Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Response:Ideas are ten a penny - It's team implementation not idea generation that counts

Cet article présente une synthèse des recherches et théories qui éclairent notre compréhension de la créativité et de la mise en oeuvre de l’innovation dans les groupes de travail. Il semble que la créativité apparaisse essentiellement au cours des premières étapes du processus, avant la mise en oeuvre. On étudie l’influence des caractéristiques de la tâche, des capacités et de l’éventail des connaissances du groupe, des demandes externes, des mécanismes d’intégration et de cohérence de groupe. La perception d’une menace, l’incertitude ou de fortes exigences entravent la créativité, mais favorisent l’innovation. La diversité des connaissances et des capacités est un bon prédicteur de l’innovation, mais l’intégration du groupe et les compétences sont indispensables pour récolter les fruits de la diversité. On examine aussi les implications théoriques et pratiques de ces considérations. In this article I synthesise research and theory that advance our understanding of creativity and innovation implementation in groups at work. It is suggested that creativity occurs primarily at the early stages of innovation processes with innovation implementation later. The influences of task characteristics, group knowledge diversity and skill, external demands, integrating group processes and intragroup safety are explored. Creativity, it is proposed, is hindered whereas perceived threat, uncertainty or other high levels of demands aid the implementation of innovation. Diversity of knowledge and skills is a powerful predictor of innovation, but integrating group processes and competencies are needed to enable the fruits of this diversity to be harvested. The implications for theory and practice are also explored.

Neuropathological changes in ten cases of neuronal intermediate filament inclusion disease (NIFID):A study using α-internexin immunohistochemistry and principal components analysis (PCA)

Ten cases of neuronal intermediate filament inclusion disease (NIFID) were studied quantitatively. The α-internexin positive neurofilament inclusions (NI) were most abundant in the motor cortex and CA sectors of the hippocampus. The densities of the NI and the swollen achromatic neurons (SN) were similar in laminae II/III and V/VI but glial cell density was greater in V/VI. The density of the NI was positively correlated with the SN and the glial cells. Principal components analysis (PCA) suggested that PC1 was associated with variation in neuronal loss in the frontal/temporal lobes and PC2 with neuronal loss in the frontal lobe and NI density in the parahippocampal gyrus. The data suggest: 1) frontal and temporal lobe degeneration in NIFID is associated with the widespread formation of NI and SN, 2) NI and SN affect cortical laminae II/III and V/VI, 3) the NI and SN affect closely related neuronal populations, and 4) variations in neuronal loss and in the density of NI were the most important sources of pathological heterogeneity. © Springer-Verlag 2005.

A quantitative study of the pathological changes in ten patients with multiple system atrophy (MSA)

The densities of the glial cytoplasmic inclusions (GCI), neuronal inclusions (NI), and abnormal neurons were studied in the frontal cortex, hippocampus, cerebellum, basal ganglia and areas of the pons and medulla in 10 cases of multiple system atrophy (MSA). GCI density was greater in the substantia nigra and globus pallidus compared with the frontal cortex and hippocampus. Abnormal neurons were most abundant in the frontal cortex, substantia nigra, and inferior olivary nucleus. NI and abnormal neuron densities were positively correlated in the globus pallidus but negatively correlated in the hippocampus. The NI and GCI were only positively correlated in the pons. GCI in the pons and inferior olivary nucleus, NI in the substantia nigra, and abnormal neurons in the frontal cortex varied significantly between cases. The MSA cases did not cluster according to disease subtype. The data suggest that: 1) the greatest densities of pathological changes occur in the substantia nigra and globus pallidus, 2) density of the GCI is unrelated to that of the NI, and 3) there is overlapping pathology between the various subtypes of MSA.

Quantification of pathological lesions in the frontal and temporal lobe of ten patients diagnosed with Pick's disease

The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick's disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.

The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than a-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than a-internexin IHC.

Privatisation in Poland:ten years after

The purpose of this article is to compare economic discussion on privatisation, expected privatisation outcomes and actual results in Poland. First it discusses the privatisation of state enterprises in the broader context of the economic transformation programme designed and introduced at the end of 1989 and the beginning of 1990. It examines the choice of privatisation methods, the political economy of privatisation and the three major policy issues: pace of privatisation, sequence of privatisation and the authority to initiate and carry out privatisation. The final section compares privatisation blueprints and actual results. The appendix presents a detailed technical guide to the privatisation methods in Poland and a basic set of figures illustrating the outcome.

Much ado about not-very-much? Assessing ten years of German citizenship reform

This article examines the development and impact of German citizenship policy over the past decade. As its point of departure, it takes the 2000 Citizenship Law, which sought to undertake a full-scale reform and liberalisation of access to German membership. The article discusses this law’s content and subsequent amendments, focusing particularly on its quantitative impact, asking why the number of naturalisations has been lower than originally expected. The article outlines current challenges to the law’s structure operation and identifies potential trajectories for its future development.

The ten myths of manufacturing:what does the future hold for UK manufacturing?

The recent recession has caused upheaval for the economies worldwide. The impact has been felt enormously all over and especially in the manufacturing sector. This report discusses significant data on China's manufacturing industry that suggests they are already growing again despite recent events, while India has continued to maintain their efforts. One question the report raises is as the balance of economic power shifts to the East, what if the future for the once great UK manufacturing industry?

A joint approach to treating dental phobia:a re-evaluation of a collaboration between community dental services and specialist psychotherapy services ten years on

Objective To audit the records of a group of patients who had previously benefited from cognitive behavioural therapy (CBT) for dental phobia.Aim To ascertain if they had returned to the use of intravenous (IV) sedation to facilitate dental treatment. Ten years ago these patients were routinely requiring IV sedation to facilitate dental treatment due to severe dental phobia.Method Sixty patients entered the original pilot project. Of those, 30 were offered CBT and 21 attended. Twenty of those patients (95.2%) were subsequently able to have dental treatment without IV sedation. In this follow-up study the electronic records of 19 of the 20 patients who had originally been successful with CBT were re-audited. Our purpose was to see if there was any record of subsequent IV sedation administration in the intervening ten years.Results Of the 19 successful CBT patients available to follow-up, 100% had not received IV sedation since the study ten years ago. This may suggest the initial benefit of CBT has endured over the ten-year period.Conclusion This study indicates that the use of CBT for patients with dental phobia proves beneficial not only in the initial treatment but that the benefits may endure over time. This results in a significant reduction in health risks to the patient from repeated IV sedation. It may also translate into significant financial savings for dental care providers. Our evidence for CBT as treatment for dental phobia suggests dental services should be implementing this approach now rather than pursuing further research. © 2011 Macmillan Publishers Limited. All rights reserved.

Gender, Work and Employment in Ten Candidate Countries of Central and Eastern Europe. Final Report. Country: Hungary

The Hungarian media shows very contradictory pictures of women today: Successful career women enjoying material well-being is one picture, while the careful mother not working outside the home, keeping together the family is another one. Between these two contradictory poles there are almost no other female actors in the media. Life produces something different. In spite of the fact that there was a big loss of jobs in 1990s, and women’s activity rate decreased while the unemployment rate increased compared to before the 1990s, woman with duel roles are still accepted and common. The first female task is looking after the family and the second one is working outside the home and earning money. In many cases there is a third role: studying in distant or evening courses. In the next chapters we go deeper into this topic. We analyse the different aspects of female labour market positions, and show some relevant characteristics of governmental parental benefits and childcare support, and examine how the new pension system effects women. We also have a quick look at trade unions and show their lack of activity around gender issues. In the labour market analysis of the position of women we use labour force surveys, institution-based labour statistics, and unemployment registers. The Appendix 1 contains short descriptions of these data sources.

Where now after ten years of Eastern enlargement?

The aim of this article is to evaluate the situation of the Central and Eastern European countries within the EU on the 10th anniversary of the Eastern Enlargement. Since 2004, the region has shown a trend to catch up with Western Europe in terms of both employment and economic performance. However, the financial and economic crisis which started in 2008 disrupted the previous trends of convergence for some, and greater differences emerged between individual countries' performances. The eastward enlargement has practically doubled labour mobility within the EU, and this phenomenon is likely to be sustained as long as income disparities between Member States persist. The 2004 and 2007 enlargements brought more welfare to the countries receiving mobile workers, whereas countries of origin bear the real risks of labour mobility from east to west. Today, it can be said that most of the newer Member States, irrespective of the varying speeds of convergence have developed within the EU as an 'inner periphery'. In order to make better use of the potential for economic growth in Central-Eastern Europe, investing in human capital should become a priority. The major question for the second decade of our enlarged European Union - aside from the reform of the monetary union - is whether the EU’s eastern region can continue to catch up without the internal socio-economic polarisation observed thus far, and whether the latter process can in fact be reversed.

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.