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1.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34953466

RESUMO

Understanding the relationship between molecular markers and a phenotype of interest is often obfuscated by patient-level heterogeneity. To address this challenge, Chang et al. recently published a novel method called Component-wise Sparse Mixture Regression (CSMR), a regression-based clustering method that promises to detect heterogeneous relationships between molecular markers and a phenotype of interest under high-dimensional settings. In this Letter to the Editor, we raise awareness to several issues concerning the assessment of CSMR in Chang et al., particularly its assessment in settings where the number of features, P, exceeds the study sample size, N, and advocate for additional metrics/approaches when assessing the performance of regression-based clustering methodologies.


Assuntos
Análise por Conglomerados , Humanos , Fenótipo
2.
Chemistry ; 30(24): e202304209, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38372165

RESUMO

It is challenging to realize the selective C-C bond cleavage of lignin ß-O-4 linkages for production of high-value aromatic chemicals due to its intrinsic inertness and complex structure. Here we report a light-driven, chlorine-radical-based protocol to realize the oxidative C-C bond cleavage in various lignin model compounds catalyzed by commercially available TPT and CaCl2, achieving high conversion and good to high product yields at room temperature. Mechanistic studies reveal that the preferential activation of Cß-H bond facilitates the oxidation and C-C bond cleavage of lignin ß-O-4 model via chlorine radical. Furthermore, this method is also applicable to the depolymerization of natural lignin extracts, furnishing the aromatic oxygenates from the cleavage of Cα-Cß bonds. This study provides experimental foundations to the depolymerization and valorization of lignin into high value-added aromatic compounds.

3.
J Gen Intern Med ; 39(8): 1423-1430, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38326585

RESUMO

BACKGROUND: Smoking rates among people living with behavioral health conditions (BHC) range from 30 to 65% and are 2-4 times higher than rates found in the general population. Starting tobacco treatment during a hospital stay is effective for smoking cessation, but little is known regarding treatment response among inpatients with BHC. OBJECTIVE: This study pooled data across multiple clinical trials to determine the relative success in quitting among participants with BHC compared to other study participants. PARTICIPANTS: Adults who smoke (≥ 18 years old) from five hospital-based smoking cessation randomized clinical trials. DESIGN: A retrospective analysis using data from the electronic health record to identify participants with primary diagnoses related to BHC. Recruitment and data analysis were conducted from 2011 to 2016. We used propensity score matching to pair patients with BHC to those with similar characteristics and logistic regression to determine differences between groups. MEASURES: The main outcome was self-reported 30-day abstinence 6 months post-discharge. RESULTS: Of 6612 participants, 798 patients had a BHC-related primary diagnosis. The matched sample included 642 pairs. Nearly 1 in 3 reported using tobacco medications after hospitalization, with no significant difference between patients with and without BHC (29.3% vs. 31.5%; OR (95% CI) = 0.90 (0.71, 1.14), p = 0.40). Nearly 1 in 5 patients with BHC reported abstinence at 6 months; however, their odds of abstinence were 30% lower than among people without BHC (OR (95% CI) = 0.70 (0.53,0.92), p = 0.01). CONCLUSION: When offered tobacco treatment, hospitalized patients with BHC were as likely as people without BHC to accept and engage in treatment. However, patients with BHC were less likely to report abstinence compared to those without BHC. Hospitals are a feasible and promising venue for tobacco treatment among inpatients with BHC. More studies are needed to identify treatment approaches that help people with BHC achieve long-term abstinence.


Assuntos
Hospitalização , Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Hospitalização/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Idoso
4.
Stat Appl Genet Mol Biol ; 22(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37937887

RESUMO

Integration of multiple 'omics datasets for differentiating cancer subtypes is a powerful technic that leverages the consistent and complementary information across multi-omics data. Matrix factorization is a common technique used in integrative clustering for identifying latent subtype structure across multi-omics data. High dimensionality of the omics data and long computation time have been common challenges of clustering methods. In order to address the challenges, we propose randomized singular value decomposition (RSVD) for integrative clustering using Non-negative Matrix Factorization: intNMF-rsvd. The method utilizes RSVD to reduce the dimensionality by projecting the data into eigen vector space with user specified lower rank. Then, clustering analysis is carried out by estimating common basis matrix across the projected multi-omics datasets. The performance of the proposed method was assessed using the simulated datasets and compared with six state-of-the-art integrative clustering methods using real-life datasets from The Cancer Genome Atlas Study. intNMF-rsvd was found working efficiently and competitively as compared to standard intNMF and other multi-omics clustering methods. Most importantly, intNMF-rsvd can handle large number of features and significantly reduce the computation time. The identified subtypes can be utilized for further clinical association studies to understand the etiology of the disease.


Assuntos
Algoritmos , Neoplasias , Humanos , Neoplasias/genética , Multiômica , Análise por Conglomerados
5.
Stat Appl Genet Mol Biol ; 22(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37489035

RESUMO

Component-wise Sparse Mixture Regression (CSMR) is a recently proposed regression-based clustering method that shows promise in detecting heterogeneous relationships between molecular markers and a continuous phenotype of interest. However, CSMR can yield inconsistent results when applied to high-dimensional molecular data, which we hypothesize is in part due to inherent limitations associated with the feature selection method used in the CSMR algorithm. To assess this hypothesis, we explored whether substituting different regularized regression methods (i.e. Lasso, Elastic Net, Smoothly Clipped Absolute Deviation (SCAD), Minmax Convex Penalty (MCP), and Adaptive-Lasso) within the CSMR framework can improve the clustering accuracy and internal consistency (IC) of CSMR in high-dimensional settings. We calculated the true positive rate (TPR), true negative rate (TNR), IC and clustering accuracy of our proposed modifications, benchmarked against the existing CSMR algorithm, using an extensive set of simulation studies and real biological datasets. Our results demonstrated that substituting Adaptive-Lasso within the existing feature selection method used in CSMR led to significantly improved IC and clustering accuracy, with strong performance even in high-dimensional scenarios. In conclusion, our modifications of the CSMR method resulted in improved clustering performance and may thus serve as viable alternatives for the regression-based clustering of high-dimensional datasets.


Assuntos
Algoritmos , Benchmarking , Análise por Conglomerados , Simulação por Computador , Fenótipo
6.
Angew Chem Int Ed Engl ; 63(16): e202401265, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38390752

RESUMO

It remains challenging to synthesize all-(meth)acrylic triblock thermoplastic elastomers (TPEs), due to the drastically different reactivities between the acrylates and methacrylates and inevitable occurrence of side reactions during polymerization of acrylates. By taking advantage of the easy structural modulation features of N-heterocyclic olefins (NHOs), we design and synthesize strong nucleophilic tetraphenylethylene-based NHOs varying in the number (i.e. mono-, dual- and tetra-) of initiating functional groups. Its combination with bulky organoaluminum [iBuAl(BHT)2] (BHT=bis(2,6-di-tBu-4-methylphenoxy)) constructs Lewis pair (LP) to realize the living polymerization of both acrylates and methacrylates, furnishing polyacrylates with ultrahigh molecular weight (Mn up to 2174 kg ⋅ mol-1) within 4 min. Moreover, these NHO-based LPs enable us to not only realize the control over the polymers' topology (i.e. linear and star), but also achieve triblock star copolymers in one-step manner. Mechanical studies reveal that the star triblock TPEs exhibit better mechanical properties (elongation at break up to 1863 % and tensile strength up to 19.1 MPa) in comparison with the linear analogs. Moreover, the presence of tetraphenylethylene group in the NHOs entitled the triblock TPEs with excellent AIE properties in both solution and solid state.

7.
J Biopharm Stat ; : 1-19, 2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37545144

RESUMO

This manuscript consists of two topics. Firstly, we explore the utility of internal pilot study (IPS) approach for reestimating sample size at an interim stage when a reliable estimate of the nuisance shape parameter of the Weibull distribution for modeling survival data is unavailable during the planning phase of a study. Although IPS approach can help rescue the study power, it is noted that the adjusted sample size can be as much as twice the initially planned sample size, which may put substantial practical constraints to continue the study. Secondly, we discuss Bayesian predictive probability for conducting interim analyses to obtain preliminary evidence of efficacy or futility of an experimental treatment warranting early termination of a clinical trial. In the context of single-arm clinical trials with time-to-event endpoints following Weibull distribution, we present the calculation of the Bayesian predictive probability when the shape parameter of the Weibull distribution is unknown. Based on the data accumulated at the interim, we propose two approaches which rely on the posterior mode or the entire posterior distribution of the shape parameter. To account for uncertainty in the shape parameter, it is recommended to incorporate its entire posterior distribution in our calculation.

8.
Ann Plast Surg ; 91(5): 617-621, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37823627

RESUMO

BACKGROUND: Tissue oximetry monitoring has shown superior outcomes to conventional monitoring methods for autologous breast reconstruction in retrospective studies with consecutive cohorts. A recent study used consecutive cohorts with tissue oximetry as the earlier cohort and found that tissue oximetry was nonsuperior. We hypothesize that improvement in microsurgical outcomes with institutional experience confounds the superiority of tissue oximetry demonstrated in prior studies. This study aimed to perform a systematic review and meta-analysis of the outcomes of tissue oximetry monitoring compared with conventional monitoring. METHODS: Relevant studies were found using PubMed, Embase, and Web of Science searches for keywords such as near-infrared spectroscopy or tissue oximetry and microsurgery. Studies included compared tissue oximetry and conventional monitoring in autologous breast reconstruction patients. Studies were excluded if they did not contain a comparison group. Random-effective models were used to analyze early returns to the operating room, the total number of partial or complete flap loss, and late fat necrosis. RESULTS: Six hundred sixty-nine studies were identified; 3 retrospective cohort studies met the inclusion criteria. A total of 1644 flaps were in the tissue oximetry cohort, and 1387 flaps were in the control cohort. One study contained tissue oximetry as the former cohort; 2 had tissue oximetry as the latter. Neither technique was superior for any measured outcomes. The estimated mean differences between tissue oximetry and conventional monitoring method were early returns, -0.06 (95% confidence interval [CI], -0.52 to 0.410; P = 0.82); partial flap loss, -0.04 (95% CI, -0.86 to 0.79; P = 0.93); complete flap loss, -1.29 (95% CI, -3.45 to 0.87; P = 0.24); and late fat necrosis -0.02 (95% CI, -0.42 to, 0.39; P = 0.94). CONCLUSIONS: In a systematic review and meta-analysis of mixed timeline retrospective cohort studies, tissue oximetry does not provide superior patient outcomes and shifts our current understanding of postoperative breast reconstruction monitoring. Prospective studies and randomized trials comparing monitoring methods need to be included in the existing literature.


Assuntos
Necrose Gordurosa , Mamoplastia , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Mamoplastia/métodos , Complicações Pós-Operatórias/diagnóstico , Oximetria
9.
Biom J ; 65(4): e2100403, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36789566

RESUMO

For sample size calculation in clinical trials with survival endpoints, the logrank test, which is the optimal method under the proportional hazard (PH) assumption, is predominantly used. In reality, the PH assumption may not hold. For example, in immuno-oncology trials, delayed treatment effects are often expected. The sample size without considering the potential violation of the PH assumption may lead to an underpowered study. In recent years, combination tests such as the maximum weighted logrank test have received great attention because of their robust performance in various hazards scenarios. In this paper, we propose a flexible simulation-free procedure to calculate the sample size using combination tests. The procedure extends the Lakatos' Markov model and allows for complex situations encountered in a clinical trial, like staggered entry, dropouts, etc. We evaluate the procedure using two maximum weighted logrank tests, one projection-type test, and three other commonly used tests under various hazards scenarios. The simulation studies show that the proposed method can achieve the target power for all compared tests in most scenarios. The combination tests exhibit robust performance under correct specification and misspecification scenarios and are highly recommended when the hazard-changing patterns are unknown beforehand. Finally, we demonstrate our method using two clinical trial examples and provide suggestions about the sample size calculations under nonproportional hazards.


Assuntos
Neoplasias , Projetos de Pesquisa , Humanos , Modelos de Riscos Proporcionais , Tamanho da Amostra , Simulação por Computador , Análise de Sobrevida
10.
Angew Chem Int Ed Engl ; 62(8): e202218248, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36577704

RESUMO

Rapid access to sequence-controlled multi-block copolymers (multi-BCPs) remains as a challenging task in the polymer synthesis. Here we employ a Lewis pair (LP) composed of organophosphorus superbase and bulky organoaluminum to effectively copolymerize the mixture of methacrylate, cyclic acrylate, and two acrylates, into well-defined di-, tri-, tetra- and even a hepta-BCP in one-pot one-step manner. The combined livingness, dual-initiation and CSC feature of Lewis pair polymerization enable us to achieve not only a trihexaconta-BCP with the highest record in 8 steps by using four-component monomer mixture as building blocks, but also the arbitrarily-regulated monomer sequence in multi-BCP, simply by changing the composition and adding order of the monomer mixtures, thus demonstrating the powerful capability of our strategy in improving the efficiency and enriching the composition of multi-BCP synthesis.

11.
Macromol Rapid Commun ; 43(16): e2200088, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35363417

RESUMO

It remains as a great challenge to realize living and controlled polymerization of renewable monomers by the boron-based Lewis pairs. Here, strong nucleophilic N-heterocyclic olefins (NHOs) or N-heterocyclic carbenes (NHCs) as Lewis bases, and boron-based compounds as Lewis acids, are employed to construct LPs for polymerization of alkyl sorbates, including (E, E)-methyl sorbate and (E, E)-ethyl sorbate. Systematic investigation reveals that the combinations of B(C6 F5 )3  with appropriate acidity and steric hindrance, and strong nucleophilic NHOs promote living and controlled polymerization of alkyl sorbates in 100% 1,4-addition manner, furnishing polymers with predicted molecular weight (Mw up to 56.6 kg mol-1 ) and narrow molecular weight distribution (D as low as 1.12). Furthermore, topology analysis shows that NHC1/B(C6 F5 )3  LP produce PMS possessing cyclic structure.


Assuntos
Boro , Ácidos de Lewis , Alcenos/química , Catálise , Ácidos de Lewis/química , Estrutura Molecular , Polimerização
12.
Angew Chem Int Ed Engl ; 61(24): e202202448, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35349218

RESUMO

Lewis pair polymerization has demonstrated its unique advantages and powerful capability in polymer synthesis. Here we employ strong nucleophilic N-heterocyclic olefin (NHO) and bulky organoaluminum to construct a frustrated Lewis pair, which can realize the compounded sequence control (CSC) copolymerization and self-assembly the mixture of dimethylaminoethyl acrylate and fluoride-functionalized methacrylate into diblock copolymers (di-BCPs) nano-assemblies through polymerization-induced self-assembly in one-pot, single-step manner within minutes. These di-BCPs were characterized by 1 H and 13 C NMR, GPC, DSC, and TEM. By utilizing appropriate solvophilic block and solvophobic block, such Lewis pair polymerization-induced self-assembly strategy enables the expeditious, room-temperature synthesis of di-BCP nanoparticles with different morphologies, including spheres, worms, vesicles, and even fibers, thus suggesting the great application potential of such method in the future.

13.
Angew Chem Int Ed Engl ; 61(8): e202114946, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-34904337

RESUMO

This work utilizes frustrated Lewis pairs consisting of tethered bis-organophosphorus superbases and a bulky organoaluminum to furnish the highly efficient synthesis of well-defined triblock copolymers via one-step block copolymerization of lignin-based syringyl methacrylate and n-butyl acrylate, through di-initiation and compounded sequence control. The resulting thermoplastic elastomers (TPEs) exhibit microphase separation and much superior mechanical properties (elongation at break up to 2091 %, tensile strength up to 11.5 MPa, and elastic recovery up to 95 % after 10 cycles) to those of methyl methacrylate-based TPEs. More impressively, lignin-based tri-BCPs can maintain TPEs properties up to 180 °C, exhibit high transparency and nearly 100 % UV shield, suggesting potential applications in temperature-resistant and optical devices.

14.
Eur Respir J ; 57(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32732330

RESUMO

Large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel function is critical for adequate airway hydration and mucociliary function. In airway epithelia, BK function is regulated by its γ-subunit, leucine-rich repeat-containing protein 26 (LRRC26). Since patients with cystic fibrosis (CF)-related diabetes mellitus (CFRD) have worse lung function outcomes, this study determined the effects of hyperglycaemia on BK function in CF bronchial epithelial (CFBE) cells in vitro and evaluated the correlation between glycaemic excursions and mRNA expression of LRRC26 in the upper airways of CF and CFRD patients.CFBE cells were redifferentiated at the air-liquid interface (ALI) in media containing either 5.5 mM or 12.5 mM glucose. BK activity was measured in an Ussing chamber. Airway surface liquid (ASL) volume was estimated by meniscus scanning and inflammatory marker expression was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). CF patients were assessed by 7 days of continuous glucose monitoring (CGM). LRRC26 mRNA expression was measured by quantitative real-time PCR from nasal cells obtained at the end of glucose monitoring.BK currents were significantly decreased in CFBE cells cultured under high glucose. These cells revealed significantly lower ASL volumes and increased inflammation, including the receptor for advanced glycation endproducts (RAGE), compared to cells cultured in normal glucose. In vivo, nasal cell expression of LRRC26 mRNA was inversely correlated with hyperglycaemic excursions, consistent with the in vitro results.Our findings demonstrate that hyperglycaemia induces inflammation and impairs BK channel function in CFBE cells in vitro These data suggest that declining lung function in CFRD patients may be related to BK channel dysfunction.


Assuntos
Fibrose Cística , Hiperglicemia , Glicemia , Automonitorização da Glicemia , Fibrose Cística/complicações , Regulador de Condutância Transmembrana em Fibrose Cística , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Alta , Muco , Receptor para Produtos Finais de Glicação Avançada , Mucosa Respiratória
15.
Macromol Rapid Commun ; 42(3): e2000491, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33200483

RESUMO

The microstructure can significantly affect the physical and mechanical properties of polymers. Five chiral binuclear aluminum methyl complexes (rac1 to rac5) are synthesized by using chiral binaphthalene diamine ligand and characterized by both 1 H and 13 C NMR spectroscopy. The crystal structures of rac3 and rac5 are also identified by single crystal X-ray diffraction. In the presence of i PrOH initiator, these aluminum complexes catalyze the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in a controlled manner and produce polymers with high to excellent isoselectivity (Pm up to 0.93). Even with a catalyst loading as low as 0.1%, polylactide with a Pm of 0.83 can still be obtained. Kinetic studies reveal the first-order dependence on monomer concentration whereas kinetic resolution polymerization provides the evidence to support that these binuclear aluminum catalysts catalyzed ROP of rac-LA adopts enantiomorphic site control mechanism. Furthermore, this strategy can also be applied to the ROP of both ε-caprolactone and δ-valeroactone.


Assuntos
Alumínio , Catálise , Dioxanos , Cinética , Polimerização
16.
Arch Phys Med Rehabil ; 102(3): 448-455, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32950465

RESUMO

OBJECTIVE: To investigate the reliability and validity of pupillary response during dual-task balance conditions in individuals with Parkinson disease (PD). DESIGN: Cross-sectional study. SETTING: University of Kansas Medical Center Parkinson's Disease and Movement Disorder Center. PARTICIPANTS: Participants (N=68) included individuals with PD (n=33) and healthy controls (n=35). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Pupillary response was the main outcome measure that was measured during the following conditions: single-task balance eyes open, single-task balance eyes occluded, dual-task eyes open, and dual-task eyes occluded. After each condition, the National Aeronautics and Space Administration-Task Load Index (NASA-TLX) was administered to assess self-reported cognitive workload. To examine the test-retest reliability of the pupillary response, the conditions were administered twice for each individual within 2 hours. Intraclass correlation coefficients (ICC) were used to analyze the test-retest reliability of pupillary response in each condition for both groups. Pearson's r correlation was used to assess the convergent validity of pupillary response against the NASA-TLX. RESULTS: The test-retest reliability was excellent for both groups in almost all conditions (ICC>0.75). There were no correlations between pupillary response and the NASA-TLX. However, increased mental demand (a subitem of the NASA-TLX) significantly correlated with increased pupillary response in individuals with PD (r=0.38; P=.03). CONCLUSIONS: Pupillary response showed excellent test-retest reliability and validity during dual-task balance for individuals with PD and healthy controls. Overall, these results suggest that pupillary response represents a stable index of cognitive workload during dual-task balance in individuals with PD.


Assuntos
Doença de Parkinson/fisiopatologia , Doença de Parkinson/reabilitação , Equilíbrio Postural/fisiologia , Pupila/fisiologia , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas
17.
Mikrochim Acta ; 188(7): 229, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34117526

RESUMO

Zeolite imidazole framework-based boronic acid-functionalized metal-organic frameworks (ZIF-67@PDA@BA-Zr-MOFs) were developed as an adsorbent for solid phase extraction (SPE) of luteolin (LTL) from peanut shell samples. Herein, ZIF-67 as a support matrix, polydopamine (PDA) as a coating to introduce amino and hydroxyl groups on the matrix surface to fix metal-organic frameworks (MOFs), zirconium tetrachloride (ZrCl4) as a precursor, terephthalic acid (TPA), and 3-carboxyphenylboronic acid (3-CPBA) as the mutual organic building blocks, and 3-CPBA was also a boronate affinity functional monomer. The effects of synthesis conditions, SPE conditions, selectivity, competitivity, reproducibility, and reusability were evaluated in detail. Under the optimal conditions, the maximum adsorption capacity is 71.4 mg g-1. The utility of ZIF-67@PDA@BA-Zr-MOFs as an adsorbent for SPE of LTL is supported by the presence of the abundant pore structure, as well as the boronate affinity sites facilitated the rapid binding of the adsorbent to the template. The concentration of the extracted LTL was determined by the high-performance liquid chromatography-ultraviolet (HPLC-UV), with calibration plots being linear in the concentration range 0.05-100 mg L-1 and a limit of detection (LOD) of 0.035 mg L-1. The method was applied to determine the LTL in peanut shell samples and recovered the target analyte in the range 85.6% to 99.2% (the standard deviations are less than 3.3%, n = 3). In addition, we incorporated boronate affinity and MOFs material into an SPE system to provide a promising strategy to detect other cis-diol-containing analytes in the complex matrix.

18.
Pharm Stat ; 20(3): 610-644, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33565236

RESUMO

Sample size calculation is an essential component of the planning phase of a clinical trial. In the context of single-arm clinical trials with time-to-event (TTE) endpoints, only a few options with limited design features are available. Motivated from ethical or practical considerations, two-stage designs are implemented for single-arm studies to obtain early evidence of futility. A major drawback of such designs is that early stopping may only occur at the conclusion of the first stage, even if lack of efficacy becomes apparent at any other time point over the course of the clinical trial. In this manuscript, we attempt to fill some existing gaps in the literature related to single-arm clinical trials with TTE endpoints. We propose a parametric maximum likelihood estimate-based test whose variance component accounts for the expected proportion of loss to follow-up and different accrual patterns (early, late, or uniform accrual). For the proposed method, we present three stochastic curtailment methods (conditional power, predictive power, Bayesian predictive probability) which can be employed for efficacy or futility testing purposes. Finally, we discuss the implementation of group sequential designs for obtaining an early evidence of efficacy or futility at pre-planned timings of interim analyses. Through extensive simulations, it is shown that our proposed method performs well for designing these studies with moderate to large sample sizes. Some examples are presented to demonstrate various aspects of the stochastic curtailment and repeated significance testing methods presented in this manuscript.


Assuntos
Ensaios Clínicos como Assunto , Futilidade Médica , Projetos de Pesquisa , Teorema de Bayes , Humanos , Funções Verossimilhança , Tamanho da Amostra
19.
Angew Chem Int Ed Engl ; 60(45): 24306-24311, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34510679

RESUMO

In this contribution, Lewis pairs (LPs) composed of N-heterocyclic olefins (NHOs) with different steric hindrance and nucleophilicity as Lewis bases (LBs) and Al-based compounds with comparable acidity but different steric hindrance as Lewis acids (LAs) were applied for 1,4-selective polymerization of (E,E)-methyl sorbate (MS) and (E,E)-ethyl sorbate (ES). The effects of steric hindrance, electron-donating ability, and acidity of LPs on MS and ES polymerization were systematically investigated. High catalytic activity and high initiation efficiency can be achieved, leading to the formation of PMS with 100 % 1,4-selectivity, tunable molecular weight (Mw up to 333 kg mol-1 ), and narrow molecular weight distribution (MWD). Block copolymerization of ES and methyl methacrylate (MMA) was also realized. Meanwhile, this system can be applied to other homologous conjugated diene substrates. Furthermore, simple chemical reactions can efficiently convert PMS to different polymers with strict (AB)n sequence structures, such as poly(sorbic acid), poly(propylene-alt-methyl acrylate), poly(propylene-alt-acrylic acid), poly(propylene-alt-allyl alcohol), and poly(ethylene-alt-2-butylene).

20.
Macromol Rapid Commun ; 41(24): e2000456, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33196123

RESUMO

It is challenging to synthesize stimuli-responsive materials with the well-balanced performance of fast stimulus-response speed, good mechanical strength, multi-functionality, and deformation diversity as well. This work reports a facile, one-step thiol-ene click polymerization strategy for preparation of water/acetone vapor-responsive hierarchical films, by using diallyl terephthalate (P) as hydrophobic ene-monomer, 1,4-diallyl-1,4-diazabicyclo [2.2.2]octane-1,4-diium bromide (B) as hydrophilic ene-monomer, and pentaerythritol tetra(3-mercaptopropionate) (PETMP) as thiol monomer. Besides, by taking advantage of the specific hydrophilic/hydrophobic induction effect of substrate and adjusting the molar ratio of P to B, P60 B40 -HPI film is fabricated on hydrophilic substrate "with plasma treatment" whereas P80 B20 -HPO film is obtained on hydrophobic substrate "without plasma treatment". Their "upper-dense and lower-porous" structural feature ensured the excellent combination of fast stimuli-response speed endowed by the porous structure and good mechanical strength enhanced by the upper dense surface. Both films are bidirectional water/acetone vapor-responsive materials, but their bending directions responding to the stimuli factors are completely opposite. This strategy showed great potential in the development of smart stimuli-responsive materials.


Assuntos
Vapor , Compostos de Sulfidrila , Química Click , Interações Hidrofóbicas e Hidrofílicas , Polimerização
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