A new generalization of Weibull distribution with application to a breast cancer data set

In this article, we propose a new generalization of the Weibull distribution, which incorporates the exponentiated Weibull distribution introduced by Mudholkar and Srivastava (IEEE Trans. Reliab. 1993; 42 :299–302) as a special case. We refer to the new family of distributions as the beta‐Weibull distribution. We investigate the potential usefulness of the beta‐Weibull distribution for modeling censored survival data from biomedical studies. Several other generalizations of the standard two‐parameter Weibull distribution are compared with regards to maximum likelihood inference of the cumulative incidence function, under the setting of competing risks. These Weibull‐based parametric models are fit to a breast cancer data set from the National Surgical Adjuvant Breast and Bowel Project. In terms of statistical significance of the treatment effect and model adequacy, all generalized models lead to similar conclusions, suggesting that the beta‐Weibull family is a reasonable candidate for modeling survival data. Copyright © 2009 John Wiley & Sons, Ltd.     

Sample size for two‐stage studies with maintenance therapy

An adaptive treatment strategy (ATS) is defined as a sequence of treatments and intermediate responses. ATS' arise when chronic diseases such as cancer and depression are treated over time with various treatment alternatives depending on intermediate responses to earlier treatments. Clinical trials are often designed to compare ATSs based on appropriate designs such as sequential randomization designs. Although recent literature provides statistical methods for analyzing data from such trials, very few articles have focused on statistical power and sample size issues. This paper presents a sample size formula for comparing the survival probabilities under two treatment strategies sharing same initial, but different maintenance treatment. The formula is based on the large sample properties of inverse‐probability‐weighted estimator. Simulation study shows strong evidence that the proposed sample size formula guarantees desired power, regardless of the true distributions of survival times. Copyright © 2009 John Wiley & Sons, Ltd.     

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bangladesh

Bangladesh faces increasing levels of chloroquine resistance, and drug sensitivity to sulfadoxine-pyremethamine is already compromised. Therefore, the Ministry of Health recently changed the national treatment guidelines to artemisinin-based combination therapies. The purpose of this study was to determine the baseline therapeutic efficacy of artemether-lumefantrine used as a six-dose regimen for the treatment of uncomplicated Plasmodium falciparum malaria. Sixty-seven patients were enrolled in the study; the cure rate in a 42-day follow-up after an adjustment by polymerase chain reaction was 94.3%. The treatment led to rapid fever (mean +/- SD = 25.82 +/- 12.14 hours) and parasite (30.36 +/- 19.43 hours) clearance. These data suggest that artemether-lumefantrine is a highly efficacious and well-tolerated treatment for uncomplicated P. falciparum malaria in Bangladesh.     

Extraosseous bone formation in the renal pelvis

PURPOSE: We evaluated the frequency and features of extraosseous bone formation in the kidneys of patients undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed in 621 patients at our institution between 1997 and 2006. In 21 cases metaplastic bone arising from the urothelium was observed. Clinical, radiographic and histopathological features of this group were studied in detail. RESULTS: Patient age ranged from 7 to 40 years (median 11). Extraosseous bone formation was identified in 7 right (33%) and 14 left (67%) kidneys. In all cases extraosseous bone was identified at the angle of the pelvis and ureter, just proximal to the ureteropelvic junction. The typical radiographic appearance of a radiopaque eccentric halo surrounding an area of lesser radiological density connected with the urothelium was seen in 10 of 13 radiographs (77%). Histopathological evaluation showed well formed trabecular bone with surface osteoblastic activity, areas of intratrabecular adipose bone marrow and hematopoietic cells in 5 cases (24%); woven bone intimately related to trabecular bone with scattered hematopoietic cells in 14 (67%); and entirely woven bone with associated mineral deposits and prominent fibroblastic proliferation in 2 (10%). CONCLUSIONS: Although rarely reported in the literature, metaplastic bone formation in the renal pelvis was seen relatively frequently in our patient population. The pathogenesis of this phenomenon is not clearly understood. Recognition of extraosseous bone is important, since it has implications for management and prognosis. In-depth studies of this phenomenon are required to arrive at any conclusions regarding its etiology.     

Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by buspirone in rats

Tardive dyskinesia (TD), a syndrome of involuntary hyperkinesias in the orofacial region that develops in patients chronically treated with neuroleptic agents is a major limitation of the therapy. Rats chronically treated with haloperidol exhibit vacuous chewing movements (VCMs) with the twitching of facial musculature and tongue protrusion. The syndrome is widely used as an animal model of TD. Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the pathogenesis and treatment of TD because repeated administration of haloperidol resulted in an increase in the effectiveness of 5-HT-1A receptors while drugs with agonist activity at 5-HT-1A receptors could attenuate haloperidol-induced VCMs. The present study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by the coadministration of buspirone could reverse the induction of VCMs and supersensitivity at 5-HT-1A receptors by haloperidol. Rats treated with haloperidol at a dose of 1 mg/kg twice a day for 2 weeks displayed VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Coadministration of buspirone attenuated haloperidol-induced VCMs after 2 weeks and completely prevented it after 5 weeks. The intensity of 8-hydroxy-2-di (n-propylamino) tetralin (8-OH-DPAT)-induced locomotion was greater in saline+haloperidol injected animals but not in buspirone+haloperidol injected animals. 8-OH-DPAT-induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in buspirone+haloperidol injected animals. It is suggested that an impaired somatodendritic 5-HT-1A receptor dependent response is a major contributing factor in the pathophysiology of TD and a normalization of the somatodendritic response by drugs may help extending therapeutics in schizophrenia.     

Intelligent optimal control with dynamic neural networks.

The application of neural networks technology to dynamic system control has been constrained by the non-dynamic nature of popular network architectures. Many of difficulties are-large network sizes (i.e. curse of dimensionality), long training times, etc. These problems can be overcome with dynamic neural networks (DNN).In this study, intelligent optimal control problem is considered as a nonlinear optimization with dynamic equality constraints, and DNN as a control trajectory priming system. The resulting algorithm operates as an auto-trainer for DNN (a self-learning structure) and generates optimal feed-forward control trajectories in a significantly smaller number of iterations. In this way, optimal control trajectories are encapsulated and generalized by DNN. The time varying optimal feedback gains are also generated along the trajectory as byproducts. Speeding up trajectory calculations opens up avenues for real-time intelligent optimal control with virtual global feedback.We used direct-descent-curvature algorithm with some modifications (we called modified-descend-controller-MDC algorithm) for the optimal control computations. The algorithm has generated numerically very robust solutions with respect to conjugate points. The adjoint theory has been used in the training of DNN which is considered as a quasi-linear dynamic system. The updating of weights (identification of parameters) are based on Broyden-Fletcher-Goldfarb-Shanno BFGS method. Simulation results are given for an intelligent optimal control system controlling a difficult nonlinear second-order system using fully connected three-neuron DNN.     

Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2

The differential distribution of two tetrodotoxin resistant (TTXr) voltage-gated sodium channels SNS (PN3) and SNS2 (NaN) in rat primary sensory neurons has been investigated. Both channels are sensory neuron specific with SNS2 restricted entirely to those small dorsal root ganglion (DRG) cells with unmyelinated axons (C-fibers). SNS, in contrast, is expressed both in small C-fiber DRG cells and in 10% of cells with myelinated axons (A-fibers). All SNS expressing A-fiber cells are Trk-A positive and many express the vanilloid-like receptor VRL1. About half of C-fiber DRG neurons express either SNS or SNS2, and in most, the channels are colocalized. SNS and SNS2 are found both in NGF-responsive and GDNF-responsive C-fibers and many of these cells also express the capsaicin receptor VR1. A very small proportion of small DRG cells express either only SNS or only SNS2. At least four different classes of A- and C-fiber DRG neurons exist, therefore, with respect to expression of these sodium channels.     

Sezary syndrome--without erythroderma

Sezary syndrome (SS), is described as the classical triad of pruritic erythroderma, lymphadenopathy, and presence of more than 10% of circulating Sezary cells in the peripheral blood. We report on unusual case of advanced cutaneous T - cell lymphoma with classical haematological and histopathological features of Sezary syndrome, but lacking the clinical features of erythroderma. A 66 year old man presented with asymptomatic multiple papules, plaques and nodules and with generalized lymphadenopathy. Peripheral smear showed more than 60% of Sezary cells. Skin and lymph node biopsy showed typical features of T-cell lymphoma and immunohistochemistry and CD marker studies showed the cells to be atypical T-lymphocytes. This unusual case is highlighted to denote that erythroderma need not be taken as a hard and fast criterion for diagnosing Sezary syndrome.     

Liposomal drug delivery systems: an update review

The discovery of liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposome drug delivery systems have played a significant role in formulation of potent drug to improve therapeutics. Recently the liposome formulations are targeted to reduce toxicity and increase accumulation at the target site. There are several new methods of liposome preparation based on lipid drug interaction and liposome disposition mechanism including the inhibition of rapid clearance of liposome by controlling particle size, charge and surface hydration. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. The liposomes are characterized with respect to physical, chemical and biological parameters. The sizing of liposome is also critical parameter which helps characterize the liposome which is usually performed by sequential extrusion at relatively low pressure through polycarbonate membrane (PCM). This mode of drug delivery lends more safety and efficacy to administration of several classes of drugs like antiviral, antifungal, antimicrobial, vaccines, anti-tubercular drugs and gene therapeutics. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are the specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc.); stealth liposomes which are especially being used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone; and bisphosphonate-liposome mediated depletion of macrophages. This review would be a help to the researchers working in the area of liposomal drug delivery.     

A contactless electrical stimulator: application to fabricate functional skeletal muscle tissue

Engineered skeletal muscle tissues are ideal candidates for applications in drug screening systems, bio-actuators, and as implantable constructs in tissue engineering. Electrical field stimulation considerably improves the differentiation of muscle cells to muscle myofibers. Currently used electrical stimulators often use direct contact of electrodes with tissue constructs or their culture medium, which may cause hydrolysis of the culture medium, joule heating of the medium, contamination of the culture medium due to products of electrodes corrosion, and surface fouling of electrodes. Here, we used an interdigitated array of electrodes combined with an isolator coverslip as a contactless platform to electrically stimulate engineered muscle tissue, which eliminates the aforementioned problems. The effective stimulation of muscle myofibers using this device was demonstrated in terms of contractile activity and higher maturation as compared to muscle tissues without applying the electrical field. Due to the wide array of potential applications of electrical stimulation to two- and three-dimensional (2D and 3D) cell and tissue constructs, this device could be of great interest for a variety of biological applications as a tool to create noninvasive, safe, and highly reproducible electric fields.