bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences of depressive symptoms in depressed and nondepressed elderly persons
Authors: Kockler M. , Heun R.
Published: October 2002

Objectives

Women suffer more frequently from major depression and depressive symptoms than men. The somatic and the atypical subtype of depression seem to be more prevalent in women. However, few studies investigated gender differences of depressive symptoms in the elderly. These gender differences in the elderly will be investigated in the present study.

Methods

In the course of a family study 236 subjects with a lifetime diagnosis of major depression aged > 50 years and 357 control subjects from the general population matched for age and gender were questioned using the Composite International Diagnostic Interview (CIDI). Chi‐square tests were used to compare the individual depressive symptoms between men and women and logistic regression analyses were performed to account for the subjects' age, cognitive performance, family and employment status.

Results

Women in the general population suffered from more depressive symptoms than men and had more appetite disturbance and joylessness. These gender differences could be entirely explained by gender differences in the family and the employment status. Men and women with a major depressive disorder presented with a distinct profile of symptoms that could not be explained by psychosocial factors: elderly depressed women presented with more appetite disturbances and elderly depressed men with more agitation.

Conclusion

Major depression in the elderly presents with partially different symptoms in men and women. The results suggest that the gender differences in the symptoms of major depression in the elderly reflect gender differences in the perception and the expression of depressive syndromes. Copyright © 2002 John Wiley & Sons, Ltd.
Cognitive and motor impairments predict functional declines in patients with vascular dementia
Authors: Boyle Patricia A. , Cohen Ronald A. , Paul Robert , Moser David , Gordon Norman
Published: October 2002

Background

Vascular dementia (VaD) is associated with impairments in cognitive, motor, and functional domains. Patients with VaD display diverse cognitive and motor deficits, however, and relationships between these impairments and independent living abilities remain unclear.

Objectives

The purpose of the present study was to investigate the contributions made by attentional/executive and motor functions in the prediction of basic and instrumental activities of daily living in 32 patients with VaD. We hypothesized that: (a) motor abilities would emerge as a significant predictor of basic activities of daily living, whereas attentional/executive abilities would not, and (b) both motor and attentional/executive abilities would emerge as significant predictors of instrumental activities of daily living.

Results

Stepwise regression analyses revealed that motor performance, but not attentional/executive abilities, accounted for a significant proportion of the variance in basic activities of daily living, and that both motor and attentional/executive abilities contributed significantly to the prediction of instrumental activities of daily living.

Conclusions

These results suggest that attentional/executive and motor impairments may underlie specific aspects of functional disability among patients with VaD. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐neurological factors are implicated in impairments in gait and mobility among patients in a clinical dementia referral population
Authors: Thomas Vince Salazar , Vandenberg Edward V. , Potter Jane F.
Published: October 2002

Although gait abnormalities have been previously noted in dementia, their non‐neurological correlates have not been examined. We used data on 900 consecutive outpatients assessed from 1994 to 1999 in the University of Nebraska Geriatric Assessment Clinic Data Base (UN‐GAC) to examine the prevalence of gait disorders and the relationship of gait disorders to physical illness in Alzheimer's disease (AD) and non‐AD dementia. Gait disorders were very prevalent at each level of cognitive function [58.7% for CDR = 0, 68.0% for CDR = 0.5, 57.9% for CDR = 1, 68.1% for CDR = 2 and 76.9% for CDR = 3, p = 0.02] and were more frequently observed in AD patients with poorer cognitive function. Among all demented patients, 45.0% of those without gait impairment were ADL independent compared to 11.8% of those with gait impairment. In adjusted logistic regression models, the presence of a gait disorder among AD patients was significantly associated with older age (Odds Ratio (OR) = 1.09, 95% Confidence Intervals (CI) = 1.04–1.15), special sensory (2.19, 1.17–4.12), and lower GI (3.57, 1.97–6.47) dysfunction. The prevalence of gait disorders is high in even mildly demented persons and associated with common and often treatable organ system dysfunction. Because gait disorders are also associated with a high prevalence of ambulatory disability, attention to co morbid illnesses implicated in gait impairment may reduce the burden of disability in this population. Copyright © 2002 John Wiley & Sons, Ltd.
The Mini‐Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer's disease
Authors: Ala Thomas A. , Hughes Larry F. , Kyrouac Gregory A. , Ghobrial Mona W. , Elble Rodger J.
Published: October 2002

Objective

Since patients with dementia with Lewy bodies (DLB) tend to have greater impairment of attention and construction and better memory ability on neuropsychological tests than patients with Alzheimer's disease (AD), we determined if the items that measure attention, memory, and construction in the Mini‐Mental State Examination (MMSE) help to distinguish DLB from AD early in the course of the dementia.

Design

We retrospectively studied the first available MMSE exam for each of our patients with DLB or AD and compared their MMSE subscores for attention, memory, and construction.

Setting

A university dementia brain bank in central Illinois, USA.

Patients

All patients with neuropathologically‐proven DLB or AD with MMSE scores≥13.

Results

We identified 17 DLB and 27 AD patients for whom we had MMSE exams. The attention and construction subtest scores of the DLB group were worse (p=0.0071 and p=0.0038, respectively) than those of the AD group. The memory subscores of the DLB group were better, although the difference did not reach statistical significance (p=0.22). When a mathematical equation was used to combine the three subscores with equal weighting ($Attention-{5\over 3}\;Memory+5\cdot Construction$), the scores of the DLB group were worse (p=0.00007). Using this equation, a score less than 5 points was associated with DLB with a sensitivity of 0.82 (95% Confidence Interval (CI)=0.57–0.96) and a specificity of 0.81 (95% CI=0.62–0.94).

Conclusions

Our findings support the work of others regarding the relative neuropsychological impairments of DLB and AD and indicate that the MMSE may be helpful in the differentiation of DLB and AD. Copyright © 2002 John Wiley & Sons, Ltd.
What are patients and their families told about the diagnosis of dementia? Results of a family survey
Authors: Holroyd Suzanne , Turnbull Quentin , Wolf Andrew M.
Published: October 2002

Background

Controversy exists as to whether dementia patients should be told their diagnosis and prognosis.

Objective

This study examined the experience of patients and families when a diagnosis of dementia is given.

Method

Fifty‐seven family members from community dementia support groups answered a questionnaire regarding the diagnosis of dementia in a family member.

Results

Family members were significantly more likely to have been told the diagnosis and symptoms to expect in dementia than patients themselves. Half of the families felt they were not given enough information regarding dementia. Interestingly, the majority of family members believed patients should be told their diagnosis and prognosis yet about half had reported that informed patients had reacted poorly to being told their diagnosis and only about a third felt it was helpful to the patient.

Conclusion

The results suggest physicians should better involve patients and their families in disclosing diagnoses and information regarding dementia. The results also suggest the current AMA guidelines to inform patients their diagnosis of dementia are inadequate to address the clinical complexities of this issue. Copyright © 2002 John Wiley & Sons, Ltd.
A pilot, randomized, open‐label trial assessing safety and pharmakokinetic parameters of co‐administration of rivastigmine with risperidone in dementia patients with behavioral disturbances
Authors: Weiser Mark , Rotmensch Heschi H. , Korczyn Amos D. , Hartman Richard , Cicin‐Sain Ana , Anand Ravi
Published: October 2002

Background

The majority of patients with Alzheimer's disease (AD) or vascular dementia display, in addition to cognitive impairment, various degrees of behavioral disturbances. As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread, many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti‐psychotic drugs to ameliorate behavioral disturbances. Despite the widespread use of this combination in clinical practice, the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials. This pilot study examined the effects of addition of risperidone 0.5–2 mg/day to patients on rivastigmine 3–12 mg/day, and vice versa.

Methods

65 patients suffering from AD, 10 from vascular dementia, and 15 from both were randomized to open label rivastigmine and risperidone, alone or in combination, for 20 weeks. Adverse events caused by co‐administration were assessed.

Results

No clinically relevant adverse interactions were observed.

Conclusions

These preliminary results indicate that rivastigmine and risperidone can be safely co‐administered. Confirmation of these results in large clinical trials studies is warranted. Copyright © 2002 John Wiley & Sons, Ltd.
Decreased cutaneous vasodilatation to isometric handgrip exercise in Alzheimer's disease
Authors: Kálmán János , Szakács Réka , Török Tamás , Rózsa Zsuzsa , Barzó Pál , Rudas László , Papp J. Gy. , Janka Zoltán
Published: October 2002

Background

Cutaneous active vasodilatation is a cholinergic nerve mediated function of the sympathetic nervous system and the disturbed function of cholinergic neurotransmission is known as a prominent feature of Alzheimer's disease (AD).

Methods

To assess this relationship, skin blood flow (SkBF) and other haemodynamic parameters were determined by a simple vasodilatory test, isometric handgrip exercise (IHG), in 22 late‐onset sporadic type AD and 20 aged control persons (AC).

Results

Significantly higher cutaneous vascular resistance and decreased SkBF were found after the stimulus in the AD group. A smaller reduction (p < 0.03) of R wave intervals on the electrocardiogram was observed in the AD group compared to the AC one. After IHG, change in systolic blood pressure was less in the AD (p < 0.01) than in the AC group.

Conclusion

Our results suggest that autonomic dysfunction affecting active vasodilator sympathetic, as well as parasympathetic functions is present in AD. Copyright © 2002 John Wiley & Sons, Ltd.
Burnout and stress amongst old age psychiatrists
Authors: Benbow Susan M. , Jolley David J.
Published: October 2002

Objective

To investigate the relationship between work patterns, burnout and stress in consultant old age psychiatrists.

Methods

We sent a postal survey to all old age psychiatrists on the Faculty of Old Age Psychiatry, Royal College of Psychiatrists, list. Participants completed a workload questionnaire, the Stress Checklist and the Maslach Burnout Inventory during a specified week.

Results

Burnout scores were unaffected by gender and team working, but old age psychiatrists scoring within the high burnout range were younger, scored highly on stress, spent less time on research, study and audit, and more time travelling. The whole group scored highly on emotional exhaustion.

Conclusions

Job plans should encourage research/study and audit, and cut down travelling. The finding related to age is not fully understood, but suggests consideration of support groups for new consultants and review of whether current training programmes adequately prepare people for work as a consultant. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐invasive assessment of language lateralization by transcranial near infrared optical topography and functional MRI
Authors: Kennan Richard P. , Kim David , Maki Atsushi , Koizumi Hideaki , Constable R. Todd
Published: October 2002

Near infrared optical topography (OT) is the simultaneous acquisition of hemoglobin absorption from an array of optical fibers on the scalp to construct maps of cortical activity. We demonstrate that OT can be used to determine lateralization of prefrontal areas to a language task that has been validated by functional MRI (fMRI). Studies were performed on six subjects using a visually presented language task. Laterality was quantified by the relative number of activated pixels in each hemisphere for fMRI, and the total hemoglobin responses in each hemisphere for OT. All subjects showed varying degrees of left hemisphere language dominance and the mean laterality indices for subjects who underwent both OT and fMRI were in good agreement. These studies demonstrate that OT gives predictions of hemispheric dominance that are consistent with fMRI. Due to the ease of use and portable nature of OT, it is anticipated that optical topography will be valuable tool for neurological examinations of cognitive function. Hum. Brain Mapping 16:183–189, 2002. © 2002 Wiley‐Liss, Inc.
Assessment of spatial normalization of whole‐brain magnetic resonance images in children
Authors: Wilke Marko , Schmithorst Vincent J. , Holland Scott K.
Published: October 2002

Commonly used frameworks for spatial normalization of brain imaging data (e.g., Talairach‐space) are based on one or more adult brains. As pediatric brains are different in size and shape from adult brains and continue to develop through childhood, we aimed to assess the influence of age on various spatial normalization parameters. One hundred forty‐eight healthy children aged 5–18 years were included in this study. The linear scaling parameters and the deformations from the non‐linear spatial normalization to both a standard adult and a custom pediatric template were analyzed within SPM99. The effect of using a brain mask on the linear and of using different levels of constraint on the non‐linear spatial normalization was assessed. Of the linear scaling factors, only the X‐dimension (left–right) showed a significant age‐correlation when based on brain tissue, whereas the overall scaling was not correlated with age. When based on the whole head, a very strong age‐effect can be found in all dimensions. Non‐linear deformations also show localized correlations with age, most pronounced in parietal and frontal areas. The total amount of volume change is significantly lower when using a pediatric template. It is also substantially influenced by the degree of regularization that is exerted on the spatial normalization parameters. Our results suggest that in the cortical areas showing a strong correlation of deformation with age, caution should be used in assigning imaging results in children to a specific morphological structure. Also, to minimize the amount of deformation during non‐linear spatial normalization, a pediatric template should be used. Further implications of our findings on developmental neuroimaging studies are discussed. Hum. Brain Mapping 17:48–60, 2002. © 2002 Wiley‐Liss, Inc.
Primary neck management among patients with cancer of the oral cavity without clinical nodal metastases: A decision and sensitivity analysis
Authors: Kaneko Satoshi , Yoshimura Takesumi , Ikemura Kunio , Shirasuna Kanemitsu , Kusukawa Jingo , Ohishi Masamichi , Shiba Ryosuke , Sunakawa Hajime , Tominaga Kazuhiro , Sugihara Kazumasa , Shinohara Masanori , Katsuki Takeshi , Yanagisawa Shigetaka , Kurokawa Hideo , Mimura Tamotsu , Ikeda Hisazumi , Yamabe Shigeru , Ozeki Satoru
Published: October 2002

Background

A standardized neck management strategy for oral cancer patients without clinical nodal metastases remains to be established. Consequently, a decision and sensitivity analysis of two neck management protocols, involving either prophylactic neck dissection or careful observation, was conducted using the Oral Cancer Registry of Kyushu, Japan.

Methods

We calculated probabilities of subclinical nodal metastases and 5‐year survival using the registry data. A two‐way sensitive analysis was conducted using the probabilities and parameters of the complete nodal metastasis resection rate (x) and a utility rating that describes the health state induced by dissection (y) compared with the neck condition in a careful‐observation group.

Results

We solved the threshold curve for y and x for the expected utility between the two groups. The results showed that prophylactic neck dissection must guarantee a complete resection of subclinical nodal metastases with no disadvantage to health state to be evaluated as equally satisfactory as careful observation.

Conclusions

Careful observation involving standardized systematic preoperative and postoperative screening of the neck seems preferable to prophylactic neck dissection for oral cancer patients without subclinical nodal metastases. © 2002 Wiley Periodicals, Inc. Head Neck 24: 582–590, 2002
Computer aided tools of ergonomics and system design
Authors: Bubb Heiner
Published: October 2002

Anthropometric digital human models are well established and used in order to get a better design of human‐adapted machines. By the application of electronics and computer operated machines, nearly arbitrary design of controlling and operating the technical equipment seems possible. So more and more the question arises: What is operable by the human operator and what leads probably to a disaster due to much stress. By applying systems ergonomic rules, this can be avoided to a far extent. In order to consider these rules already in an early state of development, it seems useful to incorporate such rules in digital human models. By this procedure, cognitive human models will be created. The combination of such models with anthropometric digital human models will lead to the possibility to carry out virtual experiments under the condition of computer aided design. So, in the future, more ergonomic knowledge will be considered by this new technique. © 2002 Wiley Periodicals, Inc.
BDNF–triggered events in the rat hippocampus are required for both short‐ and long‐term memory formation
Authors: Alonso Mariana , Vianna Monica R.M. , Depino Amaicha M. , Mello e Souza Tadeu , Pereira Patricia , Szapiro German , Viola Haydee , Pitossi Fernando , Izquierdo Ivan , Medina Jorge H.
Published: October 2002

Information storage in the brain is a temporally graded process involving different memory types or phases. It has been assumed for over a century that one or more short‐term memory (STM) processes are involved in processing new information while long‐term memory (LTM) is being formed. Because brain‐derived neutrophic factor (BDNF) modulates both short‐term synaptic function and activity‐dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM formation of a hippocampal‐dependent one‐trial fear‐motivated learning task in rats. Using a competitive RT‐PCR quantitation method, we found that inhibitory avoidance training is associated with a rapid and transient increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of function‐blocking anti‐BDNF antibody into the CA1 region of the dorsal hippocampus decreased extracellular signal–regulated kinase 2 (ERK2) activation and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 activation and facilitated STM. The infusion of anti‐BDNF antibody impaired LTM when given 15 min before or 1 and 4 hr after training, but not at 0 or 6 hr posttraining, indicating that two hippocampal BDNF‐sensitive time windows are critical for LTM formation. At the same time points, PD098059 produced no LTM deficits. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of an inhibitory avoidance learning. Additionally, they suggest that this requirement involves ERK1/2‐dependent and ‐independent mechanisms. Hippocampus 2002;12:551–560. © 2002 Wiley‐Liss, Inc.
Acute, dose‐dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: differential interactions with cognitive demand
Authors: Scholey Andrew B. , Kennedy David O.
Published: October 2002

The present paper describes three studies examining the acute effects of single doses of Ginkgo biloba (GK501), Ginseng (G115) and their combination (Ginkoba M/E, Pharmaton SA) on the performance of healthy young adults (mean age 21 years) during serial arithmetic tasks with differing cognitive load. In each double‐blind, placebo‐controlled study three different treatment doses and a placebo were administered, according to a balanced crossover design, with a 7‐day washout period between each dose. Participants' scores on two computerised serial subtraction tasks (Serial Threes and Serial Sevens) were assessed pre‐dosing and at 1, 2.5, 4 and 6 h thereafter.

A number of significant time, dose and task‐specific effects were associated with each treatment. There was a dose‐dependent improvement in speed of responding during Serial Threes following Ginkgo biloba. Different doses of Ginseng improved accuracy and slowed responses during Serial Sevens. The most striking result, however, was a highly significant and sustained increase in the number of Serial Sevens responses following 320 mg of the Ginkgo–Ginseng combination at all post‐treatment testing times. This was accompanied by improved accuracy during Serial Sevens and Serial Threes following the 640 mg and the 960 mg dose, respectively. The paper concludes with speculation into the possible mechanisms underlying these effects. Copyright © 2002 John Wiley & Sons, Ltd.
Epilepsy, psychosis and clozapine
Authors: Langosch J. M. , Trimble M. R.
Published: October 2002

Six patients with epilepsy and severe psychosis were treated with the atypical antipsychotic clozapine. The use of clozapine might be complicated in epileptic patients because of an increased risk of seizures. However, none of the reported patients had an increase of their seizure frequency, in contrast, three patients had a substantial reduction of seizures. One patient had a reduction of non‐epileptic seizures as well. In the second part of this paper, combinations of clozapine with newer and older anticonvulsants as well as their interactions and associated risks are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Sulphide oxidation under partially anoxic conditions at the bed of the Haut Glacier d'Arolla, Switzerland
Authors: Bottrell Simon H. , Tranter Martyn
Published: October 2002

Oxygen isotopic data are presented for bulk glacial meltwaters draining the Haut Glacier d'Arolla, Valais, Switzerland and for the sulphate contained within them in an attempt to assess the redox status of the subglacial chemical weathering environment. The sulphate derived from subglacial chemical weathering is so depleted in 18O that it must have formed, at least partially, in an anoxic environment. Under these conditions, Fe3+ can act as an oxidizing agent and oxygen atoms incorporated into sulphate are derived from 18O‐depleted water molecules (by contrast, dissolved O2 is strongly enriched in 18O). These data therefore support the hypothesis that sectors of the glacier bed are anoxic and that Fe3+ may act as a significant oxidizing agent under these conditions. Copyright © 2002 John Wiley & Sons, Ltd.
Downscaling of global climate models for flood frequency analysis: where are we now?
Authors: Prudhomme Christel , Reynard Nick , Crooks Sue
Published: October 2002

The issues of downscaling the results from global climate models (GCMs) to a scale relevant for hydrological impact studies are examined. GCM outputs, typically at a spatial resolution of around 3° latitude and 4° longitude, are currently not considered reliable at time scales shorter than 1 month. Continuous rainfall‐runoff modelling for flood regime assessment requires input at the daily or even hourly time‐step. A review of the different methodologies suggested in the literature to downscale GCM results at smaller spatial and temporal resolutions is presented. The methods, from simple interpolation to more sophisticated dynamical modelling, through multiple regression and weather generators, are, however, mostly based directly on GCM outputs, sometimes at daily time‐step. The approach adopted is a simple, empirical methodology based on modelled monthly changes from the HadCM2 greenhouse gases experiment for the time horizon 2050s. Three daily rainfall scenarios are derived from the same set of monthly changes, representing different possible changes in the rainfall regime. The first scenario represents an increase of the occurrence of frontal systems, corresponding to a decrease in the rainfall intensity; the second corresponds to an increase in convective storm‐type rainfall, characterized by extreme events with higher intensity; the third one assumes an increase in the monthly rainfall without any change in rainfall variability. A continuous daily rainfall‐runoff model, calibrated for the Severn catchment, was used to generate daily flow series for the 1961–90 baseline period and the 2050s, and a peaks‐over‐threshold analysis was undertaken to produce flood frequency distributions for the two time horizons. Though the three scenarios lead to an increase in the magnitude and the frequency of the extreme flood events, the impact is strongly influenced by the type of daily rainfall scenario applied. We conclude that if the next generation of GCMs produce more reliable rainfall variance estimates, then more appropriate ways of deriving rainfall scenarios could be developed using weather generators rather than empirical methods. Copyright © 2002 John Wiley & Sons, Ltd.
An evaluation of a traditional and a neural net modelling approach to flood forecasting for an upland catchment
Authors: Cameron David , Kneale Pauline , See Linda
Published: October 2002

This study evaluates two (of the many) modelling approaches to flood forecasting for an upland catchment (the River South Tyne at Haydon Bridge, England). The first modelling approach utilizes ‘traditional’ hydrological models. It consists of a rainfall–runoff model (the probability distributed model, or PDM) for flow simulation in the upper catchment. Those flows are then routed to the lower catchment using two kinematic wave (KW) routing models. When run in forecast‐mode, the PDM and KW models utilize model updating procedures. The second modelling approach uses neural network models, which use a ‘pattern‐matching’ process to produce model forecasts.Following calibration, the models are evaluated in terms of their fit to continuous stage data and flood event magnitudes and timings within a validation period. Forecast times of 1 h, 2 h and 4 h are selected (the catchment has a response time of approximately 4 h). The ‘traditional’ models generally perform adequately at all three forecast times. The neural networks produce reasonable forecasts of small‐ to medium‐sized flood events but have difficulty in forecasting the magnitude of the larger flood events in the validation period. Possible modifications to the latter approach are discussed. © Crown copyright 2002. Reproduced with the permission of Her Majesty's stationery office. Published by John Wiley & Sons, Ltd.
Impact of urbanization on suspended sediment and organic matter fluxes from small catchments in Tahiti
Authors: Wotling G. , Bouvier Ch.
Published: October 2002

This study provides an initial characterization of pollution associated with storm runoff in Tahiti. A thousand floodwater samples were collected from three representative catchments and subsequently analysed. The main pollution parameters chosen were total suspended sediment (TSS), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), total nitrogen (TN) and Total Phosphorus (TP). First, organic pollution appeared to be related closely to sediment, thus TSS could be used as a global indicator. Next, regression models between an event's TSS load and its hydrological characteristics were used to obtain annual load estimates. Great interannual variability was found to be strongly influenced by the few major floods that occur during the rainy season. Our results also emphasize the importance of the impact of urbanization on solid catchment exportation: from 60 TSS t/km2/year in a natural forested catchment, fluxes reached more than 700 TSS t/km2/year during preparatory urbanization earthworks before stabilizing at 140 TSS t/km2/year in a consolidated urbanized area. Clearly, runoff effects need to be taken into consideration for effective urban planning and for the preservation of the coastal environment in Tahiti. Copyright © 2002 John Wiley & Sons, Ltd.
Assessing the uncertainty in distributed model predictions using observed binary pattern information within GLUE
Authors: Aronica G. , Bates P. D. , Horritt M. S.
Published: October 2002

In this paper we extend the generalized likelihood uncertainty estimation (GLUE) technique to estimate spatially distributed uncertainty in models conditioned against binary pattern data contained in flood inundation maps. Untransformed binary pattern data already have been used within GLUE to estimate domain‐averaged (zero‐dimensional) likelihoods, yet the pattern information embedded within such sources has not been used to estimate distributed uncertainty. Where pattern information has been used to map distributed uncertainty it has been transformed into a continuous function prior to use, which may introduce additional errors. To solve this problem we use here ‘raw’ binary pattern data to define a zero‐dimensional global performance measure for each simulation in a Monte Carlo ensemble. Thereafter, for each pixel of the distributed model we evaluate the probability that this pixel was inundated. This probability is then weighted by the measure of global model performance, thus taking into account how well a given parameter set performs overall. The result is a distributed uncertainty measure mapped over real space. The advantage of the approach is that it both captures distributed uncertainty and contains information on global likelihood that can be used to condition predictions of further events for which observed data are not available. The technique is applied to the problem of flood inundation prediction at two test sites representing different hydrodynamic conditions. In both cases, the method reveals the spatial structure in simulation uncertainty and simultaneously enables mapping of flood probability predicted by the model. Spatially distributed uncertainty analysis is shown to contain information over and above that available from global performance measures. Overall, the paper highlights the different types of information that may be obtained from mappings of model uncertainty over real and n‐dimensional parameter spaces. Copyright © 2002 John Wiley & Sons, Ltd.
The zone of vegetation influence on baseflow revealed by diel patterns of streamflow and vegetation water use in a headwater basin
Authors: Bond Barbara J. , Jones Julia A. , Moore Georgianne , Phillips Nathan , Post David , McDonnell Jeffrey J.
Published: October 2002

Water use by vegetation can be closely linked to streamflow patterns on a variety of time scales. However, many of the details of these linkages are poorly understood. We compared diel (24 h) patterns of transpirational water use with streamflow patterns in a small headwater basin that displays a marked diel variation during summer months. The study site was in western Oregon. Our objectives were to: (1) determine the phase shift, i.e. the time lag between maximum transpiration and minimum streamflow, and the strength of the correlation at that time lag; (2) determine the amount of streamflow that is ‘missing’ during each diel cycle (i.e. the difference between base flow, defined by the daily maxima, and actual flow) and use it to estimate the zone, or area, of vegetation that influences daily streamflow patterns; (3) test and refine a conceptual model of how the coupling between vegetation water use and streamflow changes over the period of summer drought in this basin. We found that vegetation water use in the summer is coupled to streamflow over time scales of 4 to 8 h, and water‐use‐related fluctuations accounted for 1 to 6% of summer base flow. Direct evaporation from the channel was an order of magnitude less than the diel streamflow decrease. Transpiration within only 0·1 to 0·3% of the basin area accounted for the diel variation in streamflow. As the basin drained further through the summer, the coupling between vegetation and streamflow was diminished and occurred at longer time scales, and the zone of vegetation influence became smaller. This pattern is in accordance with our conceptual model, which attributes the summer decline in the strength of the vegetation–streamflow coupling to the increasing depth of plant‐available water in the soil profile. Although this study is preliminary, we believe it is an important first step in describing better the coupling of vegetation water use to streamflow. Copyright © 2002 John Wiley & Sons, Ltd.
Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S‐transferase placental form positive foci: A possible reactive oxygen species mechanism
Authors: Nishikawa Takayuki , Wanibuchi Hideki , Ogawa Motome , Kinoshita Anna , Morimura Keiichirou , Hiroi Toyoko , Funae Yoshihiko , Kishida Hideki , Nakae Dai , Fukushima Shoji
Published: October 2002

Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals. The present study was conducted to determine the promoting effects of organic arsenicals related to DMA [monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO)] on rat liver carcinogenesis using a liver medium‐term bioassay (the Ito test). Male, 10‐week‐old, F344 rats were given a single i.p. injection of diethylnitrosamine at a dose of 200 mg/kg b.w. as an initiator. Starting 2 weeks thereafter they received 100 ppm of MMA, DMA or TMAO in their drinking water, or no supplement as a control, for 6 weeks. All animals underwent 2/3 partial hepatectomy in week 3 after initiation. Quantification of glutathione S‐transferase placental form (GST‐P)‐positive foci as preneoplastic lesions in liver sections revealed significantly increased numbers and areas in all 3 treated groups compared with controls. Hepatic microsome cytochrome P‐450 content was markedly increased with all 3 arsenic treatments. Markedly elevated CYP 2B1 protein levels and CYP 2B1/2 mRNA levels were thus observed in all cases. The potency of promotion was similar for MMA, DMA and TMAO. Since hydroxyradicals were found to be generated in the relatively early phase while methylated arsenicals were metabolized in liver, the resultant oxidative stress might have promoted lesion development. © 2002 Wiley‐Liss, Inc.
Serum levels of angiogenin, basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia
Authors: Glenjen Nils , Mosevoll Knut Anders , Bruserud Øystein
Published: October 2002

Angiogenesis seems to be important both in the pathogenesis of acute myelogenous leukemia (AML) and for the susceptibility of AML blasts to chemotherapy. Recent clinical studies even suggest that antiangiogenic therapy can induce disease control in patients with AML relapse. In this context we have investigated the profile of the systemic component of angiogenic regulation in AML by characterizing the serum levels of (i) the angiogenic regulators angiogenin, basic fibroblast growth factor (bFGF) and endostatin; (ii) the endothelial cell marker soluble (s) E‐selectin. Patients with untreated AML had increased levels of angiogenin, endostatin and sE‐selectin, whereas the levels of bFGF were not significantly altered. The systemic levels of the proangiogenic bFGF, the antiangiogenic endostatin and the endothelial cell marker sE‐selectin showed significant correlations, whereas angiogenin and sE‐selectin levels were not correlated. Furthermore, intensive chemotherapy resulted in decreased systemic levels of the 2 proangiogenic mediators angiogenin and bFGF, whereas endostatin levels remained high after treatment. Although angiogenin normally is a part of the acute phase reaction, its systemic levels were not altered when patients with chemotherapy‐induced cytopenia developed complicating bacterial infections. Our results suggest that intensive chemotherapy can modulate the systemic component of angiogenic regulation in AML patients. © 2002 Wiley‐Liss, Inc.
Characterization of a novel calcium phosphate/sulphate bone cement
Authors: Nilsson M. , Fernández E. , Sarda S. , Lidgren L. , Planell J. A.
Published: October 2002

Apatitic cements have shown excellent biocompatibility and adequate mechanical properties but have slow resorption in the human body. To assure that new bone tissue grows into the bone defect, a certain porosity is necessary although hard to achieve in injectable cements with suitable mechanical properties. An attempt was made by mixing alpha‐tricalcium phosphate (α‐TCP), calcium sulphate hemihydrate (CSH) and an aqueous solution containing 2.5 wt% of Na2HPO4. The aim was to obtain a material containing two phases: a) one apatitic phase (calcium‐deficient hydroxyapatite; CDHA) and b) one resorbable phase (calcium sulphate dihydrate; CSD). α‐TCP and CSH mixtures were produced at relative intervals of 20 wt%. The liquid‐to−powder (L/P) ratio to obtain a paste was 0.32 mLg−1. The highest compressive strength (34 MPa) was obtained for the pure α‐TCP sample. The strength was, in a first approximation, directly correlated to the weight proportions of the powders. X‐ray diffraction analysis showed that the relative intensity for CDHA increased linearly, and the one for CSD decreased exponentially, when the amount of α‐TCP increased. Thus, CSH ceased to transform to CSD when the amount of α‐TCP increased. Observations in environmental scanning electron microscopy confirmed the X‐ray diffraction results. CSH‐crystals (100 μm) were embedded in the HA‐matrix permitting gradual porosity in the material when resorbed. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 600–607, 2002
Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells
Authors: Shimizu Emi , Ogata Yorimasa
Published: October 2002

Bone sialoprotein (BSP) is a major noncollagenous protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite. Recent studies have shown that BSP is also expressed by osteotropic cancers suggesting BSP might play a role in the pathogenesis of bone metastases. The present study investigates regulation of BSP transcription in rat osteosarcoma ROS 17/2.8 cells by flavonoids: genistein (an inhibitor of protein tyrosine kinases), daidzein (an inactive compound of genistein), flavone, and flavanone. Genistein, daidzein, and flavone (50 μM) increased steady state levels of BSP mRNA about 1.7‐fold at 12 h. From transient transfection assays using various sized BSP promoter‐luciferase constructs, genistein increased luciferase activities within 12 h. Constructs including the promoter sequence nucleotides (nts) −116 to −43 (pLUC3) were found to enhance transcriptional activity ∼2.6‐fold in ROS 17/2.8 cells treated with genistein (50 μM). Daidzein, flavone, and flavanone (50 μM) also increased luciferase activities. In contrast, the tyrosine kinase inhibitors, herbimycin A and lavendustin A, which do not have a flavonoid structure, did not stimulate BSP transcription. Transcriptional stimulation by genistein was almost completely abrogated in a construct that included 2 bp mutations in the inverted CCAAT box. A monoclonal antibody against NF‐YA, a CCAAT box‐binding transcription factor, inhibited formation of DNA‐NF‐Y protein complex in gel shift assays formed by nuclear extracts of ROS 17/2.8 cells. These data suggest that the inverted CCAAT box is required for flavonoid‐induced BSP expression and that the stimulatory action is dependent on the flavone structure and does not involve an inhibitory action on protein tyrosine kinase. J. Cell. Biochem. 86: 35–44, 2002. © 2002 Wiley‐Liss, Inc.
Regulation of Her2/neu promoter activity by the ETS transcription factor, ER81
Authors: Bosc Denis G. , Janknecht Ralf
Published: October 2002

Overexpression of the HER2/Neu receptor is correlated to a poor prognosis in tumor patients and leads to stimulation of mitogen‐activated protein kinase (MAPK) signaling pathways, which in turn activate transcription factors, such as the ETS protein ER81. Here, we have analyzed whether, on the other hand, ER81 may regulate the Her2/neu gene. Indeed, ER81, together with its co‐activators, p300 and CBP, activates the Her2/neu promoter, and this activation is enhanced upon stimulation of MAPK pathways as well as by oncogenic HER2/Neu protein. Furthermore, ER81 interacts with one ETS binding site in the Her2/neu promoter, whose mutation decreases ER81‐mediated transcription. Activation of the Her2/neu promoter is also diminished upon mutation of MAPK‐dependent phosphorylation sites in ER81 or upon deletion of ER81 transactivation domains. In addition, the ER81 DNA‐binding domain on its own functions as a dominant‐negative molecule, effectively repressing any stimulation of the Her2/neu promoter. Altogether, our results show that ER81 is a component of a positive regulatory feedback loop, in which the HER2/Neu protein activates ER81, as well as p300/CBP via MAPKs causing the upregulation of the Her2/neu gene. J. Cell. Biochem. 86: 174–183, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of a 1,25(OH)2‐vitamin D3‐responsive capacitative Ca2+ entry pathway in rat osteoblast‐like cells
Authors: Baldi Carolina , Vazquez Guillermo , Boland Ricardo
Published: October 2002

We investigated the existence of a capacitative Ca2+ entry (CCE) pathway in ROS 17/2.8 osteoblast‐like cells and its responsiveness to 1,25‐dihydroxy‐vitamin D3 [1,25(OH)2D3]. Depletion of inner Ca2+ stores with thapsigargin or 1,25(OH)2D3 in the absence of extracellular Ca2+ transiently elevated cytosolic Ca2+ ([Ca2+]i); after recovery of basal values, Ca2+ re‐addition to the medium markedly increased Ca2+ entry, reflecting pre‐activation of a CCE pathway. Recovery of the Ca2+ overshoot that followed the induced CCE was mainly mediated by the plasma membrane Ca2+‐ATPase. Addition of 1,25(OH)2D3 to the declining phase of the thapsigargin‐induced CCE did not modify further [Ca2+]i, indicating that steroid activation of CCE was dependent on store depletion. Pre‐treatment with 1 μM Gd3+ inhibited 30% both thapsigargin‐ and 1,25(OH)2D3‐stimulated CCE, whereas 2.5 μM Gd3+ was required for maximal inhibition (∼ 85%). The activated CCE was permeable to both Mn2+ and Sr2+. Mn2+ entry sensitivity to Gd3+ was the same as that of the CCE. However, 1‐μM Gd3+ completely prevented capacitative Sr2+ influx, whereas subsequent Ca2+ re‐addition was reduced only 30%. These results suggest that in ROS 17/2.8 cells CCE induced by thapsigargin or 1,25(OH)2D3 is contributed by at least two cation entry pathways: a Ca2+/Mn2+ permeable route insensitive to very low micromolar (1 μM) Gd3+ accounting for most of the CCE and a minor Ca2+/Sr2+/Mn2+ permeable route highly sensitive to 1 μM Gd3+. The Ca2+‐mobilizing agonist ATP also stimulated CCE resembling the Ca2+/Sr2+/Mn2+ permeable entry activated by 1,25(OH)2D3. The data demonstrates for the first time, the presence of a hormone‐responsive CCE pathway in an osteoblast cell model, raising the possibility that it could be an alternative Ca2+ influx route through which osteotropic agents influence osteoblast Ca2+ homeostasis. © Wiley‐Liss, Inc.
Theoretical study on the mechanism of the 3CH2 + NO2 reaction
Authors: Liu Jian‐Jun , Ding Yi‐Hong , Tao Yu‐Guo , Feng Ji‐Kang , Sun Chia‐Chung
Published: October 2002

The complex doublet potential energy surface of the CH2NO2 system is investigated at the B3LYP/6‐31G(d,p) and QCISD(T)/6‐311G(d,p) (single‐point) levels to explore the possible reaction mechanism of the triplet CH2 radical with NO2. Forty minimum isomers and 92 transition states are located. For the most relevant reaction pathways, the high‐level QCISD(T)/6‐311 + G(2df,2p) calculations are performed at the B3LYP/6‐31G(d,p) geometries to accurately determine the energetics. It is found that the top attack of the 3CH2 radical at the N‐atom of NO2 first forms the branched open‐chain H2CNO2 a with no barrier followed by ring closure to give the three‐membered ring isomer cC(H2)ON—O b that will almost barrierlessly dissociate to product P1 H2CO + NO. The lesser followed competitive channel is the 1,3‐H‐shift of a to isomer HCN(O)OH c, which will take subsequent cis‐trans conversion and dissociation to P2 OH + HCNO. The direct O‐extrusion of a to product P3 3O + H2CNO is even much less feasible. Because the intermediates and transition states involved in the above three channels are all lower than the reactants in energy, the title reaction is expected to be rapid, as is consistent with the measured large rate constant at room temperature. Formation of the other very low‐lying dissociation products such as NH2 + CO2, OH + HNCO and H2O + NCO seems unlikely due to kinetic hindrance. Moreover, the 3CH2 attack at the end‐O of NO2 is a barrier‐consumed process, and thus may only be of significance at very high temperatures. The reaction of the singlet CH2 with NO2 is also briefly discussed. Our calculated results may assist in future laboratory identification of the products of the title reaction. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1031–1044, 2002
Plasmin activates pro‐matrix metalloproteinase‐2 with a membrane‐type 1 matrix metalloproteinase‐dependent mechanism
Authors: Monea Sara , Lehti Kaisa , Keski‐Oja Jorma , Mignatti Paolo
Published: October 2002

Membrane‐type 1 matrix metalloproteinase (MT1‐MMP) has been implicated as a physiological activator of progelatinase A (MMP‐2). We previously reported that plasmin treatment of cells results in proMMP‐2 activation and increased type IV collagen degradation. Here, we analyzed the role of MT1‐MMP in plasmin activation of MMP‐2 using HT‐1080 cells transfected with MT1‐MMP sense or antisense cDNA. Control, vector‐transfected cells that expressed endogenous MT1‐MMP, and antisense cDNA transfectants with very low levels of MT1‐MMP did not activate proMMP‐2. Conversely, cells transfected with sense MT1‐MMP cDNA expressed high MT1‐MMP levels and processed proMMP‐2 to 68/66‐kDa intermediate activation products. Control cells and MT1‐MMP transfectants had much higher levels of cell‐associated MMP‐2 than antisense cDNA transfectants. Addition of plasmin(ogen) to control or MT1‐MMP‐transfected cells generated active, 62‐kDa MMP‐2, but was ineffective with antisense cDNA transfectants. The effect of plasmin(ogen) was prevented by inhibitors of plasmin, but not by metalloproteinase inhibitors, implicating plasmin as a mechanism for proMMP‐2 activation independent of the activity of MT1‐MMP or other MMPs. Plasmin‐mediated activation of proMMP‐2 did not result from processing of proMT1‐MMP and did not correlate with αvβ3 integrin or TIMP‐2 levels. Thus, plasmin can activate proMMP‐2 only in the presence of MT1‐MMP; however, this process does not require the catalytic activity of MT1‐MMP. © 2002 Wiley‐Liss, Inc.