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AIMS: In acute heart failure (AHF), changes of venous haemoglobin (Hb) concentrations, haematocrit (Hct), and estimated plasma volume (ePV) have been proposed as surrogates of decongestion. These estimates are based on the theoretical assumptions that changes of Hb concentrations and Hct are driven by the intravascular volume status and that the intravascular Hb pool remains stable. The objective of this study was to assess the relationship of changes of measured plasma volume (mPV) with changes of Hb, Hct, and ePV in AHF. METHODS AND RESULTS: We studied 36 AHF patients, who received two sequential assessments of mPV, measured red cell volume (mRCV) and measured total blood volume (mTBV) (48 h apart), during the course of diuretic therapy using a novel visible fluorescent injectate (VFI) technique based on the indicator dilution principle. Changes of ePV were calculated based on the Kaplan–Hakim or Strauss formula. AHF patients receiving diuretics (median intravenous furosemide equivalent 160 mg/48 h) displayed a wide range of changes of mPV (−25.4% to +37.0%). Changes in mPV were not significantly correlated with changes of Hb concentration [Pearson's r (r) = −0.241, P = 0.157], Hct (r = −0.307, P = 0.069), ePVKaplan–Hakim (r = 0.228, P = 0.182), or ePVStrauss (r = 0.237, P = 0.163). In contrast to theoretical assumptions, changes of mTBV were poorly correlated with changes of Hb concentrations and some patients displayed unanticipated variability of mRCV, suggesting an unstable intravascular red cell pool. CONCLUSIONS: Changes of Hb or Hct were not reflective of directly measured changes of intravascular volume status in AHF patients. Basing clinical assessment of decongestion on changes of Hb or Hct may misguide clinical decision-making on an individual patient level.

AIMS: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. METHODS: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. RESULTS: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r(2) , range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35-0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%-46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR. CONCLUSIONS: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.

Objective: A relationship between postoperative infections and a prolonged survival in glioblastoma patients still remains controversial. The pathogens most frequently detected in this context are Staphylococcus species. Although the interaction of S. aureus with different human cell types was investigated[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Learning a novel motor skill is dependent both on regional changes within the primary motor cortex (M1) contralateral to the active hand and also on modulation between and within anatomically distant but functionally connected brain regions. Interregional changes are particularly important in functional recovery after stroke, when critical plastic changes underpinning behavioral improvements are observed in both ipsilesional and contralesional M1s. It is increasingly understood that reduction in GABA in the contralateral M1 is necessary to allow learning of a motor task. However, the physiological mechanisms underpinning plasticity within other brain regions, most importantly the ipsilateral M1, are not well understood. Here, we used concurrent two-voxel magnetic resonance spectroscopy to simultaneously quantify changes in neurochemicals within left and right M1s in healthy humans of both sexes in response to transcranial direct current stimulation (tDCS) applied to left M1. We demonstrated a decrease in GABA in both the stimulated (left) and nonstimulated (right) M1 after anodal tDCS, whereas a decrease in GABA was only observed in nonstimulated M1 after cathodal stimulation. This GABA decrease in the nonstimulated M1 during cathodal tDCS was negatively correlated with microstructure of M1:M1 callosal fibers, as quantified by diffusion MRI, suggesting that structural features of these fibers may mediate GABA decrease in the unstimulated region. We found no significant changes in glutamate. Together, these findings shed light on the interactions between the two major network nodes underpinning motor plasticity, offering a potential framework from which to optimize future interventions to improve motor function after stroke. SIGNIFICANCE STATEMENT Learning of new motor skills depends on modulation both within and between brain regions. Here, we use a novel two-voxel magnetic resonance spectroscopy approach to quantify GABA and glutamate changes concurrently within the left and right primary motor cortex (M1) during three commonly used transcranial direct current stimulation montages: anodal, cathodal, and bilateral. We also examined how the neurochemical changes in the unstimulated hemisphere were related to white matter microstructure between the two M1s. Our results provide insights into the neurochemical changes underlying motor plasticity and may therefore assist in the development of further adjunct therapies.

Dieser Beitrag untersucht die Funktionalisierung der Biographie des schottischen Dichters Robert Burns und fragt, wie die Mythenbildung um seine Person sein dichterisches Werk so überschatten konnte, dass es hinter seiner Biographie zu verschwinden scheint. Eine vereinheitlichende Interpretation von Burns’ Gedichten ist durch deren vielfältige Themen und Positionen immer neu zum Scheitern verurteilt. Obwohl sich diese Pluralität auch in Burns’ Biographie finden lässt, wurde diese im Lauf der Jahre immer stärker funktionalisiert, so dass sie heute häufig als Katalysator für die Zusammensetzung des Burnsschen Kanons fungiert und so den Fokus auf die Biographie weiter perpetuiert.

This thesis describes several novel in-vivo proton magnetic resonance spectroscopy (MRS) techniques used to study the human brain. By measuring brain metabolites non-invasively, MRS has provided seminal contributions to our fundamental understanding of the brain as well as a wide variety of clinical conditions. However, due to the relative insensitivity and low spectral resolution of MRS, many important brain metabolites cannot be accurately quantified under standard clinical conditions. One way of in- creasing both the sensitivity and spectral resolution of MRS is to increase the static magnetic field strength. Unfortunately, increasing the static magnetic field strength also creates new technical challenges that must be resolved before any gains associated with higher magnetic field strength can be achieved. Due to increased shimming requirements and hardware limitations, many MRS experiments at higher magnetic fields are performed on a single voxel in the brain - thereby limiting any possible insight that may be shed by concurrent measurements in other regions of the brain. This thesis presents a pragmatic acquisition scheme for concurrent acquisition of high quality spectra from multiple brain regions at ultra-high field (7 Tesla). This is accomplished by dynamically updating the first order shims and flip angles and acquiring spectra in an alternating fashion. The dynamic acquisition protocol produced spectra similar to static single voxel measurements demonstrating that high spectral quality from two voxels can be acquired concurrently without specialized hardware. This dynamic acquisition scheme was then used to investigate the time-course of metabolites in both motor cortices (M1) following application of a non-invasive brain stimulation technique called transcranial direct current stimulation (tDCS). When applied over the motor cortex, tDCS has been shown to increase or decrease neuronal excitability depending on current direction. However, the pathways by which specific neuro-chemicals might mediate the tDCS-induced changes are not fully under- stood. Concurrent measurement of the tDCS time-courses revealed that anodal stimulation reduced GABA in both the anode-targeted and non-stimulated M1s. Cathodal stimulation decreased GABA and glutamate in the non-stimulated M1, with no changes in the cathode-targeted M1. Bilateral stimulation reduced glutamate in both M1 and no change in GABA. Another problem associated with in-vivo MRS is that most metabolite peaks are overlapped by broad, unwanted macromolecule and lipid signals. At higher magnetic field strengths this can introduce significant bias in metabolite measurements. One way of avoiding this potential source of quantification error is to delay signal acquisition until the broad, unwanted signals have relaxed leaving only the metabolite signals present. The main problem with waiting for these broad macromolecule signals to relax is that scalar coupled metabolites will now evolve under J-coupling - rendering them very difficult to quantify. The final project involved development of a new pulse sequence designed to suppress J-modulation. Results show that J-modulation was sufficiently suppressed at 3 T long enough for nearly all the macromolecule signal to relax (up to TE = 150 ms). This technique can also be used for straight forward T2 measurements of coupled metabolites.

The aim of this study was to acquire high-quality in vivo (1) H spectra concurrently from two voxels at ultra-high field (7 T) without specialized hardware. To this end, an acquisition scheme was developed in which first-order shims and flip angles are dynamically updated to acquire spectra from both of the brain's motor cortices in an alternating fashion. To validate this acquisition scheme, separate, static, single-voxel acquisitions were also performed for comparison. Six subjects were examined using semi-LASER spectroscopy at 7 T. Barium titanate pads were used to increase the extent of the effective transmit field (B1 (+) ). Spectra were obtained from the hand area of both motor cortices for both acquisition schemes. LCModel was used to determine neurochemical profiles in order to examine variations between acquisition schemes and volumes of interest. The dynamic two-voxel acquisition protocol produced water linewidths (full width at half-maximum between 11.6 and 12.8 Hz) and signal-to-noise ratios similar to those from static single-voxel measurements. The concentrations of 13 individual and 3 combined metabolites with Cramér-Rao lower bounds below 30% were reliably detected for both acquisition schemes, and agreed well with previous postmortem assay and spectroscopy studies. The results show that high spectral quality from two voxels can be acquired concurrently without specialized hardware. This practical technique can be applied to many neuroscience applications.

In times of scarce resources and increasing demands, an optimum IT support requires a greater service orientation and a more systematic description and management. While IT Service Management (ITSM) previously in the industry has become a standard, there are so far, only few best practice examples at universities and research institutions. The essential characteristic of this paradigm shift in the way of IT provisioning is to align IT with the specific business processes of the organization. This paper proposes an approach to ITSM for research institutes that achieves an IT and business alignment in the context of an IT service orientation, based on ITIL v3. Starting with a description of the business processes in the context of research institutions the required IT services structure can be derived. A draft of a generic business process map providing the basis for the definition and design of IT services has been found. The resulting IT service and IT function catalogues combine the business and technical view. This provides the first step towards the development of a standardized and efficient implementation reference model for ITSM in the research area. The goal of this ongoing project is to develop a practical framework for the ITSM of research institutes and an IT management information system prototype.

Sustavna, topografska i klinička anatomija čovjeka