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Linearly implicit time discretizations of semilinear parabolic equations with non-smooth initial data are studied. The analysis uses the framework of analytic semigroups which includes reaction-diffusion equations and the incompressible Navier-Stokes equations. It is shown that the order of convergence on finite time intervals is essentially one. Applications to the long-term behaviour of linearly implicit Runge-Kutta methods are given. [ABSTRACT FROM AUTHOR]

Background: While the last decade of extensive research revealed the prominent role of the claustrum for mammalian forebrain organization, i.e., widely distributed claustral-cortical circuits coordinate basic cognitive functions such as attention, it is poorly understood whether the claustrum is relevant for schizophrenia and related cognitive symptoms. We hypothesized firstly, that claustrum volumes are lower in schizophrenia and secondarily, that potentially lower volumes mediate patients' attention deficits., Methods: Based on T1-weighted MRI, advanced automated claustrum segmentation, and attention symbol coding task (SCT) in 90 patients with schizophrenia and 96 healthy controls from two independent sites, the COBRE open-source database and MUNICH dataset, we compared total-intracranial-volume-normalized claustrum volumes and SCT scores across groups via ANCOVA and related variables via correlation and mediation analysis., Results: Patients had lower claustrum volumes of about 13 % (p<0.001, Hedges g=0.63), which not only correlated with (r=0.24, p=0.014) but also mediated lower SCT scores (indirect effect ab = -1.30 ± 0.69; CI [-3.73; -1.04]). Results were not confounded by age, sex, global and claustrum-adjacent gray matter changes, scanner site, smoking, and medication., Conclusions: Results demonstrate lower claustrum volumes that mediate patients' attention deficits in schizophrenia. Data indicate the claustrum as being relevant for schizophrenia pathophysiology and cognitive functioning., (Copyright © 2024. Published by Elsevier Inc.)

Background and Hypothesis: Abnormal thalamic nuclei volumes and their link to cognitive impairments have been observed in schizophrenia. However, whether and how this finding extends to the schizophrenia spectrum is unknown. We hypothesized a distinct pattern of aberrant thalamic nuclei volume across the spectrum and examined its potential associations with cognitive symptoms., Study Design: We performed a FreeSurfer-based volumetry of T1-weighted brain MRIs from 137 healthy controls, 66 at-risk mental state (ARMS) subjects, 89 first-episode psychosis (FEP) individuals, and 126 patients with schizophrenia to estimate thalamic nuclei volumes of six nuclei groups (anterior, lateral, ventral, intralaminar, medial, and pulvinar). We used linear regression models, controlling for sex, age, and estimated total intracranial volume, both to compare thalamic nuclei volumes across groups and to investigate their associations with positive, negative, and cognitive symptoms., Study Results: We observed significant volume alterations in medial and lateral thalamic nuclei. Medial nuclei displayed consistently reduced volumes across the spectrum compared to controls, while lower lateral nuclei volumes were only observed in schizophrenia. Whereas positive and negative symptoms were not associated with reduced nuclei volumes across all groups, higher cognitive scores were linked to lower volumes of medial nuclei in ARMS. In FEP, cognition was not linked to nuclei volumes. In schizophrenia, lower cognitive performance was associated with lower medial volumes., Conclusions: Results demonstrate distinct thalamic nuclei volume reductions across the schizophrenia spectrum, with lower medial nuclei volumes linked to cognitive deficits in ARMS and schizophrenia. Data suggest a distinctive trajectory of thalamic nuclei abnormalities along the course of schizophrenia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Lasting thalamus volume reduction after preterm birth is a prominent finding. However, whether thalamic nuclei volumes are affected differentially by preterm birth and whether nuclei aberrations are relevant for cognitive functioning remains unknown. Using T1-weighted MR-images of 83 adults born very preterm (≤ 32 weeks' gestation; VP) and/or with very low body weight (≤ 1,500 g; VLBW) as well as of 92 full-term born (≥ 37 weeks' gestation) controls, we compared thalamic nuclei volumes of six subregions (anterior, lateral, ventral, intralaminar, medial, and pulvinar) across groups at the age of 26 years. To characterize the functional relevance of volume aberrations, cognitive performance was assessed by full-scale intelligence quotient using the Wechsler Adult Intelligence Scale and linked to volume reductions using multiple linear regression analyses. Thalamic volumes were significantly lower across all examined nuclei in VP/VLBW adults compared to controls, suggesting an overall rather than focal impairment. Lower nuclei volumes were linked to higher intensity of neonatal treatment, indicating vulnerability to stress exposure after birth. Furthermore, we found that single results for lateral, medial, and pulvinar nuclei volumes were associated with full-scale intelligence quotient in preterm adults, albeit not surviving correction for multiple hypotheses testing. These findings provide evidence that lower thalamic volume in preterm adults is observable across all subregions rather than focused on single nuclei. Data suggest the same mechanisms of aberrant thalamus development across all nuclei after premature birth., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Melissa Thalhammer reports financial support was provided by Studienstiftung des deutschen Volkes. Christian Sorg reports financial support was provided by Deutsche Forschungsgemeinschaft (DFG). Peter Bartmann reports financial support was provided by German Federal Ministry of Education and Science. Dieter Wolke reports financial support was provided by German Federal Ministry of Education and Science. Dieter Wolke reports financial support was provided by EU Horizon 2020. Peter Bartmann reports financial support was provided by EU Horizon 2020. Christian Sorg reports financial support was provided by Commission for Clinical Research, Technical University of Munich. Benita Schmitz-Koep reports financial support was provided by Commission for Clinical Research, Technical University of Munich. Dennis Hedderich reports financial support was provided by Commission for Clinical Research, Technical University of Munich. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aims: To investigate cortical organization in brain magnetic resonance imaging (MRI) of preterm-born adults using percent contrast of gray-to-white matter signal intensities (GWPC), which is an in vivo proxy measure for cortical microstructure., Methods: Using structural MRI, we analyzed GWPC at different percentile fractions across the cortex (0%, 10%, 20%, 30%, 40%, 50%, and 60%) in a large and prospectively collected cohort of 86 very preterm-born (<32 weeks of gestation and/or birth weight <1500 g, VP/VLBW) adults and 103 full-term controls at 26 years of age. Cognitive performance was assessed by full-scale intelligence quotient (IQ) using the Wechsler Adult Intelligence Scale., Results: GWPC was significantly decreased in VP/VLBW adults in frontal, parietal, and temporal associative cortices, predominantly in the right hemisphere. Differences were pronounced at 20%, 30%, and 40%, hence, in middle cortical layers. GWPC was significantly increased in right paracentral lobule in VP/VLBW adults. GWPC in frontal and temporal cortices was positively correlated with birth weight, and negatively with duration of ventilation (p < 0.05). Furthermore, GWPC in right paracentral lobule was negatively correlated with IQ (p < 0.05)., Conclusions: Widespread aberrant gray-to-white matter contrast suggests lastingly altered cortical microstructure after preterm birth, mainly in middle cortical layers, with differential effects on associative and primary cortices., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Microscopic studies in newborns and animal models indicate impaired myelination after premature birth, particularly for cortical myelination; however, it remains unclear whether such myelination impairments last into adulthood and, if so, are relevant for impaired cognitive performance. It has been suggested that the ratio of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging signal intensity (T1w/T2w ratio) is a proxy for myelin content. We hypothesized altered gray matter (GM) T1w/T2w ratio in premature-born adults, which is associated with lower cognitive performance after premature birth., Methods: We analyzed GM T1w/T2w ratio in 101 adults born very premature (VP) and/or at very low birth weight (VLBW) (<32 weeks of gestation and/or birth weight <1500 g) and 109 full-term control subjects at 26 years of age, controlled for voxelwise volume alterations. Cognitive performance was assessed by verbal, performance, and full scale IQ using the Wechsler Adult Intelligence Scale., Results: Significantly higher T1w/T2w ratio in VP/VLBW subjects was found bilaterally in widespread cortical areas, particularly in frontal, parietal, and temporal cortices, and in putamen and pallidum. In these areas, T1w/T2w ratio was not related to birth variables, such as gestational age, or IQ scores. In contrast, significantly lower T1w/T2w ratio in VP/VLBW subjects was found in bilateral clusters in superior temporal gyrus, which was associated with birth weight in the VP/VLBW group. Furthermore, lower T1w/T2w ratio in left superior temporal gyrus was associated with lower full scale and verbal IQ., Conclusions: Results demonstrate GM T1w/T2w ratio alterations in premature-born adults and suggest altered GM myelination development after premature birth with lasting and functionally relevant effects into early adulthood., (Copyright © 2022 Society of Biological Psychiatry. All rights reserved.)

The human claustrum is a gray matter structure in the white matter between insula and striatum. Previous analysis found altered claustrum microstructure in very preterm-born adults associated with lower cognitive performance. As the claustrum development is related to hypoxia-ischemia sensitive transient cell populations being at-risk in premature birth, we hypothesized that claustrum structure is already altered in preterm-born neonates. We studied anatomical and diffusion-weighted MRIs of 83 preterm- and 83 term-born neonates at term-equivalent age. Additionally, claustrum development was analyzed both in a spectrum of 377 term-born neonates and longitudinally in 53 preterm-born subjects. Data was provided by the developing Human Connectome Project. Claustrum development showed increasing volume, increasing fractional anisotropy (FA), and decreasing mean diffusivity (MD) around term both across term- and preterm-born neonates. Relative to term-born ones, preterm-born neonates had (i) increased absolute and relative claustrum volumes, both indicating increased cellular and/or extracellular matter and being in contrast to other subcortical gray matter regions of decreased volumes such as thalamus; (ii) lower claustrum FA and higher claustrum MD, pointing at increased extracellular matrix and impaired axonal integrity; and (iii) aberrant covariance between claustrum FA and MD, respectively, and that of distributed gray matter regions, hinting at relatively altered claustrum microstructure. Results together demonstrate specifically aberrant claustrum structure in preterm-born neonates, suggesting altered claustrum development in prematurity, potentially relevant for later cognitive performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

A universal allometric scaling law has been proposed to describe cortical folding of the mammalian brain as a function of the product of cortical surface area and the square root of cortical thickness across different mammalian species, including humans. Since these cortical properties are vulnerable to developmental disturbances caused by preterm birth in humans and since these alterations are related to cognitive impairments, we tested (i) whether cortical folding in preterm-born adults follows this cortical scaling law and (ii) the functional relevance of potential scaling aberrances. We analysed the cortical scaling relationship in a large and prospectively collected cohort of 91 very premature-born adults (<32 weeks of gestation and/or birthweight <1500 g, very preterm and/or very low birth weight) and 105 full-term controls at 26 years of age based on the total surface area, exposed surface area and average cortical thickness measured with structural magnetic resonance imaging and surface-based morphometry. We found that the slope of the log-transformed cortical scaling relationship was significantly altered in adults (very preterm and/or very low birth weight: 1.24, full-term: 1.14, P = 0.018). More specifically, the slope was significantly altered in male adults (very preterm and/or very low birth weight: 1.24, full-term: 1.00, P = 0.031), while there was no significant difference in the slope of female adults (very preterm and/or very low birth weight: 1.27, full-term: 1.12, P = 0.225). Furthermore, offset was significantly lower compared with full-term controls in both male (very preterm and/or very low birth weight: -0.546, full-term: -0.538, P = 0.001) and female adults (very preterm and/or very low birth weight: -0.545, full-term: -0.538, P = 0.023), indicating a systematic shift of the regression line after preterm birth. Gestational age had a significant effect on the slope in very preterm and/or very low birth weight adults and more specifically in male very preterm and/or very low birth weight adults, indicating that the difference in slope is specifically related to preterm birth. The shape or tension term of the scaling law had no significant effect on cognitive performance, while the size of the cortex did. Results demonstrate altered scaling of cortical surface and cortical thickness in very premature-born adults. Data suggest altered mechanical forces acting on the cortex after preterm birth., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The LIAC HWL (Sordina IORT Technologies, Vicenza, Italy) is a recently designed mobile linear accelerator for intraoperative electron radiotherapy (IOeRT), producing high dose rate electron beams at four different energy levels. It features a software tool for the visualization of 2D dose distributions, which is based on Monte Carlo simulations. The aims of this work were to (i) assess the dosimetric characteristics of the accelerator, (ii) experimentally verify calculated data exported from the software and (iii) report on commissioning as well as performance of the system during the first year of operation., Methods: The electron energies of the LIAC HWL used in this study are 6, 8, 10 and 12 MeV. Diameters of the cylindrically shaped applicators range from 3 to 10cm. We studied two applicator sets with different length ratios of proximal and terminal applicator sections. Reference dosimetry, linearity as well as short- and long-term stability were measured with a PTW Advanced Markus chamber, relative depth dose and profiles were measured using an unshielded diode. Percentage-depth-dose (PDD) and transversal dose profile (TDP) data were exported from the simulation software LIACSim and compared with our measurements., Results: The device reaches dose rates up to 40Gy/min (for 12 MeV). Surface doses for the 10cm applicators are higher than 90%, X-ray background is below 0.6% for all energies. Simulations and measurements of PDD agreed well, with a maximum difference in the depth of the 50% isodose of 0.7mm for the flat-ended applicators and 1mm for the beveled applicators. The simulations slightly underestimate the dose in the lateral parts of the field (difference < 1.8% for flat-ended applicators). The two different applicator sets were dosimetrically equivalent. Long-term stability measurements for the first year of operation ranged from -2.1% to 1.6% (mean: -0.1%)., Conclusions: The system is dosimetrically well suited for IOeRT and performed stably and reliably. The software tool for visualization of dose distributions can be used to support treatment planning, following thorough validation., (Copyright © 2020. Published by Elsevier GmbH.)

Simultaneous binding of molecules by multiple binding partners is known to strongly reduce the apparent dissociation constant of the corresponding molecular complexes, and can be used to achieve strong, non-covalent molecular interactions. Based on this principle, efficient binding of proteins to DNA nanostructures has been achieved previously by placing several aptamers in close proximity to each other onto DNA scaffolds. Here, we develop an approach for exploring design parameters, such as the geometric arrangement or the nanomechanical properties of the binding sites, that use two-dimensional DNA origami-based nanocavities that bear aptamers with known mechanical properties at defined distances and orientations. The origami structures are labelled with barcodes, which enables large numbers of binding cavities to be investigated in parallel and under identical conditions, and facilitates a direct and reliable quantitative comparison of their binding yields. We demonstrate that binding geometry and mechanical properties have a dramatic effect on origami-based multivalent binding sites, and that optimization of linker spacings and flexibilities can improve the effective binding strength of the sites substantially.

Background: The endotracheal tube (ETT) is considered the gold standard in emergency airway management, although supraglottic airway devices, especially the laryngeal tube (LT), have recently gained in importance. Although regarded as an emergency device in case of failure of endotracheal intubation in most systems, we investigated the dynamics of the use of the LT in a metropolitan ambulance service without any regulations on the choice of airway device. Methods: A retrospective, observational study on all patients from the Municipal Ambulance Service, Vienna in need of advanced airway management over a 5-year period. Differences between years were compared; influencing factors for the use of the LT were analyzed using multivariable logistic regression. Results: In total 5,175 patients (mean age 62 ± 20 years, 36.6% female) underwent advanced airway management. Of these, 15.6% received the LT. LT use increased from 20 out of 1,001 (2.0%) in 2009 to 292 of 1,085 (26.9%) in 2013 (p < 0.001). The increase between each consecutive year was also significant. Paramedics more frequently inserted the LT than physicians (RR 1.80 (95%CI 1.48-2.16); p < 0.001). Female patients received a LT less frequently (RR 0.84 (95%CI 0.72-0.97), p = 0.013). There was no difference regarding airway device due to underlying causes requiring airway management and no relationship to the NACA-score. Conclusion: In a European EMS system of physician and paramedic response, the proportion of airway managed by LT over ETT rose considerably over five years. Although the ET is still the gold standard, the LT is gaining in importance for EMS physicians and paramedics.

Background: Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers. The study focus was the role of eIF6 (an anti-association factor for the ribosomal subunits) in GBC., Methods: In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR)., Results: High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis., Conclusion: Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.

Filamentous fungi are widely used in the production of biotechnological compounds. Since their morphology is strongly linked to productivity, it is a key parameter in industrial biotechnology. However, identifying the morphological properties of filamentous fungi is challenging. Owing to a lack of appropriate methods, the detailed three-dimensional morphology of filamentous pellets remains unexplored. In the present study, we used state-of-the-art X-ray microtomography (µCT) to develop a new method for detailed characterization of fungal pellets. µCT measurements were performed using freeze-dried pellets obtained from submerged cultivations. Three-dimensional images were generated and analyzed to locate and quantify hyphal material, tips, and branches. As a result, morphological properties including hyphal length, tip number, branch number, hyphal growth unit, porosity, and hyphal average diameter were ascertained. To validate the potential of the new method, two fungal pellets were studied-one from Aspergillus niger and the other from Penicillium chrysogenum. We show here that µCT analysis is a promising tool to study the three-dimensional structure of pellet-forming filamentous microorganisms in utmost detail. The knowledge gained can be used to understand and thus optimize pellet structures by means of appropriate process or genetic control in biotechnological applications., (© 2019 Wiley Periodicals, Inc.)

Biliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, "IL-6 classic signaling") or via soluble forms (sIL-6R, "IL-6 trans-signaling"). However, little is known about the impact on cellular responses of IL-6 trans-signaling on BTC. We analyzed primary tumors as whole sections and as tissue microarrays, and also searched The Cancer Genome Atlas database. Compared to non-neoplastic, non-inflamed gallbladder tissue, IL-6Rα was downregulated in GBC, and this correlated with the patients' overall survival. Furthermore, different CCA cell lines and compounds for activation (IL-6 and Hyper-IL-6) or inhibition (Tocilizumab and sgp130Fc) of IL-6 classic signaling and trans-signaling were used to determine their effects on cellular processes between the two modes of IL-6 signaling. Inhibition of IL-6 trans-signaling by sgp130Fc reduced CCA cell line viability and apoptosis, whereas migration and proliferation were increased. We conclude that IL-6Rα expression is a good prognostic marker for GBC, and that the blocking of IL-6 trans-signaling and activation of IL-6 classic signaling have tumor promoting activity. These findings warrant the exclusion of patients with GBC or other malignancies associated with bile metabolism from IL-6R inhibitor therapy., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Inflammatory blood count biomarkers may improve recurrence risk stratification and inform long-term prognosis of cancer patients. Here, we quantify the prognostic impact of blood-based biomarkers on recurrence risk and long-term survival in a large cohort of gastrointestinal stroma tumor (GIST) patients after curative surgery., Methods: One-hundred-forty-nine consecutive GIST patients were followed-up for a median period of 4.8 years. Local recurrence, distant metastasis, and death occurred in 9, 21, and 31 patients, respectively. Time-to-event and competing risk analysis were applied to study the association between haemoglobin (Hb) level, white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) with risk of local or distant recurrence (RR), recurrence free survival (RFS), and overall survival (OS)., Results: A low Hb (p = 0.029), and elevations in the parameters WBC (p = 0.004), NLR (p = 0.015) and dNLR (p = 0.037) were associated with a poor OS in GIST patients in multivariate analysis. Moreover, a low Hb (p = 0.049) and an elevated WBC (p = 0.001), NLR (p = 0.007), dNLR (p = 0.043) and PLR (p = 0.024) were independently associated with decreased RFS after adjusting for Miettinen score. However, only an increase of dNLR/NLR showed a significant association to higher RR (p = 0.048). Inclusion of NLR or PLR to Miettinen risk score did not reasonably improve the clinical risk prediction of 2-year RFS., Conclusion: Low Hb, elevated WBC, elevated dNLR, and elevated PLR are independent prognostic factors for a worse clinical outcome in GIST patients after curative resection.

Plaque formation is confined to the arterial trunk. We assumed that due to the higher aeration of arterial compared to venous blood, higher levels of the atherogenic agent oxidized LDL might be present in arteries, contributing to plaque formation. We aimed to compare (i) the basal oxidative status of LDL in arterial and venous blood and (ii) the susceptibility of arterial and venous LDL to oxidation. The basal oxidative status of LDL was determined by measuring lipid hydroperoxide (LPO) concentrations, plasma levels of auto-antibodies against oxidized LDL, and by measuring oxidation-specific epitopes on LDL particles. The oxidizability of arterial vs. venous LDL (catalyzed by copper) was estimated by monitoring the time-course of conjugated dienes formation. Interestingly, we found the same basal oxidative status of LDL in arterial and venous plasma. LPO concentrations and levels of auto-antibodies against oxidized LDL were similar in arterial and venous plasma and amounts of oxidation-specific epitopes were similar on the respective LDL particles. Moreover, we found similar susceptibilities of arterial and venous LDL to (copper-mediated) oxidation. Lag-times until the onset of conjugated diene formation were slightly shorter in arterial compared to venous LDL in the presence of 5 μM, but not in the presence of 1 μM CuCl2. Additionally, we found significantly higher levels of the atherogenic lipoprotein(a) in arterial plasma. We conclude that not higher oxidizability of arterial LDL but higher arterial lipoprotein(a) levels might help to explain why sclerosis is confined to the arterial trunk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In psychiatry, burnout is a relevant phenomenon. A large number of individuals is feeling overburdened at work. In contrast to mental disorders, the term 'burnout' is not perceived as stigmatizing, making it therefore easier for afflicted persons to seek help. The term 'burnout syndrome' was mentioned 1974 for the first time in scientific literature. Today, there is a range of partially contradictory definitions and explanations for burnout and the burnout syndrome, respectively. In most studies, burnout is assessed by the Maslach Burnout Inventory, which is neither useful for determining the degree of pathology nor for distinguishing burnout from mental disorders such as depression. It is expected that the burnout syndrome will not be used in modern diagnostic classification systems, because of its unclear definition and conceptual contradictions. On these grounds, it appears reasonable to define burnout as long-term professional overload and a noteworthy risk factor for physical diseases and mental disorders.

Gravity experiments with very slow, so-called ultracold neutrons connect quantum mechanics with tests of Newton's inverse square law at short distances. These experiments face a low count rate and hence need highly optimized detector concepts. In the frame of this paper, we present low-background ultracold neutron counters and track detectors with micron resolution based on a 10 B converter. We discuss the optimization of 10 B converter layers, detector design and concepts for read-out electronics focusing on high-efficiency and low-background. We describe modifications of the counters that allow one to detect ultracold neutrons selectively on their spin-orientation. This is required for searches of hypothetical forces with spin-mass couplings. The mentioned experiments utilize a beam-monitoring concept which accounts for variations in the neutron flux that are typical for nuclear research facilities. The converter can also be used for detectors, which feature high efficiencies paired with high spatial resolution of [Formula: see text]. They allow one to resolve the quantum mechanical wave function of an ultracold neutron bound in the gravity potential above a neutron mirror.

As a basic principle, benefits of adaptive discretisations are an improved balance between required accuracy and efficiency as well as an enhancement of the reliability of numerical computations. In this work, the capacity of locally adaptive space and time discretisations for the numerical solution of low-dimensional nonlinear Schrödinger equations is investigated. The considered model equation is related to the time-dependent Gross-Pitaevskii equation arising in the description of Bose-Einstein condensates in dilute gases. The performance of the Fourier-pseudo spectral method constrained to uniform meshes versus the locally adaptive finite element method and of higher-order exponential operator splitting methods with variable time stepsizes is studied. Numerical experiments confirm that a local time stepsize control based on a posteriori local error estimators or embedded splitting pairs, respectively, is effective in different situations with an enhancement either in efficiency or reliability. As expected, adaptive time-splitting schemes combined with fast Fourier transform techniques are favourable regarding accuracy and efficiency when applied to Gross-Pitaevskii equations with a defocusing nonlinearity and a mildly varying regular solution. However, the numerical solution of nonlinear Schrödinger equations in the semi-classical regime becomes a demanding task. Due to the highly oscillatory and nonlinear nature of the problem, the spatial mesh size and the time increments need to be of the size of the decisive parameter [Formula: see text], especially when it is desired to capture correctly the quantitative behaviour of the wave function itself. The required high resolution in space constricts the feasibility of numerical computations for both, the Fourier pseudo-spectral and the finite element method. Nevertheless, for smaller parameter values locally adaptive time discretisations facilitate to determine the time stepsizes sufficiently small in order that the numerical approximation captures correctly the behaviour of the analytical solution. Further illustrations for Gross-Pitaevskii equations with a focusing nonlinearity or a sharp Gaussian as initial condition, respectively, complement the numerical study.

History and Clinical Findings: A 48-year-old patient had been suffering from postalimentary hypoglycemias for several months, occurring regularly 2 hours after a meal. 5 years before, repeated fundaplications as well as a selective proximal vagotomy due to reflux oesophagitis had been performed., Investigations: Physical examination revealed no pathological findings. The diurnal blood sugar profile with hourly capillary glucose measurement showed a physiological fasting glucose homeostasis and two-hour postprandial decrease of blood glucose down to 20 mg/dl. The oral glucose tolerance test revealed a noticeable insulin secretion with a pathologically increased insulin/glucose index. Scintigraphy demonstrated an initially delayed, then accelerated gastric emptying as a consequence of the selective proximal vagotomy., Diagnosis, Treatment and Course: A postalimentary hypoglycemia by hypersecretion of insulin in the context of a post-gastrectomy late dumping syndrome was diagnosed. A surgical pyloroplasty was not effective. In addition to the modification of eating habits, treatment with subcutaneous applied octreotide (Sandostatin), a somatostatin-analogue, was initiated., Conclusions: Postalimentary hypoglycemia can be assigned to late dumping syndrome in most cases already by ascribed history taking. The correct diagnosis can be achieved by an oral glucose tolerance test with measurement of insulin secretion and gastric emptying scintigraphy. Beside other therapeutical options the treatment with octreotide is a promising alternative with manageable side effects.

We analyse relevant modifications of the new German diagnosis related reimbursement system for 2004. It is difficult to judge the consequences of financing intensive care systems by such flat rates. In our surgical ICU total treatment costs were 1 050.-euro /day and 11 530.-euro /patient. Comparison of our total costs and German federal calculation 2003 for long-term ventilation revealed that our costs resulting from a tertiary unit topped the average by 36-60 %. Already the present reimbursement was not cost rewarding. Evaluation according to the 2003 criteria resulted in profound further deterioration to a cost covering of only 49 %. The 2004 system, however, allows for better differentiation of patients and should result in improved reimbursement of long-term ventilation. Further professional analysis of the DRG system is essential for its "learning" development.

Local recurrence is a serious complication of breast carcinoma that reduces quality of life and influences prognosis. The aim of this study was to determine whether local recurrences of breast carcinoma are genetically related to the primary tumours. Forty cases of locally recurrent breast carcinomas (median onset: 3.6 years after primary surgery) were analysed: 22 patients had undergone breast-conserving therapy and 18 mastectomy. Eighteen microsatellites on chromosomes 2p, 3p, 5q, 10q, 11p, 11q, 13q, 17q, 17p, 18p were amplified by PCR using fluorescent-labelled primers, automatically detected after polyacrylamide gel electrophoresis and analysed for loss of heterozygosity (LOH) or microsatellite instability (MSI). Follow-up data were available for 39 cases with a median value of 89 months. All LOH and MSI found in the primary tumours were also present in the corresponding recurrences, indicating that they are genetically related to the primary tumours and not secondary malignancies in the same breast. MSI was found in three cases, of which one harboured MSI at more than two loci. The median value of LOH per case was significantly higher in the recurrent (four per case) compared to the primary tumours (two per case; p < 0.001, Mann-Whitney test), reflecting the genotype of tumour progression. Early local recurrence was associated with specific LOH for TP53.15 (p = 0.018, log-rank test) in the primary tumours. LOH on D13S1699 or D17S855 was associated with lymph node metastases (p = 0.024 and p = 0.019, respectively; chi-square test). In addition, tumour grade, lack of oestrogen or progesterone receptor expression, young patient age and early appearance of local recurrence significantly correlated with poor survival. The development of local recurrence despite clear resection margins may result from residual DCIS distant from the invasive carcinoma, homing of circulating tumour cells, or genetically altered, histologically normal breast tissue not immediately adjacent to the invasive carcinoma., (Copyright 2002 John Wiley & Sons, Ltd.)