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In a multiphase stepped wedge cluster randomized trial (MSW‐CRT), more than one intervention will be initiated on each sequence in a fixed order. Hence, with the MSW‐CRT design, the effect of the first intervention can be evaluated when compared to control, as well as the added‐on effects of the subsequent interventions. Studies that use MSW‐CRT have been proposed, but properties of this design have not been explicitly studied. We derive closed‐form variance formulae to test the interventions' effects, which can be readily used for sample size and power calculation. Additionally, we provide relationships between variances to test the interventions' effects and design parameters. Under special conditions, some important properties include: (i) the variances to test different interventions' effects (ie, the first intervention effect and the second intervention effect) may be same; (ii) as the cluster‐period mean autocorrelation increases, the variance to test an intervention effect may first increase and then decrease; (iii) as the amount of periods between the initiations of two interventions (ie, lag) increases, the variance to test an intervention effect may remain unchanged. We illustrate the relationships between power and design parameters using the variance formulae. From a few illustrative examples, we observe that the statistical test that uses data only relevant to a specific intervention has inferior power (relative power loss <15%) compared to the test when using all the study data. Also, power is reduced when both the total number of periods and lag are decreased simultaneously (relative power loss <20%). [ABSTRACT FROM AUTHOR]

High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life‐threatening infections and failure of ASCT. Granulocyte‐colony stimulating factor (G‐CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high‐dose melphalan and G‐CSF administration. The extended PK/PD model incorporated several covariates, including G‐CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G‐CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration. [ABSTRACT FROM AUTHOR]

Claiming to be a complex approach, the updated worldwide Sustainable Development Goals agreement broadens its educational scope and acknowledges the integrated and indivisible character of human development through diverse dimensions. Complex systems research provides ways to improve our understanding of the complexity of education and to explore how education fits within the context of human development. To account for 'effect-based' research on education complexity, using the American Community Survey data, we developed a model by inferring a probabilistic network structure of diverse aspects of human development dimensions including education. We explored the model by network analysis methods to discover the intrinsic relationships among education variables and the extrinsic relationships of education with other dimensions of human development in the USA. The results confirmed the well-known rationale of the relationship between education and wealth, and expanded the understanding of complexity of education as it is part of the life course (timing of individual development) and of the cultural construction of identity. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

More than 3.5 million nonmelanoma skin cancers were treated in 2006; of these 700,000 were cutaneous squamous cell carcinomas (cSCCs). Despite clear environmental causes for cSCC, studies also suggest genetic risk factors. A cSCC susceptibility locus, Skts5, was identified on mouse chromosome 12 by linkage analysis. The orthologous locus to Skts5 in humans maps to 7p21 and 7q31. These loci show copy number increases in ∼10% of cSCC tumors. Here, we show that an additional 15-22% of tumors exhibit copy-neutral loss of heterozygosity. Furthermore, our previous data identified microsatellite markers on 7p21 and 7q31 that demonstrate preferential allelic imbalance (PAI) in cSCC tumors. On the basis of these results, we hypothesized that the human orthologous locus to Skts5 would house a gene important in human cSCC development and that tumors would demonstrate allele-specific somatic alterations. To test this hypothesis, we performed quantitative genotyping of 108 single nucleotide polymorphisms (SNPs) mapping to candidate genes at human SKTS5 in paired normal and tumor DNAs. Nine SNPs in HDAC9 ( rs801540, rs1178108, rs1178112, rs1726610, rs10243618, rs11764116, rs1178355, rs10269422 and rs12540872) showed PAI in tumors. These data suggest that HDAC9 variants may be selected for during cSCC tumorigenesis. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. Study Design: A randomized, controlled, multi-institutional, single-blinded validation study. Methods: The project encompassed four areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. Results: Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost-effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at eight different training institutions across the country using a two-arm randomized trial where study subjects were randomized to a 2-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms; 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. Conclusions: A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial. There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones. Further refinements in structural acquisition and interface design have been identified, which can be implemented prior to full incorporation into training programs and used for objective skills assessment. [ABSTRACT FROM AUTHOR]

Purpose: To compare low-field (0.15 T) intraoperative magnetic resonance imaging (iMRI)-guided tumor resection with both conventional magnetic resonance imaging (cMRI)-guided tumor resection and high-field (1.5 T) iMRI-guided resection from the clinical and economic point of view. Materials and Methods: We retrospectively compared 65 iMRI patients with 65 cMRI patients in terms of hospital length of stay, repeat resection rate, repeat resection interval, complication rate, cost to the patient, cost to the hospital, and cost effectiveness. In addition, we compared our low-field results with previously published high-field results. Results: The complication rate was lower for iMRI vs. cMRI in patients presenting for their initial tumor resection (45 vs. 57 complications, P = 0.048). The iMRI repeat resection interval was longer for this cohort (20.1 vs. 6.7 months, P = 0.020). iMRI was more cost-effective than cMRI for patients who had repeat resections ($10,690/RFY vs. $76,874/RFY, P < 0.001). We found no other clinical or economic differences between iMRI- and cMRI-guided tumor resection surgeries. Overall, we did not find the advantages to low-field iMRI that have been reported for high-field iMRI. Conclusion: There is no adequate justification for the widespread installation of low-field iMRI in its current development state. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We recently described the expression of type IV pili (Tfp) by non-typeable Haemophilus influenzae (NTHI), a common respiratory tract pathogen. Prior to that report, Tfp were not thought to be produced by NTHI as they are not observed on NTHI when grown on chocolate agar or other commonly used growth media. To further characterize growth conditions permissive for the expression of NTHI Tfp, as well as determine their role in colonization and virulence, we transformed an NTHI otitis media isolate with a reporter plasmid containing the lux gene cluster driven by the pilA promoter. Transcription from the pilA promoter was demonstrated under a variety of in vitro growth conditions and, importantly, by ex vivo imaging of luciferase-producing NTHI in infected chinchillas. Luciferase-producing NTHI were also identified within a biofilm formed by NTHI in vivo. We further demonstrated a role for NTHI PilA in adherence to human respiratory epithelial cells, in colonization of the chinchilla respiratory tract as well as a requirement for PilA in biofilm development, both in vitro and in vivo. Collectively, our data demonstrate that NTHI express PilA in vivo, and that PilA plays an important role in the pathogenesis of an upper respiratory tract infection induced by NTHI. [ABSTRACT FROM AUTHOR]