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1.
Oncologist ; 29(7): 638-e952, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38815151

RESUMEN

BACKGROUND: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice (MATCH) precision oncology platform trial enrolled children aged 1-21 years with treatment-refractory solid tumors and predefined actionable genetic alterations. Patients with tumors harboring alterations in DNA damage repair (DDR) genes were assigned to receive olaparib. METHODS: Tumor and blood samples were submitted for centralized molecular testing. Tumor and germline sequencing were conducted in parallel. Olaparib was given twice daily for 28-day cycles starting at a dose 30% lower than the adult recommended phase 2 dose (RP2D). The primary endpoint was the objective response. RESULTS: Eighteen patients matched (1.5% of those screened) based on the presence of a deleterious gene alteration in BRCA1/2, RAD51C/D, or ATM detected by tumor sequencing without germline subtraction or analysis of loss of heterozygosity (LOH). Eleven (61%) harbored a germline mutation, with only one exhibiting LOH. Six patients enrolled and received the olaparib starting dose of 135 mg/m2/dose. Two participants were fully evaluable; 4 were inevaluable because <85% of the prescribed dose was administered during cycle 1. There were no dose-limiting toxicities or responses. Minimal hematologic toxicity was observed. CONCLUSION: Most DDR gene alterations detected in Pediatric MATCH were germline, monoallelic, and unlikely to confer homologous recombination deficiency predicting sensitivity to olaparib monotherapy. The study closed due to poor accrual. CLINICALTRIALS.GOV IDENTIFIER: NCT03233204. IRB approved: initial July 24, 2017.


Asunto(s)
Reparación del ADN , Neoplasias , Ftalazinas , Piperazinas , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Adulto Joven , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Daño del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Mutación de Línea Germinal , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Ftalazinas/uso terapéutico , Ftalazinas/efectos adversos , Ftalazinas/administración & dosificación , Piperazinas/uso terapéutico , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos
2.
Oncologist ; 29(8): 723-e1093, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38873934

RESUMEN

BACKGROUND: This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations. METHODS: Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib. RESULTS: Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (n = 7) and prior BRAF inhibitor therapy (n = 7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles. CONCLUSION: There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).


Asunto(s)
Mutación , Proteínas Proto-Oncogénicas B-raf , Vemurafenib , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Vemurafenib/uso terapéutico , Vemurafenib/administración & dosificación , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Preescolar , Neoplasias/tratamiento farmacológico , Neoplasias/genética
3.
Pediatr Blood Cancer ; 71(1): e30718, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37817345

RESUMEN

BACKGROUND: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies. OBJECTIVE: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma. METHODS: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions. Eligible patients older than six months of age were enrolled. The feasibility of delivering three injections of melphalan into the ophthalmic artery every 28 days was assessed. RESULTS: Nine institutions participated in this trial. Fourteen patients were enrolled, two of whom were unevaluable for feasibility. Four patients experienced a feasibility failure. In two patients, the ophthalmic artery could not be accessed for the second IA injection, in one the artery could not be accessed for the first injection, and one patient experienced grade 4 hypotension during the procedure. CONCLUSION: Delivery of prescribed therapy within the context of this study did not meet the feasibility goals of the study with only a 67% feasibility success rate. These results should caution centers that plan to initiate this treatment and suggest investment in training to achieve technical expertise or referral to centers with expertise.


Asunto(s)
Neoplasias de la Retina , Retinoblastoma , Humanos , Niño , Lactante , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/diagnóstico , Melfalán , Estudios de Factibilidad , Estudios Retrospectivos , Estudios Prospectivos , Resultado del Tratamiento , Estudios de Seguimiento , Infusiones Intraarteriales , Arteria Oftálmica
4.
Sensors (Basel) ; 24(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38894380

RESUMEN

X-ray images typically contain complex background information and abundant small objects, posing significant challenges for object detection in security tasks. Most existing object detection methods rely on complex networks and high computational costs, which poses a challenge to implement lightweight models. This article proposes Fine-YOLO to achieve rapid and accurate detection in the security domain. First, a low-parameter feature aggregation (LPFA) structure is designed for the backbone feature network of YOLOv7 to enhance its ability to learn more information with a lighter structure. Second, a high-density feature aggregation (HDFA) structure is proposed to solve the problem of loss of local details and deep location information caused by the necked feature fusion network in YOLOv7-Tiny-SiLU, connecting cross-level features through max-pooling. Third, the Normalized Wasserstein Distance (NWD) method is employed to alleviate the convergence complexity resulting from the extreme sensitivity of bounding box regression to small objects. The proposed Fine-YOLO model is evaluated on the EDS dataset, achieving a detection accuracy of 58.3% with only 16.1 M parameters. In addition, an auxiliary validation is performed on the NEU-DET dataset, the detection accuracy reaches 73.1%. Experimental results show that Fine-YOLO is not only suitable for security, but can also be extended to other inspection areas.

5.
Pediatr Blood Cancer ; 70 Suppl 6: e30574, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37458616

RESUMEN

The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that do not fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Neoplasias Nasofaríngeas , Neoplasias de la Retina , Neoplasias de la Tiroides , Niño , Humanos , Oncología Médica
6.
Pediatr Blood Cancer ; 70(7): e30365, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37073741

RESUMEN

BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.


Asunto(s)
Hepatoblastoma , Neoplasias Hepáticas , Niño , Humanos , Hepatoblastoma/patología , Irinotecán/uso terapéutico , Vincristina , Neoplasias Hepáticas/patología , alfa-Fetoproteínas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento
7.
Cancer ; 128(5): 1057-1065, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34762296

RESUMEN

BACKGROUND: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. METHODS: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. RESULTS: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. CONCLUSIONS: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Hepatoblastoma , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Doxorrubicina/efectos adversos , Estudios de Factibilidad , Hepatoblastoma/tratamiento farmacológico , Hepatoblastoma/patología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Resultado del Tratamiento , Vincristina/efectos adversos
8.
Biometrics ; 78(2): 754-765, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33559881

RESUMEN

Systematic reviews and meta-analyses synthesize results from well-conducted studies to optimize healthcare decision-making. Network meta-analysis (NMA) is particularly useful for improving precision, drawing new comparisons, and ranking multiple interventions. However, recommendations can be misled if published results are a selective sample of what has been collected by trialists, particularly when publication status is related to the significance of the findings. Unfortunately, the missing-not-at-random nature of this problem and the numerous parameters involved in modeling NMAs pose unique computational challenges to quantifying and correcting for publication bias, such that sensitivity analysis is used in practice. Motivated by this important methodological gap, we developed a novel and stable expectation-maximization (EM) algorithm to correct for publication bias in the network setting. We validate the method through simulation studies and show that it achieves substantial bias reduction in small to moderately sized NMAs. We also calibrate the method against a Bayesian analysis of a published NMA on antiplatlet therapies for maintaining vascular patency.


Asunto(s)
Proyectos de Investigación , Teorema de Bayes , Sesgo , Metaanálisis en Red , Sesgo de Publicación
9.
Can J Stat ; 49(3): 659-677, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34690407

RESUMEN

In the group testing procedure, several individual samples are grouped and the pooled samples, instead of each individual sample, are tested for outcome status (e.g., infectious disease status). Although this cost-effectiveness strategy in data collection is both labor and time efficient, it poses statistical challenges to derive statistically and computationally efficient estimators under semiparametric models. We consider semiparametric isotonic regression models for the simultaneous estimation of the conditional probability curve and covariate effects, in which a parametric form for combining the covariate information is assumed and the monotonic link function is left unspecified. We develop an expectation-maximization algorithm to overcome the computational challenge and embed the pool-adjacent violators algorithm in the M-step to facilitate the computation. We establish the large sample behavior of the proposed estimators and examine their finite sample performance in simulation studies. We apply the proposed method to data from the National Health and Nutrition Examination Survey for illustration.

10.
Mod Pathol ; 33(3): 496-513, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31383963

RESUMEN

Pathological staging of primary anorectal mucosal melanoma is often performed according to the American Joint Commission on Cancer (AJCC) guidelines for cutaneous melanoma, as an anorectal melanoma-specific staging system does not exist. However, it remains unknown whether prognostic factors derived for cutaneous melanoma also stratify risk in anorectal melanoma. We retrospectively determined correlations between clinicopathological parameters and disease-specific survival in 160 patients. Patients were grouped by clinical stage at presentation (localized disease, regional or distant metastases). Cox proportional hazards regression models determined associations with disease-specific survival. We also summarized the somatic mutations identified in a subset of tumors analyzed for hotspot mutations in cancer-associated gene panels. Most of the patients were white (82%) and female (61%). The median age was 62 years. With a median follow-up of 1.63 years, median disease-specific survival was 1.75 years, and 121 patients (76%) died of anorectal melanoma. Patients presenting with regional (34%) or distant metastases (24%) had significantly shorter disease-specific survival compared to those with disease localized to the anorectum (42%). Of the 71 anorectal melanoma tumors analyzed for hotspot genetic alterations, somatic mutations involving the KIT gene (24%) were most common followed by NRAS (19%). Increasing primary tumor thickness, lymphovascular invasion, and absence of regression also correlated with shorter disease-specific survival. Primary tumor parameters correlated with shorter disease-specific survival in patients presenting with localized disease (tumor thickness) or regional metastases (tumor thickness, absence of regression, and lymphovascular invasion), but not in patients presenting with distant metastases. Grouping of patients according to a schema based on modifications of the 8th edition AJCC cutaneous melanoma staging system stratified survival in anorectal melanoma. Our findings support stage-specific associations between primary tumor parameters and disease-specific survival in anorectal melanoma. Moreover, the AJCC cutaneous melanoma staging system and minor modifications of it predicted survival among anorectal melanoma patients.


Asunto(s)
Neoplasias del Ano/patología , Mucosa Intestinal/patología , Melanoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Ano/mortalidad , Neoplasias del Ano/terapia , Biopsia , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
11.
Pediatr Blood Cancer ; 67(9): e28502, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32589362

RESUMEN

BACKGROUND: Eyes with Group D intraocular retinoblastoma have low salvage rates. A pilot study showed safety and efficacy of sub-Tenon's fascia carboplatin with systemic chemotherapy supporting further study. METHODS: Children with newly diagnosed bilateral intraocular retinoblastoma with at least one remaining Group C or D eye were treated with six courses of carboplatin/etoposide/vincristine (CEV) with sub-Tenon's fascia carboplatin for Group C/D eyes during courses 2-4. Local ophthalmic therapy started at course 3. The primary study objective was to determine the 1-year failure rate of Group D eyes. RESULTS: The study closed prematurely due to poor accrual and 22 of 30 patients were evaluable for failure rate, contributing 25 Group D and four Group C eyes. Among the 25 Group D eyes, there were 13 failures within the first year of study enrollment including eight needing external beam radiotherapy (EBR) and five needing enucleation, resulting in 1-year failure rate of 52%. The failure rate was significantly lower than the historical rate of 70% (P = .039). The 1-year eye preservation rate for Group D eyes was 80% (20/25). One-year failure rate for Group C eyes was 25% (1/4); 1-year preservation rate was 100% without need for EBR. Systemic toxicity included Grade 3 hearing loss in two subjects, infections, neutropenia, and thrombocytopenia. Ocular toxicities included periorbital fat atrophy (13/29 = 45% eyes), optic nerve atrophy (1/29 = 3% eyes), and restrictive fibrosis (1/29 = 3% eyes). CONCLUSIONS: Sub-Tenon's fascia carboplatin plus CEV was partially effective in Group D intraocular retinoblastoma but had unacceptable ocular toxicities.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Cápsula de Tenon , Adolescente , Adulto , Carboplatino/administración & dosificación , Niño , Preescolar , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pronóstico , Neoplasias de la Retina/patología , Retinoblastoma/patología , Vincristina/administración & dosificación , Adulto Joven
12.
Pediatr Blood Cancer ; 67(8): e28350, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32383794

RESUMEN

PURPOSE: Treatment outcomes for hepatoblastoma have improved markedly in the contemporary treatment era, principally due to therapy intensification, with overall survival increasing from 35% in the 1970s to 90% at present. Unfortunately, these advancements are accompanied by an increased incidence of toxicities. A detailed analysis of age as a prognostic factor may support individualized risk-based therapy stratification. METHODS: We evaluated 1605 patients with hepatoblastoma included in the CHIC database to assess the relationship between event-free survival (EFS) and age at diagnosis. Further analysis included the age distribution of additional risk factors and the interaction of age with other known prognostic factors. RESULTS: Risk for an event increases progressively with increasing age at diagnosis. This pattern could not be attributed to the differential distribution of other known risk factors across age. Newborns and infants are not at increased risk of treatment failure. The interaction between age and other adverse risk factors demonstrates an attenuation of prognostic relevance with increasing age in the following categories: metastatic disease, AFP < 100 ng/mL, and tumor rupture. CONCLUSION: Risk for an event increased with advancing age at diagnosis. Increased age attenuates the prognostic influence of metastatic disease, low AFP, and tumor rupture. Age could be used to modify recommended chemotherapy intensity.


Asunto(s)
Bases de Datos Factuales , Hepatoblastoma , Neoplasias Hepáticas , Adolescente , Edad de Inicio , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Hepatoblastoma/diagnóstico , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Hepatoblastoma/terapia , Humanos , Incidencia , Lactante , Recién Nacido , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Metástasis de la Neoplasia , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia
13.
J Biopharm Stat ; 30(1): 3-17, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31454295

RESUMEN

It is desirable to work efficiently and cost effectively to evaluate new therapies in a time-sensitive and ethical manner without compromising the integrity and validity of the development process. The seamless phase II/III clinical trial has been proposed to meet this need, and its efficient, ethical and economic advantages can be strengthened by its combination with innovative response adaptive randomization (RAR) procedures. In particular, well-designed frequentist RAR procedures can target theoretically optimal allocation proportions, and there are explicit asymptotic results. However, there has been little research into seamless phase II/III clinical trials with frequentist RAR because of the difficulty in performing valid statistical inference and controlling the type I error rate. In this paper, we propose the framework for a family of frequentist RAR designs for seamless phase II/III trials, derive the asymptotic distribution of the parameter estimators using martingale processes and offer solutions to control the type I error rate. The numerical studies demonstrate our theoretical findings and the advantages of the proposed methods.


Asunto(s)
Ensayos Clínicos Adaptativos como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Proyectos de Investigación/estadística & datos numéricos , Interpretación Estadística de Datos , Humanos , Modelos Estadísticos
14.
Biostatistics ; 19(1): 54-70, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28525542

RESUMEN

Evaluating and understanding the risk and safety of using medications for autoimmune disease in a woman during her pregnancy will help both clinicians and pregnant women to make better treatment decisions. However, utilizing spontaneous abortion (SAB) data collected in observational studies of pregnancy to derive valid inference poses two major challenges. First, the data from the observational cohort are not random samples of the target population due to the sampling mechanism. Pregnant women with early SAB are more likely to be excluded from the cohort, and there may be substantial differences between the observed SAB time and those in the target population. Second, the observed data are heterogeneous and contain a "cured" proportion. In this article, we consider semiparametric models to simultaneously estimate the probability of being cured and the distribution of time to SAB for the uncured subgroup. To derive the maximum likelihood estimators, we appropriately adjust the sampling bias in the likelihood function and develop an expectation-maximization algorithm to overcome the computational challenge. We apply the empirical process theory to prove the consistency and asymptotic normality of the estimators. We examine the finite sample performance of the proposed estimators in simulation studies and illustrate the proposed method through an application to SAB data from pregnant women.


Asunto(s)
Aborto Espontáneo , Algoritmos , Modelos Estadísticos , Sesgo de Selección , Adulto , Femenino , Humanos , Funciones de Verosimilitud , Embarazo
15.
Small ; 15(24): e1901848, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31062504

RESUMEN

The zinc-bromine flow battery (ZBFB) is one of the most promising technologies for large-scale energy storage. Here, nitrogen-doped carbon is synthesized and investigated as the positive electrode material in ZBFBs. The synthesis includes the carbonization of the glucose precursor and nitrogen doping by etching in ammonia gas. Physicochemical characterizations reveal that the resultant carbon exhibits high electronic conductivity, large specific surface area, and abundant heteroatom-containing functional groups, which benefit the formation and exposure of the active sites toward the Br2 /Br- redox couple. As a result, the assembled ZBFB achieves a voltage efficiency of 83.0% and an energy efficiency of 82.5% at a current density of 80 mA cm-2 , which are among the top values in literature. Finally, the ZBFB does not yield any detectable degradation in performance after a 200-cycle charging/discharging test, revealing its high stability. In summary, this work provides a highly efficient electrode material for the zinc-bromine flow battery.

16.
Biostatistics ; 18(3): 495-504, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28334132

RESUMEN

Publication bias occurs when the published research results are systematically unrepresentative of the population of studies that have been conducted, and is a potential threat to meaningful meta-analysis. The Copas selection model provides a flexible framework for correcting estimates and offers considerable insight into the publication bias. However, maximizing the observed likelihood under the Copas selection model is challenging because the observed data contain very little information on the latent variable. In this article, we study a Copas-like selection model and propose an expectation-maximization (EM) algorithm for estimation based on the full likelihood. Empirical simulation studies show that the EM algorithm and its associated inferential procedure performs well and avoids the non-convergence problem when maximizing the observed likelihood.


Asunto(s)
Funciones de Verosimilitud , Sesgo de Publicación , Algoritmos , Humanos , Metaanálisis como Asunto
17.
Am J Hematol ; 93(10): 1245-1253, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30051599

RESUMEN

The International Prognostic Scoring System-Revised (IPSS-R) is one standard for myelodysplastic syndrome (MDS) risk stratification. It divides patients into five categories including an intermediate subset (IPSS-R int-risk). Outcomes and clinical interventions for patients with IPSS-R int-risk are not well defined. We performed an analysis of outcomes of this group of patients. Out of 3167 patients, a total of 298 were identified with IPSS-R int-risk MDS and retrospectively analyzed to assess characteristics affecting outcomes. Cox proportional hazard models for overall survival (OS) were performed to identify statistically significant clinical factors that influence survival. Age of 66 years or greater, peripheral blood blasts of 2% or more, and history of red blood cell (RBC) transfusion were significantly associated with inferior survival. Based on these features, MDS patients with IPSS-R int-risk were classified into two prognostic risk groups for analysis, an int-favorable group and an int-adverse group, and had significantly divergent outcomes. Sequential prognostication was validated using two independent datasets comprising over 700 IPSS-R int-risk patients. The difference in median survival between int-favorable and int-adverse patients was 3.7 years in the test cohort, and 1.8 and 2.0 years in the two validation cohorts. These results confirm significantly variable outcomes of patients with IPSS-R int-risk and need for different prognostic systems.


Asunto(s)
Síndromes Mielodisplásicos/mortalidad , Índice de Severidad de la Enfermedad , Adulto , Factores de Edad , Anciano , Transfusión de Eritrocitos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/terapia , Células Madre Neoplásicas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
18.
Sensors (Basel) ; 17(11)2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-29112143

RESUMEN

Simultaneous localization and mapping (SLAM) is emerging as a prominent issue in computer vision and next-generation core technology for robots, autonomous navigation and augmented reality. In augmented reality applications, fast camera pose estimation and true scale are important. In this paper, we present an adaptive monocular visual-inertial SLAM method for real-time augmented reality applications in mobile devices. First, the SLAM system is implemented based on the visual-inertial odometry method that combines data from a mobile device camera and inertial measurement unit sensor. Second, we present an optical-flow-based fast visual odometry method for real-time camera pose estimation. Finally, an adaptive monocular visual-inertial SLAM is implemented by presenting an adaptive execution module that dynamically selects visual-inertial odometry or optical-flow-based fast visual odometry. Experimental results show that the average translation root-mean-square error of keyframe trajectory is approximately 0.0617 m with the EuRoC dataset. The average tracking time is reduced by 7.8%, 12.9%, and 18.8% when different level-set adaptive policies are applied. Moreover, we conducted experiments with real mobile device sensors, and the results demonstrate the effectiveness of performance improvement using the proposed method.

19.
Arch Biochem Biophys ; 605: 41-8, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27036854

RESUMEN

The recent bio-applications (i.e. bio-sensing, tissue engineering and cell proliferation etc.) are driving the fundamental research in carbon based materials with functional perspectives. High stability in carbon based coatings usually demands the high density deposition. However, the standard techniques, used for the large area and high throughput deposition of crystalline carbon films, often require very high temperature processing (typically >800 °C in inert atmosphere). Here, we present a low temperature (<150 °C) pulsed-DC plasma sputtering process, which enables sufficient ion flux to deposit dense unhydrogenated carbon thin films without any need of substrate-bias or post-deposition thermal treatments. It is found that the control over plasma power density and pulsed frequency governs the density and kinetic energy of carbon ions participating during the film growth. Subsequently, it controls the contents of sp(3) and sp(2) hybridizations via conversion of sp(2) to sp(3) hybridization by ion's energy relaxation. The role of plasma parameters on the chemical and surface properties are presented and correlated to the bio-activity. Bioactivity tests, carried out in mouse fibroblast L-929 and Sarcoma osteogenic (Saos-2) bone cell lines, demonstrate promising cell-proliferation in these films.


Asunto(s)
Carbono/química , Frío , Gases em Plasma , Animales , Atmósfera , Técnicas Biosensibles/métodos , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Humanos , Cinética , Ensayo de Materiales , Ratones , Espectrometría Raman , Especificidad por Sustrato , Propiedades de Superficie , Ingeniería de Tejidos/métodos
20.
Nutr Cancer ; 68(7): 1073-82, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27618148

RESUMEN

Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer.


Asunto(s)
Neoplasias de la Mama/etiología , Medicina Basada en la Evidencia , Hipertrigliceridemia/fisiopatología , Neoplasias de la Próstata/etiología , Triglicéridos/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Reproducibilidad de los Resultados , Riesgo
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