897 research outputs found
Marfans syndrom og fatigue : En tverrsnittsstudie i en gruppe voksne personer med verifisert Marfans syndrom
No full textHensikt: Hensikten med denne studien er å få en forståelse av fenomenet opplevd fatigue (tretthet) og hvordan det arter seg for voksne med verifisert Marfans syndrom (MFS). Jeg vil undersøke grad av fatigue og forekomst av alvorlig fatigue hos voksne med MFS, og sammenligne dette med rapportert forekomst i den generelle befolkningen og for noen aktuelle kroniske tilstander. Assosiasjoner mellom fatigue og sosiodemografiske karakteristika og selvrapporterte helseproblemer hos voksne med MFS vil bli undersøkt i multivariable analyser.
Metode: Tverrsnittsstudie med postutsendt spørreskjema. Fatigue Severity Scale (FSS), sosio-demografiske forhold og selvrapporterte helseproblemer ble undersøkt hos 72 voksne personer med MFS.
Resultater: Deltakerne rapporterte signifikant høyere FSS gjennomsnittsskår og høyere forekomst av alvorlig fatigue (gjennomsnittsskår ≥ 5), sammenlignet med rapportert nivå for den generelle befolkningen og noen kroniske tilstander. Kronisk smerte og arbeidstilknytning hadde signifikant assosiasjon til fatigue i multivariable analyser. Personer med smerte hadde høyere fatigueskår enn personer uten kronisk smerte. Personer som mottok trygdeytelser hadde høyere fatigue enn personer som var i arbeid/ under utdanning. Den endelige multivariable modellen forklarte 24 % av variasjonen i fatigueskår. Dette indikerer at det også er andre assosierte faktorer til opplevd fatigue hos voksne med MFS.
Konklusjon: Personer med MFS har høyere grad av fatigue og høyere forekomst av alvorlig fatigue, sammenlignet med den generelle befolkningen og noen kroniske tilstander som rheumatoid artritt. I multivariable analyser var kronisk smerte og arbeidstilknytning de faktorene som var signifikant assosiert med fatigue. Det er behov for videre forskning om fatigue ved MFS.
Resultater fra oppgaven er også publisert i Am J Med Genet Part A. Bathen et al 2014. 164A:1931-1939. http://dx.doi.org/10.1002/ajmg.a.3657
Van den warmen baden, ende in sunderheyt den genen die tot Aken sijn, wat crachte dat sy hebben, en[de] wie mansie ghebruycken sal [...] /
No full textDatum in colofonDrukkersmerk op titelbladVingerafdruk: 155208 - b1 A2 re$e : *b2 D2 ighHerkomst: vignet Bibliotheek SnellaertMachiels, J. Catalogus van de boeken gedrukt vóór 1600 ; F 21Valkema Blouw, P. Typographia Batava ; 1894Europeana-GoogleBook
The Jervell and Lange-Nielsen syndrome: natural history, molecular basis, and clinical outcome.
No full textBackground—Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the IKs current, are still based largely on case reports.
Methods and Results—We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (55765 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P0.01). A QTc 550 ms and history of syncope during the first year of life are independent predictors of subsequent
CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more
benign course. -Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had
CA/SD.
Conclusions—J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which -blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include
females, patients with a QTc 550 ms, those without events in the first year of life, and those with mutations on KCNE1.
Early therapy with implanted cardioverter/defibrillators must be considered
Point defects in silicon carbide for quantum technologies: Identification, tuning and control
No full textPoint defects strongly affect the electrical and optical properties of semiconductors, and are therefore of vast importance for device performance. Over recent years, however, point defects have been shown to possess properties that are highly suitable for applications related to quantum computing, sensing and communication. Single-photon emission and coherent spin manipulation at room temperature have been established for several systems, with the nitrogen-vacancy center in diamond counting among the first solid-state and semiconductor-based quantum platforms.
Despite the long coherence times and established entanglement protocols of diamond-based qubit systems, diamond is only marginally compatible with advanced device fabrication methodology, and methods for integration of quantum emitters with electrically and optically controlled devices remain immature. For this reason, silicon carbide (SiC) has gained the attention of the quantum community, having a wide band gap, low spin-orbit coupling, mature device fabrication, and playing host to several promising quantum emitters of both extrinsic and intrinsic type.
In this work, electrically and optically active point defects in silicon carbide have been studied using a combination of theoretical and experimental methods, with the aim of elucidating the role of different defects in power electronics and quantum technology devices. Hybrid density functional theory (DFT) calculations were employed to establish defect formation energies and chargestate transition levels, explore defect migration, and develop a new framework for studying the effect of electric fields on defect quantum emission. The calculations are correlated to experimental findings, where deep level transient spectroscopy (DLTS) and photo/cathodoluminescence (PL/CL) measurements reveal electrical and optical defect properties, respectively.
The thesis places a particular emphasis on the silicon vacancy (VSi) in SiC, a room temperature single-photon source and qubit candidate exhibiting long spin coherence times. By monitoring VSi emission and comparing to DLTS spectra of proton-irradiated 4H-SiC samples, the VSi(-/2-) and VSi(2-/3-) charge-state transitions are assigned to the S-center, enabling electrical control over the VSi charge state. Depositing Schottky barrier diodes (SBDs) on the 4H-SiC sample surface enhances VSi emission by almost an order of magnitude, and sequential biasing of the SBD results in VSi charge-state switching, as detected by monitoring the V1 and V10 zero-phonon lines attributed to the negatively charged VSi at a hexagonal lattice site. The framework of bulk 4H-SiC epitaxial layers is compared to that of a microparticle matrix of predominantly the 6H polytype, with the former ensuring a homogeneous environment for the qubit defect and the latter enabling self-assembly, flexibility and ease of addressability. Importantly, both external and internal perturbations to the solid-state matrix wherein the VSi is embedded are shown to influence the emitted photon energies, as evidenced by an electric field-induced Stark effect and strain tuning in SiC microparticles. Furthermore, a set of emitters observed in the vicinity of the V1/V10 lines and having consistent subset spacings of 1.45 meV and 1.59 meV are tentatively attributed to vibronic replicas of the VSi emission.
The VSi is unstable at elevated temperatures, and this thesis addresses the topics of VSi conversion and defect migration in p-type, intrinsic and n-type 4H-SiC material at 400 °C and above. Indeed, we find that hydrogen and VSi are likely to form complexes in the case that both species are present and in close proximity. In the absence of H, the VSi may convert to the carbon antisitevacancy (CAV) pair in p-type material, however, temperatures above 1000 °C are needed in n-type 4H-SiC, where both recombination with interstitials and divacancy formations prove to be more favorable annealing pathways for the VSi. The carbon vacancy (VC) is far more stable than VSi, and by comparing the two defect species using muon spin rotation (μSR) spectroscopy, we establish the μSR technique as a powerful tool for distinguishing different defect relaxation mechanisms and probing near-surface semiconductor defects in a non-destructive and depth-resolved manner. Annealing temperatures above 1200 °C are shown to be needed to induce VC migration, which is further demonstrated to be anisotropic in 4H-SiC, with the VC favoring in-plane atomic hops over the axial migration path. Finally, above temperatures of 2300 °C the lattice atoms themselves become mobile, and secondary ion mass spectrometry (SIMS) is employed to investigate the influence of a carbon cap covering the surface during annealing on self-diffusion of Si and C in 4H-SiC
Multi-Level Molecular Characterisation of Prostate Cancer
No full textProstate cancer is the most common malignancy in Norwegian men, and represents a substantial health burden. The disease is heterogeneous, ranging from slow growing and indolent, to very aggressive and lethal. One of the major unsolved clinical challenges is to accurately separate indolent from harmful disease at an early time point. This causes substantial overtreatment of patients with harmless cancers, as well as undertreatment of patients with aggressive cancers. To enable improved treatment selection, an increased understanding of the molecular characteristics of prostate cancer progression is needed. In this thesis, multi-level molecular analyses of gene expression and metabolism were performed in an integrated fashion on prostate tissue samples. The aim was to obtain more comprehensive knowledge of prostate cancer aggressiveness, and to identify candidate biomarkers for improved risk stratification of prostate cancer patients.
Gene expression analysis is a method that detects active genes; it can indicate which molecular processes occur in cells and tissue. The expression of genes is the instruction for which proteins are produced in the cells. Proteins are components of cellular signalling pathways, where the pathway activity can be altered to favour cancer survival. Activation of the Wnt signalling pathway may increase the cells’ motility, and can therefore be exploited by cancer cells to gain invasive and metastatic properties. The work in this thesis showed increased activation of a subgroup of the Wnt pathway, called the non-canonical Wnt pathway. By using a set of genes representing the non-canonical Wnt pathway (NCWP), combined with markers of increased cell mobility (epithelial-mesenchymal transition (EMT)), a gene signature coined NCWP-EMT was developed. An increased signature score suggests increased activation of this pathway. High signature score, representing increased activation of the pathway, was associated with aggressive cancer, where more patients experienced recurrent and metastatic disease after surgery. The signature may therefore have clinical potential to improve the discrimination of aggressive from indolent prostate cancer at an early time point.
One of the signature members, secreted frizzled-related protein 4 (SFRP4), was further investigated on its own. The expression level of SFRP4 was shown to be a predictor for aggressive, recurrent and metastatic disease, and this was validated in several independent patient cohorts, and in a total of 1884 patients. SFRP4 alone, may therefore have potential as a biomarker for prediction of prostate cancer outcome.
Changes in the genome can alter gene expression, and an example of this is a fusion of two genes, called TMPRSS2-ERG. This gene fusion is found in approximately half of malignant prostate tumours, however, little is known about its relation to other molecular processes, such as cancer cell metabolism. In this thesis, a distinctive metabolic profile was seen in cancer tissue possessing TMPRSS2-ERG, and this profile was similar to metabolic alterations previously observed in aggressive prostate cancer.
Metabolism in tissues and cells can be studied by magnetic resonance (MR) spectroscopy. Cancer cell metabolism differ from healthy cells, as cancer often prioritise growth which require increased energy production and synthesis of new building blocks. Reprogramming of metabolism is therefore regarded as one of the hallmarks of cancer cells. The normal prostate cells produce and excrete high levels of the metabolite citrate for the prostatic fluid. Previously, a reduced levels of citrate have been detected in prostate cancer compared with healthy tissue, and this is likely due to citrate being used for energy and fatty acid production, rather than production and excretion. Furthermore, alterations to polyamine metabolism, and in particular to spermine, are important in prostate cancer, where decreased spermine concentration has been associated with the disease. In this thesis, reduced concentrations of both citrate and spermine were detected in cancer tissue samples containing the TMPRSS2-ERG gene fusion, samples with a high score of the non-canonical Wnt pathway signature, and samples with a high expression level of SFRP4. This suggests that citrate and spermine have great potential as tissue biomarkers of prostate cancer. Importantly, these metabolic alterations were also detected by non-invasive patient MR examination, which is therefore a candidate as a prognostic tool in prostate cancer diagnosis.
To summarise, the work presented in this thesis shows that the TMPRSS2-ERG gene fusion, the non-canonical Wnt pathway, and SFRP4 expression are all associated with reprogramming of prostate cancer metabolism. Additionally, activation of the non-canonical Wnt pathway and the expression level of SFRP4 were associated with recurrent and metastatic disease after surgery. Further investigation of these aggressive molecular characteristics may lead to clinical
biomarkers for improved early risk stratification in prostate cancer patients
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des bouches Sebenitique, Mendeisienne, Tanitique, et Pélusiaque ; que le lac Bahr-Belame ou le lac sans eau sont les ruines de l’ancien cours de ce fleuve, dans lequel on trouve en pétrification d’irrévocables témoignages de débordements, de végétations, et de travaux humains , qui attestent que ce sol a été exhaussé par le cours du fleuve, et par cette perpétuelle fluctuation des sables qui marchent toujours de l’ouest à l’est; que le Nil, à une certaine époque, trouvant plus de pente au nord qu’au nord-ouest, où il couloit, s’est précipité dans le golfe que nous venons de supposer; qu’il y a formé d’abord des marais, et puis enfin le Delta. Il résulteroit de là que les premiers travaux des anciens Égyptiens , tels q ae, le lacMœris, aujourd’hui le lac Bathen et la première digue, n’ont été faits d’abord que pour retenir une partie des eaux du débordement, pour en arroser la province d’Arsinoé, qui menaçoit de devenir stérile, et que, dans un temps postérieur, le lac Mœris ou Bathen ne recevant plus assez d’eau et ne pouvant plus arroser l
Multimodal Imaging-derived Biomarkers for Early Detection and Personalized Treatment of Breast Cancer
No full textAccurate segmentation of cancer from surrounding healthy breast tissues in magnetic resonance imaging (MRI) without intravenous administration of contrast agents, is a question of wide interest. Current standard-of-care dynamic contrast-enhanced MRI (DCE) depends on Gadolinium contrast. Diffusion-weighted MRI (DWI) avoids the use of contrast since it is able to report on tissue microstructure by detecting diffusion of water molecules and has shown large potential in several breast cancer settings, including assessment of treatment response.
However, the current application of DWI for quantitative studies requires radiologists to manually define tumors based on DCE, prior to transferring the defined regions of interest (ROIs) to the DWI image space for analysis.
In this thesis, we investigated alternative methods to DCE for breast tumor definition and neoadjuvant treatment response evaluation: simultaneous positron emission tomography and MRI (PET/MRI), and optimizing an advanced DWI model, Restriction Spectrum Imaging (RSI), for use in the breast. Since meaningful assessment by the RSI model requires knowledge about the underlying breast diffusion properties, we investigated the optimal fitting of diffusion signal for all voxels in cancer and healthy breast tissues. Furthermore, the optimized RSI model was applied for neoadjuvant treatment response evaluation.
We found that tumor definition using our novel semi-automatic PET/MRI segmentation method, GMM-PET, mimics results normally attained through DCE by successfully tracking the same changes in functional parameters for assessment of neoadjuvant treatment. Secondly, optimal fitting of diffusion signal for all voxels in cancer and healthy breast tissues resulted in a three-component RSI model, with globally-determined component-specific apparent diffusion coefficients (ADCs) that decomposed the diffusion signal to correspond to major anatomical components in healthy breast tissues. These results were then applied for optimized discrimination of cancer from healthy breast tissues directly on DWI images, which yielded the derived RSI parameter, C1C2 that showed highly promising discriminatory performance superior to conventional DWI estimates. The three-component RSI model was further used to develop an automatic tissue classifier (RSI classifier) that was able to assess treatment response after only 3 weeks of neoadjuvant treatment and was found to have similar accuracy to DCE in assessing residual tumor post-therapy.
Our novel methodologies, GMM-PET and three-component RSI model-derived C1C2 parameter, can detect breast cancer without the use of Gadolinium contrast. Of particular interest, the highly promising diagnostic performance of C1C2 was determined using data acquired across different sites, scanners, and imaging acquisition protocols. This suggests a readily available clinical utility that may reduce the need to pre-identify lesions on nondiffusion modalities altogether. The finding that the automatic RSI classifier can assess early response to neoadjuvant treatment is important for improved clinical decision-making to enable tailored treatment regimens
Vestibular disease in dogs: association between neurological examination, MRI lesion localisation and outcome.
No full textOBJECTIVES
To determine whether the neurological examination correctly distinguishes between central and peripheral vestibular lesions in dogs.
MATERIALS AND METHODS
Retrospective study on dogs with vestibular disease presenting to two referral clinics in Germany.
RESULTS
Ninety-three dogs were included; neurological examination suggested central vestibular disease in 62 and a peripheral lesion in 31. MRI diagnosis was central vestibular disease in 68 dogs and peripheral in 25. Of the 62 dogs with a lesion localisation diagnosed as central vestibular by neurological exam, 61 were correctly identified (98.4%). Twenty-four of the 31 dogs diagnosed with a peripheral lesion by neurological exam had a consistent lesion on MRI (77.4%).
CLINICAL SIGNIFICANCE
The neurological examination is efficient at identifying lesions in the central vestibular system but less so for peripheral lesions. Therefore it is prudent to recommend imaging in dogs that show signs of peripheral vestibular syndrome but do not rapidly respond to treatment
Centrality dependence of inclusive J/? production in p-Pb collisions at at sNN????=5.02sNN=5.02 TeV
No full textAbstract: We present a measurement of inclusive J/ψ production in p-Pb collisions at sNN=5.02(Formula presented.) TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, pT, in the backward (−4.46 < ycms< −2.96) and forward (2.03 < ycms< 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region (−1.37 < ycms< 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The pT-differential J/ψ production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average pT and pT2 values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of pT for several centrality classes at backward and forward rapidity. At mid- and forward rapidity, the J/ψ yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing pT of the J/ψ. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions.[Figure not available: see fulltext.
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