bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple cerebral atrophy of non‐Alzheimer type: A comprehensive category for non‐specific cortical degeneration
Authors: Komori Takashi , Okazaki Haruo , Parisi Joseph E. , Kobayashi Makio
Published: October 2007

We identified 19 cases of dementia characterized by cerebral atrophy with non‐specific cortical degeneration, but without pathologic features of Alzheimer's disease or other known neurodegenerative disorders. The cases were selected by a review of 14 000 autopsies and from the clinical records of the Mayo Clinic from 1972 to 1992. Microscopically, four general topographic patterns of atrophy were identified: frontal (n=6), frontotemporal (n=4), temporal (n=3), and mesiotemporal (n=4). The characteristic microscopic findings in the atrophic cortex included neuronal loss with astrocytosis, which predominantly involved the upper cortical layers, and superficial vacuolar changes. A focal or regional accentuation of involvement with different extents and severities of change was common. Neuronal achromasia was present in seven cases. Rare to sparse ubiquitin‐positive linear structures were identified in small neurons in the second cortical layer in nine cases. Argentophilic cortical grains, predominantly in the subiculum, were detected in only three cases. Involvement of the cerebral white matter corresponded to the cortical involvement. The striatum, thalamus, or substantia nigra was affected in all cases. Hippocampal involvement was evident only in the mesiotemporal type; the prosubiculum was the most severely affected area. After analyzing similar cases which had previously been reported under diverse diagnostic terms, we propose the term ‘simple cerebral atrophy of non‐Alzheimer type’ as a tentative comprehensive category for direct correlation, encompassing a spectrum of non‐Alzheimer type dementia.
Amyloid P component immunoreactivity in brains of Alzheimer‐type dementia is reduced by formic acid pretreatment on tissue section
Authors: Iwamoto Norihiko , Nishiyama Etsuko , Ohwada Jiro , Noguchi Iwahide , Kimura Michihiro , Arai Heii
Published: October 2007

In order to elucidate the enhancement mechanism of amyloid staining by formic acid (FA) pretreatment on a tissue section, we investigated changes of immunoreactivity of amyloid P component (AP) in senile plaques of Alzheimer‐type dementia (ATD) brains. Although immunoreactivity of various amyloidogenic proteins is enhanced by FA treatment, the immunoreactivity of AP was reduced by the treatment in this study. Amyloid P is thought to deposit to amyloid structure by leakage from blood vessels. Therefore, this result suggests that the enhancement effect depends not only on the property of amyloidogenic protein itself but also on the binding form to amyloid structure.
An anaplastic cytokeratin‐immunopositive xanthomatous tumor involving the pharynx and clivus of a child: An ultrastructural and immunohistochemical study
Authors: Sasaki Kimio , Oyanagi Kiyomitsu , Kameyama Shigeki , Honda Yoshiho , Tanimura Ken‐ichi , Yoshida Seiichi , Ikuta Fusahiro
Published: October 2007

An autopsy case of an anaplastic xanthomatous tumor involving the pharynx and clivus in a 2 year old girl was investigated ultrastructurally and immunohistochemi‐cally. The tumor was manifested as an epi‐ and subdural mass in the posterior cranial fossa involving the pharynx and clivus. The tumor showed an interlacing fascicular and pleomorphic pattern. The tumor cells contained numerous intermediate filaments, which were mainly tonofilaments, and lipid droplets, but did not have junctional complex. Immunohistochemically, most of the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin, and some tumor cells were positive for myoglobin and a‐1 antichymotrypsin, but negative for S‐100, CD‐68 and glial fibrillary acidic protein. These findings suggest that this tumor was derived from epithelial cells, and showed xanthomatous appearance. A discussion of its differential diagnosis was conducted.
Pallidonigroluysian atrophy: Clinicopathological and immunohistochemical studies
Authors: Shimoda Masaru , Hosoda Yoshito , Kato Shinsuke , Kaneto Daizo , Takahashi Kazuro , Yen Shu‐Hui , Ohama Eisaku
Published: October 2007

Three autopsied cases of pallidonigroluysian atrophy (PNLA) were studied clinicopathologically and 11 previously reported cases were reviewed for the purpose of clarifying the clinicopathological characteristics of the disease. The main clinical symptoms are parkinsonism, predominantly akinesia or pure akinesia with or without effective levodopa therapy. Major lesions approximately were confined to the globus pallidus, subthalamic nucleus and substantia nigra. Gallyas‐Braak method and immunohistochemistry with a monoclonal antibody (mAb) to tau‐2 protein (tau‐2) revealed a small number of neurofibrillary tangles (NFT) and argyrophilic and tau‐2 positive structures within the cytoplasms of the glial cells in the major lesions. Immunohistochemistry with a mAb to Alzheimer NFT (Ab39) demonstrated only a few classical tangles in the globus pallidus in one case. These findings suggest that PNLA can be pathologically differentiated from progressive supranuclear palsy.
Cerebral type of Lewy body disease
Authors: Kosaka Kenji , Iseki Eizo , Odawara Toshinari , Yamamoto Takayuki
Published: October 2007

A cerebral type of Lewy body disease (LBD) is proposed. Lewy body disease was split formerly into three types: brainstem type, transitional type and diffuse type. The diffuse type is now called diffuse Lewy body disease (DLBD). These three types are characterized pathologically by the presence of a large number of Lewy bodies in the CNS. In the brainstem type, Lewy bodies are numerous in the brainstem and diencephalon nuclei, and in DLBD, a vast number are present not only in these nuclei but also in the cerebral cortex and amygdala. In the cerebral type of LBD, as many Lewy bodies are found in the cerebral cortex and in the amygdala as there are in DLBD, but only rarely are they present in the brainstem and diencephalon nuclei. Thus, this type of LBD is different from other types in that it has no parkinson pathology. Therefore, parkinsonism fails to occur throughout the whole clinical course of this disease. The existence of a cerebral type of LBD suggests that Lewy bodies occur in the cerebral cortex earlier than in the brainstem nuclei and that cortical Lewy bodies appear even when the mesocortical dopaminergic system is intact. In addition, this might explain why dementia frequently precedes parkinsonism in DLBD.
Clinical features of hereditary dentatorubropallidoluysian atrophy
Authors: Naito Haruhiko
Published: October 2007

Hereditary dentatorubropallidoluysian atrophy (DRPLA) is an inherited disease with an autosomal dominant trait. Its cardinal symptoms are myoclonus, epileptic seizures, ataxia, choreoathetosis, and dementia. The age of onset ranges from childhood to senescence. There is a particular correlation between the age at onset and clinical symptoms; progressive myoclonus epilepsy is a characteristic feature of DRPLA patients with juvenile onset, whereas those with late adult onset manifest cerebellar ataxia and choreoathetosis usually without myoclonus with or without epilepsy. The clinical forms of DRPLA may be classified into three subtypes: juvenile, early adult and late adult type.
Neuropathology of dentatorubropallidoluysian atrophy
Authors: Takeda Shigeki , Takahashi Hitoshi
Published: October 2007

We examined 12 autopsy cases of dentatorubropallidoluysian atrophy (DRPLA). We confirmed the commonly or often recognized neuropathological findings in DRPLA as follows: 1, thickening of the skull bone; 2, atrophy of the brain; 3, degeneration of the dentate nucleus and its afferent fibers; 4, degeneration of the globus pallidus‐subthalamic nucleus system; 5, atrophy of the tegmentum of the brain stem especially in the pons; 6, symmetrical necrotic small foci of the ventro‐lateral portion of the pontine tegmentum; 7, degeneration of the striatum; 8, degeneration of the superior colliculus; 9, degeneration of the gracile nucleus; 10, degeneration of the pyramidal tract; 11, mild degeneration of the cerebellar cortex; 12, mild degeneration of the cerebral cortex; and 13, degeneration of the cerebral white matter. From the histopathological point of view, DRPLA is clearly distinguished from Machado‐Joseph disease and myoclonus epilepsy associated with ragged‐red fibers. We also examined the clinico‐pathological correlations in three clinical groups which were classified as juvenile type, early adult type and late adult type. We noted that in juvenile type presenting with progressive myoclonus epilepsy syndromes as the main clinical features of DRPLA, degeneration of the globus pallidus was more severe than that of the dentate nucleus, and atrophy of the brain stem and spinal cord was mild. We also noted that in late adult type presenting with cerebellar ataxia and choreoathetoid involuntary movements without myoclonus or epilepsy or either, degeneration of the dentate nucleus was more severe than that of the globus pallidus, and severe atrophy of the brain stem and spinal cord.
Aging process of the human lumbar spinal cord: A morphometric analysis
Authors: Zhou Ming , Goto Noboru , Zhang Chen , Tang Wei
Published: October 2007

A morphometric evaluation according to the aging process was made on the human spinal cord. The staining characteristics disclosed that the posterior funiculus became paler with age, the motor neurons were partially lost in the anterior horn, and the amyloid bodies accumulated in quantity in the posterior funiculus. We made a further morphometric analysis for precise evaluation. Diameters and areas of transverse sections of the cord (Tr), white matter (W), gray matter (G) and posterior funiculus (Pf), areal ratios of posterior funiculus over transverse section (Pf/Tr), posterior funiculus over white matter (Pf/W), gray matter over white matter (G/W) and gray matter over transverse section (G/Tr), were measured and calculated on the transverse sections of the first lumbar segment, using an image analyzer and a computer. Results indicated that the area of posterior funiculus became reduced with age, but the size of transverse sectional areas had no correlation with the aging process. A significant correlation could be seen between the ratios of Pf/Tr and age on one hand, and Pf/W and age on the other. The ratios of G/W and G/Tr showed a tendency to decrease according to the aging process, although correlation analysis showed this to be of low statistical significance. In human material, the morphometric evaluations are considered to be useful in explaining several clinical phenomena in relation to geriatric neurology and in comparing various pathologic conditions with the normal aging data.
Spinal cord findings in cervical spondylotic myelopathy: A morphometric analysis
Authors: Shiraishi Naoki , Zhang Chen , Goto Noboru , Zhou Ming
Published: October 2007

Morphometric analyses and pathological studies were carried out on spinal cords from seven cases (aged 71–88 years) with cervical spondylotic myelopathy (CSM), which were taken from cadaver specimens for anatomical dissection. The transverse sections of spinal cord specimens embedded in celloidin were stained with the luxol fast blue‐periodic acid‐Schiff‐hematoxylin or the Klüver‐Barrera methods. The measured items were flatness ration, and areas of cross‐section, gray matter, and posterior funiculus at C2 to T1, and L1 levels. The measurements were carried out with the use of a combination of an electronic optical planimeter and a computer. The results showed that: (i) the most vulnerable segments in the cases of compression myelopathy were at C4‐C6; (ii) the cross‐sectional areas of the spinal cord with CSM were significantly smaller at C4‐C6 levels compared with a normal group; (iii) the flatness ratio in CSM was obviously reduced at C4‐C6 levels; (iv) the shape of the gray matter in CSM became severely flat, and the areas were significantly smaller at C4‐C8, and L1 levels. The following findings were also observed: neuronal loss in the anterior horn; the formation of slit‐like cavities in the gray matter (lateral part of the intermediate substance) at the compressed levels; and many amyloid bodies deposited in the posterior funiculus, and/or lateral funiculus. This finding had never been noted before in relation to CSM. There are three types of compression of the cervical spinal cord: whole ventral, ventromedian, and ventrolateral.
A variety of glial pathological structures by the modified Gallyas‐Braak method
Authors: Arai Nobutaka , Oda Masaya
Published: October 2007

Recent knowledge on tau‐positive glial abnormal structures and their clinico‐pathological significance were introduced. The structures outlined here, which are strikingly visualized by the modified Gallyas‐Braak method and have tauepitopes, included (i) tuft‐shaped astrocytes, (ii) thorn‐shaped astrocytes, (iii) glial coiled bodies, (iv) argyrophilic threads, (v) firework‐like structures and (vi) argyrophilic perivascular astrocytic feet. This study concludes that the tuft‐shaped astrocytes are favored in cases of progressive supranuclear palsy (PSP), and that there is a massive appearance of both the argyrophilic threads and the firework‐like structures characteristic in prototype of corticobasal degeneration (CBD). Unlike these structures, glial coiled bodies were observed in a wider range of neurological diseases such as PSP, CBD and some other cases with precocious appearance of the neurofibrillary tangles, although the glial coiled bodies were rare in routine laboratory examination and were not always uniform in their configuration. Thus, the modified Gallyas‐Braak method is useful for the diagnosing of some neurodegenerative diseases with tau abnormalities, especially of PSP and CBD. It must be noted, however, that this method could also impregnate tau‐negative structures such as glial cytoplasmic inclusions (oligodendroglial microtubular tangles) in multiple system atrophy or grumose or foamy spheroid body in various conditions, especially in PSP and CBD.
Similarities and differences among progressive among progressive supranuclear palsy, corticobasal degeneration and Pick's disease
Authors: Wakabayashi Koichi , Takahashi Hitoshi
Published: October 2007

Corticobasal degeneration CBD) bears some resemblance to progressive supranuclear palsy (PSP) with regard to its widespread neuroal and glial cytoskeletal abnormalities. In addition, CBD and Pick's disease (PD) are both characterized by circumscribed cerebral atrophy and cortical ballooned neurons. Clinically, all three disease can present with a dementia and may be confused with each other. We examined the morphology and differential distribution of glial fibrillary tangles in PSP (n= 10), CBD (n= 3) and PD with Pick bodies (n= 2). Ballooned neurons were found in two cases of PSP but were much fewer than those found in the CBD or PD. Althought the subcortical lesions in PSP and CBD were similar, the involvement of the subthalamic and dentate nuclei was less severe in the latter. Gallyas‐Breaak method revealed that tuft‐shaped astrocytes were found almost exclusively in PSP, whereas astrocytic plaques were specific for CBD. None or few argyrophilic structures were visualized in PD. These findings indicate that each disorder is a distinct pathological entity. It is possible that a subpopulation of previous cases reported as unusual case of PD without Pick bodies may be additional examples of CBD.
Alteration of glial cell line‐derived neurotrophic factor family receptor alpha‐2 mRNA expression and its co‐expression with neuronal nitric oxide synthase in pelvic ganglia following unilateral cavernous nerve injury
Authors: Hisasue Shin‐ichi , Kato Ryuichi , Kobayashi Ko , Suetomi Takahiro , Kiyama Hiroshi , Tsukamoto Taiji
Published: October 2007

Objectives:  The goal of this study was to determine the alterations of glial cell line‐derived neurotrophic factor family receptor alpha‐2 (GFRα2) mRNA expression in the major pelvic ganglia (MPG) and their relationship to the marker for the neural plasticity (growth‐associated protein 43: GAP‐43) and neuronal nitric oxide synthase (nNOS)‐positive neurons following cavernous nerve injury.

Methods:  Cavernous nerves were transected unilaterally in 24 Sprague‐Dawley rats aged 8 weeks. We used nine sham operated same animals as controls. Bilateral MPGs were harvested at 1, 3, and 6 months following nerve injury. The GFRα2 and GAP‐43 mRNA expressions of the sham group and the injury group (3 months after surgery) were investigated by reverse transcription‐polymerase chain reaction. We also investigated the expression profile of GFRα2 mRNA by in situ hybridization combined with nNOS immunostaining.

Results:  It was revealed semi‐quantitatively that the GAP43 mRNA expression moderately increased in the intact MPG, and GFRα2 mRNA was maintained in the intact MPG but not in the injured one. A histological double‐labeling study showed that the number of GFRα2 mRNA‐ and nNOS‐positive neurons increased in the intact MPG and most GFRα2 mRNA expressions were colocalized with nNOS immunostaining.

Conclusions:  The current study suggested that the GFRα2 mRNA alteration closely related to the nNOS expression following the cavernous nerve injury, which would be involved in the maintenance and recovery of erectile function.
Intraspecific diversity and dominant genotypes resist plant invasions
Authors: Crutsinger Gregory M. , Souza Lara , Sanders Nathan J.
Published: October 2007

Numerous studies have asked whether communities with many species deter invasions more so than do species‐poor communities or whether dominant species deter invasion by colonizing species. However, little is known about whether high intraspecific diversity can deter biological invasions or whether particular genotypes might deter invasions. In this study, we present experimental evidence that intraspecific diversity and particular genotypes of tall goldenrod, Solidago altissima, can act as a barrier to colonization by new species. We found that biomass of colonizing species was negatively correlated with genotypic diversity, and particular genotypes affected the richness, cover, and biomass of colonizing species. Stem density of S. altissima increased with genotypic diversity and varied among genotypes, suggesting that stem density is a key mechanism in limiting colonization dynamics in this system. Our results indicate that the loss of intraspecific diversity within a dominant plant species can increase susceptibility to plant invasions.
Rosiglitazone prevents diabetes by increasing beta‐cell mass in an animal model of type 2 diabetes characterized by reduced beta‐cell mass at birth
Authors: Holloway A. C. , Petrik J. J. , Bruin J. E. , Gerstein H. C.
Published: October 2007

Aim:  Interventions that preserve or increase beta‐cell mass may also prevent type 2 diabetes. Rosiglitazone prevents diabetes in people with high glucose levels who have impaired glucose tolerance and/or impaired fasting glucose. The effect of this drug on both glucose levels and beta‐cell mass was studied in a rat model of diabetes, characterized by reduced beta‐cell mass at birth with normoglycaemia, and progression to dysglycaemia with age.

Methods:  Female Wistar rats were given either saline (vehicle) or nicotine during pregnancy and lactation. Offspring of saline‐exposed dams were given vehicle and offspring of nicotine‐exposed dams were randomized to receive either vehicle or rosiglitazone starting at weaning. Beta‐cell mass, proliferation and apoptosis were determined at birth and at 4 and 26 weeks of age. Glucose homeostasis was examined following sequential oral glucose tolerance tests (OGTT).

Results:  Rosiglitazone treatment prevented the development of dysglycaemia in nicotine‐exposed animals. The ability of rosiglitazone to preserve normoglycaemia appeared to be because of its ability to increase beta‐cell mass through a combination of enhanced beta‐cell proliferation and decreased beta‐cell apoptosis.

Conclusions:  These results suggest that if rosiglitazone administration is started prior to the onset of glucometabolic abnormalities, it prevents the onset of dysglycaemia by partially restoring beta‐cell mass in animals with reduced beta‐cell mass at birth.
Effects of combined PPARγ and PPARα agonist therapy on reverse cholesterol transport in the Zucker diabetic fatty rat
Authors: Tanabe J. , Tamasawa N. , Yamashita M. , Matsuki K. , Murakami H. , Matsui J. , Sugimoto K. , Yasujima M. , Suda T.
Published: October 2007

Aim:  We investigated the effects of the combined therapy of PPARγ and PPARα agonists on HDL metabolism, especially concerning reverse cholesterol transport (RCT), using Zucker diabetic fatty rats (ZDF/Crl‐Leprfa rats) that are the rodent model for type 2 diabetes with obesity, hyperlipidaemia and insulin resistance.

Methods:  The ZDF rats were divided into four medicated groups as follows: pioglitazone as a PPARγ agonist (5 mg/kg/day; P group, n = 6), fenofibrate as a PPARα agonist (30 mg/kg/day; F group, n = 6), both these medications (P + F group, n = 6) and no treatment (UNT group, n = 6). Non‐diabetic rats (ZDF/GmiCrl‐lean, CON group, n = 6) served as controls. We evaluated HDL particle size and messenger RNA (mRNA) levels of the following factors: liver X receptor α (L × R α), ATP‐binding cassette A1 (ABCA1) and ABCG1 which are regulated by PPARs and are related to early stage RCT.

Results:  The significant increase in HDL particle size was demonstrated in rats of the F and P + F groups, although changes in plasma HDL‐cholesterol levels were not significant. In accordance with this finding, mRNA levels of ABCG1 in the liver increased significantly.

Conclusions:  These findings suggest the efficacy of combined therapy with PPARγ and PPARα in improving lipid metabolism, partly through the enhanced RCT, and insulin resistance in type 2 diabetes mellitus.
Efficacy of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide (P32/98) in fatty Zucker rats with incipient and manifest impaired glucose tolerance
Authors: Augstein P. , Berg S. , Heinke P. , Altmann S. , Salzsieder E. , Demuth H. U. , Freyse E. J.
Published: October 2007

Aim:  Incretin enhancers are a new class of antidiabetic drugs with promising therapeutic potential for type 2 diabetes. Therapeutic intervention in prediabetes is an attractive strategy for preventing or delaying diabetes onset. The aim of the present study was to investigate the therapeutic effects of incretin enhancement on incipient impaired glucose tolerance (iIGT) and manifest IGT (mIGT) using the dipeptidyl peptidase IV (DPP‐4) inhibitor P32/98‐ and fatty Zucker rat (ZR, fa/fa) as a model.

Methods:  ZRs were classified into groups with iIGT and mIGT (n = 10 per group). P32/98 (21.61 mg/kg body weight) was administered orally to ZR with iIGT and mIGT once daily for 6 and 3 weeks respectively. Assessments included body weight, morning blood glucose and insulin, oral glucose tolerance test (oGTT; 2 g glucose/kg), plasma parameters and blood glucose day–night profile (DNP). In addition, glucose responsiveness of isolated islets and islet morphology were analysed.

Results:  P32/98 decreased non‐fasting morning blood glucose more effectively in ZR with iIGT than in ZR with mIGT. Compared with study entry, P32/98 improved DNP of blood glucose in ZR with mIGT and nearly normalized DNP in ZR with iIGT. An acute bolus of inhibitor reduced glucose load during oGTT in rats chronically treated with placebo or P32/98. In contrast to placebo‐treated rats, rats receiving long‐term treatment with P32/98 required less insulin during oGTT. This effect was larger in rats with iIGT vs. rats with mIGT. In isolated pancreatic islets of ZR with mIGT, treatment with P32/98 decreased pancreatic insulin content and increased glucose responsiveness, while the β‐cell volume density was unaffected. P32/98 significantly reduced triglycerides and non‐esterified fatty acids. Intestinal growth was comparable between inhibitor‐ and placebo‐treated fatty rats.

Conclusions:  Enhancement of incretin with the DPP‐4 inhibitor P32/98 has therapeutic effects in hyperinsulinaemia, hyperglycaemia and IGT in ZR with iIGT and mIGT. Apparently, administration of P32/98 in ZR with iIGT results in more efficient β‐cell function, which is associated with less need for insulin to cope with deterioration of glucose tolerance. Importantly, P32/98 has a strong effect on dyslipidaemia in mIGT. P32/98 has no side effect on intestinal growth. Daily intake of P32/98 is a promising strategy for treatment of glucose intolerance and has the potential to prevent type 2 diabetes.
Polyphyly across oceans: a molecular phylogeny of the Chromodorididae (Mollusca, Nudibranchia)
Authors: Turner Lucy M. , Wilson Nerida G.
Published: October 2007

The Chromodorididae is a large and colourful family of nudibranch sea slugs distributed across the world's oceans. Most diversity is centred in the Indo‐Pacific, but several genera are present in multiple ocean basins, or across regions separated by biogeographical barriers. The monophyly of these widespread genera had not been tested previously. We used 18S rDNA, 16S rDNA and COI sequence data to generate a molecular phylogeny for this group. We recovered evidence of paraphyly or polyphyly in all of the widespread genera examined (Hypselodoris,Mexichromis,ChromodorisandGlossodoris). East AtlanticHypselodorisand west Atlantic + east PacificMexichromisspecies were more closely related to each other than they were to their Indo‐Pacific congeners. The addition of Southern Ocean species ofDigidentisdemonstrated an interesting alternative to this relationship, becoming the sister group for the east AtlanticHypselodorison the basis of 16S and 18S data, but not COI data. Sister group relationships were recovered for most monotypic or enigmatic genera.Ardeadorisis linked toGlossodoris, as isDiversidoris;Pectenodorisis sister to the Indo‐PacificMexichromisclade, andVerconiais the sister toNoumea haliclona. Controversy surrounding the placement of the three most basal genera was only partially resolved. UsingActinocyclusto root the mitochondrial trees,Cadlinellawas the unsupported sister to the Chromodorididae (excludingCadlina), andTyrinnaoccupied a relatively basal position, although this also did not receive significant statistical support. Adding nuclear 18S data gave support forCadlinaas the sister group to the rest of the Chromodorididae s.s. Otherwise, like previous molecular studies, mitochondrial genes supported an alternative position forCadlina(with other dorid genera).
Declining mortality from bladder cancer in Europe
Authors: Ferlay Jacques , Randi Giorgia , Bosetti Cristina , Levi Fabio , Negri Eva , Boyle Peter , La Vecchia Carlo
Published: October 2007

OBJECTIVE

To update trends in bladder cancer mortality in 32 European countries and the European Union (EU) as a whole, as mortality from bladder cancer has been declining in most of Western Europe since the early 1990s, but it has still been increasing in several central and eastern European countries up to the mid 1990s.

METHODS

We used data from the World Health Organization (WHO) database over the period 1970–2004. Significant changes in mortality rates were identified using join‐point regression analysis.

RESULTS

In the EU overall (27 countries), bladder cancer mortality rates (age‐standardized, world standard population) were stable up to the early 1990s at ≈ 7/100 000 men and 1.5/100 000 women, and declined thereafter by ≈ 16% in men and 12% in women, to reach values of 6 and 1.3/100,000, respectively, in the early years of the present decade. Over recent years, most countries showed decreasing trends, except Croatia and Poland in both sexes, Romania in men and Denmark in women. Truncated rates at age 35–64 years were lower in both sexes and trends for men were more favourable, with an overall decrease by >21% during the last decade. Join point regression analysis indicates that, for most countries, the trends were more favourable over recent calendar periods.

CONCLUSION

The favourable trends in men are partly or largely due to the recent declines in the prevalence of smoking in European men, together with reduced occupational exposure to occupational carcinogens. The decreases in women are more difficult to explain. Better control of urinary tract infections has probably played a role, while the role of diet and other potential urinary tract carcinogens remains undefined.
Prevailing therapeutic regimes and predictive factors for prandial insulin substitution in 26 687 children and adolescents with Type 1 diabetes in Germany and Austria
Authors: Knerr I. , Hofer S. E. , Holterhus P. M. , Näke A. , Rosenbauer J. , Weitzel D. , Wolf J. , Holl R. W.
Published: October 2007

Aims  To analyse current therapeutic strategies for prandial insulin substitution in a large number of children and adolescents with Type 1 diabetes in Germany and Austria, along with changes in therapeutic habits and outcome.

Methods  We classified the data of 26 687 patients, treated from 1995 to 2005 in 152 paediatric clinics, using a database established for quality control and scientific surveys in paediatric diabetology (DPV).

Results  Seventy‐three per cent of all patients (mean age 13.6 years., mean duration of diabetes 5.4 years.) were treated with ≥ 4 daily injections (intensified conventional treatment; ICT), 14% with continuous subcutaneous insulin infusion (CSII), 13% with 1–3 injections per day (conventional treatment). Frequency of daily injections increased with age, duration of diabetes and insulin dose. The insulin dose at breakfast was higher than for the evening meal or lunch, from diagnosis onwards. Individuals using insulin analogues received up to 11% higher insulin doses per day compared with patients treated with human insulin. The time of day, age, duration of diabetes, female gender, insulin analogues and ICT all had a significant influence on prandial insulin doses. Although the number of patients treated with ICT or CSII increased over the period of observation, mean glycated haemoglobin (HbA1c) was approximately 8.0% each year, and decreased by only 0.01%.

Conclusions  Eighty‐seven per cent of patients were treated with ICT or CSII. However, while this percentage increased over the observation period, mean HbA1c was almost constant. Longer duration of diabetes, increasing age, female gender, insulin analogues and ICT were associated with higher prandial insulin doses.
Performance and comparison of the Cockcroft–Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population
Authors: Dong X. , He M. , Song X. , Lu B. , Yang Y. , Zhang S. , Zhao N. , Zhou L. , Li Y. , Zhu X. , Hu R.
Published: October 2007

Aims  Our aim was to assess performances of the Cockcroft–Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks.

Methods  A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m2) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima‐media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared.

Results  The prevalence of low estimated GFR was 32.7% with the Cockcroft–Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft–Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft–Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks.

Conclusions  These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft–Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.
Increased serum pigment epithelium‐derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes1
Authors: Jenkins A. J. , Zhang S. X. , Rowley K. G. , Karschimkus C. S. , Nelson C. L. , Chung J. S. , O’Neal D. N. , Januszewski A. S. , Croft K. D. , Mori T. A. , Dragicevic G. , Harper C. A. , Best J. D. , Lyons T. J. , Ma J‐X.
Published: October 2007

Aims  To determine in Type 1 diabetes patients if levels of pigment epithelium‐derived factor (PEDF), an anti‐angiogenic, anti‐inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress.

Methods  Serum PEDF levels were measured by ELISA in a cross‐sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non‐diabetic control subjects. PEDF associations with complication status, pulse‐wave analysis and biochemical results were explored.

Results  PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0–9.6) µg/ml, vs. complication‐free patients [5.3 (4.7–6.0) µg/ml, P < 0.001] and control subjects [5.3 (4.6–6.1) µg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication‐free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = –0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including logeC‐reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule‐1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and logeCRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low‐density lipoprotein or paraoxonase‐1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r2 = 0.427).

Conclusions  In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.
Pregnancy‐associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy—a prospective follow‐up study
Authors: Astrup A. S. , Tarnow L. , Christiansen M. , Hansen P. R. , Parving H.‐H. , Rossing P.
Published: October 2007

Aim  Pregnancy‐associated plasma protein A (PAPP‐A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP‐A in a large cohort of Type 1 diabetic patients.

Methods  In a prospective observational follow‐up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0–10.3) years. PAPP‐A was determined at baseline.

Results  In patients with diabetic nephropathy, plasma PAPP‐A was elevated 3.6 (0.4–51.1) mIU/l [median (range)] vs. 2.1 (0.4–46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP‐A threshold of 10 mIU/l has been suggested. Thirty‐seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP‐A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP‐A was above the threshold 2.1 (95% CI 1.13–3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP‐A was significantly predictive of all‐cause mortality [P = 0.008; 2.43 (1.26–4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP‐A for all‐cause mortality was attenuated (P = 0.064).

Conclusion  We find PAPP‐A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP‐A was no longer significant.
Low‐risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B‐cells 12 months after diagnosis
Authors: Spoletini M. , Petrone A. , Zampetti S. , Capizzi M. , Zavarella S. , Osborn J. , Foffi C. , Tuccinardi D. , Pozzilli P. , Buzzetti R. ,   on behalf of the IMDIAB Group
Published: October 2007

Aims  The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B‐cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B‐cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis.

Methods  Patients were typed for HLA‐DRB1* and DQB1* loci by a reverse line blot assay using an array of immobilized sequence‐specific oligonucleotide probes. C‐peptide, insulin requirement and glycated haemoglobin (HbA1c) were determined at diagnosis and every 3 months for 12 months. The variance of C‐peptide as evidence of B‐cell loss during follow‐up was analysed using the general linear model for repeated‐measures procedure.

Results  Fasting C‐peptide in T1DM subjects with low HLA genetic risk was significantly higher when compared with subjects with moderate or high HLA genetic risk from time of diagnosis up to 12 months (P = 0.007 and P = 0.0002, respectively). Nonetheless, the changes in C‐peptide levels over a 12‐month period did not differ significantly between T1DM subjects with different HLA genetic risks.

Conclusions  Low‐risk HLA genotype in T1DM is associated with less destruction of pancreatic B‐cells up to 12 months after diagnosis. These results are useful when designing trials for therapies aimed to prevent the progression of B‐cell destruction in recent‐onset T1DM.
Distributed Texture Memory in a Multi‐GPU Environment
Authors: Moerschell Adam , Owens John D.
Published: October 2007

In this work, we demonstrate a system that allows texture memory on multiple graphics processing unit (GPUs) to be virtualized in a manner that is both scalable and transparent to the programmer. Our system is built using a directory‐based shared‐memory abstraction to allow texture memory to be distributed while staying consistent. We use texture pages as our basic memory block and discuss the data structures, threading model, and consistency mechanisms necessary to implement a paging system in a multi‐GPU environment. The system is demand‐driven, and pages will only be loaded into the texture memory of a GPU that makes a request. The main contribution of this work is the identification of the mechanisms required to implement our abstraction, as well as the discussion of its limitations in order to make it more efficient.
Local Influence in Generalized Estimating Equations
Authors: JUNG KANG‐MO
Published: October 2007

Abstract. We investigate the influence of subjects or observations on regression coefficients of generalized estimating equations (GEEs) using local influence. The GEE approach does not require the full multivariate distribution of the response vector. We extend the likelihood displacement to a quasi‐likelihood displacement, and propose local influence diagnostics under several perturbation schemes. An illustrative example in GEEs is given and we compare the results using the local influence and deletion methods.
THREE SOLITUDES IN CONTRACT: LAW, DATA, AND THEORY
Authors: MacLeod W. Bentley
Published: October 2007

This note discusses and contrasts the different perspectives that the law, empirical labor economics and contract theory bring to the study of the employment relationship. Understanding the reasons for these different perspectives should give rise to a better understanding of the employment relationship and more effective labor market policy.
REAL WAGE CYCLICALITY IN THE PANEL STUDY OF INCOME DYNAMICS
Authors: Swanson Eric T.
Published: October 2007

Previous studies of real wage cyclicality have made only sparing use of the micro‐data detail that is available in the Panel Study of Income Dynamics (PSID). The present paper brings to bear this additional detail to investigate the robustness of the previous results and to examine whether there are important cross‐sectional and demographic differences in wage cyclicality. Although real wages were procyclical across the entire distribution of workers from 1967 to 1991, the wages of lower‐income, younger, and less‐educated workers exhibited greater procyclicality. However, workers' straight‐time hourly pay rates have been acyclical, suggesting that more variable pay margins such as bonuses, overtime, late shift premia, and commissions have played a substantial if not primary role in generating procyclicality.
NEW EVIDENCE ON REAL WAGE CYCLICALITY WITHIN EMPLOYER–EMPLOYEE MATCHES
Authors: Shin Donggyun , Solon Gary
Published: October 2007

In the most thorough study to date on wage cyclicality among job stayers, Devereux's (2001) analysis of men in the Panel Study of Income Dynamics (PSID) produced two puzzling findings: (1) the real wages of salaried workers are noncyclical, and (2) wage cyclicality among hourly workers differs between two alternative wage measures. We examine these puzzles with additional evidence from other sources. Devereux's finding of noncyclical real wages among salaried job stayers is not replicated in the National Longitudinal Survey of Youth (NLSY) data. The NLSY data, however, do corroborate his finding of a discrepancy for hourly workers between the cyclicality of the two alternative wage measures. Evidence from the PSID Validation Study contradicts Devereux's conjecture that the discrepancy might be due to a procyclical bias from measurement error in average hourly earnings. Evidence from the Bureau of Labor Statistics establishment survey supports his hypothesis that overtime work accounts for part (but not all) of the discrepancy. We conclude that job stayers' real average hourly earnings are substantially procyclical and that an important portion of that procyclicality probably is due to compensation beyond base wages.
THE SPOT MARKET MATTERS: EVIDENCE ON IMPLICIT CONTRACTS FROM BRITAIN
Authors: Devereux Paul J. , Hart Robert A.
Published: October 2007

Based on the methodology of Beaudry and DiNardo (1991), this paper investigates the relative importance of the spot market and implicit contracts in the determination of British real wages. Empirical work is carried out separately for males and females with individual‐level data taken from the New Earnings Survey Panel for the years 1976–2001. In contrast to previous studies that used North American data, the spot market is found to be more important than implicit contracts in determining real wages, although we do find some support for contracting effects. Further evidence is provided through the analysis of individual wage sequences. These suggest that the downwardly rigid wage sequences implied by implicit contracts with costless worker mobility are not prevalent in Britain.
LIMITED COMMITMENT MODELS OF THE LABOUR MARKET
Authors: Thomas Jonathan P. , Worrall Tim
Published: October 2007

We present an overview of models of long‐term self‐enforcing labour contracts in which risk‐sharing is the dominant motive for contractual solutions. A base model is developed that is sufficiently general to encompass the two‐agent problem central to most of the literature, including variable hours. We consider two‐sided limited commitment and look at its implications for aggregate labour market variables. We consider the implications for empirical testing and the available empirical evidence. We also consider the one‐sided limited commitment problem for which there exists a considerable amount of empirical support.
Restructuring, Environmentalism and the Problem of Farm Safety
Authors: Hall Alan
Published: October 2007

This article examines the health and safety perceptions and practices of conventional, no till and organic grain farmers in Ontario Canada. Based on 12 intensive case studies, the analysis examines whether different restructuring and environmental orientations are related to different approaches to occupational health and safety. The analysis suggests that although there is a substantial level of awareness and knowledge of health and safety hazards among all the farmers, significant differences in practices are linked in complex and somewhat unexpected ways to the production and environmental approaches of the farmers. In particular, while economic constraints and rationales provide an overriding basis for risk‐taking across all the farmers, the level and form that this takes is shaped by farmer orientations to farm management and the environment. The article also links both the common patterns and variations in farmer practices to corporate and government discourses on the prevention of environmental and occupational injuries, suggesting that mixed messages undermine any effort to intensify farmer commitment to safety.
Multifunctionality in Agriculture and its Agents: Regional Comparisons
Authors: Dufour A. , Mauz I. , Rémy J. , Bernard C. , Dobremez L. , Havet A. , Pauthenet Y. , Pluvinage J. , Tchakérian E.
Published: October 2007

Drawing on a multidisciplinary survey carried out in three contrasting areas of the Rhône‐Alpes Region in France, this article investigates how the concept of multifunctionality has been understood and appropriated. After a retrospective look at French agricultural policy, the first part presents our analytical framework, which is inspired by the sociology of action. The second part analyses the socio‐political issues of farming in each area and the compromises established around the various functions attributed to agriculture. The third part highlights the different ways of considering and practising farming, as well as the social expectations towards agriculture. This regional comparison shows that professional identities are constructed at local levels in different places: the farms and their neighbourhood, local groups and agricultural organisations. Local agreements on agriculture and the construction of professional identities take into account multifunctionality in specific ways, which depend on the social and economic relationships that the farmers have established with their fellow citizens.