that elevated paternal dietary methyl donor intake in a mouse model, transiently applied prior to mating, resulted in offspring animals (methyl donor-rich diet (MD) F1 mice) with deficits in hippocampus-dependent learning and memory, impaired hippocampal synaptic plasticity and reduced hippocampal theta oscillations. Gene expression analyses revealed altered expression of the methionine adenosyltransferase Mat2a and BK channel subunit Kcnmb2, which was associated with changes in Kcnmb2 promoter methylation in MD F1 mice. Hippocampal overexpression of Kcnmb2 in MD F1 mice ameliorated altered spatial learning and memory, supporting a role of this BK channel subunit in the MD F1 behavioral phenotype. Behavioral and gene expression changes did not extend into the F2 offspring generation. Together, our data indicate that paternal dietary factors influence cognitive and neural functions in the offspring generation.
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Cognição/fisiologia , Suplementos Nutricionais/efeitos adversos , Herança Paterna/fisiologia , Animais , Metilação de DNA , Dieta , Epigênese Genética , Pai , Ácido Fólico/metabolismo , Hipocampo/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Metionina/metabolismo , Metionina Adenosiltransferase , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Herança Paterna/genética , Regiões Promotoras GenéticasRESUMO
Active learning methods have been shown to be superior to traditional lecture in terms of student achievement, and our findings on the use of Peer-Led Team Learning (PLTL) concur. Students in our introductory biology course performed significantly better if they engaged in PLTL. There was also a drastic reduction in the failure rate for underrepresented minority (URM) students with PLTL, which further resulted in closing the achievement gap between URM and non-URM students. With such compelling findings, we strongly encourage the adoption of Peer-Led Team Learning in undergraduate Science, Technology, Engineering, and Mathematics (STEM) courses.
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Grupos Minoritários , Ensino/métodos , Aprendizagem , Grupo AssociadoRESUMO
The objective of the study was to estimate the genetic relationships between detailed reproductive traits derived from ultrasound examination of the reproductive tract and a range of performance traits in Holstein-Friesian dairy cows. The performance traits investigated included calving performance, milk production, somatic cell score (i.e., logarithm transformation of somatic cell count), carcass traits, and body-related linear type traits. Detailed reproductive traits included (1) resumed cyclicity at the time of examination, (2) multiple ovulations, (3) early ovulation, (4) heat detection, (5) ovarian cystic structures, (6) embryo loss, and (7) uterine score, measured on a 1 (little or no fluid with normal tone) to 4 (large quantity of fluid with a flaccid tone) scale, based on the tone of the uterine wall and the quantity of fluid present in the uterus. (Co)variance components were estimated using a repeatability animal linear mixed model. Genetic merit for greater milk, fat, and protein yield was associated with a reduced ability to resume cyclicity postpartum (genetic correlations ranged from -0.25 to -0.15). Higher genetic merit for milk yield was also associated with a greater genetic susceptibility to multiple ovulations. Genetic predisposition to elevated somatic cell score was associated with a decreased likelihood of cyclicity postpartum (genetic correlation of -0.32) and a greater risk of both multiple ovulations (genetic correlation of 0.25) and embryo loss (genetic correlation of 0.32). Greater body condition score was genetically associated with an increased likelihood of resumption of cyclicity postpartum (genetic correlation of 0.52). Genetically heavier, fatter carcasses with better conformation were also associated with an increased likelihood of resumed cyclicity by the time of examination (genetic correlations ranged from 0.24 to 0.41). Genetically heavier carcasses were associated with an inferior uterine score as well as a greater predisposition to embryo loss. Despite the overall antagonistic relationship between reproductive performance and both milk and carcass traits, not all detailed aspects of reproduction performance exhibited an antagonistic relationship.
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Bovinos/genética , Lactação/genética , Reprodução/genética , Animais , Composição Corporal/genética , Contagem de Células , Gorduras/análise , Feminino , Fertilidade/genética , Genótipo , Modelos Lineares , Leite/química , Leite/citologia , Proteínas do Leite/análise , Ovário/diagnóstico por imagem , Ovulação , Fenótipo , Período Pós-Parto , Característica Quantitativa Herdável , Ultrassonografia , Útero/diagnóstico por imagemRESUMO
The objective of the study was to estimate genetic parameters of detailed reproductive traits derived from ultrasound examination of the reproductive tract as well as their genetic correlations with traditional reproductive traits. A total of 226,141 calving and insemination records as well as 74,134 ultrasound records from Irish dairy cows were used. Traditional reproductive traits included postpartum interval to first service, conception, and next calving, as well as the interval from first to last service; number of inseminations, pregnancy rate to first service, pregnant within 42 d of the herd breeding season, and submission in the first 21 d of the herd breeding season were also available. Detailed reproductive traits included resumed cyclicity at the time of ultrasound examination, incidence of multiple ovulations, incidence of early postpartum ovulation, heat detection, ovarian cystic structures, embryo loss, and uterine score; the latter was a subjectively assessed on a scale of 1 (little fluid with normal uterine tone) to 4 (large quantity of fluid with a flaccid uterine tone). Variance (and covariance) components were estimated using repeatability animal linear mixed models. Heritability for all reproductive traits were generally low (0.001-0.05), with the exception of traits related to cyclicity postpartum, regardless if defined traditionally (0.07; calving to first service) or from ultrasound examination [resumed cyclicity at the time of examination (0.07) or early postpartum ovulation (0.10)]. The genetic correlations among the detailed reproductive traits were generally favorable. The exception was the genetic correlation (0.29) between resumed cyclicity and uterine score; superior genetic merit for cyclicity postpartum was associated with inferior uterine score. Superior genetic merit for most traditional reproductive traits was associated with superior genetic merit for resumed cyclicity (genetic correlations ranged from -0.59 to -0.36 and from 0.56 to 0.70) and uterine score (genetic correlations ranged from -0.47 to 0.32 and from 0.25 to 0.52). Genetic predisposition to an increased incidence of embryo loss was associated with both an inferior uterine score (0.24) and inferior genetic merit for traditional reproductive traits (genetic correlations ranged from -0.52 to -0.42 and from 0.33 to 0.80). The results from the present study indicate that selection based on traditional reproductive traits, such as calving interval or days open, resulted in improved genetic merit of all the detailed reproductive traits evaluated in this study. Additionally, greater accuracy of selection for calving interval is expected for a relatively small progeny group size when detailed reproductive traits are included in a multitrait genetic evaluation.
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Bovinos/fisiologia , Variação Genética , Reprodução , Animais , Bovinos/genética , Feminino , Modelos Lineares , Ovário/diagnóstico por imagem , Ultrassonografia/veterinária , Útero/diagnóstico por imagemRESUMO
BACKGROUND: Current data suggest that platinum-based combination therapy is the standard first-line treatment for biliary tract cancer. EGFR inhibition has proven beneficial across a number of gastrointestinal malignancies; and has shown specific advantages among KRAS wild-type genetic subtypes of colon cancer. We report the combination of panitumumab with gemcitabine (GEM) and oxaliplatin (OX) as first-line therapy for KRAS wild-type biliary tract cancer. METHODS: Patients with histologically confirmed, previously untreated, unresectable or metastatic KRAS wild-type biliary tract or gallbladder adenocarcinoma with ECOG performance status 0-2 were treated with panitumumab 6 mg kg(-1), GEM 1000 mg m(-2) (10 mg m(-2) min(-1)) and OX 85 mg m(-2) on days 1 and 15 of each 28-day cycle. The primary objective was to determine the objective response rate by RECIST criteria v.1.1. Secondary objectives were to evaluate toxicity, progression-free survival (PFS), and overall survival. RESULTS: Thirty-one patients received at least one cycle of treatment across three institutions, 28 had measurable disease. Response rate was 45% and disease control rate was 90%. Median PFS was 10.6 months (95% CI 5-24 months) and median overall survival 20.3 months (95% CI 9-25 months). The most common grade 3/4 adverse events were anaemia 26%, leukopenia 23%, fatigue 23%, neuropathy 16% and rash 10%. CONCLUSIONS: The combination of gemcitabine, oxaliplatin and panitumumab in KRAS wild type metastatic biliary tract cancer showed encouraging efficacy, additional efforts of genetic stratification and targeted therapy is warranted in biliary tract cancer.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Panitumumabe , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Resultado do Tratamento , Proteínas ras/genética , GencitabinaRESUMO
BACKGROUND: To determine the maximal tolerated dose of erlotinib when added to 5-fluorouracil (5-FU) chemoradiation and bevacizumab and safety and efficacy of this combination in patients with locally advanced rectal cancer. PATIENTS AND METHODS: Patients with Magnetic resonance imaging (MRI) or ultrasound defined T3 or T4 adenocarcinoma of the rectum and without evidence of metastatic disease were enrolled. Patients received infusional 5-FU 225 mg/M2/day continuously, along with bevacizumab 5 mg/kg days 14, 1, 15 and 29. Standard radiotherapy was administered to 50.4 Gy in 28 fractions. Erlotinib started at a dose of 50 mg orally daily and advanced by 50 mg increments in the subsequent cohort. Open total mesorectal excision was carried out 6-9 weeks following the completion of chemoradiation. RESULTS: Thirty-two patients received one of three dose levels of erlotinib. Erlotinib dose level of 100 mg was determined to be the maximally tolerated dose. Thirty-one patients underwent resection of the primary tumor, one refused resection. Twenty-seven patients completed study therapy, all of whom underwent resection. At least one grade 3-4 toxicity occurred in 46.9% of patients. Grade 3-4 diarrhea occurred in 18.8%. The pathologic complete response (pCR) for all patients completing study therapy was 33%. With a median follow-up of 2.9 years, there are no documented local recurrences. Disease-free survival at 3 years is 75.5% (confidence interval: 55.1-87.6%). CONCLUSIONS: Erlotinib added to infusional 5-FU, bevacizumab and radiation in patients with locally advanced rectal cancer is relatively well tolerated and associated with an encouraging pCR.
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Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Quimiorradioterapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Cloridrato de Erlotinib , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Terapia Neoadjuvante , Quinazolinas/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5'-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression. METHODS: Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR). RESULTS: Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate. CONCLUSION: This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.
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Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Resultado do Tratamento , GencitabinaRESUMO
Cisheteronormative ideologies are infused into every aspect of society, including undergraduate science. We set out to identify the extent to which students can identify cisheteronormative language in biology textbooks by posing several hypothetical textbook questions and asking students to modify them to make the language more accurate (defined as "correct; precise; using language that applies to all people"). First, we confirmed that textbooks commonly use language that conflates or confuses sex and gender. We used this information to design two sample questions that used similar language. We examined what parts of the questions students modified, and the changes they recommended. When asked to modify sample textbook questions, we found the most common terms or words that students identified as inaccurate were related to infant gender identity. The most common modifications that students made were changing gender terms to sex terms. Students' decisions in this exercise differed little across three large biology courses or by exam performance. As the science community strives to promote inclusive classrooms and embrace the complexity of human gender identities, we provide foundational information about students' ability to notice and correct inaccurate language related to sex and gender in biology.
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Biologia , Identidade de Gênero , Idioma , Estudantes , Humanos , Biologia/educação , Masculino , Feminino , Avaliação EducacionalRESUMO
BACKGROUND: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. METHODS: Two schedules with sunitinib (25-50 mg per day) and IV gemcitabine (750-1250 mg m(-2)) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a 2-weeks-on-1-week-off schedule (Schedule 2/1) plus gemcitabine on days 1 and 8. The primary endpoint was determination of MTD and tolerability. RESULTS: Forty-four patients received the combination (Schedule 4/2, n=8; Schedule 2/1, n=36). With no dose-limiting toxicities (DLTs) at maximum dose levels on Schedule 2/1, MTD was not reached. Grade 4 treatment-related AEs and laboratory abnormalities included cerebrovascular accident, hypertension, and pulmonary embolism (n=1 each), and neutropenia (n=3), thrombocytopenia and increased uric acid (both n=2), and lymphopenia (n=1). There were no clinically significant drug-drug interactions. Antitumor activity occurred across dose levels and tumour types. In poor-risk and/or high-grade renal cell carcinoma patients (n=12), 5 had partial responses and 7 stable disease ≥ 6 weeks. CONCLUSION: Sunitinib plus gemcitabine on Schedule 2/1 with growth factor support was well tolerated and safely administered at maximum doses of each drug, without significant drug-drug interactions.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/farmacocinética , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologia , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Pirróis/farmacocinética , Sunitinibe , GencitabinaRESUMO
OBJECTIVES: The data presented in this note were collected during a multi-year project conducted in the context of large-enrollment introductory biology course at a large private R-1 research institution in the Northeastern United States. The project aimed to examine the impact of Peer-Led Team Learning (PLTL) on the recruitment and retention of marginalized groups in Science, Technology, Engineering, and Mathematics (STEM) majors. While several results from the project have been published, additional data of interest have yet to be reported. This data note reports on additional associations between PLTL participation and improved outcomes for students from groups that have historically been excluded in STEM. Additional data reported herein were collected to determine if students in the course experienced imposter phenomenon, and whether PLTL may be associated with reduced levels of imposter feelings. DATA DESCRIPTION: The data in this note includes academic information such as final course grades and academic level; socio-demographic information such as gender identity, minority status, and first-generation status; and information on student recruitment, retention, imposter feelings, and participation in Peer-Led Team Learning (PLTL). These data might be useful and of value to education researchers and undergraduate STEM instructors who are interested in improving equity in STEM education.
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Transtornos de Ansiedade , Identidade de Gênero , Masculino , Feminino , Humanos , Estudantes , BiologiaRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in a significant proportion of esophageal and gastric carcinomas. Although previous studies have examined tyrosine kinase inhibitors of EGFR, there remains limited data regarding the role of EGFR-directed monoclonal antibody therapy in these malignancies. We carried out a multi-institutional phase II study of cetuximab, a monoclonal antibody against EGFR, in patients with unresectable or metastatic esophageal or gastric adenocarcinoma. PATIENTS AND METHODS: Thirty-five patients with previously treated metastatic esophageal or gastric adenocarcinoma were treated with weekly cetuximab, at an initial dose of 400 mg/m(2) followed by weekly infusions at 250 mg/m(2). Patients were followed for toxicity, treatment response, and survival. RESULTS: Treatment with cetuximab was well tolerated; no patients were taken off study due to drug-related adverse events. One (3%) partial treatment response was noted. Two (6%) patients had stable disease after 2 months of treatment. Median progression-free survival and overall survival were 1.6 and 3.1 months, respectively. CONCLUSION: Although well tolerated, cetuximab administered as a single agent had minimal clinical activity in patients with metastatic esophageal and gastric adenocarcinoma. Ongoing studies of EGFR inhibitors in combination with other agents may define a role for these agents in the treatment of esophageal and gastric cancer.
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Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Cetuximab , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Instructors can teach evolution using any number of species contexts. However, not all species contexts are equal, and taxa choice can alter both cognitive and affective elements of learning. This is particularly true when teaching evolution using human examples, a promising method for evolution instruction that nevertheless comes with unique challenges. In this study, we tested how an evolution lesson focused on a human example may impact students' engagement, perceived content relevance, learning gains, and level of discomfort, when compared to the same lesson using a non-human mammal example. We use this isomorphic lesson and a pre-post study design administered in a split-section introductory biology classroom to isolate the importance of the species context. RESULTS: For two of the four measurements of interest, the effect of using human examples could not be understood without accounting for student background. For learning gains, students with greater pre-class content knowledge benefited more from the human examples, while those with low levels of knowledge benefited from the non-human example. For perceived relevance, students who were more accepting of human evolution indicated greater content relevance from the human example. Regardless of condition, students with lower evolution acceptance reported greater levels of discomfort with the lesson. CONCLUSIONS: Our results illustrate the complexities of using human examples to teach evolution. While these examples were beneficial for many students, they resulted in worse outcomes for students that were less accepting of evolution and those who entered the course with less content knowledge. These findings demonstrate the need to consider diverse student backgrounds when establishing best practices for using human examples to teach evolution. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12052-021-00148-w.
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Randomized trials of chemoradiation for esophageal cancer have included very few patients age > or = 75. In this retrospective study, we describe the outcomes and toxicity of full-dose chemoradiation in elderly patients with esophageal cancer. Patients, age > or = 75, treated with full-dose chemoradiation for esophageal carcinoma from 2002 to 2008 were retrospectively reviewed. Thirty-four patients were identified with a median age of 79.5 (range 75-89). The median Eastern Cooperative Oncology Group performance status was 1 (range 0-3) and the median Adult Comorbidity Evaluation-27 score was 1 (range 0-3). Twenty-eight patients received definitive and six received neoadjuvant chemoradiation. The median radiation dose delivered was 50.4 Gray (range 3.6-68.4 Gray). Platinum-based chemotherapy was used in 79.4% of patients. Fifty percent of the patients completed all planned radiation therapy (RT) and chemotherapy; 85.3% completed RT. Acute toxicity > or = grade 4 occurred in 38.2% of patients, and 70.6% of the patients required hospitalization, emergency department visit, and/or RT break. Median follow-up was 14.5 months among 7 survivors, and median survival was 12.0 months (95% confidence interval [CI]: 9.7 to 24.1 months). The actuarial overall survival at 2 years was 29.7% (95% CI: 16.6 to 52.6%). There were four treatment-related deaths. The median time to any recurrence was 10.4 months. Nineteen patients had a local and/or distant recurrence. In conclusion, elderly patients experienced substantial morbidity from chemoradiation, and long-term survival was low. Future efforts to improve treatment tolerability in the elderly are needed.
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Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Masculino , Doses de Radiação , Radioterapia/efeitos adversos , Estudos RetrospectivosRESUMO
BACKGROUND: Recent studies have examined the addition of docetaxel to fluorouracil and cisplatin in advanced esophagogastric cancer. PATIENTS AND METHODS: We carried out a phase I dose-escalation study of weekly docetaxel, cisplatin, and irinotecan (TPC), given on days 1 and 8 every 3 weeks, in patients with chemonaive solid tumors. Subsequently, we completed a multiinstitutional phase II study of TPC in patients with previously untreated, metastatic esophagogastric cancer. RESULTS: Thirty-nine patients were enrolled in the phase I trial; a weekly schedule of TPC was well tolerated. On that basis, docetaxel 30 mg/m(2), cisplatin 25 mg/m(2), and irinotecan 65 mg/m(2) were selected for the phase II trial, where in the first 18 patients irinotecan 65 mg/m(2) caused too much diarrhea and was reduced to 50 mg/m(2). Among 56 eligible patients with previously untreated, metastatic esophagogastric cancer enrolled in the phase II trial, three complete and 27 partial responses were observed (overall response rate=54%), and 15 patients (30%) had stable disease. Median progression-free survival was 7.1 months, and median survival was 11.9 months. At the final irinotecan dose of 50 mg/m(2), grade 3 or higher toxicity included diarrhea (26%), neutropenia (21%), nausea (18%), fatigue (16%), anorexia (13%), and thrombosis/embolism (13%). CONCLUSIONS: Weekly TPC is an active and well-tolerated regimen for patients with esophagogastric cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cisplatino/administração & dosagem , Docetaxel , Neoplasias Esofágicas/patologia , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Gástricas/patologia , Taxoides/administração & dosagemRESUMO
This study investigated predictive risk factors of condylar remodeling changes after counterclockwise maxillomandibular advancement (CCW-MMA) and disc repositioning surgery. Forty-one female patients (75 condyles) treated with CCW-MMA and disc repositioning had cone beam computed tomography (CBCT) scans taken pre-surgery, immediately after surgery, and at an average 16 months post-surgery. Pre- and post-surgical three-dimensional models were superimposed using automated voxel-based registration on the cranial base to evaluate condylar displacements after surgery. Regional registration was performed to assess condylar remodeling in the follow-up period. Three-dimensional cephalometrics, shape correspondence (SPHARM-PDM), and volume measurements were applied to quantify changes. Pearson product-moment correlations and multiple regression analysis were performed. Highly statistically significant correlation showed that older patients were more susceptible to overall condylar volume reduction following CCW-MMA and disc repositioning (P≤0.001). Weak but statistically significant correlations were observed between condylar remodeling changes in the follow-up period and pre-surgical facial characteristics, magnitude of the surgical procedure, and condylar displacement changes. After CCW-MMA and disc repositioning, the condyles moved mostly downwards and medially, and were rotated medially and counterclockwise; displacements in the opposite direction were correlated with a greater risk of condylar resorption. Moreover, positional changes with surgery were only weakly associated with remodeling in the follow-up period, suggesting that other risk factors may play a role in condylar resorption.
Assuntos
Remodelação Óssea , Avanço Mandibular/métodos , Côndilo Mandibular/cirurgia , Osteoartrite/cirurgia , Disco da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Adolescente , Adulto , Placas Ósseas , Parafusos Ósseos , Criança , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Côndilo Mandibular/diagnóstico por imagem , Osteotomia Mandibular , Pessoa de Meia-Idade , Osteoartrite/diagnóstico por imagem , Fatores de Risco , Disco da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. RESULTS: One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dioxóis/uso terapêutico , Isoquinolinas/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Dioxóis/efeitos adversos , Dioxóis/farmacocinética , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Tetra-Hidroisoquinolinas , Trabectedina , Resultado do TratamentoRESUMO
PURPOSE: We performed a phase I study of a day (D) 1 and D4 bortezomib administration once every 2 weeks to determine the recommended phase II dose and toxicity profile, and the extent of 20S proteasome inhibition obtained. PATIENTS AND METHODS: Patients with solid tumors or lymphomas were treated with bortezomib at 0.25 to 1.9 mg/m2 on D1 and D4, every 2 weeks. 20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. RESULTS: On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. Other DLTs included diarrhea and fatigue; grade 3 thrombocytopenia was also noted. Reversible inhibition of 20S proteasome activity was dose dependent and best fit a total dose (mg) per fraction rather than mg/m2; 70% of baseline activity was inhibited by a dose of 3.0 to 3.5 mg given on D1 and on D4 every other week. Antitumor effects short of confirmed partial responses were observed in patients with melanoma, non-small-cell lung cancer, and renal cell carcinoma. CONCLUSION: Bortezomib (PS-341) is a novel antineoplastic agent that is well tolerated at doses not exceeding 3.0 mg (equivalent to 1.75 mg/m2), repeated on D1 and D4 every other week. This dose correlates with 70% inhibition of 20S proteasome activity. DLTs include neuropathy, fatigue, and diarrhea.
Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Ácidos Borônicos/farmacologia , Ácidos Borônicos/farmacocinética , Pirazinas/farmacologia , Pirazinas/farmacocinética , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/uso terapêutico , Bortezomib , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/patologia , Complexo de Endopeptidases do Proteassoma/sangue , Inibidores de Proteassoma , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.