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Showing papers by "Martin Luther University of Halle-Wittenberg published in 2010"


Journal ArticleDOI
TL;DR: The quality assessment of non-randomized studies is an important component of a thorough meta-analysis of non randomized studies and can dramatically influence the interpretation of meta-analyses, and can even reverse conclusions regarding the effectiveness of an intervention.
Abstract: The quality assessment of non-randomized studies is an important component of a thorough meta-analysis of nonrandomized studies. Low quality studies can lead to a distortion of the summary effect estimate. Recent guidelines for the reporting of meta-analyses of observational studies recommend the assessment of the study quality (MOOSE) [1]. In principal, three categories of quality assessments tools are available: scales, simple checklists, or checklists with a summary judgment (for details see Sanderson et al. 2007 [2]). The results of the quality assessment can be used in several ways such as forming inclusion criteria for the meta-analysis, informing a sensitivity analysis or metaregression, weighting studies, or highlighting areas of methodological quality poorly addressed by the included studies [3]. It has been criticized that the use of summary scores involve inherent weighting of component items including items that may not be related to the validity of the study findings [2]. Sanderson et al. [2] recently identified overall 86 tools for assessing the quality of non-randomized studies. Their review "highlighted the lack of a single obvious candidate tool for assessing quality of observational epidemiological studies" [2]. In the field of randomized trials, it has been shown that the choice of quality scale can dramatically influence the interpretation of meta-analyses, and can even reverse conclusions regarding the effectiveness of an intervention [4]. Wells et al. [5] proposed a scale for assessing the quality of published non-randomized studies in meta-analyses,

10,420 citations


Journal ArticleDOI
TL;DR: Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men, and provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.
Abstract: BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

2,264 citations


Journal ArticleDOI
TL;DR: The discovery of TAL effectors is described, which act as transcriptional activators in the plant cell nucleus and are determined by a novel modular DNA-binding domain.
Abstract: Xanthomonads are bacterial plant pathogens that cause diseases on many plant species, including important crops. Key to pathogenicity of most Xanthomonas pathovars is a Hrp-type III secretion (T3S) system that translocates effector proteins into plant cells. Within the eukaryotic cell, the effectors are thought to perform a variety of tasks to support bacterial virulence, proliferation, and dissemination. We are only beginning to understand the host targets of different effectors. The largest effector family found in Xanthomonas spp. is the AvrBs3/PthA or TAL (transcription activator-like) family. TAL effectors act as transcriptional activators in the plant cell nucleus. Specificity of TAL effectors is determined by a novel modular DNA-binding domain. Here, we describe the discovery of TAL effectors and their structure, activity, and host targets.

968 citations


Journal ArticleDOI
15 Jun 2010-Geoderma
TL;DR: In paddy soils, the management-induced, microbially mediated redox processes control the dynamics of soil minerals and soil organic matter, which are strongly related to the microbial accessibility of C and N, but also of Fe as discussed by the authors.

869 citations


Journal ArticleDOI
TL;DR: New classification schemes for berth allocation problems and quay crane scheduling problems are developed and particular focus is put on integrated solution approaches which receive increasing importance for the terminal management.

722 citations


Journal ArticleDOI
TL;DR: CAC scoring results in a high reclassification rate in the intermediate-risk cohort, demonstrating the benefit of imaging of subclinical coronary atherosclerosis and supporting its application, especially in carefully selected individuals with intermediate risk.

690 citations



Journal ArticleDOI
TL;DR: A four-year study involving more than 1200 bee colonies from about 120 apiaries which were monitored for the entire study period can demonstrate for several factors that they are significantly related to the observed winter losses of the monitored honey bee colonies.
Abstract: The Western honey bee, Apis mellifera, is the most important animal pollinator in agriculture worldwide providing more than 90% of the commercial pollination services. Due to the development in agriculture the demands for honey bee pollination are steadily increasing stressing the pollination capacity of the global managed honey bee population. Hence, the long-term decline of managed honey bee hives in Europe and North-America is of great concern and stimulated intensive research into the possible factors presumably causing honey bee colony collapse. We here present a four-year study involving more than 1200 bee colonies from about 120 apiaries which were monitored for the entire study period. Bee samples were collected twice a year to analyze various pathogenic factors including the ectoparasitic mite Varroa destructor, fungi (Nosema spec., Ascosphaera apis), the bacterium Paenibacillus larvae, and several viruses. Data on environmental factors, beekeeping management practice, and pesticides were also collected. All data were statistically analyzed in respect to the overwintering mortality of the colonies. We can demonstrate for several factors that they are significantly related to the observed winter losses of the monitored honey bee colonies: (i) high varroa infestation level, (ii) infection with deformed wing virus (DWV) and acute bee paralysis virus (ABPV) in autumn, (iii) queen age, and (iv) weakness of the colonies in autumn. No effects could be observed for Nosema spec. or pesticides. The implications of these findings will be discussed.

612 citations


Journal ArticleDOI
TL;DR: A method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules is presented.
Abstract: Mass spectrometry has become the analytical method of choice in metabolomics research. The identification of unknown compounds is the main bottleneck. In addition to the precursor mass, tandem MS spectra carry informative fragment peaks, but the coverage of spectral libraries of measured reference compounds are far from covering the complete chemical space. Compound libraries such as PubChem or KEGG describe a larger number of compounds, which can be used to compare their in silico fragmentation with spectra of unknown metabolites. We created the MetFrag suite to obtain a candidate list from compound libraries based on the precursor mass, subsequently ranked by the agreement between measured and in silico fragments. In the evaluation MetFrag was able to rank most of the correct compounds within the top 3 candidates returned by an exact mass query in KEGG. Compared to a previously published study, MetFrag obtained better results than the commercial MassFrontier software. Especially for large compound libraries, the candidates with a good score show a high structural similarity or just different stereochemistry, a subsequent clustering based on chemical distances reduces this redundancy. The in silico fragmentation requires less than a second to process a molecule, and MetFrag performs a search in KEGG or PubChem on average within 30 to 300 seconds, respectively, on an average desktop PC. We presented a method that is able to identify small molecules from tandem MS measurements, even without spectral reference data or a large set of fragmentation rules. With today's massive general purpose compound libraries we obtain dozens of very similar candidates, which still allows a confident estimate of the correct compound class. Our tool MetFrag improves the identification of unknown substances from tandem MS spectra and delivers better results than comparable commercial software. MetFrag is available through a web application, web services and as java library. The web frontend allows the end-user to analyse single spectra and browse the results, whereas the web service and console application are aimed to perform batch searches and evaluation.

577 citations


Journal ArticleDOI
TL;DR: This study provides the first evidence for an oncogenic activity ofmiR‐155, miR‐203, miM‐210 and miR-222 in the development of pancreatic cancer as has been reported for other tumor types.
Abstract: Pancreatic cancer is the eighth most common cancer and has an overall 5-year survival rate lower than 10%. Because of their ability to regulate gene expression, microRNAs can act as oncogenes or tumor-suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated. We measured the levels of miR-155, miR-203, miR-210, miR-216, miR-217 and miR-222 by quantitative RT-PCR in a cohort of 56 microdissected pancreatic ductal adenocarcinomas (PDAC). These microRNAs were chosen as they had previously been shown to be differentially expressed in pancreatic tumors compared to normal tissues. The possible association of microRNA expression and patients' survival was examined using multivariate Cox's regression hazard analyses. Interestingly, significant correlations between elevated microRNA expression and overall survival were observed for miR-155 (RR = 2.50; p = 0.005), miR-203 (RR = 2.21; p = 0.017), miR-210 (RR = 2.48; p = 0.005) and miR-222 (RR = 2.05; p = 0.035). Furthermore, tumors from patients demonstrating elevated expression levels of all 4 microRNAs possessed a 6.2-fold increased risk of tumor-related death compared to patients whose tumors showed a lower expression of these microRNAs. This study provides the first evidence for an oncogenic activity of miR-155, miR-203, miR-210 and miR-222 in the development of pancreatic cancer as has been reported for other tumor types. Furthermore, the putative target genes for these microRNAs suggest a complex signaling network that can affect PDAC tumorigenesis and tumor progression.

439 citations


Journal ArticleDOI
TL;DR: In this paper, the notion of media enjoyment in the context of film viewing is discussed, with a special focus on the domain of more serious, poignant, and pensive media experiences typically associated with genres such as drama, history, documentary, or art films.
Abstract: This article elaborates upon the notion of media enjoyment in the context of film viewing by proposing a complementary type of gratification that we conceptualize as appreciation. Three studies were conducted to tap into the multidimensionality of viewers' entertainment gratifications with a special focus on the domain of more serious, poignant, and pensive media experiences typically associated with genres such as drama, history, documentary, or art films. These studies provide evidence of and measurement for gratifications related to fun and suspense, but also gratifications related to moving and thought-provoking entertainment experiences, with all three gratifications leading to perceptions of entertainment having a more long-lasting or enduring effect. The results are discussed with regard to the theoretical conceptualization of entertainment gratification.

Journal ArticleDOI
TL;DR: In this review, the current knowledge on the infection strategies and regulatory networks controlling secreted virulence factors from Xanthomonas species are summarized.
Abstract: Plant pathogenic bacteria of the genus Xanthomonas cause a variety of diseases in economically important monocotyledonous and dicotyledonous crop plants worldwide Successful infection and bacterial multiplication in the host tissue often depend on the virulence factors secreted including adhesins, polysaccharides, LPS and degradative enzymes One of the key pathogenicity factors is the type III secretion system, which injects effector proteins into the host cell cytosol to manipulate plant cellular processes such as basal defense to the benefit of the pathogen The coordinated expression of bacterial virulence factors is orchestrated by quorum-sensing pathways, multiple two-component systems and transcriptional regulators such as Clp, Zur, FhrR, HrpX and HpaR Furthermore, virulence gene expression is post-transcriptionally controlled by the RNA-binding protein RsmA In this review, we summarize the current knowledge on the infection strategies and regulatory networks controlling secreted virulence factors from Xanthomonas species

Journal ArticleDOI
TL;DR: In this article, the Cosserat-type theories of plates and shells are discussed as a special application of this model, and the authors show that they can explain additional effects in solid and fluid mechanics in a more satisfying manner.
Abstract: One of the research direction of Horst Lippmann during his whole scientific career was devoted to the possibilities to explain complex material behavior by generalized continua models. A representative of such models is the Cosserat continuum. The basic idea of this model is the independence of translations and rotations (and by analogy, the independence of forces and moments). With the help of this model some additional effects in solid and fluid mechanics can be explained in a more satisfying manner. They are established in experiments, but not presented by the classical equations. In this paper the Cosserat-type theories of plates and shells are debated as a special application of the Cosserat theory.

Journal ArticleDOI
TL;DR: Current research focuses on establishing predictive factors for CID like uridine diphosphate glucuronosyltransferase-1A1 polymorphisms for irinotecan or dihydropyrimidine-dehydrogenase insufficiency for fluoropyrimidines.
Abstract: Diarrhea is one of the main drawbacks for cancer patients. Possible etiologies could be radiotherapy, chemotherapeutic agents, decreased physical performance, graft versus host disease and infections. Chemotherapy-induced diarrhea (CID) is a common problem, especially in patients with advanced cancer. The incidence of CID has been reported to be as high as 50-80% of treated patients (≥30% CTC grade 3-5), especially with 5-fluorouracil bolus or some combination therapies of irinotecan and fluoropyrimidines (IFL, XELIRI). Regardless of the molecular targeted approach of tyrosine kinase inhibitors and antibodies, diarrhea is a common side effect in up to 60% of patients with up to 10% having severe diarrhea. Furthermore, the underlying pathophysiology is still under investigation. Despite the number of clinical trials evaluating therapeutic or prophylactic measures in CID, there are just three drugs recommended in current guidelines: loperamide, deodorized tincture of opium and octreotide. Newer strategies and more effective agents are being developed to reduce the morbidity and mortality associated with CID. Recent research focusing on the prophylactic use of antibiotics, budesonide, probiotics or activated charcoal still have to define the role of these drugs in the routine clinical setting. Whereas therapeutic management and clinical work-up of patients presenting with diarrhea after chemotherapy are rather well defined, prediction and prevention of CID is an evolving field. Current research focuses on establishing predictive factors for CID like uridine diphosphate glucuronosyltransferase-1A1 polymorphisms for irinotecan or dihydropyrimidine-dehydrogenase insufficiency for fluoropyrimidines.

Journal ArticleDOI
TL;DR: In this article, the authors summarized particular features of commonly used phospholipids and their application spectrum within oral drug formulation and elucidates current strategies to improve bioavailability and disposition of orally administered drugs.
Abstract: Phospholipids become increasingly important as formulation excipients and as active ingredients per se. The present article summarizes particular features of commonly used phospholipids and their application spectrum within oral drug formulation and elucidates current strategies to improve bioavailability and disposition of orally administered drugs. Advantages of phospholipids formulations not only comprise enhanced bioavailability of drugs with low aqueous solubility or low membrane penetration potential, but also improvement or alteration of uptake and release of drugs, protection of sensitive active agents from degradation in the gastrointestinal tract, reduction of gastrointestinal side effects of non-steroidal anti-inflammatory drugs and even masking of bitter taste of orally applied drugs. Technological strategies to achieve these effects are highly diverse and offer various possibilities of liquid, semi-liquid and solid lipid-based formulations for drug delivery optimization.

Journal ArticleDOI
TL;DR: An overview of the current state of research in the field of biaxial nematic liquid crystalline materials is given in this paper, where the major theoretical concepts are outlined, including the classification to different symmetries, the importance of cooperativity and cluster formation for the development of BN order and the conditions for the establishment of field induced and spontaneous BN in nematic phases.
Abstract: An overview over the current state of research in the field of biaxial nematic liquid crystalline materials is given. After a short introduction, providing some general aspects and summarizing the classical approaches, the main part focuses on recent developments of new concepts for designing biaxial nematics. First, the major theoretical concepts are outlined, including the classification to different symmetries, the importance of cooperativity and cluster formation for the development of biaxial order and the conditions for the establishment of field induced and spontaneous biaxiality in nematic phases. These new concepts also require the re-evaluation of the tools used for the identification of phase biaxiality, which are discussed briefly. In the second part, recent progress in the design of potential biaxial nematic materials, especially focussing on bent-core molecules with nematic phases, is reported and, finally, comparisons with phase biaxiality as observed in smectic liquid crystals are made.

Journal ArticleDOI
TL;DR: The crystal structure of the GLP-1 receptor extracellular domain in complex with the competitive antagonist exendin-4 is solved and shows that important hydrophobic ligand-receptor interactions are conserved in agonist- and antagonist-bound forms of the extacellular domain, but certain residues in the ligands-binding site adopt a GLp-1-specific conformation.

Journal ArticleDOI
24 May 2010-Oncogene
TL;DR: Altered microRNA signatures are identified as potent markers for ATCs that promote de-/transdifferentiation (EMT) and invasion of these neoplasias and TGFBR1 inhibition could have a significant potential for the treatment of A TCs and possibly other invasive tumors.
Abstract: Anaplastic thyroid carcinomas (ATCs) arise from epithelial thyroid cells by mesenchymal de-/transdifferentiation and rapidly invade the adjacent tissue. Specific microRNA signatures were suggested to distinguish ATCs from normal thyroid tissue and other thyroid carcinomas of follicular origin. Whether distinct microRNA patterns correlate with de-/transdifferentiation and invasion of ATCs remained elusive. We identified two significantly decreased microRNA families that unambiguously distinguish ATCs from papillary and follicular thyroid carcinomas: miR-200 and miR-30. Expression of these microRNAs in mesenchymal ATC-derived cells reduced their invasive potential and induced mesenchymal-epithelial transition (MET) by regulating the expression of MET marker proteins. Supporting the role of transforming growth factor (TGF)beta signaling in modulating MET/epithelial-mesenchymal transition (EMT), expression of SMAD2 and TGFBR1, upregulated in most primary ATCs, was controlled by members of the miR-30 and/or miR-200 families in ATC-derived cells. Inhibition of TGFbeta receptor 1 (TGFBR1) in these cells induced MET and reduction of prometastatic miR-21, but caused an increase of the miR-200 family. These findings identify altered microRNA signatures as potent markers for ATCs that promote de-/transdifferentiation (EMT) and invasion of these neoplasias. Hence, TGFBR1 inhibition could have a significant potential for the treatment of ATCs and possibly other invasive tumors.

Journal ArticleDOI
04 Mar 2010-Blood
TL;DR: This study supports a molecular network involving miR-223, C/EBPalpha, and E2F1 as major components of the granulocyte differentiation program, which is deregulated in AML.

Journal ArticleDOI
TL;DR: In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone.
Abstract: Objective: Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCIcentered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS. Design: A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004 (ClinicalTrials.gov ID NCT00469248). Setting: Tertiary care university hospital. Patients and Interventions: Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP. Measurements and Main Results: Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 2.88) than survivors (18.1 1.66, p < 0.05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results. Conclusions: In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point. (Crit Care Med 2010; 38:000‐000)

Journal ArticleDOI
TL;DR: The most important phenotypic characters for distinguishing species within the C. cladosporioides complex, which represents a monophyletic subclade within the genus, are shape, width, length, septation and surface ornamentation of conidia and conidiophores; length and branching patterns of conidial chains and hyphal shape and arrangement.

Journal ArticleDOI
TL;DR: Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from NACT as well as predict mid-course response within the triple negative groups.
Abstract: In order to explore the effect of neoadjuvant chemotherapy (NACT) on clinical mid-course and pathological complete response (pCR) at surgery in different biological breast cancer subtypes. The GeparTrio study included 2,072 patients with operable or locally advanced breast cancer. After two cycles with docetaxel, doxorubicin and cyclophosphamide (TAC) patients were randomized according to their clinical response. Clinical and biological factors were assessed for predicting clinically mid-course response and pCR at surgery. The overall pCR rate, defined as no invasive residuals in breast and axilla, was 20.5%. The highest pCR rate of 57% was observed in patients below 40 years of age with triple negative or grade 3 tumors. Independent factors for mid-course response and pCR were: young age, non-T4 tumors, high grade, and hormone receptor status, the strongest single predictive factor. Within the biological subtypes, grading was an independent factor to predict pCR for luminal tumors, clinical tumor stage for the HER2 like tumors and age for the triple negative ones. Grading gave independent information for mid-course response within the triple negative group. No factor predicted mid-course response within the other groups. Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from NACT.

Journal ArticleDOI
TL;DR: Most newly diagnosed MTC patients, i.e. those with pretherapeutic basal calcitonin levels greater than 200 pg/ml, may need bilateral compartment-oriented neck surgery to reduce the number of reoperations.
Abstract: Context: Preoperative neck ultrasonography may yield false-negative findings in more than one-third of medullary thyroid cancer (MTC) patients. If not cleared promptly, cervical lymph node metastases may emerge subsequently. Reoperations entail an excess risk of surgical morbidity and may be avoidable. Objective: This comprehensive investigation aimed to evaluate in a head-to-head comparison the clinical utility of pretherapeutic biomarker serum levels (basal calcitonin; stimulated calcitonin; carcinoembryonic antigen) for indicating extent of disease and providing biochemical stratification of pretherapeutic MTC risk. Design: This was a retrospective analysis. Setting: The setting was a tertiary referral center. Patients: Included were 300 consecutive patients with previously untreated MTC. Interventions: The intervention was compartment-oriented surgery. Main Outcome Measure: Stratified biomarker levels were correlated with histopathologic extent of disease. Results: Higher biomarker levels reflected la...

Journal ArticleDOI
01 Oct 2010-Polymer
TL;DR: In this article, the amorphous and partially ordered phases of the three polymers listed in the title are discussed based on information on structure, thermodynamic stability, and large-amplitude molecular motion.

Journal ArticleDOI
TL;DR: The clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement in 44 late-onset GSD2 patients with various stages of disease severity.
Abstract: Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid α-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers’ maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers’ test, the CK levels and the 6-min walk test (341 ± 149.49 m, median 342.25 m at baseline; 393 ± 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.


Journal ArticleDOI
TL;DR: The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management.
Abstract: Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with anti-angiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0.4% in the single-arm study. There was a trend towards increased ONJ incidence in patients who received bisphosphonate therapy versus those with no bisphosphonate exposure (0.9 vs. 0.2%, respectively, in the pooled analysis of the randomised trials; 2.4 vs. 0%, respectively, in ATHENA). In conclusion, this is the largest analysis of ONJ in patients receiving bevacizumab for LR/MBC. The 0.3–0.4% incidence is considerably lower than previously suggested with anti-angiogenic therapy in a small retrospective analysis. The risk of ONJ appeared to be increased in patients exposed to bisphosphonates, a pattern consistent with observations before the introduction of anti-angiogenic therapy to breast cancer management. The 0.9–2.4% incidence seen in bisphosphonate-exposed patients receiving bevacizumab is within the 1–6% range reported for bisphosphonates alone. Good oral hygiene, dental examination, and avoidance of invasive dental procedures remain important in patients receiving bisphosphonates, irrespective of bevacizumab administration.

Journal ArticleDOI
TL;DR: MiR-BART6-5p RNAs suppress the EBNA2 viral oncogene required for transition from immunologically less responsive type I and type II latency to the more immunoreactive type III latency as well as Zta and Rta viral proteins essential for lytic replication, revealing the regulatory function of miR- BART6 in EBV infection and latency.

Journal ArticleDOI
TL;DR: The authors' data largely confirmed currently used remission and response criteria in naturalistically treated patients as well as comparing the validity of different HAMD, MADRS and BDI cut-offs.

Journal ArticleDOI
TL;DR: In this paper, a series of regioregular poly(3-hexylthiophene) with well-defined molecular weight (5−19 kg/mol) using DSC, small angle and wide-angle X-ray scattering, and AFM was reported.
Abstract: We report on structural investigations of a series of regioregular poly(3-hexylthiophene) with well-defined molecular weight (5−19 kg/mol) using DSC, small angle and wide-angle X-ray scattering, and AFM. With increasing temperature, we identify three ordered phases, namely 3D crystalline, 2D crystalline with disordered side chains, and a layered phase of smectic symmetry, followed by complete melting. Although all samples crystallize in extended chain conformation, the lower molecular weight material exhibits a lower crystallinity, most likely caused by noncrystallizable end groups. The crystallinity increases strongly with increasing molecular weight, which could be a possible explanation for the known dependence of charge transport properties on molecular weight.