bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robotics in urology: an update
Authors: Nedas T G , Challacombe B J , Dasgupta P 
Published: February 2006

AbstractUrology has been quick to realise the advantages of surgical robots. We describe the main devices currently in use, the advantages and disadvantages of robotic‐assisted surgery and the current and potential urological applications focussing on robot‐assisted radical prostatectomy. Copyright © 2005 Robotic Publications Ltd.
Respiration tracking in radiosurgery without fiducials
Authors: Schweikard A , Shiomi H , Adler J 
Published: February 2006

AbstractIn robotic radiosurgery, a focused beam of radiation is moved by a robot arm. We investigated methods for soft‐tissue navigation using robotic radiosurgery. In previous work we described a method for real‐time tracking based on correlation between the motion of implanted fiducial markers and external skin markers. In this work we extend our method of correlation‐based tracking to tracking without implanted fiducials. We propose to use deformation algorithms on CT data sets combined with registration of digitally reconstructed radiographs and intra‐treatment X‐ray images to obtain intermittent information on the target location. This information is then combined with our basic correlation method to achieve real‐time tracking. Our study investigates the feasibility of this approach from the point of view of computing time and required level of user interaction. The term 7D registration is coined to describe the underlying method for performing this task. Copyright © 2005 Robotic Publications, Ltd.
Disease cluster detection: a critique and a Bayesian proposal
Authors: Lawson Andrew B. 
Published: February 2006

AbstractThis paper reviews issues in the analysis of non‐focussed clustering, and proposes a novel approach to cluster modelling that can be used in a surveillance context. The novel approach involves the use of local likelihood models for the analysis of clustering in small area health data. Local likelihood is used when interdependence between data events at locations is modelled directly, as opposed to the modelling of a hidden process of cluster centres. This approach allows the use of conventional posterior sampling. It also allows a less parameterized approach to the form of clusters detected. The idea of a spatially dependent lasso which provides the local maxima for the aggregation of locations is considered as an approximation. The methods are applied to a well known data set and compared with Satscan, and a conditional logistic Bayesian model. Copyright © 2006 John Wiley & Sons, Ltd.
Improved hypothesis testing for coefficients in generalized estimating equations with small samples of clusters
Authors: McCaffrey Daniel F. , Bell Robert M. 
Published: February 2006

AbstractThe sandwich standard error estimator is commonly used for making inferences about parameter estimates found as solutions to generalized estimating equations (GEE) for clustered data. The sandwich tends to underestimate the variability in the parameter estimates when the number of clusters is small, and reference distributions commonly used for hypothesis testing poorly approximate the distribution of Wald test statistics. Consequently, tests have greater than nominal type I error rates. We propose tests that use bias‐reduced linearization, BRL, to adjust the sandwich estimator and Satterthwaite or saddlepoint approximations for the reference distribution of resulting Wald t‐tests. We conducted a large simulation study of tests using a variety of estimators (traditional sandwich, BRL, Mancl and DeRouen's BC estimator, and a modification of an estimator proposed by Kott) and approximations to reference distributions under diverse settings that varied the distribution of the explanatory variables, the values of coefficients, and the degree of intra‐cluster correlation (ICC). Our new method generally worked well, providing accurate estimates of the variability of fitted coefficients and tests with near‐nominal type I error rates when the ICC is small. Our method works less well when the ICC is large, but it continues to out‐perform the traditional sandwich and other alternatives. Copyright © 2006 John Wiley & Sons, Ltd.
A maximum likelihood method for studying gene–environment interactions under conditional independence of genotype and exposure
Authors: Cheng K. F. 
Published: February 2006

AbstractGiven the biomedical interest in gene–environment interactions along with the difficulties inherent in gathering genetic data from controls, epidemiologists need methodologies that can increase precision of estimating interactions while minimizing the genotyping of controls. To achieve this purpose, many epidemiologists suggested that one can use case‐only design. In this paper, we present a maximum likelihood method for making inference about gene–environment interactions using case‐only data. The probability of disease development is described by a logistic risk model. Thus the interactions are model parameters measuring the departure of joint effects of exposure and genotype from multiplicative odds ratios. We extend the typical inference method derived under the assumption of independence between genotype and exposure to that under a more general assumption of conditional independence. Our maximum likelihood method can be applied to analyse both categorical and continuous environmental factors, and generalized to make inference about gene–gene–environment interactions. Moreover, the application of this method can be reduced to simply fitting a multinomial logistic model when we have case‐only data. As a consequence, the maximum likelihood estimates of interactions and likelihood ratio tests for hypotheses concerning interactions can be easily computed. The methodology is illustrated through an example based on a study about the joint effects of XRCC1 polymorphisms and smoking on bladder cancer. We also give two simulation studies to show that the proposed method is reliable in finite sample situation. Copyright © 2006 John Wiley & Sons, Ltd.
Nested frailty models using maximum penalized likelihood estimation
Authors: Rondeau V. , Filleul L. , Joly P. 
Published: February 2006

AbstractThe frailty model is a random effect survival model, which allows for unobserved heterogeneity or for statistical dependence between observed survival data. The nested frailty model accounts for the hierarchical clustering of the data by including two nested random effects. Nested frailty models are particularly appropriate when data are clustered at several hierarchical levels naturally or by design. In such cases it is important to estimate the parameters of interest as accurately as possible by taking into account the hierarchical structure of the data. We present a maximum penalized likelihood estimation (MPnLE) to estimate non‐parametrically a continuous hazard function in a nested gamma‐frailty model with right‐censored and left‐truncated data. The estimators for the regression coefficients and the variance components of the random effects are obtained simultaneously. The simulation study demonstrates that this semi‐parametric approach yields satisfactory results in this complex setting. In order to illustrate the MPnLE method and the nested frailty model, we present two applications. One is for modelling the effect of particulate air pollution on mortality in different areas with two levels of geographical regrouping. The other application is based on recurrent infection times of patients from different hospitals. We illustrate that using a shared frailty model instead of a nested frailty model with two levels of regrouping leads to inaccurate estimates, with an overestimation of the variance of the random effects. We show that even when the frailty effects are fairly small in magnitude, they are important since they alter the results in a systematic pattern. Copyright © 2006 John Wiley & Sons, Ltd.
Optimum blood sampling time windows for parameter estimation in population pharmacokinetic experiments
Authors: Graham Gordon , Aarons Leon 
Published: February 2006

AbstractClinical trials requiring the collection of pharmacokinetic information often specify blood samples to be taken at fixed times. This may be feasible when trial participants are in a controlled environment such as in early phase clinical trials, however it becomes problematic in trials where patients are in an out‐patient clinic setting such as in late phase drug development. In such a situation it is common to take blood samples when it is convenient for all involved and may result in data that are uninformative. This paper proposes an approach to pharmacokinetic study design that allows greater flexibility as to when blood samples can be taken and still result in data that allows satisfactory parameter estimation. The sampling window approach proposed in this paper is based on determining time intervals around theD‐optimum pharmacokinetic sampling times. These intervals are determined by allowing the sampling window design to result in a specified level of efficiency when compared to the fixed timesD‐optimum design. Several approaches are suggested for dealing with this design problem. Copyright © 2006 John Wiley & Sons, Ltd.
NMR Diffusometry and Dynamic Light Scattering Studies of Amylopectin: Effect of Shearing and Heating on the Size Distribution and Diffusion Behaviour
Authors: Wassenius Helena , Löfroth Jan‐Erik , Nydén Magnus 
Published: February 2006

AbstractThe influence of different factors on the diffusion behaviour of cationized potato amylopectin (CAP) in water was investigated by NMR Diffusometry and Dynamic Light Scattering (DLS). The sample preparation procedure was found to have a fundamental influence on the size and size distribution evolution of the different samples, whereas the addition of NaN3 or the replacement of CAP by non‐cationic potato amylopectin (PAP) did not influence the diffusion behaviour. NMR samples were prepared by re‐dissolving a freeze‐dried CAP sample in D2O at ambient temperature or by heating. Some samples were sheared, reducing their average aggregate size by a factor of 40. The unheated samples had a large average molecular size, indicating incomplete aggregate dissolution. The single‐fit average diffusion coefficient Dav,init showed a strong time evolution for the unheated samples, increasing with a factor of 1000 over 20 days for both sheared and unsheared samples. This effect was mainly attributed to incomplete sample dissolution, leading to a time evolution of the molecular size and size distribution. For heated samples, Dav,init oscillated around a much higher value indicating the occurrence of sub‐molecular sized fragments and possibly also a time‐coherent rearrangement of the sample. The size distribution was very large for both heated and unheated samples, with σlnD values of up to 2.5 and diffusion coefficients ranging from 10‐14 to 10‐11 m2/s in the same sample. DLS measurements corroborated the conclusions drawn from the results found by NMR diffusometry, but the complementary use of DLS and NMR diffusometry also highlighted the difference between the two methods for size determination. With NMR diffusometry, the proportion of small molecules may be slightly exaggerated, whereas the scattering methods mostly used in previous studies may underestimate their importance, resulting in a larger mean aggregate size than may actually be the case. This study thus draws the attention to the importance of the analysis method for the size and size distribution of amylopectin samples.
The Influence of Thiocyanate Ions on the Formation of the Starch‐Iodine Complex
Authors: Cornell Hugh J. , Rix Colin J. 
Published: February 2006

AbstractThe redox reaction between thiocyanate and iodine species present in an aqueous solution of KI results in the formation of thiocyanogen, (SCN)2. This reaction interferes with the formation of inclusion complexes of a potato amylose with iodine species such as I3‐ and I5‐. As these ions react with thiocyanate ions (SCN‐) the blue colour of the amylose‐iodine complex diminishes. The rate of this decrease depends upon the concentration of both the SCN‐ and the iodine, and appears to follow pseudo‐second order kinetics. Using a UV/visible spectrophotometer the reaction of iodine with KSCN can be followed, with or without amylose, and shows a lowering in concentration of iodine species absorbing at 290–300 nm, together with a lowering in absorbance at 630 nm, due to a lesser amount of the amylose‐iodine complex. Interference with iodine complex formation was also noted with a potato amylopectin. The technique provides the basis for the study of other reactions of iodine such as that with selenocyanate (SeCN‐).
New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. I. Modification of the heritable translocation test
Authors: Adler Ilse‐Dore 
Published: February 2006

AbstractTwo alternative modifications of the experimental protocol for the heritable translocation test are described. One of them proposes to mate F1 males and F1 females within one experimental group and eliminate normal pairs by a sequential decision procedure based on litter sizes. Pairs that do not meet the criteria for normal litter size have to be separated and tested against normal partners. Male translocation suspects are analyzed cytogenetically for the presence of a reciprocal translocation. Female translocation suspects or XO suspects are verified through analysis of their male and female progeny. The second modification of the heritable translocation test omits fertility testing and proposes to cytogenetically analyze 25 diakineses‐metaphases I from each F1 male in the test.Using either one or both protocols it was shown that 20 mg/kg of methyl methanesulfonate (MMS) induced 1.3% heritable translocations in late spermatids and early spermatozoa. With 2.5 mg/kg of mitomycin C, 0.3% and 0.4% translocation carriers were recovered from treated primary spermatocytes and early spermatids, respectively. A dose of 300 R gamma rays resulted in 1.6% translocations in spermatozoa and 4.8% translocations in primary spermatocytes.The advantage of the modified fertility test lies in the doubling of the sample size by including the females. However, a disadvantage is the amount of time and labor that is necessary to verify female translocation carriers. The cytogenetic translocation test protocol with all F1 males is considered more reliable and faster. It lacks the possibility of error entailed in the decision procedure by fertility testing, and it requires less time, personnel, and animal space.
Dominant lethality in Xenopus laevis induced with triethylenemelamine (TEM)
Authors: McKinnell Robert G. , Kren Betsy T. , Bergad Robert , Schultheis Melissa , Byrne Timothy , Schaad J. W. 
Published: February 2006

AbstractAdult male South African clawed toads, Xenopus laevis, were injected intraperitoneally with triethylenemelamine (TEM) dissolved in water over a dose range of 13–1,300 μg/kg or with water (controls). Mating of the treated males with untreated females was induced seven days later by injection of human chorionic gonadotropic hormone (HCG). Accumulated lethality one week after fertilization among progeny was dose related. Morphological abnormalities among embryos that survived to hatching were similarly dose related. Because anatomically anomalous embryos may have impaired behavior, swimming capacity was tested, and anomalies in swimming behavior were also found to be dose related. Finally, short‐term cell cultures were made on minced embryos to obtain chromosome spreads. Structural aberrations, rings, dicentrics, etc of somatic chromosomes were also dose related.
Tumor promoter 12‐0‐tetradecanoylphorbol 13‐acetate mimics epidermal growth factor‐induced precocious tooth eruption in the rodent
Authors: Sim F. Russell P. , Salomon David S. , Nylen Marie U. , Pratt Robert M. 
Published: February 2006

AbstractDaily injections of epidermal growth factor (EGF) or the tumor promoter, 12‐0‐tetradecanoylphorbol 13‐acetate (TPA) to neonatal Swiss Webster S/W (NIH) mice caused precocious tooth eruption. However, TPA, unlike EGF, did not enhance eyelid opening. The response was correlated with the tumor‐promoting activity of various phorbol congeners. Furthermore, TPA‐induced tooth eruption appeared to be prostaglandin‐dependent, whereas EGF‐induced eruption was insensitive to the prostaglandin inhibitors.
Genetic effects of procarbazine in the yeast Saccharomyces cerevisiae, strain D4
Authors: Frezza Domenico , Bianchi Vera 
Published: February 2006

AbstractProcarbazine (PCZ) was tested for its ability to induce mitotic gene conversions at the ade and trp loci of Saccharomyces cerevisiae, strain D4. The influence of the following factors was examined: growth phase of the yeast cells (log vs stationary phase), pH of the treatment solution, and addition of mouse S9 fractions prepared from different organs. The drug was found more toxic and mutagenic at low doses (up to 25 mg/ml) for log phase cells, and scarcely toxic but highly mutagenic, even at high doses, for stationary phase cells. PCZ activity was reduced by acidic pH, and suppressed by S9 mix.Gene conversions were also analyzed in the intrasanguineous host‐mediated assay performed in mice orally administered with PCZ. In such conditions PCZ was ineffective in stimulating mitotic gene conversions, probably owing to its inactivation in the acidic environment of the gastroenteric tract.
Genetic effects of drug interaction in tuberculosis patients and their fate
Authors: Jaju Madhuri , Jaju Manjula , Ahuja Y. R. 
Published: February 2006

AbstractIn this paper we will discuss the genetic consequences of drug interaction in tuberculosis patients. Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations of isoniazid (INH), thiacetazone (TAZ), para‐aminosalicylic acid (PAS), and streptomycin (SM). The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs). A total of 179 subjects were analyzed. In combination these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually. Four of the drug combinations, INH+TAZ, INH+PAS, INH+TAZ+SM, and INH + PAS + SM, induced a significant increase in the frequency of aberrations, whereas INH+SM did not induce aberrations. In fact, SM appeared to reduce the frequency of aberrations. SCEs were increased in only two patients: one treated with INH + TAZ and the other with INH + PAS. The frequency of aberrations after withdrawal of therapy was decreased; it was slightly higher than the controls, though it was insignificant. The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes. Though the drug‐induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combinations of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out.
Lack of in vivo and in vitro genotoxicity with the nonsteroid, antiinflammatory agent sodium meclofenamate
Authors: Kropko Melvin L. , Fitzgerald J. E. , De la Iglesia Felix A. 
Published: February 2006

AbstractSodium meclofenamate (Meclomen®), CI‐583, is an anthranilic acid salt developed as a nonsteroidal, antiinflammatory agent. A multitest battery of short‐term tests was employed to characterize the genotoxic and mutagenic potential of the compound by measuring point mutations in bacteria, induction of sister‐chromatid exchange, chromosome aberrations, and gene mutations in mammalian cells in vitro. In vitro assays included metabolic activation. The in vivo assay was for chromosome aberrations in bone marrow cells from rats. At toxicity‐limited doses for each assay, no activity was detected in the bacterial or mammalian cell mutation assays, and sister‐chromatid exchange frequencies were not increased over control rates. When sodium meclofenamate was evaluated in vitro, chromosome aberrations were induced under metabolic activation in CHO cells. Chromosome aberrations and clastogenic activity were not demonstrated after oral administration of Meclomen® to male rats. It was concluded that sodium meclofenamate does not possess overt mutagenic potential under these conditions. The activity seen in vitro with CHO cells after metabolic activation did not correlate with the results from the other tests and was attributed to the formation of reactive metabolites not present or formed in in vivo systems.
An extended evaluation of an in vivo teratology screen utilizing postnatal growth and viability in the mouse
Authors: Gray Leon Earl , Kavlock Robert J. 
Published: February 2006

AbstractA teratology test system proposed by Chernoff and Kavlock [3,4] utilizes growth and viability for 3 days after birth to prioritize chemicals for standard teratology testing. The present study is an extended observation of the growth and viability of Chernoff and Kavlock's animals from 41 treatments for 250 days to determine if neonatal weight reductions persisted throughout life, if mortality occurred later in life or, if other serious abnormalities developed that could not be anticipated from the neonatal data. One chemical which was positive in the present study would be a false negative in the standard teratology test and the Chernoff/Kavlock Assay (CKA). Congo red did not cause frank malformations or mortality but it specifically altered reproductive function in the offspring. Two chemicals produced a variety of unusual abnormalities that were not apparent in the neonates, indicating that postnatal testing is necessary to determine the full teratogenic potential of some compounds. Mice exposed prenatally to cytosine arabinoside became hydrocephalic and 30% of them lacked lower incisors. Nitrofen caused hydrocephaly, the age of eye‐opening was delayed, a few of the mice had no eyes, and most of the mice lacked Harderian glands. Eighteen of the 41 treatments caused mortality of 15%, or greater, by day 3, and four of these treatments resulted in additional mortality past the neonatal period. No compound caused a decrease in viability after the neonatal period without also reducing days 1 or 3 litter sizes, validating the use of this measurement in the CKA. Cytosine arabinoside was administered later in gestation than the CKA dosing regime and caused a marginally significant increase in mortality near birth but killed over 50% of the pups after weaning. Altering the duration or period of exposure in the CKA may necessitate a longer postnatal evaluation than presently recommended [3,4]. Neonatal weight, the second parameter used in the CKA to prioritize chemicals for additional testing, appears to be less useful than viability. It was a poor predictor of subsequent growth, some early weight effects persisted, while most of those concurrent with maternal weight reductions were transient. A correlation analysis of the parameters measured in the CKA and in the present study, excluding the compounds that produce frank malformations, indicated that compounds that reduced maternal weight gain during dosing had fewer live pups and growth was transiently retarded. Compounds could be tested in the CKA at a dose that result in less than a 20% reduction in maternal weight gain during dosing without confounding maternal toxicity with postnatal effects.