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Previous studies reported inconsistent findings on autophagy activation in skeletal muscles after acute exercise. In this study, we investigated the effect of a single bout of exhaustive treadmill exercise on AMPK and autophagy activations in mice gastrocnemius muscle in vivo. Male ICR/CD-1 mice were randomly divided into the control and exercise groups. The later was subjected to a single bout of exhaustive treadmill exercise. Changes of AMPK, phosphorylation of AMPK

This study aimed to elucidate the role of transcription factor EB (TFEB) in protecting C2C12 myotubes against palmitate (PA)-induced insulin resistance (IR) and explored its mechanism associated with autophagy. PA treatment significantly decreased insulin sensitivity in myotubes and downregulated TFEB protein expression. TFEB overexpression significantly reversed the PA-suppressed glucose transporter 4 (GLUT4) protein expression and improved intracellular glucose uptake and consumption, and also alleviated the decrease of autophagy markers induced by PA. The effect of TFEB overexpression on GLUT4 was also abolished by the autophagy inhibitor 3-MA. In addition, AMPKɑ2-DN inhibited or abolished the effects of TFEB overexpression on upregulation of GLUT4 and PA-induced decrease of autophagy marker expressions. Taken together, our data demonstrated that upregulation of TFEB improved PA-induced IR in C2C12 myotubes by enhancing autophagy and upregulating AMPK activity. TFEB, as a critical regulator of glucose homeostasis in skeletal muscle cells, may be a potential therapeutic target for IR and Type 2 diabetes.

Oral cavity lymphomas constitute only 3% of all lymphomas in the general population but are the third most common oral malignancy. A 67-year-old female with a history of osteoporosis, Graves' disease and non-Hodgkin's lymphoma was referred to the Department of Dental Specialties with a chief complaint of persistent soft tissue swelling facial to the maxillary incisors of possible non-odontogenic origin. To expedite care, the patient was first seen via teledentistry and subsequently appointed for an in-person evaluation and treatment. Examination revealed 1-3 mm probing depths and a firm, non-tender, non-fluctuant mass in the facial soft tissues approximating teeth nos. 7-10. Biopsy of the affected area was performed. A diagnosis of recurrent follicle center cell lymphoma, a form of non-Hodgkin's lymphoma, was rendered. The patient was subsequently referred to the Oncology and Hematology team, followed for 6 weeks and remained symptom-free. This case underlies the importance of teledentistry to expedite care and manage patient expectations. Additionally, it also underscores the importance of microscopic examination of tissue samples from oral lesions that appear non-odontogenic in nature and reinforces the role of dentistry in uncovering the oral-systemic link.

This study aimed to explore whether APOC1 expression has a function in the biological behavior of clear cell renal cell carcinoma (ccRCC) cells and its possible mechanism. Bioinformatics analysis of data TCGA and OnComine was conducted to explore the expression pattern and prognostic value of APOC1, as well as the relationship between APOC1 expression and clinical indicators. Loss‐ and gain‐ of APOC1 function assays were carried out to assess the biological functions of APOC1. Western blotting was applied to detect protein expression. We revealed that APOC1 was upregulated in ccRCC tissues. APOC1 expression was related to gender, grade, pathologic‐T, pathologic‐stage, and pathologic‐M in patients with ccRCC. Meanwhile, Kaplan–Meier analysis evidenced that the high APOC1 expression indicated unfavorable outcomes of ccRCC. Functional experiments in vitro revealed that upregulation of APOC1 in UT33A cells promoted cell proliferation, invasion, and migration, while downregulation of APOC1 in 786‐O cells had the opposite effect. Furthermore, epithelial mesenchymal transition (EMT) was activated in cells with upregulated APOC1 but inhibited in cells with down‐regulated APOC1. Collectively, our data suggested that APOC1 was overexpressed in ccRCC cells and promoted the malignant biological behaviors and EMT of ccRCC cells.

To evaluate the clinical utility of neutrophil (n)CD64 index to diagnose pulmonary tuberculosis (PTB) and extrapulmonary TB (ePTB) and to predict the outcome of Mycobacterium tuberculosis infection. We recruited 189 patients with active TB and 140 controls and measured the differential expression of nCD64 index using flow cytometry. The receiver operating characteristics (ROC) curve analysis was performed to estimate the diagnostic performance of the nCD64 index and T‐SPOT.TB assay for the diagnosis of TB. Furthermore, we analysed whether the nCD64 index in patients with TB was correlated with inflammatory indicators. Finally, we assessed the prognosis of patients by following the dynamic changes of the nCD64 index once a week. The nCD64 index was significantly higher in active TB group (PTB and ePTB), than in the anti‐TB and healthy controls (HC) groups. The sensitivity and specificity of nCD64 index for the differential diagnosis of PTB and pneumonia (PN) patients were 68.33% and 77.55%, respectively. The sensitivity and specificity of nCD64 index for the diagnosis of tuberculous meningitis (TBM) were 53.85% and 100%, respectively. Furthermore, there was a weak correlation between the nCD64 index and inflammatory indicators. More importantly, with the improvement in patient condition, the nCD64 index started to decline in the first week of anti‐TB therapy and significantly decreased at 4 weeks after treatment. Our study demonstrated that the CD64 assay is a rapid, non‐invasive and stable method for clinical application, and the nCD64 index can serve as a potential biomarker for the diagnosis and prognosis of TB.

Neuroinflammation is believed to play a primary role in the pathogenesis of most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and schizophrenia. Currently, suitable in vitro neuroinflammation models for studying cellular interactions and inflammatory mechanisms at the neurovascular unit are still scarce. In this study, we established an experimentally flexible tri-culture neuroinflammation model combining murine microglial cells (N11), mouse neuroblastoma Nuro2A cell lines and brain microvascular endothelial MVEC(B3) cells in a transwell co-culture system stimulated with lipopolysaccharides. Neuroinflammation was induced in this tri-culture model as manifested by activated N11 cells via toll-like receptor 4, resulting in increased release of proinflammatory mediators (nitric oxide, interleukin-6 and tumour necrosis factor-α) through the activation of nuclear factor-κB signalling pathway. The released inflammatory cytokines from N11 in turn, damaged the tight junction in microvascular endothelial MVEC(B3) cells, increased permeability of endothelial barrier, and induced tau phosphorylation and up-regulated caspase-3 expression in mouse neuroblastoma Nuro2A cell lines, leading to neuroinflammation injury. In summary, this tri-culture inflammation model mimics the microenvironment, the cellular crosstalk and the molecular events that take place during neuroinflammation. It provides a robust in vitro model for studying neuroinflammation mechanisms and screening for potential therapeutics to treat various neurodegenerative diseases.

Much attention has been paid on doping TiO2 to narrow its band gap to promote the absorption of visible light and restrain the recombination of electron-hole pairs to improve its efficiency in photoelectrocatalysis (PEC) under visible-light irradiation. However, the oxidation potential energy of photo-induced holes for the modified catalysts by visible-light excitation is lower than that without modification by UV excitation. In this work, we synthesized a co-coupled TiO2 electrode (denoted ERT) with the Er3+ :YAlO3 and reduced graphene oxide (RGO), achieving the synergetic effect of visible-light-to-UV up-conversion and response and great electron transfer ability. The effects of external bias voltage, electrolyte concentration and pH on the PEC activity were studied with the methylene blue (MB) as the target pollutant. The results indicated that PEC by the ERT electrode showed the highest MB removal compared with those by the electrodes coupled with RGO or Er3+ :YAlO3 alone. In addition, the kinetic rate constant of the PEC process using the ERT electrode was higher than the sum of those of the photocatalytic and electrocatalytic processes. The optimal conditions for PEC by the ERT electrode were an external bias voltage of 1.0 V, 0.1 mol L-1 Na2 SO4 and pH = 10.

Cathode design is indispensable for building Li-O2 batteries with long cycle life. A composite of carbon-wrapped Mo2C nanoparticles and carbon nanotubes is prepared on Ni foam by direct hydrolysis and carbonization of a gel composed of ammonium heptamolybdate tetrahydrate and hydroquinone resin. The Mo2C nanoparticles with well-controlled particle size act as a highly active oxygen reduction reactions/oxygen evolution reactions (ORR/OER) catalyst. The carbon coating can prevent the aggregation of the Mo2C nanoparticles. The even distribution of Mo2C nanoparticles results in the homogenous formation of discharge products. The skeleton of porous carbon with carbon nanotubes protrudes from the composite, resulting in extra voids when applied as a cathode for Li-O2 batteries. The batteries deliver a high discharge capacity of ≈10 400 mAh g−1 and a low average charge voltage of ≈4.0 V at 200 mA g−1. With a cutoff capacity of 1000 mAh g−1, the Li-O2 batteries exhibit excellent charge–discharge cycling stability for over 300 cycles. The average potential polarization of discharge/charge gaps is only ≈0.9 V, demonstrating the high ORR and OER activities of these Mo2C nanoparticles. The excellent cycling stability and low potential polarization provide new insights into the design of highly reversible and efficient cathode materials for Li-O2 batteries.

The prevalence of invasive Fusobacterium nucleatum (Fn) within the serrated neoplasia pathway of the proximal colon has seldom been investigated. We examined the invasive Fn and bacterial biofilms in 35 proximal hyperplastic polyps (HPs), 33 sessile serrated adenomas (SSAs), 48 proximal colorectal cancers (CRCs) and 10 matched metastatic lymph nodes using 16S rRNA fluorescence in situ hybridization (FISH). Samples of normal mucosa, traditional adenomas (TAs), distal HPs, distal CRCs and matched lymph nodes with or without metastases were used as controls. The prevalence of invasive Fn within proximal HPs (65.7%) and SSAs (78.8%) were significantly higher than that of proximal TAs (28.9%) and distal TAs (24.4%; p

Summary Informative identification of the within-subject correlation is essential in longitudinal studies in order to forecast the trajectory of each subject and improve the validity of inferences. In this paper, we fit this correlation structure by employing a time adaptive autoregressive error process. Such a process can automatically accommodate irregular and possibly subject-specific observations. Based on the fitted correlation structure, we propose an efficient two-stage estimator of the unknown coefficient functions by using a local polynomial approximation. This procedure does not involve within-subject covariance matrices and hence circumvents the instability of calculating their inverses. The asymptotic normality of resulting estimators is established. Numerical experiments were conducted to check the finite sample performance of our method and an example of an application involving a set of medical data is also illustrated.

Two methods based on data envelopment analysis DEA and PageRank are proposed to rank college athletic coaches. The DEA-based method uses four processes: first, the input factors must undergo the Kendall Consistency Check to ensure the feasibility and consistency of the result; second, the Data Reduction Factor epitomizes the input-output factors; third, the Range Transfer Approach standardizes the parameters and fourth, Efficiency Assessment Values for each coach are computed using a DEA model. The PageRank-based method involves building a network for matching coaches whose algorithms are used for the ranking. Sensitivity analysis and general analysing methods are applied to examine and analyse the ranking results for baseball, basketball and football coaches. The PageRank-based method also considers dynamic and diffusion relationships among coaches. The results are analysed to reveal possible features to improve the method.

Based on the full optimized molecular geometric structure at B3LYP/cc-pvtz method, the newly designed compound 4, 10-dinitro-2, 6,8, 12-tetraoxa-4, 10-diazatetracyclo[5.5.0.05, 903, 11]dodecane (TEX) was investigated. Additionally, the IR spectrum, the thermal stability, and the detonation performance were predicted. The obtained crystal structure of TEX belongs to Pbca space group and lattice parameters are Z = 8, a = 8.614 A, b = 12.877 A, c = 26.065 A, ρ = 2.015 g·cm–3. Calculation results show that TEX has better detonation properties than HMX and is a high energy density compound with better stability.

The cobalt-catalyzed cross-coupling of organozinc bromides is described. In the case of arylzinc reagents, the same cobalt catalyst, CoBr2(phen), can be used for both the synthesis of the organozinc species and the cross-coupling reaction. In the case of alkylzinc halides, which allow access to dialkylalkynes, the method used for the preparation of the organozinc species has a significant impact on the yields.

We consider a problem where a firm produces a variety of fresh products to supply two markets: an export market and a local market. A public transportation service is utilized to deliver the products to the export market, which is cheap, but its schedule is often disrupted severely. Each time this happens, the firm faces the following questions. (i) For a product that has been finished and is waiting for delivery to the export market, should it continue to wait, at an increasing risk of decay, and when should the waiting be terminated and the product be put to the local market? (ii) For a product that has not been finished, should its processing be postponed, so as to reduce the loss from decay after its completion? (iii) What is the best sequence to process the remaining products, according to the information available? We develop, in this study, a model to address these and other related questions. We find optimal policies that minimize the total expected loss in both the make-to-order and make-to-stock production systems, respectively. For each finished product, we reveal relationships among the desirable waiting time, the price at the local market, and the decaying cost. For unfinished products, we find the optimal start times and processing sequence. Numerical experiments are also conducted to evaluate the optimal policies.

Summary The effects of amiodarone on ventricular electrophysiological parameters, especially the dispersion of ventricular repolarization, were investigated in a canine model of congestive heart failure (CHF). Dogs were randomized to either a control, amiodarone, CHF, or CHF+amiodarone group. Dogs in the CHF and CHF+amiodarone groups underwent 4–5 weeks of rapid ventricular pacing; dogs in the control and amiodarone groups underwent sham operation only. Amiodarone (20 mg/kg per day) was administered orally, beginning on postoperative Day 1, in the treatment groups; ventricular electrophysiological variables were evaluated 4–5 weeks after rapid pacing or sham operation. In CHF dogs, the transmural dispersion ventricular repolarization time (TDVRT) increased significantly. Amiodarone significantly decreased the TDVRT in CHF dogs. The ventricular fibrillation threshold (VFT) decreased in the CHF group. Amiodarone increased the VFT in CHF dogs. The TDVRT increased in CHF dogs, but amiodarone decreased TDVRT and increased VFT in these dogs. These results suggest a beneficial effect of amiodarone on malignant arrhythmias and may provide the basis for its use in CHF patients.

Recurrent event data arise frequently from medical research. Examples include repeated infections, recurrence of tumors, relapse of leukemia, repeated hospitalizations, recurrence of symptoms of a disease, and so on. In the analysis of recurrent event data, the proportional rates model assumes that the regression coefficients are time invariant. In reality, however, these parameters may vary over time, and the temporal covariate effects on the event process are of great interest. In this article, we formulate a class of semiparametric marginal rates models, which incorporate a mixture of time-varying and time-independent parameters, to analyze recurrent event data. For statistical inference on model parameters, an estimation procedure is developed and asymptotic properties of the proposed estimators are established. In addition, we develop tests for investigating whether or not covariate effects vary with time. The finite-sample behaviors of the proposed methods are examined in simulation studies. An example of application of the proposed methodology is illustrated on a set of data from a clinic study on chronic granulomatous disease.

A PCM continuum model, at the B3LYP, B3P86, and B3PW91 three-parameter hybrid DFT methods with 6-311G** basis set, is used to study the bond dissociation energies (BDEs) of benzyl nitrites. Compared the computed results with the experimental values, it is noted that B3PW91 functional is the best method to compute the BDEs of benzyl nitrites. The solvent and substituent effects on the BDEs of the ONO bond are analyzed, and it is shown that the BDE of the ONO bond decreases with the increment of the Hammett constants of substituent groups on benzene for benzyl nitrites except C6H5CH2ONO. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012

The partially linear in-slide model (PLIM) is a useful tool to make econometric analyses and to normalize microarray data. In this article, by using series approximations and a least squares procedure, we propose a semiparametric least squares estimator (SLSE) for the parametric component and a series estimator for the non-parametric component. Under weaker conditions than those imposed in the literature, we show that the SLSE is asymptotically normal and that the series estimator attains the optimal convergence rate of non-parametric regression. We also investigate the estimating problem of the error variance. In addition, we propose a wild block bootstrap-based test for the form of the non-parametric component. Some simulation studies are conducted to illustrate the finite sample performance of the proposed procedure. An example of application on a set of economical data is also illustrated.

Biomaterial scaffolds provide a potentially powerful means of creating precisely engineered bone tissue substitutes with appropriate architecture and mechanical properties. Despite many efforts, there are few satisfactory products available for clinical use, and significant challenges remain in the design of smart constructs, especially for mechanically functional scaffolds. For successful long-term repair of bone, a scaffold must be strong yet have degradation kinetics matching the healing rate of remodeling bone. Here we report a new family of elastomer-toughened composite scaffolds fabricated from poly(glycerol sebacate) and Bioglass ® . These synthetic scaffolds have very similar mechanical properties to that of cancellous bone of the same porosity, and exhibit a mechanically steady state over an extended period in a physiologic environment. The second feature is of great importance to bone tissue engineering, where a lag phase of degradation following implantation is highly desirable in order to provide support to the damaged or fragmented bone tissue. This work shows that a mechanically smart construct with the three-stage profile (lag, log, and plateau phases) of ideal degradation kinetics in mechanical function is achievable with synthetic biomaterials.

This paper is concerned with the statistical inference on seemingly unrelated varying coefficient partially linear models. By combining the local polynomial and profile least squares techniques, and estimating the contemporaneous correlation, we propose a class of weighted profile least squares estimators (WPLSEs) for the parametric components. It is shown that the WPLSEs achieve the semiparametric efficiency bound and are asymptotically normal. For the non-parametric components, by applying the undersmoothing technique, and taking the contemporaneous correlation into account, we propose an efficient local polynomial estimation. The resulting estimators are shown to have mean-squared errors smaller than those estimators that neglect the contemporaneous correlation. In addition, a class of variable selection procedures is developed for simultaneously selecting significant variables and estimating unknown parameters, based on the non-concave penalized and weighted profile least squares techniques. With a proper choice of regularization parameters and penalty functions, the proposed variable selection procedures perform as efficiently as if one knew the true submodels. The proposed methods are evaluated using wide simulation studies and applied to a set of real data.

Theoretical study of several S-nitrosothiols biological molecules has been performed using quantum computational ab initio RHF and density functional B3LYP and B3PW91 methods with 6-31G(d,p) basis set. Geometries obtained from DFT calculations were used to perform natural bond orbital (NBO) analysis. It is noted that the weakness in the SN sigma bond is due to nO1σ delocalization and is responsible for the longer SN bond length in S-nitrosothiols. It is also noted that decreased occupancy of the localized σSN orbital in the idealized Lewis structure or increased occupancy of σ of the non-Lewis orbital, and their subsequent impact on molecular stability and geometry (bond lengths) are related with the resulting p character of the corresponding sulfur natural hybrid orbital of σSN bond orbital. In addition, the charge transfer energy decreases with the increasing of the Hammett constants of substituent groups, and the partial charge distribution on the skeletal atoms shows that the electrostatic repulsion or attraction between atoms can give a significant contribution to the intramolecular and intermolecular interaction. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

Discrete-time survival data typically possess three features: discreteness, ties, and concomitant information, which require appropriate discrete-time models to analyze. In this paper, we first review some existing discrete-time survival models and then extend them to discrete-time cure survival models, which account for the presence of long-term survivors (cured individuals). The maximum likelihood estimation as well as approximate partial likelihood approaches are used to estimate the model parameters. Simulation results are shown to support the suitability of such models for discrete-time survival data with long-term survivors. An example of applications on a set of bladder tumor recurrence data is also presented.

Aim: To study the association between age and clinical characteristics of renal cell carcinoma in adult patients. Methods: Three hundred and ten patients with renal cell carcinoma were classified into three groups: ≤40 years group, 41–59 years group and ≥60 years group. The clinical characteristics of the three groups were compared to define the association. Results: The male/female ratio was 1.3/1, 2.0/1, 3.3/1 in the three groups, respectively, and a significant difference appeared when comparing the ≤40 years group to the ≥60 years group (P = 0.010). The respective percentage of incidental renal cell carcinoma was 27.9%, 43.2%, 31.2%, and it was significantly higher in the 41–59 years group than the ≥60 years group (P = 0.047). The incidence of poorly differentiated renal cell carcinoma decreased with age increasing (11.6% vs 5.2% vs 2.7%), and there was significant difference between the ≤40 years group and the ≥60 years group (P = 0.038). In the ≤40 years group, the incidence of lymph node metastasis was 18.6%, which was significantly higher than the other two groups (P

BACKGROUND Preneoplastic lung lesions and early-stage lung carcinomas are associated with molecular abnormalities. The authors performed a pilot study to evaluate the use of DNA fluorescence in situ hybridization (FISH) probes to ascertain whether these biomarkers can predict nonsmall cell lung carcinoma (NSCLC). METHODS Fourteen bronchial brushings ipsilateral to the tumor (BB/Ts), tumor touch imprints, and touch imprints of the bronchus adjacent to the tumor obtained from 15 patients with early-stage NSCLC were analyzed. The LAVysion multicolor probe set consisting of probes to 5p15, 6, 7p12, and 8q2 and the in-house probes 3p22.1 and 10q22 was used. Using the LAVysion multicolor probe set, 25 epithelial cells were counted and considered positive if > 5 cells were abnormal. Using 3p22.1 and 10q22, ≥ 100 nuclei per slide were scored. The results were tabulated as the percentage of cells with deletions compared with the centromeric probes 3 and 10. Greater than 2% of the deletions were positive for 3p22.1 and 10q22. Bronchial washings from patients without lung tumors were used as controls. RESULTS The BB/Ts were negative for malignant cells by cytologic evaluation and the LAVysion probe set; however, the combined in-house probes for 3p22.1 and 10q22 tested on BB/Ts predicted cancer in 100% of cancer patients. FISH positivity in the lung cancers was 100% for 3p22.1 deletions, 79% for 10q22 deletions, and 57% for LAVysion probes. When compared with the bronchial epithelium, tumor cells showed a 3.7-fold excess of 3p22.1 deletions, a 2-fold excess of 10q22 deletions, and a 12.6-fold excess of abnormal cells. CONCLUSIONS The current study indicated that detection of molecular abnormalities in bronchial epithelial cells via FISH was very useful in identifying patients at high risk for developing lung carcinoma. The molecular abnormalities identified in the BB/Ts were detected at elevated levels in the tumor specimens. Cancer (Cancer Cytopathol) 2005. © 2004 American Cancer Society.

We study a class of new scheduling problems which involve types of teamwork tasks. Each teamwork task consists of several components, and requires a team of processors to complete, with each team member to process a particular component of the task. Once the processor completes its work on the task, it will be available immediately to work on the next task regardless of whether the other components of the last task have been completed or not. Thus, the processors in a team neither have to start, nor have to finish, at the same time as they process a task. A task is completed only when all of its components have been processed. The problem is to find an optimal schedule to process all tasks, under a given objective measure. We consider both deterministic and stochastic models. For the deterministic model, we find that the optimal schedule exhibits the pattern that all processors must adopt the same sequence to process the tasks, even under a general objective function GC = F(f1(C1), f2(C2), … , fn(Cn)), where fi(Ci) is a general, nondecreasing function of the completion time Ci of task i. We show that the optimal sequence to minimize the maximum cost MC = max fi(Ci) can be derived by a simple rule if there exists an order f1(t) ≤ … ≤ fn(t) for all t between the functions {fi(t)}. We further show that the optimal sequence to minimize the total cost TC = ∑ fi(Ci) can be constructed by a dynamic programming algorithm. For the stochastic model, we study three optimization criteria: (A) almost sure minimization; (B) stochastic ordering; and (C) expected cost minimization. For criterion (A), we show that the results for the corresponding deterministic model can be easily generalized. However, stochastic problems with criteria (B) and (C) become quite difficult. Conditions under which the optimal solutions can be found for these two criteria are derived. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004

We consider the problem of scheduling a set of jobs on a single machine subject to random breakdowns. We focus on the preemptive-repeat model, which addresses the situation where, if a machine breaks down during the processing of a job, the work done on the job prior to the breakdown is lost and the job will have to be started from the beginning again when the machine resumes its work. We allow that (i) the uptimes and downtimes of the machine follow general probability distributions, (ii) the breakdown process of the machine depends upon the job being processed, (iii) the processing times of the jobs are random variables following arbitrary distributions, and (iv) after a breakdown, the processing time of a job may either remain a same but unknown amount, or be resampled according to its probability distribution. We first derive the optimal policy for a class of problems under the criterion to maximize the expected discounted reward earned from completing all jobs. The result is then applied to further obtain the optimal policies for other due date-related criteria. We also discuss a method to compute the moments and probability distributions of job completion times by using their Laplace transforms, which can convert a general stochastic scheduling problem to its deterministic equivalent. The weighted squared flowtime problem and the maintenance checkup and repair problem are analyzed as applications. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004

Five to 10 per cent of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukaemia (CML) have variant translocations involving chromosomes other than 9 and 22. We investigated the characteristics and outcome of patients with variant translocations treated with imatinib. Among 721 patients, 44 (6%) had variant translocations, involving one (n = 39) or two (n = 4) additional chromosomes. Nineteen patients (44%) were in chronic (12 previously untreated), 24 (55%) in accelerated and one (2%) in blastic phase. A major cytogenetic response was achieved in 14 (74%) patients treated in chronic phase and in 14 (58%) treated in accelerated phase. Six of 13 (46%) evaluable patients had deletion of derivative chromosome 9, and there was a trend for a lower response rate in these patients. We compared the 43 patients in chronic or accelerated phase to 678 patients with classic Ph treated with imatinib. The only significant difference in clinical characteristics was a higher frequency of accelerated phase among those with variant translocations (56%) compared with those with classic translocations (38%). No differences in outcome were evident. In a multivariate analysis, variant Ph translocations had no impact in response rate, overall survival or duration of response. We conclude that patients with variant Ph translocations have a similar prognosis to those with classic Ph translocations when treated with imatinib.

BACKGROUND Systemic fungal infections remain the leading cause of mortality in patients with newly diagnosed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS). The objective of the current study was to determine whether intravenous itraconazole (I.V. ITRA) reduced the incidence of probable/proven fungal infections in this group of patients, and compare the results with those of a historic control group treated with fluconazole plus itraconazole capsules (F+I). METHODS Patients with AML and high-risk MDS who underwent induction chemotherapy received 200 mg of i.v. itraconazole over 60 minutes every 12 hours during the first 2 days followed by 200 mg given i.v. once daily. RESULTS One hundred patients were enrolled, 96 of whom were evaluable. Approximately 48% of the patients in the group of patients treated with IV ITRA as well as in the F+I group completed prophylaxis. Nine patients (9%) in the study group developed either proven/probable fungal infections (Candida glabrata in 5 patients, C. tropicalis in 1 patient, C krusei in 1 patient, and Fusarium in 2 patients) compared with 3 patients (4%) with proven fungal infection in the historic control group (C. tropicalis in 1 patient and Aspergillus in 2 patients). There were no significant differences noted between the two groups with regard to the percentage of patients who developed proven/probable or possible fungal infection as well as with regard to survival. These results also were obtained after adjusting for relevant prognostic factors (creatinine and bilirubin). The most common toxicity encountered with the use of IV ITRA was NCI Grade 3-4 hyperbilirubinemia (6%). CONCLUSIONS Despite its theoretic advantages, the authors found no evidence that IV ITRA is superior to itraconazole capsules, at least when the latter is combined with fluconazole. Cancer 2004. © 2003 American Cancer Society.

BACKGROUND Patients with chronic lymphocytic leukemia (CLL) that transforms to Richter syndrome (RS) frequently show atypical lymphocytes in bone marrow; however, a diagnosis of RS requires confirmation of the presence of sheets of large cells in bone marrow or lymph nodes. METHODS In this study, the authors evaluated the clinical significance of scattered large cells in bone marrow. They assessed the possibility of predicting transformation to RS in bone marrow smears by counting the percentages of prolymphocytes and large cells in 78 patients with CLL and 29 patients with lymph node biopsy-confirmed RS. RESULTS The percentage of large cells was found to be correlated with decreasing survival in a continuous fashion (P = 0.006). It is interesting to note that patients who had > 7% large cells in the bone marrow and elevated β2-microglobulin (β2-M) levels (> 5 mg/L) had a survival duration identical to that of patients with RS, and these factors together were a strong predictor of RS (P < 0.001). CONCLUSIONS Patients with CLL who had bone marrow that contained > 7% large cells and who had β2-M levels > 5 mg/L had a disease that was similar to RS, and the combination of large cells and β2-M can be used as a surrogate marker for RS. Cancer 2004. © 2004 American Cancer Society.

We develop a new parametric model using the three-parameter Burr XII distribution for the analysis of survival data with long-term survivors, which includes the previous Weibull mixture model as a special case. The new model is applied to the analysis of a set of leukaemia data for which previous attempts in the literature using traditional parametric models were unsatisfactory due to lack of fit. It is shown that the new model improves the fit to the leukaemia data significantly and is thus capable of providing more credible answers to a variety of statistical inference problems that are of interest to medical researchers and practitioners.

Summary. As the abnormal expression of p53 protein is prognostically significant in some human cancers, its significance in patients with B-cell chronic lymphocytic leukaemia (CLL) was assessed. Two investigators evaluated the percentage of bone marrow mononuclear cells that stained for p53, using biopsies stained with anti-p53 monoclonal antibody (DO-7), and graded the degree of staining (0, +, ++, +++). Samples from a cohort of 90 patients with CLL were studied (median age 60 years, range 30–89 years; 57 patients were (63%) previously untreated, 22 patients (24%) had received one or two prior regimens, 11 patients had received (12%) three to seven regimens. The overall percentage of cells positive for p53 staining was a median of 43 (range 1–88). No investigator effect was detected either in overall percentage cells rated p53 positive or on the degree of staining (Pearson's correlation coefficient 0·980, P-value

BACKGROUND Imatinib mesylate induces high rates of hematologic and cytogenetic response in patients with chronic myelogenous leukemia (CML). During therapy with imatinib, up to 45% of patients with CML reportedly experience myelosuppression ≥ Grade 3, requiring interruption of therapy and/or dose reductions. The significance of myelosuppression for response to imatinib is unknown. METHODS The authors analyzed 143 patients with late chronic-phase CML who were treated with imatinib after failing interferon. Univariate and multivariate analyses were performed to determine patient characteristics that were correlated with myelosuppression response and the association between myelosuppression and cytogenetic response. RESULTS Neutropenia ≥ Grade 3 (according to National Cancer Institute Common Toxicity Criteria) occurred in 64 patients (45%), and thrombocytopenia ≥ Grade 3 occurred in 31 patients (22%). Any myelosuppression ≥ Grade 3 was associated with a lower rate of major (P = 0.04) or complete (P = 0.01) cytogenetic responses. This was more pronounced with myelosuppression that lasted > 2 weeks. The major cytogenetic response rate was 58% with Grade ≥ 3 myelosuppression compared with a rate of 75% without Grade ≥3 myelosuppression (P = 0.03); the complete cytogenetic response rates were 36% and 63%, respectively (P = 0.001). In a multivariate analysis, pretreatment platelet count, imatinib dose reductions, and duration of myelosuppression were associated significantly with response. CONCLUSIONS Myelosuppression is an independent adverse factor for achieving cytogenetic response with imatinib in patients with CML. Intervention with hematopoietic growth factors in patients with CML who are treated with imatinib should be investigated. Cancer 2004;100:116–21. © 2003 American Cancer Society.

The cobalt-catalyzed cross-coupling of organozinc bromides is described. In the case of arylzinc reagents, the same cobalt catalyst, CoBr2(phen), can be used for both the synthesis of the organozinc species and the cross-coupling reaction. In the case of alkylzinc halides, which allow access to dialkylalkynes, the method used for the preparation of the organozinc species has a significant impact on the yields.

This study assessed the feasibility of combining the water washing and electrokinetic (EK) treatments for the removal of Pb, Cd, Cr, and Cu from two municipal solid waste incineration (MSWI) fly ashes. Two approaches were compared: a direct electrokinetic (DEK) treatment and a combined method using water washing before the electrokinetic (WEK) treatment. The following experimental EK parameters were evaluated: electric current, pH, and treatment time (168 h). The analytical results from a toxicity characteristic leaching procedure (TCLP) showed that one fly ash sample was within the regulatory limits after either approach. However, the second fly ash sample was only within the limits following the WEK technique because the WEK technique was able to decrease the high Pb level of 58.6% in the exchangeable and carbonates fractions to 9.5% in this sample. The water washing step first extracted the soluble salts KCl, NaCl, SiCl4, and CaClOH and decreased the interference from the large chloride concentration, thereby promoting the ability of the subsequent EK treatment to stabilize heavy metals as less reactive complexes. Therefore, the WEK technique is recommended over the DEK technique for treating fly ash. © 2014 American Institute of Chemical Engineers Environ Prog, 33: 1235–1241, 2014