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Showing papers by "University of Kiel published in 2002"


Journal ArticleDOI
TL;DR: Patients with Crohn's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54, to discontinue corticosteroids, and to maintain their response for a longer period of time, if inflIXimab treatment is maintained every 8 weeks.

3,870 citations


Journal ArticleDOI
TL;DR: Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells.

2,424 citations


Journal ArticleDOI
Pavel Kroupa1
04 Jan 2002-Science
TL;DR: Combining IMF estimates for different populations in which the stars can be observed individually unveils an extraordinary uniformity of the IMF, which appears to hold for populations including present-day star formation in small molecular clouds.
Abstract: The distribution of stellar masses that form in one star formation event in a given volume of space is called the initial mass function (IMF). The IMF has been estimated from low-mass brown dwarfs to very massive stars. Combining IMF estimates for different populations in which the stars can be observed individually unveils an extraordinary uniformity of the IMF. This general insight appears to hold for populations including present-day star formation in small molecular clouds, rich and dense massive star-clusters forming in giant clouds, through to ancient and metal-poor exotic stellar populations that may be dominated by dark matter. This apparent universality of the IMF is a challenge for star formation theory, because elementary considerations suggest that the IMF ought to systematically vary with star-forming conditions.

1,733 citations


Posted Content
TL;DR: In this paper, a comprehensive evaluation of the empirical evidence on productivity, wages and exports spillovers in developing, developed and transitional economies is presented. But, although theory can identify a range of possible spillover channels, robust empirical support for positive spillovers is hard to find.
Abstract: Many governments offer significant inducements to attract inward investment, motivated by the expectation of spillover benefits. This paper begins by reviewing possible sources of spillovers. It then provides a comprehensive evaluation of the empirical evidence on productivity, wages and exports spillovers in developing, developed and transitional economies. Although theory can identify a range of possible spillover channels, robust empirical support for positive spillovers is hard to find. The reasons for this are explored and the paper concludes with a review of policy aspects.

1,508 citations


Journal ArticleDOI
TL;DR: In this paper, a Fortran 90 program (REDFIT) is presented that overcomes this problem by fitting a first-order autoregressive (AR1) process, being characteristic for many climatic processes, directly to unevenly spaced time series.

1,048 citations


Journal ArticleDOI
TL;DR: High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin's disease irrespective of length of initial remission.

968 citations


Journal ArticleDOI
TL;DR: The resulting network exhibits a scale-free link distribution and pronounced small-world behavior, as observed in other social networks, implying that the spreading of e-mail viruses is greatly facilitated in real e- mail networks compared to random architectures.
Abstract: We study the topology of e-mail networks with e-mail addresses as nodes and e-mails as links using data from server log files. The resulting network exhibits a scale-free link distribution and pronounced small-world behavior, as observed in other social networks. These observations imply that the spreading of e-mail viruses is greatly facilitated in real e-mail networks compared to random architectures.

954 citations


Journal ArticleDOI
TL;DR: In this article, all manifestations of pores in silicon are reviewed and discussed with respect to possible applications, with particular emphasis on macropores, which are classified in detail and reviewed in the context of pore formation models.
Abstract: All manifestations of pores in silicon are reviewed and discussed with respect to possible applications. Particular emphasis is put on macropores, which are classified in detail and reviewed in the context of pore formation models. Applications of macro-, meso-, and micropores are discussed separately together with some consideration of specific experimental topics. A brief discussion of a stochastic model of Si electrochemistry that was found useful in guiding experimental design for specific pore formation concludes the paper.

749 citations


Journal ArticleDOI
TL;DR: In this paper, in situ measurements and a model-assimilated dataset reveals a strong influence of subsurface thermocline variability on sea surface temperature (SST) in this upwelling zone.
Abstract: A unique open-ocean upwelling exists in the tropical South Indian Ocean (SIO), a result of the negative wind curl between the southeasterly trades and equatorial westerlies, raising the thermocline in the west. Analysis of in situ measurements and a model-assimilated dataset reveals a strong influence of subsurface thermocline variability on sea surface temperature (SST) in this upwelling zone. El Nino-Southern Oscillation (ENSO) is found to be the dominant forcing for the SIO thermocline variability, with SST variability off Sumatra, Indonesia, also making a significant contribution. When either an El Nino or Sumatra cooling event takes place, anomalous easterlies appear in the equatorial Indian Ocean, forcing a westward-propagating downwelling Rossby wave in the SIO. In phase with this dynamic Rossby wave, there is a pronounced copropagation of SST. Moreover, a positive precipitation anomaly is found over, or just to the south of, the Rossby wave-induced positive SST anomaly, resulting in a cyclonic circulation in the surface wind field that appears to feedback onto the SST anomaly. Finally, this downwelling Rossby wave also increases tropical cyclone activity in the SIO through its SST effect. This coupled Rossby wave thus offers potential predictability for SST and tropical cyclones in the western SIO. These results suggest that models that allow for the existence of upwelling and Rossby wave dynamics will have better seasonal forecasts than ones that use a slab ocean mixed layer. The lagged-correlation analysis shows that SST anomalies off Java, Indonesia, tend to precede those off Sumatra by a season, a time lead that may further increase the Indian Ocean predictability.

739 citations


Posted Content
Holger Ernst1
TL;DR: In this article, the authors reviewed the findings of empirical work into the success factors of new product development (NPD) and summarized the most important findings in a compact and structured way.
Abstract: The continuous development and market introduction of new products can be an important determinant of sustained company performance. For approximately 30 years, conceptual and empirical research has been undertaken to identify the critical success factors of new products. This paper reviews the findings of empirical work into the success factors of new product development (NPD). It is the prime objective of this work to summarize the most important findings in a compact and structured way. In addition, shortcomings of previous empirical work on NPD success factors will be discussed and suggestions for improvement in future empirical NPD studies will be made.

680 citations


Journal ArticleDOI
TL;DR: The R702W, G908R, and 3020insC mutations are strong independent risk factors for CD and are associated particularly with ileal disease.

Book
01 Jan 2002
TL;DR: The 19 chapters presented in this multi-author monograph give a consolidated overview of the research results achieved in the theory of automata, logics, and infinite games during the past 10 years.
Abstract: A central aim and ever-lasting dream of computer science is to put the development of hardware and software systems on a mathematical basis which is both firm and practical. Such a scientific foundation is needed especially for the construction of reactive programs, like communication protocols or control systems. For the construction and analysis of reactive systems an elegant and powerful theory has been developed based on automata theory, logical systems for the specification of nonterminating behavior, and infinite two-person games. The 19 chapters presented in this multi-author monograph give a consolidated overview of the research results achieved in the theory of automata, logics, and infinite games during the past 10 years. Special emphasis is placed on coherent style, complete coverage of all relevant topics, motivation, examples, justification of constructions, and exercises.

Journal ArticleDOI
TL;DR: The method for algae differentiation described here opens up new research areas, monitoring and supervision tasks related to photosynthetic primary production in aquatic environments.
Abstract: Fingerprints of excitation spectra of chlorophyll (Chl) fluorescence can be used to differentiate 'spectral groups' of microalgae in vivo and in situ in, for example, vertical profiles within a few seconds. The investigated spectral groups of algae (green group, Chlorophyta; blue, Cyanobacteria; brown, Heterokontophyta, Haptophyta, Dinophyta; mixed, Cryptophyta) are each characterised by a specific composition of photosynthetic antenna pigments and, consequently, by a specific excitation spectrum of the Chl fluorescence. Particularly relevant are Chl a, Chl c, phycocyanobilin, phycoerythrobilin, fucoxanthin and peridinin. A laboratory-based instrument and a submersible instrument were constructed containing light-emitting diodes to excite Chl fluorescence in five distinct wavelength ranges. Norm spectra were determined for the four spectral algal groups (several species per group). Using these norm spectra and the actual five-point excitation spectrum of a water sample, a separate estimate of the respective Chl concentration is rapidly obtained for each algal group. The results of dilution experiments are presented. In vivo and in situ measurements are compared with results obtained by HPLC analysis. Depth profiles of the distribution of spectral algal groups taken over a time period of few seconds are shown. The method for algae differentiation described here opens up new research areas, monitoring and supervision tasks related to photosynthetic primary production in aquatic environments.

Journal ArticleDOI
TL;DR: In this article, the spatial distribution of centennial-scale climate records of MIS 3 glacial, terrestrial and marine sites have been compiled in three tables according to their temporal resolution and publication status.

Journal ArticleDOI
20 Jun 2002-Nature
TL;DR: The effects of consumers and nutrients on diversity consistently depend on each other, and that the direction of their effects and peak diversity shift between sites of low and high productivity, suggesting human impacts on nutrient supply and food-web structure have strong and interdependent effects on species diversity and ecosystem functioning, and must therefore be managed together.
Abstract: A key question in ecology is which factors control species diversity in a community1, 2, 3. Two largely separate groups of ecologists have emphasized the importance of productivity or resource supply, and consumers or physical disturbance, respectively. These variables show unimodal relationships with diversity when manipulated in isolation4, 5, 6, 7, 8. Recent multivariate models9, 10, however, predict that these factors interact, such that the disturbance–diversity relationship depends on productivity, and vice versa. We tested these models in marine food webs, using field manipulations of nutrient resources and consumer pressure on rocky shores of contrasting productivity. Here we show that the effects of consumers and nutrients on diversity consistently depend on each other, and that the direction of their effects and peak diversity shift between sites of low and high productivity. Factorial meta-analysis of published experiments confirms these results across widely varying aquatic communities. Furthermore, our experiments demonstrate that these patterns extend to important ecosystem functions such as carbon storage and nitrogen retention. This suggests that human impacts on nutrient supply11 and food-web structure12, 13 have strong and interdependent effects on species diversity and ecosystem functioning, and must therefore be managed together.

Journal ArticleDOI
Thomas Bohlen1
TL;DR: This implementation greatly expands the applicability of the 3-D elastic/viscoelastic finite-difference modelling technique by providing an efficient, portable and practical C-program.

Journal ArticleDOI
TL;DR: A distinct relation between NOD2 genotype and phenotype of Crohn's disease is recorded, which could lead to the development of new therapeutic paradigms.

Journal ArticleDOI
TL;DR: Overall, SRP plus systemic antimicrobial groups demonstrated better results in CAL and PPD change than SRP alone or with placebo groups, and showed a statistically significant additional benefit for spiramycin (PPD change) and amoxicillin/metronidazole (CAL change) in deep pockets.
Abstract: Background: Scaling and root planing (SRP) are the bases of non-surgical therapy in the treatment of periodontitis. However, results from this therapy are often unpredictable and dependable from many different factors. Objectives: The aim of this systematic review was to evaluate the effectiveness of the adjunctive use of systemic antimicrobials with scaling and root planing (SRP) vs. SRP alone in the treatment of chronic (CP) or aggressive periodontitis (AgP). Search strategy: Use of computerized databases, namely MEDLINE, the Cochrane Oral Health Group Specialty Trials Register and EMBASE; reference lists from relevant articles were hand-searched; and a hand-search of selected journals until April 2001. Selection criteria: Studies were selected if they were designed as controlled clinical trials in which systemically healthy patients with either AgP or CP were treated with SRP plus systemic antimicrobials in comparison with SRP alone or with placebo, for a minimum of 6 months. Main outcome measures were clinical attachment level (CAL) change and probing pocket depth (PPD) change. Data collection and analysis: Two reviewers extracted independently information regarding quality and study characteristics, in duplicate. Kappa scores determined their agreement. Main results were collected and grouped by drug, disease and PPD category. For the quantitative data synthesis, the data was pooled (when mean differences and standard errors were available), and either a Fixed Effects or Random Effects meta-analysis was used for the analysis. Results: After an initial selection, 158 papers were identified by the manual and electronic searches; 25 papers were eligible for inclusion. Their quality assessment showed that randomization and allocation concealment methods were seldom reported and blindness was usually not defined clearly. In general, selected studies showed high variability and lack of relevant information for an adequate assessment. Overall, SRP plus systemic antimicrobial groups demonstrated better results in CAL and PPD change than SRP alone or with placebo groups. Only limited meta-analyses could be performed, due to the difficulties in pooling the studies and the lack of appropriate data. This analysis showed a statistically significant additional benefit for spiramycin (PPD change) and amoxicillin/metronidazole (CAL change) in deep pockets. Conclusion: Systemic antimicrobials in conjunction with SRP, can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of CAL and PPD change, and reduced risk of additional CAL loss. However, differences in study methodology and lack of data precluded an adequate and complete pooling of data for a more comprehensive analyses. It was difficult to establish definitive conclusions, although patients with deep pockets, progressive or ‘active’ disease, or specific microbiological profile, can benefit more from this adjunctive therapy.

Journal ArticleDOI
TL;DR: P38α signaling is involved in the pathophysiology of IBD, and ELISA screening of the supernatants of Crohn’s disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-α.
Abstract: Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are relapsing chronic inflammatory disorders which involve genetic, immunological, and environmental factors. The regulation of TNF-alpha, a key mediator in the inflammatory process in IBD, is interconnected with mitogen-activated protein kinase pathways. The aim of this study was to characterize the activity and expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2 were significantly activated in IBD, with p38alpha showing the most pronounced increase in kinase activity. Protein expression of p38 and JNK was only moderately altered in IBD patients compared with normal controls, whereas ERK1/2 protein was significantly down-regulated. Immunohistochemical analysis of inflamed mucosal biopsies localized the main expression of p38alpha to lamina propria macrophages and neutrophils. ELISA screening of the supernatants of Crohn's disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab) resulted in a highly significant transient increase of p38alpha activity during the first 48 h after infusion. A significant infliximab-dependent p38alpha activation was also observed in THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB 203580. In conclusion, p38alpha signaling is involved in the pathophysiology of IBD.

Journal ArticleDOI
TL;DR: In this paper, the major and trace element and Sr-Nd-Pb-O-C isotopic compositions are presented for carbonatites from the Cape Verde (Brava, Fogo, Sao Tiago, Maio and Sao Vicente) and Canary (Fuerteventura) Islands.
Abstract: Major and trace element and Sr–Nd–Pb–O–C isotopic compositions are presented for carbonatites from the Cape Verde (Brava, Fogo, Sao Tiago, Maio and Sao Vicente) and Canary (Fuerteventura) Islands. Carbonatites show pronounced enrichment in Ba, Th, REE, Sr and Pb in comparison to most silicate volcanic rocks and relative depletion in Ti, Zr, Hf, K and Rb. Calcio (calcitic)-carbonatites have primary (mantle-like) stable isotopic compositions and radiogenic isotopic compositions similar to HIMU-type ocean island basalts. Cape Verde carbonatites, however, have more radiogenic Pb isotope ratios (e.g. 206Pb/204Pb=19.3–20.4) than reported for silicate volcanic rocks from these islands (18.7–19.9; Gerlach et al. 1988; Kokfelt 1998). We interpret calcio-carbonatites to be derived from the melting of recycled carbonated oceanic crust (eclogite) with a recycling age of ~1.6 Ga. Because of the degree of recrystallization, replacement of calcite by secondary dolomite and elevated ∂13C and ∂18O, the major and trace element compositions of the magnesio (dolomitic)-carbonatites are likely to reflect secondary processes. Compared with Cape Verde calcio-carbonatites, the less radiogenic Nd and Pb isotopic ratios and the negative Δ7/4 of the magnesio-carbonatites (also observed in silicate volcanic rocks from the Canary and Cape Verde Islands) cannot be explained through secondary processes or through the assimilation of Cape Verde crust. These isotopic characteristics require the involvement of a mantle component that has thus far only been found in the Smoky Butte lamproites from Montana, which are believed to be derived from subcontinental lithospheric sources. Continental carbonatites show much greater variation in radiogenic isotopic composition than oceanic carbonatites, requiring a HIMU-like component similar to that observed in the oceanic carbonatites and enriched components. We interpret the enriched components to be Phanerozoic through Proterozoic marine carbonate (e.g. limestone) recycled through shallow, subcontinental–lithospheric–mantle and deep, lower-mantle sources.

Journal ArticleDOI
TL;DR: A general scheme of selecting stimulation parameters in DBS is described and clinical and neurophysiological arguments for such a standardized algorithm are provided and noninvasive technical trouble shooting is described by using programming features of the commercially available neurostimulation devices.
Abstract: The clinical success of deep brain stimulation (DBS) for treating Parkinson's disease, tremor, or dystonia critically depends on the quality of postoperative neurologic management. Movement disorder specialists becoming involved with this therapy need to acquire new skills to optimally adapt stimulation parameters and medication after implantation of a DBS system. In clinical practice, the infinite number of possible parameter settings in DBS can be reduced to few relevant combinations. In this article, the authors describe a general scheme of selecting stimulation parameters in DBS and provide clinical and neurophysiological arguments for such a standardized algorithm. They also describe noninvasive technical trouble shooting by using programming features of the commercially available neurostimulation devices.

Journal ArticleDOI
TL;DR: In this article, the authors analyse the organic matter in the mineral horizons of two forest soils with different pedogenetic history and assess the quantity, turnover and chemical composition of SOM stored in the subsoil compared to the topsoil (A horizon and litter layers).

Journal ArticleDOI
Carsten Liess1, S. Lüsse, N. Karger, Martin Heller1, Claus-C. Glüer1 
TL;DR: Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI.

Journal ArticleDOI
TL;DR: It is shown that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently without supplementary host conditioning, which sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts.
Abstract: Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation of fully allogeneic bone marrow or blood-borne stem cells is still associated with major obstacles, such as graft-versus-host disease or cytoreductive conditioning-related toxicity. Here we show that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation of a potentially alloreactive immune response sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts. Graft survival was strictly correlated with a state of mixed chimerism, which required functional thymic host competence. Our results provide a rationale for using preimplantation-stage stem cells as vehicles in gene therapy and for the induction of long-term graft acceptance.

Journal ArticleDOI
TL;DR: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer and side effects related to estrogen suppression were initially higher with goserelin, but when gose Relin treatment stopped, reduced to a level below that observed in the CMF group.
Abstract: PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, ...

Journal ArticleDOI
TL;DR: The data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes.
Abstract: In LAMP-2-deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. In LAMP-2-deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy. However, an endocytic tracer reached the autophagic vacuoles, indicating delivery of endo/lysosomal constituents to autophagic vacuoles. Enzyme activity measurements showed that the trafficking of some lysosomal enzymes to lysosomes was impaired. Immunoprecipitation of metabolically labeled cathepsin D indicated reduced intracellular retention and processing in the knockout cells. The steady-state level of 300-kDa mannose 6-phosphate receptor was slightly lower in LAMP-2-deficient hepatocytes, whereas that of 46-kDa mannose 6-phosphate receptor was decreased to 30% of controls due to a shorter half-life. Less receptor was found in the Golgi region and in vesicles and tubules surrounding multivesicular endosomes, suggesting impaired recycling from endosomes to the Golgi. More receptor was found in autophagic vacuoles, which may explain its shorter half-life. Our data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes. Autophagic vacuoles may accumulate due to impaired capacity for lysosomal degradation.

Journal ArticleDOI
TL;DR: Here, it is demonstrated that this assumption is sufficient to reproduce major nontrivial features of social networks: short path length, high clustering, and scale-free or exponential link distributions.
Abstract: How do we make acquaintances? A simple observation from everyday experience is that often one of our acquaintances introduces us to one of his or her acquaintances. Such a simple triangle interaction may be viewed as the basis of the evolution of many social networks. Here, it is demonstrated that this assumption is sufficient to reproduce major nontrivial features of social networks: short path length, high clustering, and scale-free or exponential link distributions.

Journal ArticleDOI
TL;DR: It is demonstrated that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain and provides evidence for genetic heterogeneity within this disorder.
Abstract: Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.

Journal ArticleDOI
TL;DR: The results of the latest International Society of Paediatric Oncology (SIOP) trials and studies showed that certain histological features which remain after preoperative chemotherapy, such as blastema, are of prognostic significance while others are not as discussed by the authors.
Abstract: The previous International Society of Paediatric Oncology (SIOP) trials and studies recognized three prognostic groups of renal tumors of childhood: low risk, intermediate risk, and high risk tumors, which were further defined in the SIOP (Stockholm) Working Classification of Renal Tumors of Childhood (1994). The results of the latest SIOP Trials and Studies showed that certain histological features which remain after preoperative chemotherapy, such as blastema, are of prognostic significance while others are not. Therefore, in the next SIOP Trials and Study a revised classification of renal tumors will be followed. It still recognizes the three tumor risk groups with different types in each of them, but for treatment purposes, only three major types of nephroblastoma need to be recognized: completely necrotic (low risk tumor), blastemal (high risk tumor), and others (intermediate risk tumors). Patients will be treated according to tumor histology and stage. Trials which include preoperative chemotherapy have shown that the presence of necrotic tumor or chemotherapy induced changes in the renal sinus or perirenal fat can be ignored for distinguishing between stage I and II, but if present at resection margins or lymph nodes, it should be regarded as stage III. Prognostic significance of all histological component of Wilms tumors will be studied prospectively in the new trial.

Journal ArticleDOI
TL;DR: The present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello–thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations.
Abstract: Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and limbic) deficits. The motor signs of PD include hypokinetic signs such as akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the hallmark of PD and of its animal models, still the pathophysiology of the parkinsonian symptoms and especially of parkinsonian tremor are under debate. The most extreme hypotheses argue about peripheral versus central nervous system origin, intrinsic cellular oscillator versus network oscillators, and basal ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology. Recent studies support the view that parkinsonian symptoms are most likely due to abnormal synchronous oscillating neuronal activity within the basal ganglia. Peripheral factors do only play a minor role for the generation, maintenance, and modulation of PD tremor and other signs. The most likely candidates producing these neuronal oscillations are the weakly coupled neural networks of the basal ganglia-thalamo-cortical loops. However, the present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello-thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations. Neurosurgical procedures, such as lesions or high-frequency stimulation of different parts of the loop, might resume the normal unsynchronized activity of the basal ganglia circuitry, and, therefore, ameliorate the clinical symptoms of Parkinson's disease.