Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms
available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations,
including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization
(SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study
was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm
was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations
followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties
of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias
was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or
under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for
all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm
was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation
is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in
July 2009). 相似文献
Follicular lymphomas (FLs) are a heterogeneous group of tumors, but prognostic factors are evaluated insufficiently in this common hematologic neoplasm. While bcl-6 and CD10 are expressed characteristically in FLs, their significance for biologic behavior of FL has not been studied previously. Samples from 73 patients with FL and clinical follow-up from 7 to 231 months were evaluated by immunohistochemical analysis. Patients with high levels of bcl-6 expression had favorable overall survival (OS) (P = .003), disease-specific survival (DSS) (P = .033), and time to treatment failure (P = .003) compared with patients with low levels of bcl-6 expression. Multivariate analysis showed that the results for OS, DSS, and time to treatment failure were independent of the international prognostic index. Patients with CD10+ FLs also had longer OS (P = .001), DSS (P = .007), and time to treatment failure (P = .004), and grade 1 FL was associated with better OS (P = .01) and a statistical trend for longer DSS (P = .05) and time to treatment failure (P = .05), but these results were not independent of bcl-6 expression or the international prognostic index in multivariate analysis. 相似文献
n= 665, 51%)
had an ISS ranging from 0 to 34 (mean 13) had wounds ranging from G1ST
(soft tissue wounds caused by low energy transfer) to G3VF (massive
wounds with fractures and injury of vital structures) according to the
RCWC, with PSS/IS scores from 2 to 105 (mean 60). Statistically
significant correlation was found between ISS and PSS/IS as well as
RCWC and PSS/IS. Cytokines (IL-1, TNFalpha) and amino acids
responded to a blast injury in similar manner as to gunshot wounds with
a greater ISS or more severe RCWC injury type. The subjective
sensations in blasted patients (deafness, thoracic pain, vertigo) and
mediators, confirmed in previous experimental investigations as
important factors in the pathogenesis of blast injuries
(TxA2, sulfidopeptide leukotrienes) were relationed only to
the PSS/IS.RID=" ID=" <E5>Correspondence to:</E5> I. Cernak, M.D., Ph.D. 相似文献
Adolescent smoking is a major public health problem. While the socioeconomic status (SES) of the neighbourhood and that of the family are known to play a role in smoking onset and progression, it is not clear whether it modifies the association between parental influences and adolescent behaviour. The purpose of this study is to investigate family correlates of adolescent smoking experimentation and to explore the modifying role of socioeconomic context and European geographical area in a sample of European adolescents. This is a secondary analysis of the baseline survey of the European Drug Addiction Prevention (EU-Dap) trial which took place in seven European countries and involved 7079 students. School SES was used as indicator of socioeconomic context. European countries were aggregated in two geographical areas: North-Central and South. The associations between parental, family factors, and adolescents smoking experimentation were analysed through multilevel mixed-effect logistic regression models, stratified by school SES and European geographical area. Parental smoking, permissiveness towards tobacco, family conflicts, problematic relationships, low connectedness, and low parental control were significantly associated with adolescent smoking experimentation. Paternal smoking was a stronger correlate of adolescent smoking in low SES schools, while maternal smoking in high SES schools. Parental permissiveness was a stronger correlate in low SES schools. Family conflicts and low parental control were correlates only in low SES schools. The associations did not substantially differ between European geographical areas, with the exception of parental smoking that was a stronger correlate in the North, and parental control that was a correlate only in the South of Europe. To reduce inequalities in tobacco-related outcomes, prevention efforts in low socioeconomic contexts appear to be a public health priority. Parental smoking, permissiveness, family relationships, and connectedness should be addressed in preventive programs.
Objectives: To compare three positions for defecation by measuring abdominal pressure and the anorectal angle simultaneously. Methods: We recruited six healthy volunteers. The videomanometric measures included simultaneous fluoroscopic images, abdominal pressures, subtracted rectal pressures and anal sphincter pressures. Three positions were used: sitting, sitting with the hip flexing at 60 ° with respect to the rest of the body, and squatting with the hip flexing at 22.5 ° with respect to the rest of the body. Results: Basal abdominal pressure before defecation on hip‐flex sitting was lower than that with normal sitting, although the difference did not reach statistical significance. Basal abdominal pressure before defecation on squatting (26 cmH2O) was lower than that with normal sitting (P < 0.01). Abdominal pressure increase (strain) on hip‐flex sitting was lower than that with normal sitting, although this difference did not reach statistical significance. Similarly, the abdominal pressure increase on squatting was smaller than that with normal sitting, and yet the difference did not reach statistical significance. The rectoanal angle on defecation on hip‐flex sitting did not differ from that with normal sitting. The rectoanal angle on defecation on squatting (126 °) was larger than that with normal sitting (100 °) (P < 0.05), and was also larger than that with hip‐flex sitting (99 °) (P < 0.01). Conclusion: The results of the present study suggest that the greater the hip flexion achieved by squatting, the straighter the rectoanal canal will be, and accordingly, less strain will be required for defecation. 相似文献
The synthesis of nanostructured sub-microspheres of TiO2 anatase with hierarchical nano- and mesoporosity was successfully achieved by using an innovative approach that applies the principles of acidic digestion to microwave (MW) solvothermal synthesis. This process, termed flash microwave-assisted solvothermal (FMS) synthesis, facilitates the formation of spherical particles without surfactants or templating agents, exploiting the rapid reaction kinetics engendered by MW heating. Unlike many other MW-assisted solvothermal methods, the application of constant MW power leads to a rapid increase of the autogenous pressure, inducing burst-nucleation of small primary crystallites and subsequent rapid agglomeration into secondary particles, with reaction times reduced to minute-timescales. The use of non-aqueous polar solvents such as ethanol is key to the production of regular spheres with a narrow size distribution, composed of nanocrystallites. Morphology, porosity, specific surface area, phase composition, crystallite size and optical properties of the particles can be controlled via a judicious selection of physical and chemical synthesis parameters, especially precursor choice and acid concentration. The complex structure of the particles leads to surface areas of up to ca. 500 m2 g−1 with intergranular mesoporosity. The as-synthesised FMS particles show increased adsorption under dark conditions and selective de-ethylation of rhodamine B under visible light compared to a commercial photocatalyst (Degussa P25). The photodegradation mechanism hinges on the capacity of the spheres to accept electrons from the photoexcited state of molecules at the particle surface, with the large sphere surface area maximising adsorption capacity and improving the efficiency of the photocatalytic processes. The singular characteristics and properties of the particles could pave the way for further applications in water purification and optoelectronic devices.Photoactive nanostructured TiO2 sub-microspheres can be fabricated by “microwave flash synthesis” in minute timescales. 相似文献
The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential. 相似文献