bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of the high‐temperature crack tip fields using reference stress concepts
Authors: HABIBULLAH M. S. , PONTER A. R. S.
Published: March 2006

In a previous paper, it was shown that an estimation approach to crack tip properties under cyclic creep loading conditions was described, using a methodology based on the linear matching method (LMM). The calculations revealed the possibility of obtaining the crack tip parameters, C* (n), for cracked structures subjected to both mechanical loads and temperatures, using the HRR field criterion as the crack tip condition. In this paper, those calculated values of C* (n) are re‐interpreted and presented in terms of the reference stresses, insensitive to the constitutive models and creep exponent. These reference stress values are compared with those currently used for life assessment of high‐temperature plant, showing that current practice is significantly conservative for thermal loading.
Testing the Time‐Variancy of Explanatory Factors of Strategic Change1
Authors: Vicente‐Lorente José David , Zúñiga‐Vicente JoséÁngel
Published: March 2006

The article proposes an empirical framework able to: (1) assess the relative validity of both adaptive and inertial views of strategic change and (2) verify the potential time‐ or context‐dependency by testing the structural stability of the empirical model, in Spanish banks, 1983–1997. Results offer inconclusive findings regarding (1) but strong evidence to answer (2). The assumption of structural stability is rejected and the effect of many explanatory factors considered in the empirical model varies over time as some factors show different effects and/or significance levels depending on the period considered. These findings suggest that explanatory models of strategic change should be viewed as ‘time‐’ or ‘context‐dependent’. The article provides a conceptual model in which alternative explanations operate in a sequential way. The results highlight, first, that inconclusive past findings about adaptive versus inertial views should be reviewed under this new evidence, and future empirical research must assure that its methods and interpretations are robust to potential structural breakdowns; and second, the limitations raised by the static approach offered by the available theories/models when approaching the dynamic and complex nature of strategic change. Theoretical developments and implications for managerial practice are suggested.
The Ethics of Management Research: An Exploratory Content Analysis
Authors: Bell Emma , Bryman Alan
Published: March 2006

Management academics have tended to rely on ethics codes developed by social researchers in related fields to inform their research practice. The point of this paper is to question whether this remains a viable approach in the current climate that is characterized by a significant increase in ethical regulation across the social sciences. We suggest that management researchers face ethical issues of a different nature to those most frequently confronted by other social science researchers, and argue for more explicit acknowledgement of contextual factors involved in management research. An exploratory analysis of the content of ethics codes formulated by nine social scientific associations is undertaken to identify the main ethical principles they cover and to analyse their underlying ethical tone. Drawing attention to the principle of reciprocity, which is found in very few codes, we suggest that an ethics code could be used to formulate new ways of thinking about management research relationships. Despite the risk that ethics codes may encourage instrumental compliance with minimal ethical obligations, we suggest they also have the potential to reflect a more aspirational agenda. The development of an ethics code for management research should therefore be seen as a potentially worthwhile project.
The Consequences of Perceived Age Discrimination Amongst Older Police Officers: Is Social Support a Buffer?*
Authors: Redman Tom , Snape Ed
Published: March 2006

This paper considers the psychological consequences of perceived age discrimination, and the buffering effect of social support. Findings suggest that age discrimination acts as a stressor, with negative effects on job and life satisfaction, perceived power and prestige of the job, and affective and normative commitment, along with positive effects on withdrawal cognitions and continuance commitment. For work‐based social support, there were positive main effects on job and life satisfaction, power and prestige of the job, and affective and normative commitment, and a negative main effect on withdrawal cognitions. However, there were no significant moderating effects for work‐based social support, and we found the anticipated buffering effect for non‐work‐based social support only for life satisfaction, with reverse buffering for job satisfaction and normative commitment
Image Registration in a Coarse Three‐Dimensional Virtual Environment
Authors: Laycock R. G. , Day A. M.
Published: March 2006

In recent years, the availability of off‐the‐shelf geometric data for an urban environment has increased. During rendering, ground level images are mapped onto the façades of the buildings to improve the visual quality of the scene. This paper focuses on a technique that enables ground level images to be automatically integrated into an existing coarse three‐dimensional environment. The approach utilises the planar nature of architectural scenes to enable the automatic extraction of a building façade from an image and its registration into the virtual environment.
Repressive coping style and autonomic reactions to two experimental stressors in healthy men and women
Authors: JØRGENSEN MICHAEL MARTINI , ZACHARIAE ROBERT
Published: March 2006

Autonomic and affective responses to two different stress tasks were measured in 45 males and 74 females, categorized as repressive, true low‐anxious, true high‐anxious, and defensive high‐anxious. Electrodermal activity (EDA) was used as a measure of sympathetic activity and the high frequency (HF) spectral component of heart rate variability as a measure of parasympathetic activity. Contrary to our predictions, reactivity of repressors did not differ from the reactivity of true low‐anxious participants. The results draw attention to previous inconsistent findings within the literature on repressive coping style and autonomic nervous system dysregulation. It is suggested that future research could benefit from the use of more consistent operationalizations of the repressive coping construct and from comparing alternative measures of repressive coping within the same study.
Quadratic Artificial Likelihood Functions Using Estimating Functions
Authors: WANG JINFANG
Published: March 2006

Abstract.  A vector‐valued estimating function, such as the quasi‐score, is typically not the gradient of any objective function. Consequently, an analogue of the likelihood function cannot be unambiguously defined by integrating the estimating function. This paper studies an analogue of the likelihood inference in the framework of optimal estimating functions. We propose a quadratic artificial likelihood function for an optimal estimating function. The objective function is uniquely identified as the potential function from the vector field decomposition by imposing some natural restriction on the divergence‐free part. The artificial likelihood function is shown to resemble a genuine likelihood function in a number of respects. A bootstrap version of the artificial likelihood function is also studied, which may be used for selecting a root as an estimate from among multiple roots to an estimating equation.
A Simulation‐based Goodness‐of‐fit Test for Random Effects in Generalized Linear Mixed Models
Authors: WAAGEPETERSEN RASMUS
Published: March 2006

Abstract.  The goodness‐of‐fit of the distribution of random effects in a generalized linear mixed model is assessed using a conditional simulation of the random effects conditional on the observations. Provided that the specified joint model for random effects and observations is correct, the marginal distribution of the simulated random effects coincides with the assumed random effects distribution. In practice, the specified model depends on some unknown parameter which is replaced by an estimate. We obtain a correction for this by deriving the asymptotic distribution of the empirical distribution function obtained from the conditional sample of the random effects. The approach is illustrated by simulation studies and data examples.
Impacts of land use and fire on the loss and degradation of lowland forest in 1983–2000 in East Kutai District, East Kalimantan, Indonesia
Authors: Dennis Rona A. , Colfer Carol P.
Published: March 2006

Deforestation and forest degradation are proceeding rapidly in the lowland forests of Indonesian Borneo. Time series analysis of satellite imagery provides an ideal means of quantifying landscape change and identifying the pathways which lead to the changes. This study investigates the forest and land cover changes by classifying Landsat MSS (Multispectral Scanner), TM (Thematic Mapper) and ETM+ (Enhanced Thematic Mapper Plus) images over three time periods (1983–90, 1990–98, and 1998–2000), creating land cover maps for each year and change trajectories for each year‐pair. The study area chosen covers an area of 2160 km2 of undulating topography and alluvial plains in the East Kutai District of East Kalimantan Province, which in the 1980s was covered mostly with lowland dipterocarp forest; today the landscape is a patchwork dominated by oil palm and timber plantations and degraded forest. We relate land cover change data to land use allocation and to fire impacts based on fire hotspot distribution and fire damage information. The multidate land cover change trajectories provide an insight into the forest loss and degradation pathways over the 17‐year period spanning the first entry of commercial logging concessionaires, followed by a government‐sponsored transmigration scheme, government‐licensed timber and oil palm plantations and, finally, the devastating fires of 1998. The results show a mean deforestation rate of 42 km2 or 6 per cent per year for 1983–2000, rising to 10 per cent per year for 1990–98; by 2000, 70 per cent of forest initially damaged by fire and drought during the 1982–83 El Niño event was classified as non‐forest. Although our study area is perhaps a worst‐case scenario in terms of land use planning outcomes, the lessons from this research are directly applicable to scenario prediction for informed forest and land use planning and monitoring.
Utility of Landsat 7 satellite data for continued monitoring of forest cover change in protected areas in Southeast Asia
Authors: Trigg Simon N. , Curran Lisa M. , McDonald Alice K.
Published: March 2006

Satellite instruments, particularly the Landsat TM (Thematic Mapper) and ETM+ (Enhanced Thematic Mapper Plus) series of sensors, are important tools in the interdisciplinary study of tropical forests that are increasingly integrated into studies that monitor changes in vegetation cover within tropical forests and tropical protected areas, and also applied with other types of data to investigate the drivers of land cover change. However, further advances in the use of Landsat to study and monitor tropical forests and protected areas are threatened by the scan line corrector failure on the ETM+ sensor, as well as uncertainty about the continuity of the Landsat mission. Given these problems, this paper illustrates how ETM+ data were used in an interdisciplinary study that effectively monitored forest cover change in Gunung Palung National Park in West Kalimantan, Indonesian Borneo. Following 31 May 2003, when the ETM+ sensor's scan line corrector failed, we analysed how this failure impedes our ability to perform a similar study from this date onwards. This analysis uses six simulated post‐scan line corrector failure (SLC‐off) images and reveals that data gaps caused by SLC‐off introduce maximum errors of 1.47 per cent and 4.04 per cent in estimates of forest cover and rates of forest loss, respectively. The analysis also demonstrates how SLC‐off has transformed ETM+ data from a complete inventory dataset to a statistical sample with variable sample fraction, and notes how this data loss will confound the use of Landsat data to model land cover change in a spatially explicit manner. We discuss potential limited uses of SLC‐off data and suggest alternative sensors that may provide essential remotely sensed data for monitoring tropical forests in Southeast Asia.
Driving forces of tropical deforestation: The role of remote sensing and spatial models
Authors: Chowdhury Rinku Roy
Published: March 2006

Remote sensing technologies are increasingly used to monitor landscape change in many parts of the world. While the availability of extensive and timely imagery from various satellite sensors can aid in identifying the rates and patterns of deforestation, modelling techniques can evaluate the socioeconomic and biophysical forces driving deforestation processes. This paper briefly reviews some emerging spatial methodologies aimed at identifying driving forces of land use change and applies one such methodology to understand deforestation in Mexico. Satellite image classification, change analysis and econometric modelling are used to identify the rates, hotspots and drivers of deforestation in a case study of the southern Yucatán peninsular region, an enumerated global hotspot of biodiversity and tropical deforestation. In particular, the relative roles of biophysical and socioeconomic factors in driving regional deforestation rates are evaluated. Such methodological approaches can be applied to other regions of the forested tropics and contribute insights to conservation planning and policy.
Delta sleep‐inducing peptide (DSIP): a still unresolved riddle
Authors: Kovalzon Vladimir M. , Strekalova Tatyana V.
Published: March 2006

Delta sleep‐inducing peptide (DSIP) was isolated from rabbit cerebral venous blood by Schoenenberger‐Monnier group from Basel in 1977 and initially regarded as a candidate sleep‐promoting factor. However, the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although DSIP itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure. DSIP structure is different from any other known representative of the various peptide families. In this mini‐review we hypothesize the existence of a DSIP‐like peptide(s) that is responsible (at least partly) for DSIP‐like immunoreactivity and DSIP biological activity. This assumption is based on: (i) a highly specific distribution of DSIP‐like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow‐wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS‐promoting activity of a naturally occurring dermorphin‐decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep‐suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP‐like peptide and its role in neuroendocrine regulation.
ABCA2 is a marker of neural progenitors and neuronal subsets in the adult rodent brain
Authors: Broccardo Cyril , Nieoullon Vincent , Amin Rada , Masmejean Frédérique , Carta Sonia , Tassi Sara , Pophillat Matthieu , Rubartelli Anna , Pierres Michel , Rougon Geneviève , Nieoullon André , Chazal Genèvieve , Chimini Giovanna
Published: March 2006

The notion that the ATP‐binding cassette transporter‐A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression. Our data support and extend the previous reports on ABCA2 expression by oligodendrocytes. They evidence that ABCA2 (i) is located in intracellular vesicles, identified in transfected cells as lysosome‐related organelles only partially overlapping with classical endolysosomes; (ii) is a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin+ cells differentiated in vitro from embryonic stem cells; (iii) persists, in the adult rodent brain, in a subset of GABAergic and glutamatergic neurons. Considering that the latter are targets of Alzheimer's lesions, these data provide a new rationale to explore the neuropathological consequences of ABCA2 functional dysregulations.
Caspase cleaved presenilin‐1 is part of active γ‐secretase complexes
Authors: Hansson Camilla A. , Popescu Bogdan O. , Laudon Hanna , Cedazo‐Minguez Angel , Popescu Laurentiu M. , Winblad Bengt , Ankarcrona Maria
Published: March 2006

γ‐Secretase is a key enzyme involved in the processing of the β‐amyloid precursor protein into amyloid β‐peptides (Aβ). Aβ accumulates and forms plaques in Alzheimer's disease (AD) brains. A progressive neurodegeneration and cognitive decline occurs during the course of the disease, and Aβ is believed to be central for the molecular pathogenesis of AD. Apoptosis has been implicated as one of the mechanisms behind the neuronal cell loss seen in AD. We have studied preservation and activity of the γ‐secretase complex during apoptosis in neuroblastoma cells (SH‐SY5Y) exposed to staurosporine (STS). We report that the known components (presenilin, Nicastrin, Aph‐1 and Pen‐2) interact and form active γ‐secretase complexes in apoptotic cells. In addition, the fragments corresponding to the PS1 N‐terminal fragment and the caspase‐cleaved PS1 C‐terminal fragment (PS1‐caspCTF) were found to form active γ‐secretase complexes when co‐expressed in presenilin (PS) knockout cells. Interestingly, PS1‐caspCTF replaced the normal PS1 C‐terminal fragment and was co‐immunoprecipitated with the γ‐secretase complex in SH‐SY5Y cells exposed to STS. In addition, Aβ was detected in medium from apoptotic HEK APPswe cells. Together, the data show that γ‐secretase complexes containing PS1‐caspCTF are active, and suggest that this proteolytic activity is also important in dying cells and may affect the progression of AD.
Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo
Authors: Patel Anant B. , de Graaf Robin A. , Martin David L. , Battaglioli Gino , Behar Kevin L.
Published: March 2006

In this study we tested the hypothesis that the 65‐kDa isoform of glutamate decarboxylase (GAD65) mediates activity‐dependent GABA synthesis as invoked by seizures in anesthetized rats. GABA synthesis was measured following acute GABA‐transaminase inhibition by gabaculine using spatially localized 1H NMR spectroscopy before and after bicuculline‐induced seizures. Experiments were conducted with animals pre‐treated with vigabatrin 24 h earlier in order to reduce GAD67 protein and also with non‐treated controls. GAD isoform content was quantified by immunoblotting. GABA was higher in vigabatrin‐treated rats compared to non‐treated controls. In vigabatrin‐treated animals, GABA synthesis was 28% lower compared to controls [p < 0.05; vigabatrin‐treated, 0.043 ± 0.011 µmol/(g min); non‐treated, 0.060 ± 0.014 µmol/(g min)] and GAD67 was 60% lower. No difference between groups was observed for GAD65. Seizures increased GABA synthesis in both control [174%; control, 0.060 ± 0.014 µmol/(g min) vs. seizures, 0.105 ± 0.043 µmol/(g min)] and vigabatrin‐treated rats [214%; control, 0.043 ± 0.011 µmol/(g min); seizures, 0.092 ± 0.018 µmol/(g min)]. GAD67 could account for at least half of basal GABA synthesis but only 20% of the two‐fold increase observed in vigabatrin‐treated rats during seizures. The seizure‐induced activation of GAD65 in control cortex occurs concomitantly with a 2.3‐fold increase in inorganic phosphate, known to be a potent activator of apoGAD65in vitro. Our results are consistent with a major role for GAD65 in activity‐dependent GABA synthesis.
Cocaine induced inflammatory response in human neuronal progenitor cells
Authors: Crawford Fiona C. , Wood Marcie L. , Wilson Sarah E. , Mathura Venkatarajan S. , Hollen Tyler R. , Geall Freya , Kolippakkam Deepak N. , Mullan Michael J.
Published: March 2006

We have employed a genomic approach in homogenous cell culture to investigate the fundamental transcriptional responses which occur in neurons over time as a consequence of a single 30‐min exposure to cocaine. Data from 24 Affymetrix microarrays, representing eight treatment groups, were analyzed by GeneChip Operating Software and then further mined by hierarchical clustering, anova, and Ingenuity Pathway Analysis software to examine known molecular pathways impacted by the observed transcriptional changes. For each time point under investigation, the data sets of genes exhibiting altered expression in treated cells compared with control were interrogated with a specific focus on differential expression of genes involved in immunomodulation and inflammation. The existing literature on the effects of cocaine in a diverse array of experimental paradigms demonstrates a significant modulation of inflammation and immune mechanisms, but these have typically been studies of chronic exposure in immune‐competent cells. Our data show a time‐dependent up‐regulation of genes associated with pro‐inflammatory and immune responses, peaking at 24 h as confirmed by all methods of analysis, suggesting a specific neuronal immunomodulatory response to acute cocaine exposure.
Tissue transglutaminase overexpression in the brain potentiates calcium‐induced hippocampal damage
Authors: Tucholski Janusz , Roth Kevin A. , Johnson Gail V. W.
Published: March 2006

Tissue transglutaminase (tTG) post‐translationally modifies proteins in a calcium‐dependent manner by incorporation of polyamines, deamination or crosslinking. Moreover, tTG can also bind and hydrolyze GTP. tTG is the major transglutaminase in the mammalian nervous system, localizing predominantly in neurons. Although tTG has been clearly demonstrated to be elevated in neurodegenerative diseases and in response to acute CNS injury, its role in these pathogenic processes remains unclear. Transgenic mice that overexpress human tTG (htTG) primarily in CNS neurons were generated to explore the role of tTG in the nervous system and its contribution to neuropathological processes. tTG transgenic mice were phenotypically normal and were born with the expected Mendelian frequency. However, when challenged systemically with kainic acid, tTG transgenic mice, in comparison to wild‐type (WT) mice, developed more extensive hippocampal neuronal damage. This was evidenced by a decreased number of healthy neurons, and increased terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) labeling as an indicator of neuronal cell death in the kainic acid‐treated transgenic mice. Moreover, the duration and severity of seizures developed by htTG transgenics in response to kainic acid administration were significantly more pronounced than those observed in WT mice. These data indicate for the first time that tTG may play an active role in excitatory amino acid‐induced neuronal cell death, which has been postulated to be an important component of acute CNS injury and chronic CNS neurodegenerative conditions.
Chronic stress decreases the expression of sympathetic markers in the pineal gland and increases plasma melatonin concentration in rats
Authors: Dagnino‐Subiabre Alexies , Orellana Juan A. , Carmona‐Fontaine Carlos , Montiel Juan , Díaz‐Velíz Gabriela , Serón‐Ferré María , Wyneken Ursula , Concha Miguel L. , Aboitiz Francisco
Published: March 2006

Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic‐related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and α‐tubulin, while the same treatment did not affect the expression of the non‐specific sympathetic markers Erk1 and Erk2, and glyceraldehyde‐3‐phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.
Evaluation of risk and clinical outcome of mast cell tumours in pug dogs
Authors: McNiel E. A. , Prink A. L. , O'Brien T. D.
Published: March 2006

Mast cell tumours (MCT) are common in dogs and characterized by diverse biologic behaviour. Our objective was to evaluate the risk of MCT in pugs and to describe the clinical behaviour of MCT in this breed. Data obtained from the Veterinary Medicine Database demonstrate significantly increased frequency of MCT in pugs compared with other dogs (OR = 2.28, 95% CI = 1.81–2.86). The medical records for 25 purebred pugs with a histologic diagnosis of MCT were reviewed. Multiple cutaneous tumours were documented in 14 (56 %) of the dogs. Histologic review of 64 tumours from these dogs confirmed that most tumours (94%) were low to intermediate grade. Sixty‐four per cent of these dogs are still living, while only three dogs (12%) have died due to mast cell disease. A median survival time has not been reached. The median follow‐up time is 660 days from the diagnosis of the first MCT. We conclude that MCT in pugs are relatively benign, despite the presence of multiple cutaneous tumours in most cases. Multiple tumours in breeds with predisposition to MCT may indicate separate primaries rather than advanced stage disease.
Efficacy and toxicity of BOPP and LOPP chemotherapy for the treatment of relapsed canine lymphoma*
Authors: LeBlanc A. K. , Mauldin G. E. , Milner R. J. , LaDue T. A. , Mauldin G. N. , Bartges J. W.
Published: March 2006

Mechlorethamine (Mustargen®, Oncovin®(vincristine), procarbazine and prednisone (MOPP) chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of MOPP after substitution of CCNU (lomustine, LOPP protocol) or BCNU (carmustine, BOPP protocol) for mechlorethamine in 60 dogs with relapsed lymphoma. Seven of 14 (50%) dogs treated with BOPP responded, for a median of 129.5 days for complete responders (range 9–354 days) and a median of 140 days for partial responders (range 4–276 days). Twenty‐three of 44 (52%) dogs treated with LOPP responded for a median of 112 days for complete responders (range 48–250 days) and a median of 84.5 days for partial responders (range 69–290 days). Two dogs receiving a combination of LOPP and BOPP partially responded for 28 and 163 days, respectively. With BOPP chemotherapy, nine dogs (20.5%) and seven dogs (50%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seven dogs (50%) had one or more episodes of Grade II or higher gastrointestinal toxicity. While receiving LOPP chemotherapy, 28 dogs (63.6%) and 17 dogs (38.6%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seventeen dogs (38.6%) had one or more episodes of Grade II or higher gastrointestinal toxicity. Overall, there were 17 non‐fatal treatment‐related episodes of sepsis requiring hospitalization. Eight dogs (13%) died or were euthanized because of treatment‐related sepsis and/or chemotherapy‐related complications. Severe haematologic toxicity, coupled with the improved response duration observed in dogs receiving reduced doses during B/L‐OPP rescue, underscores the need for protocol optimization.
Can general practitioners improve the level of diagnosis? An introduction to clinical conference seminars for Alzheimer's disease
Authors: SHIGETA Masahiro
Published: March 2006

In order to make earlier diagnoses and to start the treatment of dementing diseases, the education of general practitioners (GPs) is important. We developed the training program for GPs concerning diagnoses, treatment and management of dementia, mainly Alzheimer's disease. The contents of the program consist of the role of GPs, essential knowledge of dementia symptoms, how to recognize the dementia patients, how to interview patients, how to assess medication requirements and how to explain the disease and treatment to the patients and their families. The program included video presentation and simulated patients as well as flip boards.
What tools are available for screening and diagnosis? Interactive One‐minute Screening Tool
Authors: NAKAMURA Yu
Published: March 2006

The Interactive One‐minute Screening Tool, which is based on the One‐minute Screening Tool, one of the key tools in the Clinical Conference Seminar, is has been computerized with a touch screen. The interactive tool comprises only three items: delayed recall, orientation to time, and visuospatial cognition. The tool is noninvasive, quick and simple to operate. Analysis of the data established a cut‐off value of 12% to discriminate between Alzheimer's disease patients and normal individuals. The sensitivity and specificity of the test are excellent, at 96% and 97%, respectively.
Mild cognitive impairment: biological diagnostic markers for early stages of Alzheimer's disease
Authors: URAKAMI Katsuya
Published: March 2006

Background:  With the aging population in Japan, the inevitable increase in the prevalence of Alzheimer's disease (AD) and the difficulty in diagnosing the condition. Reliable early diagnostic biomarkers for early stage of AD are needed.

Method:  We examined a total 570 CSF samples from a variety of diseases, including AD, other types of dementia and controls to quantitate levels of tau protein phosphorylated at serine 199 by sandwich ELISA. WGA‐binding glycoproteins were measured by western blot analysis.

Results:  The CSF phosphorylated tau protein levels in the AD group were significantly elevated compared to those in all the other non‐AD groups. CSF phosphorylated tau protein levels in the AD progressed from mild cognitive impairment (MCI) group were significantly elevated compared to those in no progression AD from MCI groups and controls. A comparison of the phosphorylated tau protein: WGA‐glycoprotein fragment A ratio for AD and other tauopathies showed that this ratio has potential for differentiating between AD and other tauopathies, particularly dementia with Lewy bodies.

Conclusion:  Our data showed that measuring cerebrospinal fluid (CSF) levels of phosphorylated tau protein may be useful as an early diagnostic marker in AD and MCI. Furthermore, the measurement of WGA‐binding glycoprotein in CSF may provide a useful tool for differentiating AD from dementia of Lewy bodies and other tauopathies.
Parkinson's disease with dementia and dementia with Lewy body disease: two syndromes, the same disease?
Authors: SELLAL François
Published: March 2006

The diagnosis of Parkinson's disease with dementia (PDD) or dementia with Lewy bodies (DLB) relies on an arbitrary distinction between the time of onset of motor and cognitive symptoms. These syndromes share many clinical, genetic and neurobiological similarities. From a pathological point of view, both conditions are associated to Lewy bodies (LB), but the exact role of LB is not straightforward. Their presence in some brain areas is not always well correlated to clinical symptoms. The process by which they are associated, directly or otherwise, to neuronal damage and synaptic loss remains to be elucidated. Moreover Alzheimer's disease pathology is more frequent and more closely related to cognitive disorders in DLB than in PDD, but the mechanisms linking LB to beta‐amyloid pathology are unknown. Longitudinal studies will be necessary to determine the pathogenesis underlying clinical symptoms of PDD and DLB. However, it is probable that in a near future PDD and DLB will be recognized as the same disease with two different courses.
Vascular dementia: possible role of the ischemic lesions in mild dementia
Authors: TAKAHASHI Satoshi
Published: March 2006

Until the first half of the 1980s, vascular disorders were the leading cause of dementia patients living in major cities of Japan; at present, Alzheimer's disease is the most common cause. The primary reason for the increase in the relative incidence of dementia due to Alzheimer's disease is the decrease in the number of cases of vascular dementia due to primary and secondary prevention of cerebrovascular disorders. However, no drug can effectively prevent lacunar infarct and the incidence of infarcts in the deep cerebral white matter has not significantly decreased, the prevalence of elderly patients with Alzheimer's disease associated with cerebral infarct is rapidly increasing.

The increased relative incidence of Alzheimer's disease in Japan is also attributable to increases in the number of elderly persons and number of patients diagnosed with mild dementia. The living environment of senior citizens in Japan has changed over the last few decades by advances in the level of technology commonly used in society and by increases in the number of nuclear families. Mildly demented patients with hippocampal atrophy and ischemic lesion were increased in number. However differentiating vascular dementia from Alzheimer's disease in elderly demented patients with hippocampal atrophy associated with ischemic lesions remains difficult, asymptomatic cerebral infarcts significantly affect frontal lobular function especially in elderly persons. Appropriate prevention and treatment of ischemia in these patients may help to reduce the number of dementia patients.
Current Understanding of Delayed Anticonvulsant Hypersensitivity Reactions
Authors: Krauss Gregory
Published: March 2006

Hypersensitivity syndrome (HSS) reactions are one of the most feared idiosyncratic drug reactions and are most common with exposure to antiepileptic drugs (AEDs), sulfonamides, nonsteroidal antiinflammatory drugs, corticosteroids, and allopurinol. HSS is associated with chemotoxic and T-cell–mediated inflammatory injuries in barrier tissue systems that contain cytochrome oxidases (e.g., skin, mucosa, liver, and lungs) and can be seen as a derangement in the defense system against xenobiotics—bioactive foreign molecules. The mechanisms for anticonvulsant HSS are incompletely understood but involve genetic susceptibility, with accumulation of AEDs and oxidized metabolites causing major histocompatibility complex (MHC) and non–MHC–dependent clonal activation of T cells and subsequent cytokine/chemokine production in T cells, keratinocytes, and other target cells. This review discusses the classification and possible mechanisms for anticonvulsant HSS.
An Estimator of Number of Species from Quadrat Sampling
Authors: Haas Peter J. , Liu Yushan , Stokes Lynne
Published: March 2006

Summary We consider the problem of estimating the number of distinct species S in a study area from the recorded presence or absence of species in each of a sample of quadrats. A generalized jackknife estimator of S is derived, along with an estimate of its variance. It is compared with the jackknife estimator for S proposed by Heltshe and Forrester (1983, Biometrics39, 1–12) and the empirical Bayes estimator of Mingoti and Meeden (1992, Biometrics48, 863–875). We show that the empirical Bayes estimator has the form of a generalized jackknife estimator under a specific model for species distribution. We compare the new estimators of S to the empirical Bayes estimator via simulation. We characterize circumstances under which each is superior.
Flexible Modeling via a Hybrid Estimation Scheme in Generalized Mixed Models for Longitudinal Data
Authors: Leung Lai Tze , Shih Mei‐Chiung , Wong Samuel Po‐Shing
Published: March 2006

SummaryTo circumvent the computational complexity of likelihood inference in generalized mixed models that assume linear or more general additive regression models of covariate effects, Laplace's approximations to multiple integrals in the likelihood have been commonly used without addressing the issue of adequacy of the approximations for individuals with sparse observations. In this article, we propose a hybrid estimation scheme to address this issue. The likelihoods for subjects with sparse observations use Monte Carlo approximations involving importance sampling, while Laplace's approximation is used for the likelihoods of other subjects that satisfy a certain diagnostic check on the adequacy of Laplace's approximation. Because of its computational tractability, the proposed approach allows flexible modeling of covariate effects by using regression splines and model selection procedures for knot and variable selection. Its computational and statistical advantages are illustrated by simulation and by application to longitudinal data from a fecundity study of fruit flies, for which overdispersion is modeled via a double exponential family.
Incomplete Generalized U‐Statistics for Food Risk Assessment
Authors: Bertail Patrice , Tressou Jessica
Published: March 2006

Summary This article proposes statistical tools for quantitative evaluation of the risk due to the presence of some particular contaminants in food. We focus on the estimation of the probability of the exposure to exceed the so‐called provisional tolerable weekly intake (PTWI), when both consumption data and contamination data are independently available. A Monte Carlo approximation of the plug‐in estimator, which may be seen as an incomplete generalized U‐statistic, is investigated. We obtain the asymptotic properties of this estimator and propose several confidence intervals, based on two estimators of the asymptotic variance: (i) a bootstrap type estimator and (ii) an approximate jackknife estimator relying on the Hoeffding decomposition of the original U‐statistics. As an illustration, we present an evaluation of the exposure to Ochratoxin A in France.
Multivariate Extensions of McNemar's Test
Authors: Klingenberg Bernhard , Agresti Alan
Published: March 2006

Summary This article considers global tests of differences between paired vectors of binomial probabilities, based on data from two dependent multivariate binary samples. Difference is defined as either an inhomogeneity in the marginal distributions or asymmetry in the joint distribution. For detecting the first type of difference, we propose a multivariate extension of McNemar's test and show that it is a generalized score test under a generalized estimating equations (GEE) approach. Univariate features such as the relationship between the Wald and score tests and the dropout of pairs with the same response carry over to the multivariate case and the test does not depend on the working correlation assumption among the components of the multivariate response. For sparse or imbalanced data, such as occurs when the number of variables is large or the proportions are close to zero, the test is best implemented using a bootstrap, and if this is computationally too complex, a permutation distribution. We apply the test to safety data for a drug, in which two doses are evaluated by comparing multiple responses by the same subjects to each one of them.
Regularized Estimation in the Accelerated Failure Time Model with High‐Dimensional Covariates
Authors: Huang Jian , Ma Shuangge , Xie Huiliang
Published: March 2006

SummaryWe consider two regularization approaches, the LASSO and the threshold‐gradient‐directed regularization, for estimation and variable selection in the accelerated failure time model with multiple covariates based on Stute's weighted least squares method. The Stute estimator uses Kaplan–Meier weights to account for censoring in the least squares criterion. The weighted least squares objective function makes the adaptation of this approach to multiple covariate settings computationally feasible. We useV‐fold cross‐validation and a modified Akaike's Information Criterion for tuning parameter selection, and a bootstrap approach for variance estimation. The proposed method is evaluated using simulations and demonstrated on a real data example.
The Canadian National Outcomes Measurement Study in Schizophrenia: overview of the patient sample and methodology
Authors: Smith G. , Malla A. , Williams R. , Kopala L , Love L. , Balshaw R.
Published: March 2006

Objective:  The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is a prospective survey of routine clinical practice.

Method:  Patients with schizophrenia or a related disorder were consecutively enrolled from all regions of Canada. Both academic and community psychiatric clinics were included and patients were followed up for 2 years. Clinical and functional status, quality of life, medication and economic costs were assessed at enrollment and monitored throughout the follow‐up period.

Results:  Patients attending an academic clinic tended to be younger and more severely ill than those from community clinics. Both types of sites prescribed atypical neuroleptics to more than three‐quarters of the patients. The majority of those enrolled were unemployed and living in poverty. Poor clinical status was associated with poverty.

Conclusion:  The CNOMSS provides demographic, clinical and treatment‐related information about a large Canada‐wide sample of psychiatric patients. The following three articles in this issue of Acta Psychiatrica Scandinavica explore issues related to medication, quality of life and resource utilization.
Medication decisions and clinical outcomes in the Canadian National Outcomes Measurement Study in Schizophrenia
Authors: Williams R. , Kopala L. , Malla A. , Smith G. , Love L. , Balshaw R.
Published: March 2006

Objective:  To evaluate over a 2‐year period, patients from academic/non‐academic centres, from each region of Canada, to determine whether location or other variables such as medication type, gender or income was associated with outcome as defined by non‐hospitalization and persistence on original treatment.

Method:  A total of 448 patients were recruited from academic and non‐academic centres across all provinces of Canada and followed up for 2 years.

Results:  Patients from British Columbia had significantly lower rates of hospitalization than patients from other provinces. Male patients showed greater symptomatic improvement at 2 years from initial assessment compared to females. Patients on clozapine, risperidone and olanzapine were least likely to be hospitalized.

Conclusion:  There were some regional differences noted in both utilization of types of antipsychotic medications and hospitalization rates. In this sample of stable out‐patients over 70% who started on monotherapy with clozapine, risperidone, olanzapine and quetiapine remained on the same medication over the 2‐year study period.
Outcome on quality of life in a Canadian national sample of patients with schizophrenia and related psychotic disorders
Authors: Malla A. , Williams R. , Kopala L. , Smith G. , Talling D. , Balshaw R.
Published: March 2006

Objective:  To examine changes in subjective and objective dimensions of quality of life (QoL) in a large Canadian sample of patients with diagnosis of schizophrenia or schizoaffective disorder treated in academic and non‐academic settings over a 2‐year period.

Method:  Patients recruited in the study across the country were assessed for QoL and functioning using the Client and Provider versions of the Wisconsin Quality of Life Questionnaire (WQoL) and the Short Form‐36 (SF‐36) at baseline (n = 448), 1 year (n = 308–353) and 2 years (188–297). Data were analyzed to examine change across time using multivariate analyses controlling for potential influence of variables such as age, regional variation, gender, duration of illness, type of treatment taken and baseline measures of symptoms and QoL.

Results:  The weighted quality of life index (W‐QoL‐I) showed a significant change on both the client and the provider versions of the WQoL while the physical and mental composites of the SF‐36 showed change only at 2 years. These changes were influenced significantly by baseline scores on W‐QoL‐I and in the case of provider version of the WQoL by baseline Brief Psychiatric Rating Scale (BPRS) scores. Regional variation or type of medication had no impact on improvement in QoL.

Conclusion:  Within a naturalistic sample of schizophrenia patients treated and followed in routine care the overall QoL showed an improvement over time but this improvement was not influenced by the type of medication prescribed.
Evaporative Water Loss in Nine Insular Populations of the LizardAnolis cristatellusGroup in the British Virgin Islands
Authors: Dml'el Razi , Perry Gad , Lazell James
Published: March 2006

We studied water loss in eight insular populations of the lizardAnolis cristatellus wileyaeand in one population ofA. ernestwilliamsiin the British Virgin Islands. We found a strong negative correlation between habitat aridity and total and cutaneous water loss rate (ranging from 1.5–10.3 mg g−1h−l) and a strong positive correlation between habitat aridity and integument resistance to water loss (28.5−199.0 s cm−1). Water loss and integumentary resistance ofA. ernestwilliamsiwere similar to what would be predicted forA. cristatellusliving in the same habitat. The Guana Island population ofA. cristatelluswas significantly different from all other populations. We believe two processes are responsible; phenotypic plasticity explains most of the observed variability, but genetic differentiation may be responsible for the distinction of lizards from Guana.
Anoline Diversity in Three Differentially Altered Habitats in the Sierra de Baoruco, República Dominicana, Hispaniola1
Authors: Lenart Lori A. , Powell Robert , Parmerlee John S. , Lathrop Amy , Smith Donald D.
Published: March 2006

We examined three disturbed, but distinctly different, sites on the historically forested eastern slope of the Sierra de Baoruco, Provincia de Barahona, República Dominicana, in order to evaluate the impact of habitat alteration on the composition of anoline lizard communities. Five species of Anolis (A. bahorucoensis, A. barahonae, A. coelestinus, A. sybotes, A. distichus) are known to occur in the immediate area of our study sites. Only three were found in the most substantially altered clear‐cut site, whereas all five species occupied the most heterogeneous habitat, a coffee plantation characterized by a three‐tiered canopy. Similarly, numbers of individuals of all but one species were greatest in the plot that most closely resembled the natural forests in this area. Calculated niche breadths, based on analysis of stomach contents, of the three species found in all sites increased with the degree of habitat alteration. The higher number of A. coelestinus in more heavily altered sites may be attributed to density compensation.