bluuebunny/crossref_metadata_2025 huggingface dataset:
A first‐order volume of fluid convection model in three‐dimensional space
Authors: Kim Seong‐O. , Sim Yoonsub , Kim Eui‐Kwang
Published: August 2002

To improve the numerical analysis of free surface convections and reconstruction in a three‐dimensional space, a first‐order algorithm is developed based on the volume of fluid (VOF) theory. The methodology applied to the first‐order method (FOM) is to define a first‐order surface as near to the horizontal as possible while satisfying the defined volume fraction of a cell. The developed method is compared against the donor cell method of zeroth‐order through simulation of the transitional and rotational convection of liquid spheres. Although the donor cell method shows relatively good predictions for the sphere of a large diameter, it shows poor performance of large distortions for a sphere of a relatively small diameter. However, the FOM developed in this study always shows quite satisfactory prediction results for free surface convection. Copyright © 2001 John Wiley & Sons, Ltd.
On the use of the Galerkin method for 3D numerical modelling of the general circulation: the South Atlantic eperiment
Authors: Harari Joseph , Giarolla Emanuel
Published: August 2002

A linear three‐dimensional hydrodynamical numerical model, with the application of the Galerkin Method for the vertical dependence, is here presented. The spherical coordinate system is used, in order to allow large‐scale simulations. The equations and mathematical development of the model are shown in detail, together with the boundary and initial conditions, and the sequence of equations' solution. The model is applied to the South Atlantic Ocean, for estimating typical seasonal circulations, and the results are summarized in maps of currents at surface and 1000 m depth, and in transport values of the Brazil Current between 30°S and 40°S. Copyright © 2002 John Wiley & Sons, Ltd.
A simplified quasi‐two‐dimensional model for gain optimization in carbon dioxide gasdynamic lasers (GDL)
Authors: Bahrampour A. R. , Farrahi R.‐M. , Radjabalipour M.
Published: August 2002

In this paper a simplified quasi‐two‐dimensional model for small signal gain optimization in gasdynamic laser is introduced. In order to obtain a homogeneous medium with maximum optical gain in the active medium, by nozzle shape formation, the shock occurrence position is controlled and is postponed to some point behind the laser active medium. Then the method of calculus of variation is used to find the supersonic part of the nozzle of a gasdynamic laser with maximum gain in the active medium. The interesting result is that the supersonic part of such a nozzle consists of a wedge as the accelerating part of the nozzle, a smooth surface for the uniformization, and finally a channel for the relaxation of the medium. (The middle section is characterized as the geometrical locus of points whose characteristic curves are concurrent at a certain point.) It is also shown that, overlooking a minor difference in the gain, the nozzle can be chosen to be a shock free one with the ultimate optical uniformity. Copyright © 2002 John Wiley & Sons, Ltd.
Forecasting UK industrial production over the business cycle
Authors: Simpson Paul W. , Osborn Denise R. , Sensier Marianne
Published: August 2002

This paper examines the information available through leading indicators for modelling and forecasting the UK quarterly index of production. Both linear and non‐linear specifications are examined, with the latter being of the Markov‐switching type as used in many recent business cycle applications. The Markov‐switching models perform relatively poorly in forecasting the 1990s production recession, but a three‐indicator linear specification does well. The leading indicator variables in this latter model include a short‐term interest rate, the stock market dividend yield and the optimism balance from the quarterly CBI survey. Copyright © 2001 John Wiley & Sons, Ltd.
Bootstrap prediction intervals for autoregressive models of unknown or infinite lag order
Authors: Kim Jae H.
Published: August 2002

Recent studies on bootstrap prediction intervals for autoregressive (AR) model provide simulation findings when the lag order is known. In practical applications, however, the AR lag order is unknown or can even be infinite. This paper is concerned with prediction intervals for AR models of unknown or infinite lag order. Akaike's information criterion is used to estimate (approximate) the unknown (infinite) AR lag order. Small‐sample properties of bootstrap and asymptotic prediction intervals are compared under both normal and non‐normal innovations. Bootstrap prediction intervals are constructed based on the percentile and percentile‐tmethods, using the standard bootstrap as well as the bootstrap‐after‐bootstrap. It is found that bootstrap‐after‐bootstrap prediction intervals show small‐sample properties substantially better than other alternatives, especially when the sample size is small and the model has a unit root or near‐unit root. Copyright © 2002 John Wiley & Sons, Ltd.
Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma
Authors: Wang Gang , Zhao Yan , Liu Xiaoming , Wang Lu , Wu Chungen , Zhang Weiling , Liu Wanqing , Zhang Pingping , Cong Wenming , Zhu Yuanrong , Zhang Lisheng , Chen Saijuan , Wan Dafang , Zhao Xintai , Huang Wei , Gu Jianren
Published: August 2002

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi‐quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21–p23, 4q, 16q21–q23.3, 13q, 8p21–p23, and 6q24–q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21–p23 (55%), 4q (35–51%), 16q21–q23.3 (52%), 17p12 (49%), 13q (39–46%), 8p21–p23 (41–45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33–q34, 9q13–31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples. © 2001 Wiley‐Liss, Inc.
Nonrandom distribution of interspersed repeat elements in the BCR and ABL1 genes and its relation to breakpoint cluster regions
Authors: Jeffs Aaron R. , Wells Elisabeth , Morris Christine M.
Published: August 2002

The Philadelphia translocation, t(9;22)(q34;q11), is the microscopically visible product of recombination between two genes, ABL1 on chromosome 9 and BCR on chromosome 22, and gives rise to a functional hybrid BCR‐ABL1 gene with demonstrated leukemogenic properties. Breakpoints in BCR occur mostly within one of two regions: a 5 kb major breakpoint cluster region (M‐Bcr) and a larger 35 kb minor breakpoint cluster region (m‐Bcr) towards the 3′ end of the first BCR intron. By contrast, breakpoints in ABL1 are reported to occur more widely across a >200 kb region which spans the large first and second introns. The mechanisms that determine preferential breakage sites in BCR, and which cause recombination between BCR and ABL1, are presently unknown. In some cases, Alu repeats have been identified at or near sequenced breakpoint sites in both genes, providing indications, albeit controversial, that they may be relevant. For the present study, we carried out a detailed analysis of genomic BCR and ABL1 sequences to identify, classify, and locate interspersed repeat sequences and to relate their distribution to precisely mapped BCR‐ABL1 recombination sites. Our findings confirm that Alu are the most abundant class of repeat in both genes, but that they occupy fewer sites than previously estimated and that they are distributed nonrandomly. r‐Scan statistics were applied to provide a measure of repeat distribution and to evaluate extremes in repeat spacing. A significant lack of Alu elements was observed across the major and minor breakpoint cluster regions of BCR and across a 25‐kb region showing a high frequency of breakage in ABL1. These findings counter the suggestion that occurrence of Alu at BCR‐ABL1 recombination sites is likely by chance because of the high density of Alu in these two genes. Instead, as yet unidentified DNA conformation or nucleotide characteristics peculiar to the preferentially recombining regions, including those Alu elements present within them, more likely influence their fragility. © 2001 Wiley‐Liss, Inc.
Stratigraphy, sedimentology, and site formation at Konispol Cave, Southwest Albania
Authors: Schuldenrein Joseph
Published: August 2002

Recent geoarchaeological investigations at Konispol Cave (Epirus), Albania concluded nearly a decade of interdisciplinary human ecological investigations. Questions of site formation, cave history, and environmental change were examined through microstratigraphic study and sedimentological analysis. Artifacts and occupation layers from Upper Paleolithic through Iron Age times were preserved in three discrete sediment complexes. Sedimentology supplemented by micromorphology isolated the principal characteristics of the sediment complexes. The chronology and site formation history was characterized sequentially by: (1) initial deposition and/or pedogenesis of basal sediment; (2) sheetflow, spring discharge, and ponding in the cavern; (3) rockfall, roof attrition, and solution weathering; (4) episodic flushing and reworking of allogenic sediment; (5) human activities; (6) autogenic reworking and diagenesis of human debris and slope sediment. The changing history of the cave is linked to regional paleoenvironmental and land use signals in Epirus and the greater Aegean from the Last Glacial Maximum (LGM) to the late Holocene. © 2001 John Wiley & Sons, Inc.
A novel reporter strain to follow Cre‐mediated recombination in T and NK cells
Authors: Wurtz Olivier , Pophillat Matthieu , Schmitt‐Verhulst Anne‐Marie , Guerder Sylvie
Published: August 2002

Summary: The Cre‐loxP system permits the generation of mouse models in which the fate of a cell can be followed through time. Such approach is of great value in immunology because it may allow lineage studies and the dissection of the contribution of specific effector T cells to long‐term memory responses or autoimmune responses. An essential component of such a strategy is the development of appropriate reporter strains of mice in which the inducible reporter molecule is not immunogenic and is well expressed at the cell surface of T cells. We describe here a novel reporter strain of mice that is designed to fulfill these criteria and show that this strain permits the monitoring of Cre‐mediated recombination in both T cells and NK cells. genesis 32:287–292, 2002. © 2002 Wiley‐Liss, Inc.
A vestigial:scalloped TEA domain chimera rescues the wing phenotype of a scalloped mutation in Drosophila melanogaster
Authors: Srivastava Ajay , MacKay Julie O. , Bell John B.
Published: August 2002

Summary: The development of the Drosophila wing requires both scalloped and vestigial functions. Using a fusion between full‐length Vestigial and the Scalloped TEA domain, the fusion protein can rescue scalloped wing mutations because within wing development, Scalloped and Vestigial cooperatively act as a transcription complex. Scalloped provides the necessary DNA binding function via the TEA domain and Vestigial promotes the activation of target genes. We also demonstrate that the putative nuclear localization signal contained in the TEA domain of Scalloped is likely responsible for the nuclear localization of Vestigial. The fusion protein is also capable of activating a known target gene of the native complex and thus represents a tool that will be helpful in rapidly identifying target genes of the Sd/Vg complex that are involved in wing differentiation. The functionality of the fusion suggests that only the TEA domain of Scalloped is critical for wing development and the rest of the protein (about 70%) is dispensable. This result is novel and should stimulate further studies of sd in other tissues in view of the fact that scalloped is a vital gene in Drosophila. genesis 33:40–47, 2002. © 2002 Wiley‐Liss, Inc.
Molecular characterization of Cephalothorax, the Tribolium ortholog of Sex combs reduced
Authors: Curtis Carmelle D. , Brisson Jennifer A. , DeCamillis Mark A. , Shippy Teresa D. , Brown Susan J. , Denell Robin E.
Published: August 2002

Summary: Sex combs reduced (Scr), a Hox gene located in the Antennapedia complex of Drosophila melanogaster, is required for the proper development of the labial and first thoracic segments. The Tribolium castaneum genetically defined locus Cephalothorax (Cx) is a candidate Scr ortholog based on the location of Cx in the beetle Homeotic complex and mutant effects on the labial and first thoracic segments. To address this hypothesis, we have cloned and characterized the Tribolium ortholog of Scr (TcScr). The transcription unit is less complex and encodes a smaller protein than Scr. The predicted amino acid sequence of the Tribolium protein shares motifs with orthologous proteins from multiple species. In addition, we have analyzed the TcScr expression pattern during embryonic development. TcScr is expressed in parts of the maxillary, labial, and first thoracic segments in a pattern similar to but not identical to Scr. Furthermore, TcScr RNA interference results in a phenocopy of the Cephalothorax (Cx) mutant phenotype in which the labial palps are transformed into antennae and the head and first thoracic segment are fused. All of the available results indicate that Cx is the Tribolium ortholog of Scr. genesis 30:12–20, 2001. © 2001 Wiley‐Liss, Inc.
Cardiomyopathy in mice with paternal uniparental disomy for chromosome 12
Authors: Villar A.J. , Carlson E.J. , Gillespie A.M. , Ursell P.C. , Epstein C.J
Published: August 2002

Summary: Mice inheriting both copies of MMU12 either maternally or paternally demonstrate imprinting effects. Whereas maternal uniparental disomy 12 (matUPD12) fetuses are growth retarded and die perinatally, paternal UPD12 (patUPD12) fetuses die during late gestation and exhibit placentomegaly and skeletal muscle maturation defects. To examine further the developmental consequences of UPD12, we intercrossed mouse stocks heterozygous for Robertsonian translocation chromosomes (8.12) and (10.12). We report that at 13.5–14.5 dg patUPD12 hearts exhibit increased ventricular diameter, thinner, less compact myocardium, and deep intertrabecular recesses when compared to controls. These data provide evidence for cardiac failure, a lethal condition, and suggest a role for an imprinted gene(s) in normal heart development. genesis 30:274–279, 2001. © 2001 Wiley‐Liss, Inc.
Characteristics of genetic markers and maps for cost‐effective genome screens using diallelic markers
Authors: Goddard Katrina A.B. , Wijsman Ellen M.
Published: August 2002

New technologies for genotyping diallelic markers (SNPs) were recently developed that may be lower in cost, and more easily automated than microsatellite markers (STRPs). The reduction in genotyping costs resulting from such automation may significantly impact the overall cost of studies of complex traits, which generally require large sample sizes. Use of multiple SNPs in linkage analysis can recapture the linkage information otherwise lost with such markers. Here we derive a measure of the multilocus polymorphic information content (MPIC) in the context of linkage analysis for a cluster of SNPs, and we explore the characteristics of uniform vs. clustered SNP maps, relative to STRP maps. Issues addressed in comparing the map structures include the information content for clustered or single markers, and map accuracy. To be cost‐effective, SNPs should have a common allele frequency between 0.5–0.75. No more than five loci per cluster are needed. Some linkage disequilibrium between loci in a cluster is tolerable. In the ideal case, a uniformly spaced SNP map is more cost‐effective than one composed of clustered loci. However, the genotyping cost per marker for diallelic markers can be at most 60% of the genotyping cost per marker for STRPs. The consequences of using clustered vs. uniform SNP maps are considered in the context of map inaccuracy and use of multipoint vs. pairwise linkage analysis. Overall, when marker information, map accuracy, and flexibility of analysis are jointly considered, an optimal solution may be use of maps with 2–3 SNPs per cluster. Genet. Epidemiol. 22:205–220, 2002. © 2002 Wiley‐Liss, Inc.
Allele sharing and allelic association I: Sib pair tests with increased power
Authors: Lazzeroni Laura C.
Published: August 2002

Affected sib pair data contain information about allele sharing and allelic association. Either of these features can point to the presence of a risk‐related gene. This study introduces the elliptical sib pair test, a generalization of traditional sib pair tests. The proposed test can be implemented using any of three strategies, the choice of which depends on the anticipated combination of sharing and association. The elliptical sib pair test can achieve substantial gains in power relative to traditional tests for likely alternative hypotheses at little or no cost for other alternatives. The proposed test is valid under most models of genetic risk, disease etiology, and genotype‐haplotype distributions. This study also provides new insight into the trade‐off between tests of allelic association and tests of allele sharing. Genet. Epidemiol. 22:328–344, 2002. © 2002 Wiley‐Liss, Inc.
Determining trait locus position from multipoint analysis: Accuracy and power of three different statistics
Authors: Greenberg David A. , Abreu Paula C.
Published: August 2002

Previous work using two‐point linkage analysis showed that performing a lod score (LOD) analysis twice, once assuming dominant and once assuming recessive inheritance, and then taking the larger of the two values (designated MMLS) usually has more power to detect linkage than any other method tested. Using computer simulation for a variety of complex inheritance models, we demonstrated power for the MMLS comparable with analysis assuming the true model. However, reports in the literature suggested that the MMLS approach might fail to detect linkage using multipoint analysis due to genetic model misspecification. Here, we tested the robustness of the MMLS approach under multipoint analysis. We simulated data under complex inheritance models, including heterogeneity, epistatic, and additive models. We examined the expected maximum LOD, LOD assuming heterogeneity (HLOD), and nonparametric linkage statistics and the corresponding estimated position in a chromosomal interval of 10 markers with 10% recombination between markers. The mean estimates of position were generally good for all three statistics except when heterogeneity existed, where the LOD and the NPL did not perform as well as the HLOD. The MMLS approach was as robust using multipoint as using two‐point linkage analysis. LOD and/or the HLOD generally had more power to detect linkage than NPL across a variety of generating models, even after correcting for the multiple tests. For finding linkage to one locus of several contributing to disease expression, assuming the dominant and recessive models with reduced penetrance is a good approximation of the mode of inheritance at that locus. Genet. Epidemiol. 21:299–314, 2001. © 2001 Wiley‐Liss, Inc.
A postulated granite near Builth Wells, Mid‐Wales, and its local and regional significance
Authors: Goddard P. , Kearey P.
Published: August 2002

New gravity measurements taken to the northeast of Builth Wells reveal, after removal of a regional field, a negative gravity anomaly of 28 gravity units magnitude and some 7 km × 5 km in extent. The anomaly can be modelled in terms of a near‐surface, three‐dimensional body some 1.7 km in thickness with a density contrast of − 0.30 Mg m−3, which corresponds to an actual density of 2.45 Mg m−3. We interpret this body as a granite whose low density is the result of the percolating fluids which it heated and ultimately gave rise to the hydrothermal system near Builth Wells. This is the first indication of the possible presence of a granite that is associated with the back‐arc basin that formed during the subduction of the lapetus Ocean beneath Eastern Avalonia. Copyright © 2002 John Wiley & Sons, Ltd.
Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS
Authors: Blakemore W.F. , Chari D.M. , Gilson J.M. , Crang A.J.
Published: August 2002

Transplantation of myelin‐forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X‐irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs). By transplanting neonatal OPCs into OPC‐depleted tissue, we were able to examine the speed with which neonatal OPCs repopulate OPC‐depleted tissue. Using antibodies to NG‐2 proteoglycan and in situ hybridisation to detect platelet‐derived growth factor alpha‐receptor Rα (PDGFRα) mRNA to visualise OPCs, we were able to show that neonatal OPCs repopulate OPC‐depleted normal tissue 3–5 times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC densities to near‐normal values and when demyelinating lesions were made in tissue into which transplanted OPCs had been incorporated 1 month previously, we were able to show that the transplanted cells retain a robust ability to remyelinate axons after their integration into host tissue. In order to model the situation that would exist in a large OPC‐depleted area of demyelination such as may occur in humans; we depleted tissue of its endogenous OPC population and placed focal demyelinating lesions at a distance (≤1 cm) from a source of neonatal OPCs. In this situation, cells would have to repopulate depleted tissue in order to reach the area of demyelination. As the repopulation process would take time, this model allowed us to examine the consequences of delaying the interaction between OPCs and demyelinated axons on remyelination. Using this approach, we have obtained data that suggest that delaying the time of the interaction between OPCs and demyelinated axons restricts the expression of the remyelinating potential of transplanted OPCs. GLIA 38:155–168, 2002. © 2002 Wiley‐Liss, Inc.
Neuropsychiatric disturbance in Alzheimer's disease clusters into three groups: the Cache County study
Authors: Lyketsos Constantine G. , Sheppard Jeannie‐Marie E. , Steinberg Martin , Tschanz Jo Ann T. , Norton Maria C. , Steffens David C. , Breitner John C. S.
Published: August 2002

Objective

We investigated the frequency and inter‐relationship of neuropsychiatric disturbances in a population sample of persons suffering from Alzheimer's disease (AD).

Method

Screening 5,092 elderly residents (90% of the population aged 65 and older) of Cache County, Utah, for dementia, we identified 198 persons with AD using a comprehensive neuropsychiatric examination protocol. This examination included the Neuropsychiatric Inventory (NPI), a widely used measure of dementia‐associated neuropsychiatric disturbances.

Results

Overall, 60% of individuals with AD reported one or more neuropsychiatric symptoms. A latent class analysis revealed that these participants could be classified into three groups (classes) based on their neuropsychiatric symptom profile. The largest class included cases with no neuropsychiatric symptoms (40%) or with a mono‐symptomatic disturbance (19%). A second class (28%) exhibited a predominantly affective syndrome, while a third class (13%) had a psychotic syndrome.

Conclusion

Data from this first US population‐based study of AD‐associated neuropsychiatric disturbances suggest that a significant majority of persons with AD suffer from one or more neuropsychiatric disturbance. Based on phenomenological study, the spectrum of neuropsychiatric symptoms in AD can be empirically classified into three groups: an affective syndrome, a psychotic syndrome and other neuropsychiatric disturbance. The biologic and predictive validity of this classification merits further investigation. Copyright © 2001 John Wiley & Sons, Ltd.
Prophylactic therapy with lithium in elderly patients with unipolar major depression
Authors: Wilkinson David , Holmes Clive , Woolford Janet , Stammers Susan , North Janine
Published: August 2002

Objectives

To compare the relapse rate of elderly depressed patients taking low dose lithium as an additional therapy with antidepressant medication to those receiving antidepressant medication alone.

Methods

Fifty elderly subjects recovering from a major depressive illness taking continuation antidepressants were randomised, in a double blind study, to receive additional lithium carbonate or placebo and followed up over a two year period for evidence of relapse.

Results

Relapse rate was significantly greater in those subjects taking antidepressant medication alone compared to subjects taking additional lithium therapy. After six months four (17%) subjects taking antidepressant medication alone had relapsed, whereas none of the subjects taking additional lithium had relapsed. After two years eight (33%) subjects taking antidepressant medication alone had relapsed, whereas only one (4%) of the subjects taking additional lithium had relapsed.

Conclusion

This preliminary study suggests that long‐term low dose lithium therapy is well tolerated and protects elderly patients from a relapse of depressive illness. Copyright © 2002 John Wiley & Sons, Ltd.
Enantioselective reduction of dialkyl 4‐(dialkoxyphosphoryl)‐3‐oxobutanoates by baker's yeast
Authors: Yuan Chengye , Wang Ke , Li Jinfeng , Li Zuyi
Published: August 2002

Dialkyl 4‐(dialkoxyphosphoryl)‐3‐oxobutanoates (1), upon yeast‐mediated bioreduction, afforded chiral dialkyl 4‐(dialkoxyphosphoryl)‐3‐hydroxybutanoates (2) in moderate to good yields and ee values. Significant improvement was reported for the preparation of dialkyl 4‐(dialkoxyphosphoryl)‐3‐oxobutanoates (1), the key substrates of this bioreductive conversion. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:153–156, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10011
Autoxidation of acridanyl and benzhydryl carbanions adjacent to sulfur groups leading to CS bond cleavage with weak chemiluminescence
Authors: Motoyoshiya Jiro , Inoue Hisashi , Takaguchi Yutaka , Aoyama Hiromu
Published: August 2002

Autoxidation of acridanyl and benzhydryl carbanions stabilized by sulfur groups gave the corresponding ketones via radical intermediates, being accompanied by a weak light emission. While oxidation of 9‐sulfenylacridanes (1a and 1b) in the presence of tert‐BuOK showed direct chemiluminescence (CL) due to excited 10‐methylacridone, that of benzhydryl phenyl sulfide (2) and benzhydryldimethylsulfomium bromide (3) displayed CL in the presence of a fluorescer, 9,10‐dibromoanthracene (DBA), due to excited benzophenone. The yields of excited species in the present oxidation are low but comparable to acyclic peroxide systems. The bimolecular energy transfer from triplet benzophenone to DBA was established in CL of the sulfonium ylide from 3. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:252–257, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10025
Comparison of computational studies of internal stabilization of 1‐butadienyllithiums and representative 1‐chloro‐1‐lithio‐2‐phenylalkenes
Authors: Nelson Donna J. , Brammer Christopher
Published: August 2002

Comparison of molecular orbital calculations of 1‐butadienyllithiums and representative 1‐chloro‐1‐lithio‐2‐phenylalkenes, carried out by using MNDO and AM1, reveals that the major stabilizing interaction with lithium in these systems is predicted to be agostic bonding between lithium and hydrogen. MNDO and AM1 calculations for 1‐chloro‐1‐lithio‐2‐phenylethenes give evidence for agostic bonding between lithium and the ortho H, such as compressed pertinent bond angles and increased pertinent bond lengths. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:263–269, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10027
Syntheses of some new azolopyrido‐[4′,3′:4,5]thieno[2,3‐d]pyrimidines
Authors: Ahmed Essam Kh.
Published: August 2002

Diethyl 2‐[(ethoxythioxomethyl)amino]‐4,5,6,7‐tetrahydrothieno[2,3‐c]‐pyridine‐3,6‐dicarboxylate 2, prepared from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahydrothieno[2,3‐c]pyridine‐3,6‐dicarboxylate 1 by boiling in anhydrous ethanol, was converted into pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidine derivatives 3, 4 by treatment with hydrazine hydrate. The tetracyclic systems imidazo[1,2‐a]pyrido‐[4′,3′:4,5]thieno[2,3‐d]pyrimidine 9 and pyrido[4′,3′:4,5]thieno[2,3‐d][1,3]thiazolo‐[3,2‐a]pyrimidine 10 were synthesized by the reaction of 2 with 1,2‐diaminoethane and aminoethanethiol, respectively. The hydrazino derivative 4 underwent cyclization reactions with orthoesters and nitrous acid to give the corresponding pyrido[4′,3′:4,5]thieno[2,3‐d][1,2,4]triazolo[1,5‐a]pyrimidines 5, 6 and pyrido[4′,3′:4,5]thieno[3,2‐e][1,2,3,4]tetrazolo[1,5‐a]pyrimidine 8, respectively. Moreover, reactions of 3 with cyanogen bromide, N‐carbethoxyhydrazine, carbon disulfide, and ethylchloroformate resulted in the formation of the new pyrido[4′,3′:4,5]thieno[2,3‐d][1,3,4]thiadiazolo[3,2‐a]pyrimidine derivatives 12–15. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:280–286, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10030
A convenient synthesis of N‐t‐butyl‐N′‐aminocarbonyl‐N‐(substituted)benzoyl‐hydrazine containing α‐aminoalkylphosphonate groups in a one‐pot procedure
Authors: Wang Qingmin , Li Zaiguo , Huang Runqiu , Cheng Junran
Published: August 2002

A variety of novel N‐t‐butyl‐N′‐aminocarbonyl‐N‐(substituted)benzoylhydrazines containing α‐aminoalkylphosphonate groups were synthesized. Treatment of α‐aminoalkylphosphonates with triphosgene yielded α‐isocyanatoalkylphosphonates, and subsequent addition with N‐t‐butyl‐N‐substituted benzoylhydrazines provided the title compounds in a one‐pot procedure with good yields. The triphosgene‐mediated reaction for the synthesis of α‐isocyanatoalkylphosphonates enjoys a number of advantages: the reaction is carried out under mild condition in good yield, triphosgene is relatively safe to handle because of its low vapor pressure and high stability, and the experimental procedure is simple. This method can be applicable to the synthesis of other α‐isocyanatoalkyl‐phosphonates and urylenediphosphonates. The structures of all of the products and by‐products were confirmed by 1H NMR, 31P NMR, IR and mass spectroscopy, and elemental analysis. We also found that some of the compounds possess potential antitobacco mosaic virus (TMV) activities and anticancer activities. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:68–72, 2001
Testing efficacy with detection controlled estimation: an application to telemedicine
Authors: Bradford W. David , Kleit Andrew N. , Krousel‐Wood M. A. , Re Richard N.
Published: August 2002

Detection controlled estimation (DCE) is a powerful new econometric estimator in the family of missing data estimators. By collecting measures from a variety of inspectors or inspection technologies, DCE is able to make inferences about the entire population, even when that population is not directly observed. Using this innovative method, we were able to assess whether telemedicine technology could be substituted for in‐person visits when providing maintenance care for patients with hypertension. Our findings indicate that there is no support for the proposition that telemedicine is less effective than in‐person visits for determining whether patients have high blood pressure. Indeed, our results imply that telemedicine misses 7% fewer cases of high blood pressure than in‐person visits do. The results of this study indicate that DCE may be an effective tool for use in cost‐effectiveness or cost‐benefit analysis in health care. Copyright © 2001 John Wiley & Sons, Ltd.
Econometric issues in testing the age neutrality of health care expenditure
Authors: Salas Christian , Raftery James P.
Published: August 2002

A recent study by Zweifel et al. (Zweifel P, Felder S, Meiers M. Ageing of the population and health care expenditure: a red herring? Health Economics 1999; 8: 485–496) suggests that age is not related to health care expenditure among the elderly once ‘closeness to death’ is controlled for. If correct, this finding has major policy implications, but flaws in the econometric analysis undermine its credibility. We highlight two in particular, and propose methods to deal with them. Copyright © 2001 John Wiley & Sons, Ltd.
Estimation of the transition matrix of a discrete‐time Markov chain
Authors: Craig Bruce A. , Sendi Peter P.
Published: August 2002

Discrete‐time Markov chains have been successfully used to investigate treatment programs and health care protocols for chronic diseases. In these situations, the transition matrix, which describes the natural progression of the disease, is often estimated from a cohort observed at common intervals. Estimation of the matrix, however, is often complicated by the complex relationship among transition probabilities. This paper summarizes methods to obtain the maximum likelihood estimate of the transition matrix when the cycle length of the model coincides with the observation interval, the cycle length does not coincide with the observation interval, and when the observation intervals are unequal in length. In addition, the bootstrap is discussed as a method to assess the uncertainty of the maximum likelihood estimate and to construct confidence intervals for functions of the transition matrix such as expected survival. Copyright © 2002 John Wiley & Sons, Ltd.
Statistical determination of cost‐effectiveness frontier based on net health benefits
Authors: Laska Eugene M. , Meisner Morris , Siegel Carole , Wanderling Joseph
Published: August 2002

Statistical methods are given for producing a cost‐effectiveness frontier for an arbitrary number of programs. In the deterministic case, the net health benefit (NHB) decision rule is optimal; the rule funds the program with thelargest positiveNHB at eachλ, the amount a decision‐maker is willing to pay for an additional unit of effectiveness. For bivariate normally distributed cost and effectiveness variables and a specifiedλ, a statistical procedure is presented, based on the method ofconstrained multiple comparisons with the best(CMCB), for determining the program with the largest NHB. A one‐tailedttest is used to determine if the NHB is positive. To obtain a statistical frontier in theλ‐NHB plane, we develop a method to produce the region in which each program has the largest NHB, by pivoting a CMCB confidence interval. A one‐sided version of Fieller's theorem is used to determine the region where the NHB of each program is positive. At eachλ, the pointwise error rate is bounded by a prespecifiedα. Upper bounds on the familywise error rate, the probability of an error at any value ofλ, are given. The methods are applied to a hypothetical clinical trial of antipsychotic agents. Copyright © 2002 John Wiley & Sons, Ltd.
Discounting and clinical decision making: Physicians, patients, the general public, and the management of asymptomatic abdominal aortic aneurysms
Authors: Höjgård S. , Enemark U. , Lyttkens C. H. , Lindgren A. , Troëng T. , Weibull H.
Published: August 2002

Clinical decisions often entail in intertemporal trade‐off. Moreover, they often involve physicians of different specialities. In an experiment dealing with the management of small asymptomatic abdominal aortic aneurysms (a clinically relevant problem) we find that specialists in internal medicine exhibit higher implicit discount rates than vascular surgeons, general practitioners, and actual and prospective patients. Several personal characteristics expected to be directly related to pure time‐preference and risk aversion (gender, smoking habits, age, place of employment) have the hypothesised effects. Additionally, financial incentives appear to affect the estimated implicit discount rates of physicians, but are unlikely to have caused the inter‐group differences. Differences in discount rates could lead to variations in clinical practice, which may conflict with equality of treatment or equal access to health care. Copyright © 2002 John Wiley & Sons, Ltd.
Squamous cell carcinoma of the head and neck in solid organ transplant recipients
Authors: Preciado Diego A. , Matas Arthur , Adams George L.
Published: August 2002

Background

The increased incidence of cancer after solid organ transplantation is well established in the literature, yet outcome studies in this population are rare. Excluding skin cancers, squamous cell carcinomas make up most head and neck cancers in transplant recipients.

Methods

At our institution, of 5300 solid organ transplant recipients, 34 have had head and neck cancer develop. We reviewed the records of the 23 recipients whose cancer was treated here.

Results

Only 6 of the 23 recipients were alive at the time of our chart review. Of these, three had already survived 5 years. The 10 recipients diagnosed early (stage I or II) had significantly longer survival after cancer diagnosis than the 13 diagnosed at an advanced stage (stage III or IV) (96.0 mo vs 9.0 mo,p< .001). In all, 14 (60.8%) of the 23 recipients died of cancer within 2 years after diagnosis, 12 (50.2%) within 12 months. The sum of the daily doses of immunosuppressive drugs at cancer diagnosis was significantly greater for recipients who died within 2 years (p= .02). Furthermore, the difference in average doses of both prednisone (p= .001) and azathioprine (p= .028) was also significantly greater for those who died within 2 years. The average dose of cyclosporine was also greater, but this difference did not reach statistical significance (p= .18). The average dose of prednisone was significantly lower for recipients diagnosed early (p= .001). This correlation between high immunosuppressive drug doses and worse outcome has not been shown previously.

Conclusions

Solid organ transplant recipients who are diagnosed with advanced head and neck cancer while receiving high doses of immunosuppressive drugs fare extremely poorly. High doses of immunosuppressive drugs, most notably prednisone, correlate significantly with advanced diagnosis of head and neck cancer and earlier death. © 2002 Wiley Periodicals, Inc. Head Neck 24: 319–325, 2002; DOI 10.1002/hed.10055
Survival in patients with recurrent squamous cell head and neck carcinoma treated with bio‐chemotherapy
Authors: Airoldi Mario , De Stefani Antonella , Marchionatti Sara , Pedani Fulvia , Gabriele Pietro , Ragona Riccardo , Cortesina Giorgio , Bumma Cesare
Published: August 2002

Background

We have shown that rIL‐2 administration in recurrent head and neck cancers induces a tumor‐specific T‐lymphocyte reactivity and tumor regression; in a pilot study we have shown a safe and effective administration of rIL2 after cisplatin + 5‐fluorouracil. Long‐term results are not known.

Methods

Thirty patients with recurrent‐persistent head and neck cancer were treated with cisplatin (100 mg‐m2) d.1,5‐fluorouracil (1 gr‐m2‐d c.i. 96 h), and SQ rIL‐2 (4.5 M IU day 8 to 12 and 15 to 19) every 3 weeks.

Results

The overall response rate was 53.3% (95% CI; 34.4–72.3%): 26.6% complete response (CR) (8 patients) and 26.6% partial response (PR) (8 patients); 6 patients had SD (20%), 8 had PD (26.6%). The median follow‐up was 36 months (range, 28–44).The median CR duration is 16.2 months (8.5–39+); the median survival duration of this group has not been reached. The median PR duration was 7.2 months (3–10); the median survival was 13.3 months (10–26). The median overall survival was 14 months.

Conclusions

The most impressive finding is the very long survival of CRs patients. This outcome has been reported in other cancer patients with a CR after IL‐2 therapy. © 2001 John Wiley & Sons, Inc. Head Neck 23: 298–304, 2001.
Treatment of early stage squamous‐cell carcinoma of the glottic larynx: Endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapy
Authors: Bron Lue P. , Soldati Daniela , Zouhair Ahmed , Ozsahin Mahmut , Brossard Edgar , Monnier Philippe , Pasche Philippe
Published: August 2002

Background

Both surgery and radiotherapy are recognized treatments of T1‐T2 squamous cell carcinoma of the larynx. We retrospectively analyze and compare the oncological outcome of patients treated in a single institution, either by endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy.

Methods

The medical records of 156 patients treated between 1983 and 1996 with either surgery (n= 75) or radiotherapy (n= 81) were reviewed. Male to female ratio, median age, and T‐stage distribution were comparable.

Results

With a median follow‐up time of 59 months, the 5‐year cause‐specific survival rate of 93% was identical for both groups. The actuarial incidence of metachronous second primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery and 77% after radiotherapy. Anterior commissure infiltration was shown to represent a negative predictive factor of local control for radiotherapy (p= .01). Salvage treatment brought ultimate local control to 96% of patients after surgery and 94% after radiation therapy with long‐term laryngeal preservation rate altered significantly (p= .05) in the group of patients who received radiotherapy (90.1% vs 97.4%).

Conclusion

The treatment of laryngeal cancer is always a compromise between oncological efficiency and preservation of function. Our data suggest that, assuming proper selection of patients, radiation therapy and surgery yield similar local control and survival rates. The functional disadvantages after surgery are moderate and clearly counterbalanced by a significant decrease in long‐term laryngeal preservation rate after radiotherapeutic treatment. © 2001 John Wiley & Sons, Inc. Head Neck 23: 823–829, 2001.
Nicotine affects the signaling of the death pathway, reducing the response of head and neck cancer cell lines to DNA damaging agents
Authors: Onoda Naoyoshi , Nehmi Alisar , Weiner David , Mujumdar Sunita , Christen Randolph , Los Gerrit
Published: August 2002

Background

Growing evidence suggests that tobacco can affect the responsiveness of cancer cells to treatment, particularly those of head and neck cancer. This article describes the effects of nicotine on the signaling of the death pathway, resulting in a decreased cytotoxicity of various anticancer agents such as cisplatin and gamma‐radiation.

Methods

Colony‐forming assays (CFA), using the head and neck cancer cell lines UMSCC10b and UMSCC5 and DNA fragmentation assays, were used to determine the effect of nicotine on cytotoxicity of various anticancer agents, whereas PCR and a JNK activity test were used to study the effect of nicotine on message expression levels and activity of the JNK signaling pathway.

Results

Nicotine consistently reduced the cytotoxic effect of DNA‐damaging agents, such as cisplatin, UV, and gamma radiation, in UMSCC10b cells, increasing their IC50 values by twofold, 1.7‐fold, and 1.8‐fold, respectively. These results were confirmed in a second squamous cell carcinoma cell line (UMSCC5), demonstrating an increase in IC50 values for cDDP by twofold and 1.9‐fold in the UMSCC10b andUMSCC5, respectively. In addition, nicotine reduced the DNA fragmentation 48 h after cDDP exposure in UMSCC10b and UMSCC5 cell lines by 30% and 33%, respectively. The latter, however, was not the result of an effect of nicotine on either the uptake of cDDP or repair of the cDDP‐DNA‐adducts. To further substantiate the adverse effect of nicotine, the JNK and gadd153 signaling pathways were studied. JNK activity was decreased by 1.8‐fold, as well as the expression of its downstream target c‐jun (1.9‐fold), when tumor cells were exposed to cisplatin in the presence of nicotine. In addition, the gadd153 message was affected and reduced by 1.8‐fold.

Conclusions

Nicotine adversely affects the cytotoxicity of DNA‐damaging agents. Nicotine does not interfere with the repair of the damage but directly affects the signaling of the death pathway, reducing the signaling of the JNK1 pathway. The latter results in a decrease in efficacy of the anticancer treatment in tumors exposed to nicotine. © 2001 John Wiley & Sons, Inc. Head Neck 23: 860–870, 2001.
Management of swallowing in supraglottic and extended supraglottic laryngectomy patients
Authors: Wasserman Tamara , Murry Thomas , Johnson Jonas T. , Myers Eugene N.
Published: August 2002

Background

Aspiration of food and liquid following supraglottic and supracricoid laryngectomy has been documented and found to be the most frequent major postoperative complication that extends hospitalization. The advantages as well as disadvantages of discharging a patient with percutaneous endoscopic gastrostomy (PEG) placement and home therapy versus an aggressive in‐hospital dysphagia management program remain controversial. The present investigation examines an aggressive in‐patient postoperative dysphagia management program following decannulation.

Methods

Twenty‐one patients participated in a four‐part dysphagia management program following decannulation: patient education, indirect therapy, swallowing evaluation, and nutrition education.

Results

Eleven patients achieved functional swallowing goals prior to discharge with no reports of pneumonia or rehospitalization over a 3‐month follow‐up period. Six patients were discharged with a tracheostomy and duo tube; five of these patients were started on an oral diet the same day of decannulation. Four patients decannulated prior to discharge did not achieve functional swallowing.

Conclusion

Certain patients can achieve functional swallowing goals prior to discharge and avoid the cost and surgical placement of a PEG. This group required an additional 2 to 3 days of hospitalization; however, the usual and customary charges for aggressive dysphagia management in this group were exceeded by charges for PEG placement and in‐home therapy according to pricing guidelines for the hospital where these patients were treated. Specific patient profiles of those who were unsuccessful relate to extent of surgery, ie, supraglottic + base of tongue (SUPRA + BOT) and supraglottic + vocal fold (SUPRA + VF) resection, and non‐compliance. Complicated patients often require longer rehabilitation and may benefit from a PEG at the time of surgery. © 2001 John Wiley & Sons, Inc. Head Neck 23: 1043–1048, 2001.
Effects of hippocampal lesions on delayed nonmatching‐to‐sample in monkeys: A reply to Zola and Squire (2001)†
Authors: Baxter Mark G. , Murray Elisabeth A.
Published: August 2002

Hippocampus 2001;11:201–203. Published 2001 Wiley‐Liss, Inc.