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Showing papers by "University of Hamburg published in 2008"


Journal ArticleDOI
TL;DR: The Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN as mentioned in this paper was designed to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1)
Abstract: The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

5,193 citations


Journal ArticleDOI
TL;DR: Adding cetuximab to platinum-based chemotherapy with fluorouracil (platinum-fluorouracils) significantly prolonged the median overall survival and improved overall survival when given as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.
Abstract: Background Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck. Methods We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles. Patients with stable disease who received chemotherapy plus cetuximab continued to receive cetuximab until disease progression or unacceptable toxic effects, whichever occurred first. Results

2,940 citations


Journal ArticleDOI
TL;DR: Evidence supports reliability and validity of the G AD-7 as a measure of anxiety in the general population and can be used to compare a subject's GAD-7 score with those determined from a general population reference group.
Abstract: Background:The 7-item Generalized Anxiety Disorder Scale (GAD-7) is a practical self-report anxiety questionnaire that proved valid in primary care. However, the GAD-7 was not yet validated in the general population and thus far, normative data are not available.Objectives:To investigate reliability

2,730 citations


Journal ArticleDOI
TL;DR: An overview of the state of the art for transcranial direct current stimulation (tDCS) is offered, which suggests that it can induce beneficial effects in brain disorders and facilitate and standardize future tDCS studies.

2,539 citations


Journal ArticleDOI
05 Sep 2008-Cell
TL;DR: The generation of induced pluripotent stem cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance are described, offering an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.

2,195 citations


Journal ArticleDOI
10 Apr 2008-Nature
TL;DR: This data reinforce several previously identified clades that split deeply in the animal tree, unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data, and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists.
Abstract: Long-held ideas regarding the evolutionary relationships among animals have recently been upended by sometimes controversial hypotheses based largely on insights from molecular data. These new hypotheses include a clade of moulting animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs and annelids (Lophotrochozoa). Many relationships remain disputed, including those that are required to polarize key features of character evolution, and support for deep nodes is often low. Phylogenomic approaches, which use data from many genes, have shown promise for resolving deep animal relationships, but are hindered by a lack of data from many important groups. Here we report a total of 39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla, including 11 phyla previously lacking genomic or expressed-sequence-tag data. Analysed in combination with existing sequences, our data reinforce several previously identified clades that split deeply in the animal tree (including Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long-standing issues for which there was strong conflicting support in earlier studies with less data (such as velvet worms rather than tardigrades as the sister group of arthropods), and provide molecular support for the monophyly of molluscs, a group long recognized by morphologists. In addition, we find strong support for several new hypotheses. These include a clade that unites annelids (including sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs as sister to that assemblage, and the placement of ctenophores as the earliest diverging extant multicellular animals. A single origin of spiral cleavage (with subsequent losses) is inferred from well-supported nodes. Many relationships between a stable subset of taxa find strong support, and a diminishing number of lineages remain recalcitrant to placement on the tree.

1,787 citations


Journal ArticleDOI
TL;DR: In this article, the authors used the Advanced Microwave Scanning Radiometer-EOS (AMSR-E) to estimate sea ice concentration from the channels near 90 GHz, despite the enhanced atmospheric influence in these channels.
Abstract: [1] Recent progress in sea ice concentration remote sensing by satellite microwave radiometers has been stimulated by two developments: First, the new sensor Advanced Microwave Scanning Radiometer-EOS (AMSR-E) offers spatial resolutions of approximately 6 × 4 km at 89 GHz, nearly 3 times the resolution of the standard sensor SSM/I at 85 GHz (15 × 13 km). Second, a new algorithm enables estimation of sea ice concentration from the channels near 90 GHz, despite the enhanced atmospheric influence in these channels. This allows full exploitation of their horizontal resolution, which is up to 4 times finer than that of the channels near 19 and 37 GHz, the frequencies used by the most widespread algorithms for sea ice retrieval, the NASA-Team and Bootstrap algorithms. The ASI algorithm used combines a model for retrieving the sea ice concentration from SSM/I 85-GHz data proposed by Svendsen et al. (1987) with an ocean mask derived from the 18-, 23-, and 37-GHz AMSR-E data using weather filters. During two ship campaigns, the correlation of ASI, NASA-Team 2, and Bootstrap algorithms ice concentrations with bridge observations were 0.80, 0.79, and 0.81, respectively. Systematic differences over the complete AMSR-E period (2002–2006) between ASI and NASA-Team 2 are below −2 ± 8.8%, and between ASI and Bootstrap are 1.7 ± 10.8%. Among the geophysical implications of the ASI algorithm are: (1) Its higher spatial resolution allows better estimation of crucial variables in numerical atmospheric and ocean models, for example, the heat flux between ocean and atmosphere, especially near coastlines and in polynyas. (2) It provides an additional time series of ice area and extent for climate studies.

1,105 citations


Journal ArticleDOI
TL;DR: The evidence that disseminating tumour cells have a variety of uses for understanding tumour biology and improving cancer treatment is reviewed.
Abstract: Most cancer deaths are caused by haematogenous metastatic spread and subsequent growth of tumour cells at distant organs. Disseminating tumour cells present in the peripheral blood and bone marrow can now be detected and characterized at the single-cell level. These cells are highly relevant to the study of the biology of early metastatic spread and provide a diagnostic source in patients with overt metastases. Here we review the evidence that disseminating tumour cells have a variety of uses for understanding tumour biology and improving cancer treatment.

1,103 citations


Journal ArticleDOI
TL;DR: A framework for comparative software defect prediction experiments is proposed and applied in a large-scale empirical comparison of 22 classifiers over 10 public domain data sets from the NASA Metrics Data repository, showing an appealing degree of predictive accuracy, which supports the view that metric-based classification is useful.
Abstract: Software defect prediction strives to improve software quality and testing efficiency by constructing predictive classification models from code attributes to enable a timely identification of fault-prone modules. Several classification models have been evaluated for this task. However, due to inconsistent findings regarding the superiority of one classifier over another and the usefulness of metric-based classification in general, more research is needed to improve convergence across studies and further advance confidence in experimental results. We consider three potential sources for bias: comparing classifiers over one or a small number of proprietary data sets, relying on accuracy indicators that are conceptually inappropriate for software defect prediction and cross-study comparisons, and, finally, limited use of statistical testing procedures to secure empirical findings. To remedy these problems, a framework for comparative software defect prediction experiments is proposed and applied in a large-scale empirical comparison of 22 classifiers over 10 public domain data sets from the NASA Metrics Data repository. Overall, an appealing degree of predictive accuracy is observed, which supports the view that metric-based classification is useful. However, our results indicate that the importance of the particular classification algorithm may be less than previously assumed since no significant performance differences could be detected among the top 17 classifiers.

1,086 citations


Journal ArticleDOI
TL;DR: A software tool for the de novo detection of full length LTR retrotransposons in large sequence sets and its ability to efficiently handle large datasets from finished or unfinished genome projects, its flexibility in incorporating known sequence features into the prediction, and its availability as an open source software.
Abstract: Transposable elements are abundant in eukaryotic genomes and it is believed that they have a significant impact on the evolution of gene and chromosome structure While there are several completed eukaryotic genome projects, there are only few high quality genome wide annotations of transposable elements Therefore, there is a considerable demand for computational identification of transposable elements LTR retrotransposons, an important subclass of transposable elements, are well suited for computational identification, as they contain long terminal repeats (LTRs) We have developed a software tool LTRharvest for the de novo detection of full length LTR retrotransposons in large sequence sets LTRharvest efficiently delivers high quality annotations based on known LTR transposon features like length, distance, and sequence motifs A quality validation of LTRharvest against a gold standard annotation for Saccharomyces cerevisae and Drosophila melanogaster shows a sensitivity of up to 90% and 97% and specificity of 100% and 72%, respectively This is comparable or slightly better than annotations for previous software tools The main advantage of LTRharvest over previous tools is (a) its ability to efficiently handle large datasets from finished or unfinished genome projects, (b) its flexibility in incorporating known sequence features into the prediction, and (c) its availability as an open source software LTRharvest is an efficient software tool delivering high quality annotation of LTR retrotransposons It can, for example, process the largest human chromosome in approx 8 minutes on a Linux PC with 4 GB of memory Its flexibility and small space and run-time requirements makes LTRharvest a very competitive candidate for future LTR retrotransposon annotation projects Moreover, the structured design and implementation and the availability as open source provides an excellent base for incorporating novel concepts to further improve prediction of LTR retrotransposons

995 citations


Journal ArticleDOI
TL;DR: Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function and the increased number of early postoperative arrhythmic events after myoblast transplantation warrants further investigation.
Abstract: Background— Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic. Methods and Results— This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction ≤35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). ...

Journal ArticleDOI
26 Nov 2008-JAMA
TL;DR: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.
Abstract: Context Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown Objective To determine why depressive symptoms are associated with an increased risk of cardiovascular events Design and Participants The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 48 (14) years Setting Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008 Main Outcome Measures Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ) We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators Results A total of 341 cardiovascular events occurred during 4876 person-years of follow-up The age-adjusted annual rate of cardiovascular events was 100% among the 199 participants with depressive symptoms (PHQ score ≥10) and 67% among the 818 participants without depressive symptoms (hazard ratio [HR], 150; 95% confidence interval, [CI], 116-195; P = 002) After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 131; 95% CI, 100-171; P = 04) Additional adjustment for potential biological mediators attenuated this association (HR, 124; 95% CI, 094-163; P = 12) After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 105; 95% CI, 079-140; P = 75) Conclusion In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity

Journal ArticleDOI
TL;DR: The heightened lL‐6 secretion from LPMNC from non‐involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologie mechanisms involved in the initiation of inflammation may differ between ulceralive colitis and Crohn's disease.
Abstract: The perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulation of cytokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-1 beta, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isolated from involved inflammatory bowel disease (IBD) mucosa spontaneously produced increased amounts of TNF-alpha, and IL-6, and IL-1 beta. The TNF-alpha secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-alpha and IL-1 beta by LPMNC from patients with either ulcerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from non-involved ulcerative colitis mucosa secreted markedly increased levels of IL-6 compared with non-involved Crohn's disease mucosa or control mucosa. The heightened IL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologic mechanisms involved in the initiation of inflammation may differ between ulcerative colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoscopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.

Journal ArticleDOI
TL;DR: Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aorta stenosis and may be extended to lower risk patients if the initial promise holds to be true after careful evaluation.
Abstract: Aims To critically review the available transcatheter aortic valve implantation techniques and their results, as well as propose recommendations for their use and development. Methods and results A committee of experts including European Association of Cardio-Thoracic Surgery and European Society of Cardiology representatives met to reach a consensus based on the analysis of the available data obtained with transcatheter aortic valve implantation and their own experience. The evidence suggests that this technique is feasible and provides haemodynamic and clinical improvement for up to 2 years in patients with severe symptomatic aortic stenosis at high risk or with contraindications for surgery. Questions remain mainly concerning safety and long-term durability, which have to be assessed. Surgeons and cardiologists working as a team should select candidates, perform the procedure, and assess the results. Today, the use of this technique should be restricted to high-risk patients or those with contraindications for surgery. However, this may be extended to lower risk patients if the initial promise holds to be true after careful evaluation. Conclusion Transcatheter aortic valve implantation is a promising technique, which may offer an alternative to conventional surgery for high-risk patients with aortic stenosis. Today, careful evaluation is needed to avoid the risk of uncontrolled diffusion.

Journal ArticleDOI
TL;DR: In this article, density functional calculations of electronic structure, total energy, structural distortions, and magnetism for hydrogenated single-layer, bilayer, and multilayer graphenes are performed.
Abstract: Density-functional calculations of electronic structure, total energy, structural distortions, and magnetism for hydrogenated single-layer, bilayer, and multilayer graphenes are performed. It is found that hydrogen-induced magnetism can survive only at very low concentrations of hydrogen (single-atom regime) whereas hydrogen pairs with optimized structure are usually nonmagnetic. Chemisorption energy as a function of hydrogen concentration is calculated, as well as energy barriers for hydrogen binding and release. The results confirm that graphene can be perspective material for hydrogen storage. Difference between hydrogenation of graphene, nanotubes, and bulk graphite is discussed.

Journal ArticleDOI
TL;DR: A review of new developments in theoretical and experimental electronic-structure investigations of half-metallic ferromagnets (HMFs) is presented in this article, where the effects of electron-magnon interaction in HMFs and their manifestations in magnetic, spectral, thermodynamic, and transport properties are considered.
Abstract: A review of new developments in theoretical and experimental electronic-structure investigations of half-metallic ferromagnets (HMFs) is presented. Being semiconductors for one spin projection and metals for another, these substances are promising magnetic materials for applications in spintronics (i.e., spin-dependent electronics). Classification of HMFs by the peculiarities of their electronic structure and chemical bonding is discussed. The effects of electron-magnon interaction in HMFs and their manifestations in magnetic, spectral, thermodynamic, and transport properties are considered. Special attention is paid to the appearance of nonquasiparticle states in the energy gap, which provide an instructive example of essentially many-body features in the electronic structure. State-of-the-art electronic calculations for correlated d-systems are discussed, and results for specific HMFs (Heusler alloys, zinc-blende structure compounds, CrO2, and Fe3O4) are reviewed.

Journal ArticleDOI
TL;DR: Giovanni Raimondo*, Jean-Pierre Allain, Maurizia R. Brunetto, Marie-Annick Buendia, Ding-Shinn Chen, Massimo Colombo, Antonio Craxi, Francesco Donato, Carlo Ferrari, Giovanni B. Gaeta, Wolfram H. Gerlich,Massimo Levrero, Stephen Locarnini, Thomas Michalak, Mario U. Zanetti, Fabien Zoulim

Journal ArticleDOI
31 Dec 2008
TL;DR: In this measurement, the first of this type, the High Energy Stereoscopic System is able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements, finding evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.
Abstract: The very large collection area of ground-based gamma-ray telescopes gives them a substantial advantage over balloon/satellite based instruments in the detection of very-high-energy (>600 GeV) cosmic-ray electrons. Here we present the electron spectrum derived from data taken with the H.E.S.S. system of imaging atmospheric Cherenkov telescopes. In this measurement, the first of this type, we are able to extend the measurement of the electron spectrum beyond the range accessible to direct measurements. We find evidence for a substantial steepening in the energy spectrum above 600 GeV compared to lower energies.

Journal ArticleDOI
TL;DR: Elderly persons were able to learn three-ball cascade juggling, but with less proficiency compared with 20-year-old adolescents, and gray-matter changes in the older brain related to skill acquisition were observed in area hMT/V5 (middle temporal area of the visual cortex).
Abstract: It has been suggested that learning is associated with a transient and highly selective increase in brain gray matter in healthy young volunteers. It is not clear whether and to what extent the aging brain is still able to exhibit such structural plasticity. We built on our original study, now focusing on healthy senior citizens. We observed that elderly persons were able to learn three-ball cascade juggling, but with less proficiency compared with 20-year-old adolescents. Similar to the young group, gray-matter changes in the older brain related to skill acquisition were observed in area hMT/V5 (middle temporal area of the visual cortex). In addition, elderly volunteers who learned to juggle showed transient increases in gray matter in the hippocampus on the left side and in the nucleus accumbens bilaterally.

Journal ArticleDOI
TL;DR: The enriched AOA, which is provisionally classified as “Candidatus Nitrososphaera gargensis,” is the first described thermophilic ammonia oxidizer and the first member of the crenarchaeotal group I.1b for which ammonium oxidation has been verified on a cellular level.
Abstract: The recent discovery of ammonia-oxidizing archaea (AOA) dramatically changed our perception of the diversity and evolutionary history of microbes involved in nitrification. In this study, a moderately thermophilic (46°C) ammonia-oxidizing enrichment culture, which had been seeded with biomass from a hot spring, was screened for ammonia oxidizers. Although gene sequences for crenarchaeotal 16S rRNA and two subunits of the ammonia monooxygenase (amoA and amoB) were detected via PCR, no hints for known ammonia-oxidizing bacteria were obtained. Comparative sequence analyses of these gene fragments demonstrated the presence of a single operational taxonomic unit and thus enabled the assignment of the amoA and amoB sequences to the respective 16S rRNA phylotype, which belongs to the widely distributed group I.1b (soil group) of the Crenarchaeota. Catalyzed reporter deposition (CARD)–FISH combined with microautoradiography (MAR) demonstrated metabolic activity of this archaeon in the presence of ammonium. This finding was corroborated by the detection of amoA gene transcripts in the enrichment. CARD-FISH/MAR showed that the moderately thermophilic AOA is highly active at 0.14 and 0.79 mM ammonium and is partially inhibited by a concentration of 3.08 mM. The enriched AOA, which is provisionally classified as “Candidatus Nitrososphaera gargensis,” is the first described thermophilic ammonia oxidizer and the first member of the crenarchaeotal group I.1b for which ammonium oxidation has been verified on a cellular level. Its preference for thermophilic conditions reinvigorates the debate on the thermophilic ancestry of AOA.

Journal ArticleDOI
01 Jan 2008-Spine
TL;DR: These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.
Abstract: A modified Delphi study conducted with 28 experts in back pain research from 12 countries. OBJECTIVE. To identify standardized definitions of low back pain that could be consistently used by investigators in prevalence studies to provide comparable data. SUMMARY OF BACKGROUND DATA. Differences in the definition of back pain prevalence in population studies lead to heterogeneity in study findings, and limitations or impossibilities in comparing or summarizing prevalence figures from different studies. METHODS. Back pain definitions were identified from 51 articles reporting population-based prevalence studies, and dissected into 77 items documenting 7 elements. These items were submitted to a panel of experts for rating and reduction, in 3 rounds (participation: 76%). Preliminary results were presented and discussed during the Amsterdam Forum VIII for Primary Care Research on Low Back Pain, compared with scientific evidence and confirmed and fine-tuned by the panel in a fourth round and the preparation of the current article. RESULTS. Two definitions were agreed on a minimal definition (with 1 question covering site of low back pain, symptoms observed, and time frame of the measure, and a second question on severity of low back pain) and an optimal definition that is made from the minimal definition and add-ons (covering frequency and duration of symptoms, an additional measure of severity, sciatica, and exclusions) that can be adapted to different needs. CONCLUSION. These definitions provide standards that may improve future comparisons of low back pain prevalence figures by person, place and time characteristics, and offer opportunities for statistical summaries.

Journal ArticleDOI
TL;DR: A potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Journal ArticleDOI
Arne May1
30 Jun 2008-Pain
TL;DR: The author suggests that the gray matter change observed in chronic pain patients are the consequence of frequent nociceptive input and should thus be reversible when pain is adequately treated.
Abstract: Recently, local morphologic alterations of the brain in areas ascribable to the transmission of pain were detected in patients suffering from phantom pain, chronic back pain, irritable bowl syndrome, fibromyalgia and two types of frequent headaches. These alterations were different for each pain syndrome, but overlapped in the cingulate cortex, the orbitofrontal cortex, the insula and dorsal pons. These regions function as multi-integrative structures during the experience and the anticipation of pain. As it seems that chronic pain patients have a common "brain signature" in areas known to be involved in pain regulation, the question arises whether these changes are the cause or the consequence of chronic pain. The author suggests that the gray matter change observed in chronic pain patients are the consequence of frequent nociceptive input and should thus be reversible when pain is adequately treated.

Journal ArticleDOI
TL;DR: This work sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem cells (hiPSCs), and developed a strategy to induce hiPSC formation at high frequency.

Journal ArticleDOI
01 Oct 2008-JAMA
TL;DR: There is evidence that LTPP is an effective treatment for complex mental disorders, and further research should address the outcome of LTPP in specific mental disorders and should include cost-effectiveness analyses.
Abstract: Context The place of long-term psychodynamic psychotherapy (LTPP) within psychiatry is controversial. Convincing outcome research for LTPP has been lacking. Objective To examine the effects of LTPP, especially in complex mental disorders, ie, patients with personality disorders, chronic mental disorders, multiple mental disorders, and complex depressive and anxiety disorders (ie, associated with chronic course and/or multiple mental disorders), by performing a meta-analysis. Data Sources Studies of LTPP published between January 1, 1960, and May 31, 2008, were identified by a computerized search using MEDLINE, PsycINFO, and Current Contents, supplemented by contact with experts in the field. Study Selection Only studies that used individual psychodynamic psychotherapy lasting for at least a year, or 50 sessions; had a prospective design; and reported reliable outcome measures were included. Randomized controlled trials (RCTs) and observational studies were considered. Twenty-three studies involving a total of 1053 patients were included (11 RCTs and 12 observational studies). Data Extraction Information on study characteristics and treatment outcome was extracted by 2 independent raters. Effect sizes were calculated for overall effectiveness, target problems, general psychiatric symptoms, personality functioning, and social functioning. To examine the stability of outcome, effect sizes were calculated separately for end-of-therapy and follow-up assessment. Results According to comparative analyses of controlled trials, LTPP showed significantly higher outcomes in overall effectiveness, target problems, and personality functioning than shorter forms of psychotherapy. With regard to overall effectiveness, a between-group effect size of 1.8 (95% confidence interval [CI], 0.7-3.4) indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96% of the patients in the comparison groups (P = .002). According to subgroup analyses, LTPP yielded significant, large, and stable within-group effect sizes across various and particularly complex mental disorders (range, 0.78-1.98). Conclusions There is evidence that LTPP is an effective treatment for complex mental disorders. Further research should address the outcome of LTPP in specific mental disorders and should include cost-effectiveness analyses.

Journal ArticleDOI
Susanne Krege, Jörg Beyer, Rainer Souchon1, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg2, István Bodrogi, Carsten Bokemeyer3, Eva Cavallin-Ståhl4, Johannes Classen, C Clemm, Gabriella Cohn-Cedermark5, Stéphane Culine, Gedske Daugaard6, Pieter H.M. De Mulder7, Maria De Santis, Maike de Wit, Ronald de Wit8, H. G. Derigs, Klaus Peter Dieckmann, Annette Dieing9, Jean Pierre Droz, Martin Fenner, Karim Fizazi10, Aude Flechon, Sophie D. Fosså, Xavier Garcia del Muro, Thomas Gauler11, Lajos Géczi, Arthur Gerl, Jose Ramon Germa-Lluch, Silke Gillessen2, Jörg T. Hartmann12, Michael Hartmann, Axel Heidenreich, Wolfgang Hoeltl, Alan Horwich13, Robert Huddart13, Michael Jewett, Johnathan Joffe, William G. Jones14, László Kisbenedek, Olbjørn Klepp, S. Kliesch15, Kai Uwe Koehrmann16, Christian K. Kollmannsberger17, Markus A. Kuczyk18, Pilar Laguna, Oscar Leiva Galvis, Volker Loy19, Malcolm David Mason12, Graham M. Mead20, Rolf Mueller, Craig R. Nichols21, Nicola Nicolai, Tim Oliver22, D. Ondruš, Gosse O N Oosterhof, Luis Paz Ares, Giorgio Pizzocaro21, Jörg Pont, Tobias Pottek, Thomas Powles, Oliver Rick2, Giovanni Rosti, Roberto Salvioni, Jutta Scheiderbauer2, Hans U. Schmelz9, Heinz Schmidberger23, Hans-Joachim Schmoll24, Mark Schrader9, Felix Sedlmayer, Niels E. Skakkebæk, Aslam Sohaib11, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind25, Eva Winter, Lori Wood, Hans von der Maase 
TL;DR: F refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials, and expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer.

Journal ArticleDOI
TL;DR: This study reveals the existence of a surface dipole built into molecular layers and offers design guidelines for improved organic-organic heterojunctions, hole- or electron-blocking layers and reduced barriers for charge-carrier injection in organic electronic devices.
Abstract: Although an isolated individual molecule clearly has only one ionization potential, multiple values are found for molecules in ordered assemblies. Photoelectron spectroscopy of archetypical pi-conjugated organic compounds on metal substrates combined with first-principles calculations and electrostatic modelling reveal the existence of a surface dipole built into molecular layers. Conceptually different from the surface dipole at metal surfaces, its origin lies in details of the molecular electronic structure and its magnitude depends on the orientation of molecules relative to the surface of an ordered assembly. Suitable pre-patterning of substrates to induce specific molecular orientations in subsequently grown films thus permits adjusting the ionization potential of one molecular species over up to 0.6 eV via control over monolayer morphology. In addition to providing in-depth understanding of this phenomenon, our study offers design guidelines for improved organic-organic heterojunctions, hole- or electron-blocking layers and reduced barriers for charge-carrier injection in organic electronic devices.

Journal ArticleDOI
TL;DR: In this paper, the periods of cambial activity and cell differentiation were assessed on a weekly time-scale on histological sections of Cambium and wood tissue collected over 2 to 5 years per site from 1998 to 2005 from the stems of seven conifer species.
Abstract: Aim To identify temperatures at which cell division and differentiation are active in order to verify the existence of a common critical temperature determining growth in conifers of cold climates. Location Ten European and Canadian sites at different latitudes and altitudes. Methods The periods of cambial activity and cell differentiation were assessed on a weekly time-scale on histological sections of cambium and wood tissue collected over 2 to 5 years per site from 1998 to 2005 from the stems of seven conifer species. All data were compared with daily air temperatures recorded from weather stations located close to the sites. Logistic regressions were used to calculate the probability of xylogenesis and of cambium being active at a given temperature. Results Xylogenesis lasted from May to October, with a growing period varying from 3 to 5 months depending on location and elevation. Despite the wide geographical range of the monitored sites, temperatures for onset and ending of xylogenesis converged towards narrow ranges with average values around 4–5, 8–9 and 13–14 °C for daily minimum, mean and maximum temperature, respectively. On the contrary, cell division in the cambium stopped in July−August, when temperatures were still high. Main conclusions Wood formation in conifers occurred when specific critical temperatures were reached. Although the timing and duration of xylogenesis varied among species, sites and years, the estimated temperatures were stable for all trees studied. These results provide biologically based evidence that temperature is a critical factor limiting production and differentiation of xylem cells in cold climates. Although daily temperatures below 4−5 °C are still favourable for photosynthesis, thermal conditions below these values could inhibit the allocation of assimilated carbon to structural investment, i.e. xylem growth.

Journal ArticleDOI
26 Nov 2008-Neuron
TL;DR: This work combined magnetoencephalography in a spatially cued motion discrimination task with source-reconstruction techniques and characterized attentional effects on neuronal synchronization across key stages of the human dorsal visual pathway to suggest that attentional selection is mediated by frequency-specific synchronization between prefrontal, parietal, and early visual cortex.

Journal ArticleDOI
TL;DR: In this article, the authors present an approach to reconstruct spatially explicit changes in global agricultural areas (cropland and pasture) and the resulting changes in land cover over the last millennium.
Abstract: [1] Humans have substantially modified the Earth's land cover, especially by transforming natural ecosystems to agricultural areas. In preindustrial times, the expansion of agriculture was probably the dominant process by which humankind altered the Earth system, but little is known about its extent, timing, and spatial pattern. This study presents an approach to reconstruct spatially explicit changes in global agricultural areas (cropland and pasture) and the resulting changes in land cover over the last millennium. The reconstruction is based on published maps of agricultural areas for the last three centuries. For earlier times, a country-based method is developed that uses population data as a proxy for agricultural activity. With this approach, the extent of cropland and pasture is consistently estimated since AD 800. The resulting reconstruction of agricultural areas is combined with a map of potential vegetation to estimate the resulting historical changes in land cover. Uncertainties associated with this approach, in particular owing to technological progress in agriculture and uncertainties in population estimates, are quantified. About 5 million km2 of natural vegetation are found to be transformed to agriculture between AD 800 and 1700, slightly more to cropland (mainly at the expense of forested area) than to pasture (mainly at the expense of natural grasslands). Historical events such as the Black Death in Europe led to considerable dynamics in land cover change on a regional scale. The reconstruction can be used with global climate and ecosystem models to assess the impact of human activities on the Earth system in preindustrial times.