bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetics of breast cancer: Polycyclic aromatic hydrocarbons as risk factors
Authors: Jeffy Brandon D. , Chirnomas Ryan B. , Romagnolo Donato F.
Published: August 2002

In the absence of a causal relationship between the incidence of sporadic breast cancer and occurrence of mutations in breast cancer susceptibility genes, efforts directed to investigating the contribution of environmental xenobiotics in the etiology of sporadic mammary neoplasia are warranted. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants, which have been shown to induce DNA damage and disrupt cell cycle progression. In this report we discuss published data pointing to PAHs as a risk factor in carcinogenesis, and present findings generated in our laboratory suggesting that the mammary tumorigenicity of PAHs may be attributable, at least in part, to disruption of BRCA‐1 expression by reactive PAH‐metabolites. We report that benzo[a]pyrene (B[a]P), selected as a prototype PAH, disrupts BRCA‐1 transcription in estrogen receptor (ER)‐positive but not ER‐negative breast cancer cells. The reduced potential for BRCA‐1 expression in B[a]P‐treated cells coincides with disruption of cell cycle kinetics and accumulation of p53. These effects are counteracted by the AhR‐antagonist α‐naphthoflavone (ANF), and in breast cancer cells expressing mutant p53 or the E6 human papilloma virus protein. We suggest that exposure to PAHs may be a predisposing factor in the etiology of sporadic breast cancer by disrupting the expression of BRCA‐1. Environ. Mol. Mutagen. 39:235–244, 2002. © 2002 Wiley‐Liss, Inc.
Model selection: Full Bayesian approach
Authors: de Bragança Pereira Carlos Alberto , Stern Julio Michael
Published: August 2002

We show how the Full Bayesian Significance Test (FBST) can be used as a model selection criterion. The FBST was presented in Pereira and Stern as a coherent Bayesian significance test. Copyright © 2001 John Wiley & Sons, Ltd.
Parameter identification of inelastic structures under dynamic loads
Authors: Zhang Haochuan , Foliente Greg C. , Yang Yongmin , Ma Fai
Published: August 2002

The generalized model of differential hysteresis contains 13 control parameters with which it can curve‐fit practically any hysteretic trace. Three identification algorithms are developed to estimate the control parameters of hysteresis for different classes of inelastic structures. These algorithms are based upon the simplex, extended Kalman filter, and generalized reduced gradient methods. Novel techniques such as global search and internal constraints are incorporated to facilitate convergence and stability. Effectiveness of the devised algorithms is demonstrated through simulations of two inelastic systems with both pinching and degradation characteristics in their hysteretic traces. Owing to very modest computing requirements, these identification algorithms may become acceptable as a design tool for mapping the hysteretic traces of inelastic structures. Copyright © 2002 John Wiley & Sons, Ltd.
Key parameters governing the performance of soft tunnel coating for seismic isolation
Authors: Kim Dae‐Sang , Konagai Kazuo
Published: August 2002

A method to cover a tunnel lining with a soft and thin coating is discussed herein as a possible measure for mitigating seismic damage to tunnels. Long‐term earthquake observations at different tunnel sites within a variety of alluvial soil deposits have demonstrated that a circular tunnel is liable to deform in such a way that its two diagonal diameters crossing each other expand and contract alternately. Narrowing down vibration modes, in order to discuss this particular and the most important mode, any of the essential items of the soil–tunnel system, namely the soil, the coating and the tunnel lining, has only one degree of freedom, allowing the coating effect to be simply evaluated in terms of a limited number of key parameters. Copyright © 2001 John Wiley & Sons, Ltd.
Feasibility of using impedance‐based damage assessment for pipeline structures
Authors: Park Gyuhae , Cudney Harley H. , Inman Daniel J.
Published: August 2002

This paper presents the feasibility of using an impedance‐based health monitoring technique in monitoring a critical civil facility. The objective of this research is to utilize the capability of the impedance method in identifying structural damage in those areas where a very quick condition monitoring is urgently needed, such as in a post‐earthquake analysis of a pipeline system. The basic principle behind this technique is to utilize high‐frequency structural excitation (typically greater than 30 kHz) through surface‐bonded piezoelectric sensors/actuators to detect changes in structural point impedance due to the presence of damage. Real‐time damage detection in pipes connected by bolted joints was investigated, and the capability of the impedance method in tracking and monitoring the integrity of the typical civil facility has been demonstrated. Data collected from the tests illustrates the capability of this technology to detect imminent damage under normal operating conditions and immediately after a natural disaster. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling three‐dimensional flow structures and patterns of boundary shear stress in a natural pool–riffle sequence
Authors: Booker D. J. , Sear D. A. , Payne A. J.
Published: August 2002

Fluid–sediment interactions control river channel forms and processes. Analysis of spatial hydraulic patterns and the resulting boundary shear stress are required to aid understanding of river system behaviour. In this paper, the hydraulic processes active in a natural pool–riffle sequence are simulated using a three‐dimensional computational fluid dynamics (CFD) model. Methods employed for the prescription of model boundary conditions are outlined. Model calculations are assessed using comparisons with field observations acquired over a range of flows. Simulations are then used to illustrate flow structures and patterns of boundary shear stress for a near‐bankfull and an intermediate flow event. Results are used to assess existing theories that seek to explain the development and maintenance of pool–riffle sequences. Simulated results suggest that near‐bed velocities and bed shear stresses decrease on riffles and increase in pools as discharge increases. Model simulations indicate that secondary flow acts to route near‐bed flow over the downstream side of riffles and into the pool‐head away from the centre of pools. Implications for sediment transport and pool maintenance are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Subaerial river bank erosion processes and their interaction with other bank erosion mechanisms on the River Arrow, Warwickshire, UK
Authors: Couper Pauline R. , Maddock Ian P.
Published: August 2002

River bank erosion occurs primarily through a combination of three mechanisms: mass failure, fluvial entrainment, and subaerial weakening and weathering. Subaerial processes are often viewed as ‘preparatory’ processes, weakening the bank face prior to fluvial erosion. Within a river basin downstream process ‘domains’ occur, with subaerial processes dominating the upper reaches, fluvial erosion the middle, and mass failure the lower reaches of a river. The aim of this paper is to demonstrate that (a) subaerial processes may be underestimated as an erosive agent, and (b) process dominance has a temporal, as well as spatial, aspect.
 Bank erosion on the River Arrow, Warwickshire, UK, was monitored for 16 months (December 1996 to March 1998) using erosion pins. Variations in the rate and aerial extent of erosion are considered with reference to meteorological data. Throughout the first 15 months all erosion recorded was subaerial, resulting in up to 181 mm a−1 of bank retreat, compared with 13 to 27 mm a−1 reported by previous researchers. While the role of subaerial processes as ‘preparatory’ is not contended, it is suggested that such processes can also be erosive.
 The three bank erosion mechanisms operate at different levels of magnitude and frequency, and the River Arrow data demonstrate this. Thus the concept of process dominance has a temporal, as well as spatial aspect, particularly over the short time‐periods often used for studying processes in the field. Perception of the relative efficacy of each erosive mechanism will therefore be influenced by the temporal scale at which the bank is considered. With the advent of global climate change, both these magnitude–frequency characteristics and the consequent interaction of bank erosion mechanisms may alter. It is therefore likely that recognition of this temporal aspect of process dominance will become increasingly important to studies of bank erosion processes. Copyright © 2001 John Wiley & Sons, Ltd.
A quantitative evaluation of Playfair's law and its use in testing long‐term stream erosion models
Authors: Niemann Jeffrey D. , Gasparini Nicole M. , Tucker Gregory E. , Bras Rafael L.
Published: August 2002

Playfair's law (J. Playfair, illustrations of the Huttonian Theory of the Earth, 1802) requires any two tributaries in a river network to lower at the same rate near their junction. Although this law holds exactly at the junction, it is unclear how well it holds in the vicinity of the junction. This issue has practical importance because Playfair's law has been used to estimate parameters for detachment‐limited models of erosion. If the incision rate of a stream is modelled as βAmSn, where β is an erodibility parameter, A is the area drained by the stream, and S is the local gradient of the channel, then the ratio of the parameters m/n can be estimated from junctions by assuming that Playfair's law holds over the distance used to determine S for each tributary. In this paper, Playfair's law and associated m/n estimates are evaluated for simulated basins with constant and temporally varying uplift rates (or baselevel lowering rates). The results demonstrate that estimates of m/n may be biased for basins with upward‐concave stream profiles because the local slope must be approximated with an average upstream slope. In addition, when uplift rate varies temporally, knickpoints are shown to travel through the basins with constant vertical velocity. Because incision rates vary within the basin, Playfair's law only holds exactly at the junctions. These effects are more important when slopes are measured over longer distances. Finally, measurement techniques are presented which address these potential biases. Copyright © 2001 John Wiley & Sons, Ltd.
The effects of survey frequency on estimates of scour and fill in a braided river model
Authors: Lindsay John B. , Ashmore Peter E.
Published: August 2002

An erratum has been published for this article in Earth Surface Processes and Landforms 27(7) 2002, 795.

Estimates of scour and fill in rivers that are derived by differencing topographic surfaces are known to be negatively biased by local compensation of scour and fill between surveys but the magnitude of bias is not well known. This study examines the effect of survey frequency on volumes of scour and fill over a period of active channel braiding in a small‐scale river model. A 100 min, high temporal resolution time series of digital elevation models is artificially coarsened by selectively removing models. The resulting four overlapping time series have survey intervals of 10 min, 20 min, 50 min and 100 min. Cumulative scour and fill volumes for the 100 min period are compared between the four series. It is concluded that the decay in measured volumes of scour and fill with increased survey interval can be described using inverse functions. Cumulative scour–fill volumes are approximately 420 per cent greater over the study period for 10 min survey intervals than for a 100 min interval. After the 100 min period of competent flow, nearly 65 per cent of the channel area experienced significant compensation of scour and fill. Several compensation mechanisms were identified in association with braided channel kinetics, including lateral channel migration, the migration of bed forms, and channel avulsion. It is demonstrated that by negatively biasing scour, fill and net estimates, this error significantly affects morphological approaches to the estimation of bed load sediment transport. Copyright © 2002 John Wiley & Sons, Ltd.
Mediated equilibrium: the influence of riparian vegetation and wood on the long‐term evolution and behaviour of a near‐pristine river
Authors: Brooks Andrew P. , Brierley Gary J.
Published: August 2002

Analysis of the contemporary geomorphology, vegetation and in‐channel wood within the relatively pristine Thurra River in southeastern Australia provides insight into river behaviour prior to European disturbance. This sand‐bed river has an extremely low channel capacity with a pronounced pool–riffle morphology. Lateral migration rates are low (11–24 mm a−1), as are floodplain aggradation rates (average = 0·27 mm a−1). Sedimentological evidence is used to place contemporary channel dynamics within a 16 ka evolutionary framework. The floodplain has continuously aggraded over this interval, despite a number of avulsions and numerous meander cutoffs. Avulsions occur on a timeframe of once in 5 ka or more, while cutoffs occur around once in 1 ka. The morphology and evolution of the Thurra River are appraised in terms of a mediated equilibrium condition, in which channel capacity, hydraulics, bedload transport rates, bank erosion rates and in‐channel deposition are substantially influenced by vegetation and wood within the channel and on the floodplain. Copyright © 2002 John Wiley & Sons, Ltd.
Chemical composition and antimicrobial activity of Rosmarinus officinalis L. oils from Sardinia and Corsica
Authors: Pintore Giorgio , Usai Marianna , Bradesi Pascale , Juliano Claudia , Boatto Gianpiero , Tomi Félix , Chessa Mario , Cerri Riccardo , Casanova Joseph
Published: August 2002

A detailed analysis of Rosmarinus officinalis L. essential oil from Sardinia and Corsica (α‐pinene/verbenone/bornyl acetate chemotype) was carried out using GC–RI, GC–MS and 13C‐NMR, on the bulk sample or after repeated chromatography. Fifty‐eight compounds were identified. The antimicrobial activity of two Sardinian samples was investigated and both exhibited a moderate antibacterial activity. Gram‐positive bacteria were more sensitive (MIC 2.5–4 mg/ml) than Gram‐negative bacteria. Killing time experiments demonstrated that prolonged times (60 min) are needed to completely inactivate the bacterial inoculum. Copyright © 2001 John Wiley & Sons, Ltd.
A verticillane‐type diterpene fromBoswellia carteriiessential oil
Authors: Basar Simla , Koch Angelika , König Wilfried A.
Published: August 2002

The essential oil ofBoswellia carteriiresinoid (olibanum) was investigated by GC–MS. In addition to known compounds, a new verticillane‐type diterpene was isolated and identified by NMR investigations as verticilla‐4(20),7,11‐triene. Copyright © 2001 John Wiley & Sons, Ltd.
Higher‐order finite element discretizations in a benchmark problem for incompressible flows
Authors: John Volker , Matthies Gunar
Published: August 2002

We present a numerical study of several finite element discretizations applied to a benchmark problem for the two‐dimensional steady state incompressible Navier–Stokes equations defined in Schäfer and Turek (The benchmark problem ‘Flow around a cylinder’. In Flow Simulation with High‐Performance Computers II. Notes on Numerical Fluid Mechanics, vol. 52, Hirschel EH (ed.). Vieweg: Wiesbaden, 1996; 547–566). The discretizations are compared with respect to the accuracy of the computed benchmark parameters. Higher‐order isoparametric finite element discretizations turned out to be by far the most accurate. The discrete systems obtained with higher‐order discretizations are solved with a modified coupled multigrid method whose behaviour within the benchmark problem is also studied numerically. Copyright © 2001 John Wiley & Sons, Ltd.
An analysis and comparison of the time accuracy of fractional‐step methods for the Navier–Stokes equations on staggered grids
Authors: Armfield S. , Street R.
Published: August 2002

Fractional‐step methods solve the unsteady Navier–Stokes equations in a segregated manner, and can be implemented with only a single solution of the momentum/pressure equations being obtained at each time step, or with the momentum/pressure system being iterated until a convergence criterion is attained.The time accuracy of such methods can be determined by the accuracy of the momentum/pressure coupling, irrespective of the accuracy to which the momentum equations are solved. It is shown that the time accuracy of the basic projection method is first‐order as a result of the momentum/pressure coupling, but that by modifying the coupling directly, or by modifying the intermediate velocity boundary conditions, it is possible to recover second‐order behaviour. It is also shown that pressure correction methods, implemented in non‐iterative or iterative form and without special boundary conditions, are second‐order in time, and that a form of the non‐iterative pressure correction method is the most efficient for the problems considered. Copyright © 2002 John Wiley & Sons, Ltd.
Term premia and the maturity composition of the Federal debt: new evidence from the term structure of interest rates
Authors: Bekdache Basma
Published: August 2002

This paper models bond term premia empirically in terms of the maturity composition of the federal debt and other observable economic variables in a time‐varying framework with potential regime shifts. We present regression and out‐of sample forecasting results demonstrating that information on the age composition of the Federal debt is useful for forecasting term premia. We show that the multiprocess mixture model, a multi‐state time‐varying parameter model, outperforms the commonly used GARCH model in out‐of‐sample forecasts of term premia. The results underscore the importance of modelling term premia, as a function of economic variables rather than just as a function of asset covariances as in the conditional heteroscedasticity models. Copyright © 2001 John Wiley & Sons, Ltd.
The homogeneity restriction and forecasting performance of VAR‐type demand systems: an empirical examination of US meat consumption
Authors: Wang Zijun , Bessler David A.
Published: August 2002

This paper compares the forecast performance of vector‐autoregression‐type (VAR) demand systems with and without imposing the homogeneity restriction in the cointegration space. US meat consumption (beef, poultry and pork) data are studied. One up to four‐steps‐ahead forecasts are generated from both the theoretically restricted and unrestricted models. A modified Diebold–Mariano test of the equality of mean squared forecast errors (MSFE) and a forecast encompassing test are applied in forecast evaluation. Our findings suggest that the imposition of the homogeneity restriction tends to improve the forecast accuracy when the restriction is not rejected. The evidence is mixed when the restriction is rejected. Copyright © 2002 John Wiley & Sons, Ltd.
The data measurement process for UK GNP: stochastic trends, long memory, and unit roots
Authors: Patterson Kerry
Published: August 2002

Much published data is subject to a process of revision due, for example, to additional source data, which generates multiple vintages of data on the same generic variable, a process termed the data measurement process or DMP. This article is concerned with several interrelated aspects of the DMP for UK Gross National Product. Relevant questions include the following. Is the DMP well behaved in the sense of providing a single stochastic trend in the vector time series of vintages? Is one of the vintages of data, for example the ‘final’, the sole vintage generating the long‐memory component? Does the multivariate framework proposed here add to the debate on the existence of a unit root in GNP? The likely implicit assumptions of users (that the DMP is well behaved and the final vintage is ‘best’) can be cast in terms of testable hypotheses; and we show that these ‘standard’ assumptions have not always been empirically founded. Copyright © 2002 John Wiley & Sons, Ltd.
The good earthworm: How natural processes preserve upland Archaic archaeological sites of western Illinois, U.S.A.
Authors: Van Nest Julieann
Published: August 2002

In western Illinois, many soil profiles developed into upland loess deposits (Peoria Silt) contain Archaic period artifacts greater than 3500 yr B.P. in stone zones below plow level. For artifacts in prairie and prairie‐forest transition soils (not forest soils), depth distribution curves suggest they were buried in biomantles by small soil fauna. Artifacts of sizes archaeologists routinely collect generally move down while retaining fine‐scale horizontal integrity. The process results in stratigraphic separation of Archaic and Woodland period components that otherwise would commingle at the surface. The characteristic distribution of known upland sites, narrowly rimming stream valley headwaters, reflects incomplete burial of materials on steeper forested slopes. On adjacent gently sloping upper shoulder segments of valleys where grassy cover more strongly influences soil development (and by inference on broad level uplands where true prairie soils occur), Archaic artifacts will be buried in the biomantle and go undetected by surface surveyors. © 2002 John Wiley & Sons, Inc.
The effects of temporal and spatial patterns of Holocene erosion and alluviation on the archaeological record of the Central and Eastern Great Plains, U.S.A.
Authors: Bettis E. Arthur , Mandel Rolfe D.
Published: August 2002

Patterns of erosion and deposition act as a filter that strongly influences the disposition of the archaeological record of the Central and Eastern Plains of the North American Midcontinent. Detailed studies of alluvial valley stratigraphy in four drainage basins in the region reveal temporal and spatial patterns of fluvial system behavior that control the preservation and visibility of past human activity. These basins are located on a 600‐km‐long longitudinal gradient extending from semiarid southwestern Kansas to moist‐subhumid central Iowa. Despite significant environmental variability along this transect, basin‐wide patterns of Holocene erosion and deposition are similar across the study area. From ca. 11,000 to 8000 yr B.P., aggradation, punctuated by slow alluviation and/or stability around 10,000 yr B.P., was the dominant process in large and some small valleys. The early and middle Holocene (ca. 8000–5000 yr B.P.) was a period of net erosion and sediment movement in small valleys, sediment storage in large valleys, and episodic aggradation on alluvial fans. During the late Holocene (post‐5000 yr B.P.), alluvial fans stabilized, small valleys became zones of net sediment storage, and aggradation slowed in large valleys. Basin‐wide aggradation followed by entrenchment and channel migration characterizes fluvial activity during the Historic period. Consideration of the effects of these temporal and spatial patterns of Holocene erosion and alluviation on the archaeological record is crucial for developing efficient cultural resource sampling strategies and for accurately interpreting the archaeological record. © 2002 John Wiley & Sons, Inc.
The hidden record: Late Holocene landscapes and settlement archaeology in the Lower Ohio River Valley
Authors: Stafford C. Russell , Creasman Steven D.
Published: August 2002

From extensive backhoe trenching and coring in the Great Miami–Ohio River confluence region, in conjunction with a large suite of radiocarbon ages, we have identified large tracts of late Holocene alluvium. Thick blankets of Historic alluvium (post‐settlement) may also cover levees of the Ohio River. In conjunction with other studies in the Outer Bluegrass Region of the lower Ohio River valley, it is possible to document an association between floodplain Mollisols, Inceptisols, and Entisols and late Holocene‐aged landforms. Levees appear to have stabilized between 1000 and 2000 yr B.P. Although buried soils are rare, archaeological materials were ubiquitous in late Holocene Landform Sediment Assemblages. Because a substantial volume of valley fill is late Holocene in age, Woodland sites of all types are frequently buried, and Fort Ancient sites may be buried by Historic alluvium. Therefore, if Woodland or later settlement studies in this region are based on surface evidence alone, they are likely to be biased. © 2002 John Wiley & Sons, Inc.
Tests for genetic association using family data
Authors: Shih Mei‐Chiung , Whittemore Alice S.
Published: August 2002

We use likelihood‐based score statistics to test for association between a disease and a diallelic polymorphism, based on data from arbitrary types of nuclear families. The Nonfounder statistic extends the transmission disequilibrium test (TDT) to accommodate affected and unaffected offspring, missing parental genotypes, phenotypes more general than qualitative traits, such as censored survival data and quantitative traits, and residual correlation of phenotypes within families. The Founder statistic compares observed or inferred parental genotypes to those expected in the general population. Here the genotypes of affected parents and those with many affected offspring are weighted more heavily than unaffected parents and those with few affected offspring. We illustrate the tests by applying them to data on a polymorphism of the SRD5A2 gene in nuclear families with multiple cases of prostate cancer. We also use simulations to compare the power of these family‐based statistics to that of the score statistic based on Cox’s partial likelihood for censored survival data, and find that the family‐based statistics have considerably more power when there are many untyped parents. The software program FGAP for computing test statistics is available athttp://www.stanford.edu/dept/HRP/epidemiology/FGAP. Genet. Epidemiol. 22:128–145, 2002. © 2002 Wiley‐Liss, Inc.
Tectono‐sedimentary evolution of the northernmost margin of the NE German Basin between uppermost Carboniferous and Late Permian (Rotliegend)
Authors: Rieke H. , Kossow D. , McCann T. , Krawczyk C.
Published: August 2002

The tectono‐sedimentary evolution of the Rotliegend deposits of the northernmost margin of NE German Basin (NEGB) has been analysed on the basis of detailed sedimentary logs of 300 m of core material together with the re‐evaluation of 600 km of seismic lines. Three distinct phases were recognized. During the initial Phase I, basin geometry was largely controlled by normal faulting related to deep‐seated ductile shearing leading to a strong asymmetric shape, with a steep fault‐controlled eastern margin and a gently, dipping western margin. The results of forward modelling along a cross‐section fit the basin geometry in width and depth and reveal a footwall uplift of c. 1000 m. Adjacent to the steep faults, local sedimentation of Lithofacies Type I was confined to non‐cohesive debris flow‐dominated alluvial fans, whereas the gently dipping western margin was dominated by alluvial‐cone sedimentation.

During the post‐extensional period (Phase II), cooling of the lithosphere generated additional accommodation space. The sediments of Lithofacies Type II, comprising mainly clast‐supported conglomerates, are interpreted as braided ephemeral stream flow‐surge deposits. Tectonic quiescence and an increase in flood events resulting from wetter climate led to progradation of this facies over the entire region. At the end of this period, the accommodation space was almost completely filled resulting in a level topography.

Phase III was controlled by the thermal‐induced subsidence of the southerly located NEGB in post‐Illawarra times. The formerly isolated region tilted towards the SW, thus forming the northern margin of the NEGB during uppermost Havel and Elbe Subgroup times. The sediments of Lithofacies Type III were divided into a marginal sandstone‐dominated environment and a finer‐grained facies towards the SW. The former consists of poorly‐sorted coarse‐grained sandstones of a proximal and medial ephemeral stream floodplain facies. The latter comprise mud flat fines and fine‐grained distal ephemeral stream deposits. The end of the tectono‐sedimentary evolution is marked by the basinwide Zechstein transgression. Copyright © 2001 John Wiley & Sons, Ltd.
The Romagna Apennines, Italy: an eroded duplex
Authors: Feroni A. Cerrina , Leoni L. , Martelli L. , Martinelli P. , Ottria G. , Sarti G.
Published: August 2002

The study of clast composition carried out on the alluvial gravels of the Romagna Apennines of northern Italy has provided evidence for an extensive covering of allochthonous units (Ligurian nappe and Epiligurian succession) above the Miocene foredeep deposits (Marnoso‐Arenacea Formation), which has been subsequently eroded during the Late Miocene–Pleistocene uplift. This result is confirmed by the burial history outlined in the Marnoso‐Arenacea Formation through vitrinite reflectance and apatite fission‐track analyses. The Romagna Apennines represent, therefore, a regional tectonic window where the thrust system that displaced the Marnoso‐Arenacea Formation crops out. The geometric relations between this thrust system and the basal thrust of the Ligurian nappe, exposed at the boundaries of the Romagna Apennines (Sillaro Zone and Val Marecchia klippe), are consistent with a duplex structure. Thus, the Romagna Apennines thrust system is an eroded duplex. The duplex roof‐thrust corresponds to the surface of the synsedimentary overthrust of the Ligurian nappe on the Marnoso‐Arenacea Formation; the floor‐thrust is located in the pelagic pre‐foredeep deposits (Schlier Formation). Copyright © 2001 John Wiley & Sons, Ltd.
Expression of the complement C3a and C5a receptors after permanent focal ischemia: An alternative interpretation
Authors: Barnum Scott R. , Ames Robert S. , Maycox Peter R. , Hadingham Sarah J. , Meakin Jackie , Harrison David , Parsons Andrew A.
Published: August 2002

The receptors for the complement anaphylatoxins C3a and C5a are expressed by glial cells and neurons in normal and inflamed brain. Previous studies demonstrated modest elevations in mRNA expression of these receptors in a model of focal cerebral ischemia. Using a similar model system for both mice and rats, we report markedly different patterns of anaphylatoxin receptor mRNA expression in cerebral ischemia. C5a receptor expression was dramatically elevated within 3 h after middle cerebral artery occlusion, while C3aR expression was reduced to 25% of control animals. By 24 h post‐occlusion, expression of both receptors was higher than at any other time point examined. This increased expression at late time points after occlusion is most likely the result of massive infiltration of leukocytes expressing the receptors. We also observed increased receptor mRNA expression in sham‐operated animals, indicating that the procedures used for arterial occlusion affects mechanisms regulating receptor expression. This latter result highlights the importance of including this important control group in ischemic model systems for proper interpretation of changes in gene expression. GLIA 38:169–173, 2002. © 2002 Wiley‐Liss, Inc.
Glutamate transporters and retinal excitotoxicity
Authors: Izumi Yukitoshi , Shimamoto Keiko , Benz Ann M. , Hammerman Seth B. , Olney John W. , Zorumski Charles F.
Published: August 2002

Glutamate appears to play a major role in several degenerative retinal disorders. However, exogenous glutamate is only weakly toxic to the retina when glutamate transporters on Müller glial cells are operational. In an ex vivo rat retinal preparation, we previously found that exogenous glutamate causes Müller cell swelling but does not trigger excitotoxic neurodegeneration unless very high concentrations that overwhelm the capacity of glutamate transporters are administered. To determine the role of glutamate transporters in Müller cell swelling and glutamate‐mediated retinal degeneration, we examined the effects ofDL‐threo‐β‐benzyloxyaspartate (TBOA), an agent that blocks glutamate transport but that unlike most available transport inhibitors is neither a substrate for transport nor a glutamate receptor agonist. We found that TBOA triggered severe retinal neurodegeneration attenuated by ionotropic glutamate receptor antagonists. TBOA‐induced neuronal damage was also diminished by riluzole, an agent that inhibits endogenous glutamate release. In the presence of riluzole, to inhibit glutamate release plus TBOA to block glutamate uptake, the addition of low concentrations of exogenous glutamate triggered severe excitotoxic neuronal damage without inducing Müller cell swelling. We conclude that TBOA‐sensitive glutamate transporters play an important role in regulating the neurodegenerative effects of glutamate in the rat retina. GLIA 39:58–68, 2002. © 2002 Wiley‐Liss, Inc.
Astrocyte and endothelial cell expression of ADAM 17 (TACE) in adult human CNS
Authors: Goddard Diane R. , Bunning Rowena A.D. , Woodroofe M. Nicola
Published: August 2002

ADAM 17, also known as TACE, is an important sheddase for a number of proteins, including tumor necrosis factor‐α (TNF‐α), transforming growth factor‐α (TGF‐α), L‐selectin, p75, and p55 TNF receptors, and interleukin‐1 receptor II (IL‐1RII). The presence of ADAM 17 mRNA in adult mouse and rat CNS was recently reported (Karkkainen et al. Mol Cell Neurosci 15:547–560, 2000). However, the cellular origin of ADAM 17 remains unknown. In this study, we have used an anti‐ADAM 17 antibody in an immunohistochemical study of its distribution in human adult CNS tissue. Cells with astrocytic and endothelial morphology were ADAM 17‐positive. This finding was further confirmed using double immunofluorescence with antibodies against GFAP and von Willebrand factor, which label astrocytes and endothelial cells, respectively. This study demonstrates that ADAM 17 is expressed by astrocytes and endothelial cells in normal brain tissue and may have a role in normal brain function. GLIA 34:267–271, 2001. © 2001 Wiley‐Liss, Inc.
Immune function of microglia
Authors: Aloisi Francesca
Published: August 2002

During the past decade, mechanisms involved in the immune surveillance of the central nervous system (CNS) have moved to the forefront of neuropathological research mainly because of the recognition that most neurological disorders involve activation and, possibly, dysregulation of microglia, the intrinsic macrophages of the CNS. Increasing evidence indicates that, in addition to their well‐established phagocytic function, microglia may also participate in the regulation of non specific inflammation as well as adaptive immune responses. This article focuses on the signals regulating microglia innate immune functions, the role of microglia in antigen presentation, and their possible involvement in the development of CNS immunopathology. GLIA 36:165–179, 2001. © 2001 Wiley‐Liss, Inc.
Control of glial immune function by neurons
Authors: Neumann Harald
Published: August 2002

The immune status of the central nervous system (CNS) is strictly regulated. In the healthy brain, immune responses are kept to a minimum. In contrast, in a variety of inflammatory and neurodegenerative diseases, including multiple sclerosis, infections, trauma, stroke, neoplasia, and Alzheimer's disease, glial cells such as microglia gain antigen‐presenting capacity through the expression of major histocompatibility complex (MHC) molecules. Further, proinflammatory cytokines, such as tumor necrosis factor‐α (TNF), interleukin‐1β (IL‐1β), and interferon‐γ (IFN‐γ), as well as chemokines, are synthesized by resident brain cells and T lymphocytes invade the affected brain tissue. The proinflammatory cytokines stimulate microglial MHC expression in the lesioned CNS areas only. However, the induction of brain immunity is strongly counterregulated in intact CNS areas. For instance, recent work demonstrated that microglia are kept in a quiescent state in the intact CNS by local interactions between the microglia receptor CD200 and its ligand, which is expressed on neurons. Work done in our laboratory showed that neurons suppressed MHC expression in surrounding glial cells, in particular microglia and astrocytes. This control of MHC expression by neurons was dependent on their electrical activity. In brain tissue with intact neurons, the MHC class II inducibility of microglia and astrocytes by the proinflammatory cytokine IFN‐γ was reduced. Paralysis of neuronal electric activity by neurotoxins restored the induction of MHC molecules on microglia and astrocytes. Loss of neurons or their physiological activity would render the impaired CNS areas recognizable by invading T lymphocytes. Thus, immunity in the CNS is inhibited by the local microenvironment, in particular by physiologically active neurons, to prevent unwanted immune mediated damage of neurons. GLIA 36:191–199, 2001. © 2001 Wiley‐Liss, Inc.
Galantamine: a randomized, double‐blind, dose comparison in patients with Alzheimer's disease
Authors: Wilkinson D. , Murray J. ,   the Galantamine Research Group
Published: August 2002

Objectives

To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD).

Background

Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD.

Method

A multicentre, randomized, parallel, double‐blind, placebo‐controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild‐to‐moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS‐cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS).

Results

Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS‐cog; the treatment difference was 3 points on the intention‐to‐treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24‐mg/day dose, p < 0.05) and CGIC (36‐mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents.

Conclusion

This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease. Copyright © 2001 John Wiley & Sons, Ltd.
Treatment as usual (TAU) control practices in the PROSPECT Study: managing the interaction and tension between research design and ethics
Authors: Reynolds Charles F. , Degenholtz Howard , Parker Lisa S. , Schulberg H. C. , Mulsant Benoit H. , Post Edward , Rollman Bruce ,   the PROSPECT Study Group
Published: August 2002

The use of treatment as usual (TAU) as a control condition may pose the considerable challenge of maintaining both scientific rigor and meeting high ethical standards in experiments on human subjects. The authors illustrate the tension and explore the relationship between research design and ethics, especially the interaction between the two, in the NIMH‐funded PROSPECT study (Prevention of Suicide in Primary Care Elderly – Collaborative Trial). The goal of PROSPECT is to determine whether placement of a depression health specialist in primary care practices will have a favorable impact on rates of depression, hopelessness and suicidal ideation in elderly primary care patients with major or persistent minor depression. PROSPECT randomly assigns practices either to an intervention arm (which includes the provision of depression health specialists) or to an enhanced care arm (TAU, with the addition of screening and assessment services). TAU, enhanced by the provision of screening and assessment services, is to be used as a benchmark for measuring the effectiveness of PROSPECT's intervention. However, TAU in the epidemiological and clinical literature has also been linked to high rates of suicide in the elderly related to unrecognized and untreated or under‐treated depression. The authors present their approach to managing the tension, or interaction, between the use of TAU for scientific and public health purposes and the requirement for beneficence, that is, the duty to assure the safety of human subjects in research and to do no harm. Through enhancements of TAU, by the provision of information to primary care physicians concerning the psychiatric status of their patients, the investigators attempt to meet the challenge of maintaining rigor and meeting high ethical standards. Copyright © 2001 John Wiley & Sons, Ltd.
Access to a community aged psychiatry service by elderly from non‐English‐speaking backgrounds
Authors: Hassett Anne , George Kuruvilla
Published: August 2002

Objective

With the ageing of Australia's ethnic communities, aged mental health services need to examine issues pertaining to accessibility and appropriateness in the context of this sociodemographic change. The aim of this review of referrals to a community aged‐psychiatry service was to compare for differences between patients from non‐English‐speaking backgrounds (NESB) and English‐speaking backgrounds (ESB).

Method

Sociodemographic and clinical variables were retrospectively collated for a 12‐month period and analysed according to NESB and ESB status. The 1996 Australian Census data were used for comparison of catchment area representation of different ethnic groups.

Results

40.8% of patients referred to the service were from NESB, and 78.8% of these were assessed with an interpreter. Taken as broad ethnic groups, the referral of elderly European migrants was similar to their representation in the local population, while elderly migrants from Asia and other non‐European backgrounds were under‐represented. Sociodemographic differences were found in that the elderly from NESB were more likely to be poorly educated, have a low proficiency in English, and to have been employed in unskilled occupations. On the other hand, patterns of referral, diagnosis, past psychiatric history and outcome did not differ significantly between the two groups. Clinical variables relating to referral source, past psychiatric history, and outcome did not differ significantly across the two groups.

Conclusions

This 12‐month review of referrals to an aged psychiatry community service found that nearly half were of elderly patients from NESB. The lower utilisation of the service by certain ethnic groups may reflect obstacles in their pathway to care. Alternatively, strong family networks, or a lower prevalence of mental illness in these elderly, may explain the findings in this report. Copyright © 2002 John Wiley & Sons, Ltd.
Spatial‐temporal structures of human alpha rhythms: Theory, microcurrent sources, multiscale measurements, and global binding of local networks
Authors: Nunez Paul L. , Wingeier Brett M. , Silberstein Richard B.
Published: August 2002

A theoretical framework supporting experimental measures of dynamic properties of human EEG is proposed with emphasis on distinct alpha rhythms. Robust relationships between measured dynamics and cognitive or behavioral conditions are reviewed, and proposed physiological bases for EEG at cellular levels are considered. Classical EEG data are interpreted in the context of a conceptual framework that distinguishes between locally and globally dominated dynamic processes, as estimated with coherence or other measures of phase synchronization. Macroscopic (scalp) potentials generated by cortical current sources are described at three spatial scales, taking advantage of the columnar structure of neocortex. New EEG data demonstrate that both globally coherent and locally dominated behavior can occur within the alpha band, depending on narrow band frequency, spatial measurement scale, and brain state. Quasi‐stable alpha phase structures consistent with global standing waves are observed. At the same time, alpha and theta phase locking between cortical regions during mental calculations is demonstrated, consistent with neural network formation. The brain‐binding problem is considered in the context of EEG dynamic behavior that generally exhibits both of these local and global aspects. But specific experimental designs and data analysis methods may severely bias physiological interpretations in either local or global directions. Hum. Brain Mapping 13:125–164, 2001. © 2001 Wiley‐Liss, Inc.
The impact of non‐compliance on the cost‐effectiveness of pharmaceuticals: a review of the literature
Authors: Hughes Dyfrig A. , Bagust Adrian , Haycox Alan , Walley Tom
Published: August 2002

Non‐compliance with drug therapies not only limits their effectiveness, but in some instances, is associated with grave clinical sequelae and substantial economic burden. It is important, therefore, to consider non‐compliance in economic evaluations. A review of pharmacoeconomic evaluations, which have applied sensitivity analysis to non‐compliance rates, was undertaken to evaluate the impact of non‐compliance on the cost‐effectiveness of different drug therapies. Although 22 evaluations satisfied the inclusion criteria, additional information was obtained from the authors of most studies, as the published details were inadequate. The majority of evaluations assumed altered effectiveness owing to reduced compliance in the absence of supportive clinical evidence. Because of the disparity in the nature of the outcomes, the measures of non‐compliance and the time horizon of the studies evaluated, it was not possible to compare the magnitude of the impact of non‐compliance among different drug–disease combinations. However, it was evident that non‐compliance always results in a reduction in efficacy, but its impact on costs varied substantially. The importance of incorporating measures of compliance is highlighted, as failing to account for ‘real world’ compliance rates in pharmacoeconomic evaluations may lead to selection of sub‐optimal treatment strategies. Copyright © 2001 John Wiley & Sons, Ltd.
Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma
Authors: Brown James S. , Lowe Derek , Kalavrezos Nicholas , D'Souza Jacob , Magennis Patrick , Woolgar Julia
Published: August 2002

Background

An understanding of the patterns, spread, and routes of tumor invasion of the mandible is essential in deciding the appropriate level and extent of mandibular resection in oral squamous cell carcinoma.

Methods

A prospective study of histologic patterns of tumor invasion and routes of tumor entry into the mandible was performed in a consecutive series of 100 previously untreated patients.

Results

The pattern of tumor invasion of the mandible depended on the depth of invasion both in the hard (p = .001) and soft tissues (p = .001). There was evidence that the pattern of invasion was related to histologic prognostic indicators of the disease, such as extracapsular spread from invaded lymph nodes (p = .03). The route of tumor entry was at the point of abutment to the mandible (direct) in all 13 cases, invading the dentate part of the mandible. Fifty‐five percent (23 of 42) of tumors invading the edentulous ridge entered through the occlusal (superior) surface. Direct entry to the mandible in the edentulous ridge was more likely for tumors arising in the tongue, floor of the mouth and the buccal mucosa compared with alveolar or retromolar sites (p = .003)

Conclusions

Larger or more deeply invading tumors in the soft tissue are more likely to invade the mandible and show the more aggressive (invasive) form of tumor spread, reducing the options of a more conservative (rim) resection. Tumors tend to enter the mandible at the point of abutment, which in both the dentate and edentulous jaw is often at the junction of the reflected and attached mucosa. A point of tumor entry below the occlusal ridge or gingival crest should be assumed when planning rim or marginal resections of the mandible. © 2002 Wiley Periodicals, Inc. Head Neck 24: 370–383, 2002; DOI 10.1002/hed.10062