Search

(1999). Muscular Anschluss: German bodies and Austrian imitators. The International Journal of the History of Sport: Vol. 16, Superman Supreme, pp. 62-81.

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-naïve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-naïve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.

This article's objective is to analyse determinants and outcomes of financial participation in Europe. It starts off with a definition of the instruments, a review of the literature in the field of financial participation and a discussion on the relevance of financial participation in selected European countries. Choosing a rather inductive approach, the authors develop a model for financial participation. Based on the Cranfield data, the significance of the variables used in the model is tested. Union density, number of employees, public limited company status, geographical market and policy regarding pay and benefits came out as significant determinants for financial participation at company level. The environment, however, also bears influence. Organizations in Germany, France, Great Britain and Sweden show significantly different practices. Employee share ownership and profit sharing cannot only increase financial performance but also allow for efficient human resource management. Profit sharing increases profits and decreases absenteeism as well as staff turnover. The findings for employee share ownership are not that straightforward.

Several studies have documented that 18F-FDG PET is more accurate than CT for assessment of tumor response to chemotherapy in patients with Hodgkin's lymphoma (HL) and high-grade (aggressive) non-Hodgkin's lymphoma (NHL) ( [1][1],[2][2] ). On the basis of these data, the International Workshop

In this contribution the dynamical behaviour of a semi-infinite rod subjected to a longitudinal load moving along the rod's skin is investigated both analytically and numerically. By means of the analytical results the numerical model is validated and thus can be used for more advanced studies e. g. concerning dynamic fibre pull-out phenomena. These forthcoming studies involve spatially moving boundary conditions which are also modeled within the present model in a first step. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)

It is shown that the spin asymmetry of the elastic transmission of electrons through ferromagnetic films can approach unity. The polycrystalline Co films are a few nanometers thick and saturated with the magnetization $\stackrel{\ensuremath{\rightarrow}}{M}$ in the plane. The contribution of spin-productive scattering events is below $5%$. If the electron spin at incidence is chosen to be perpendicular to $\stackrel{\ensuremath{\rightarrow}}{M}$, it rotates into the direction of $\stackrel{\ensuremath{\rightarrow}}{M}$ and also precesses around it.

This article raises the question of to what extent functional flexibility is an operatively designed approach with which European companies confront current short‐term changes in their environment, and whether functional flexibility is integrated into long‐term human resource strategies. The proposition is tested that organisations with a strategic human resource management in the sense of a coordinated, objective‐oriented personnel management pattern, show a higher probability of using job rotation than organisations lacking a strategic‐oriented human resource management approach.

The recent discovery of oscillations in interlayer exchange coupling as a function of nonmagnetic spacer layer thickness has led to a widespread interest in oscillatory magnetic properties in layered structures for both basic and applied reasons. In this overview, several oscillatory magnetic properties are discussed for a particular model system. We have chosen epitaxial fcc Co films grown on Cu(100) as a base structure and have selected additional epitaxial overlayers to study interlayer exchange coupling, induced magnetic moments, magneto-optical properties, and magnetic anisotropy.

Sporttreiben kostet Geld and Zeit. Es entstehen Kosten fir die Sportausiibung selbst, also fiir Mitgliedschaft in Sportvereinen oder bei gewerblichen Sportanbietern, fur Sportgerate and Sportkleidung, fur Trainer, Nutzungsrechte an Sportstatten und -geraten, fur Eintrittskarten zu Sportveranstaltungen; es entstehen Kosten fiir die Fahrt zwischen Wohn-/Arbeitsort and Sportgelegenheit sowie Zusatzkosten etwa fur Verpflegung and Unterbringung. Man benotigt Zeit fur die Sportausiibung selbst, weiter fur die Anfahrt zur Sportgelegenheit, u. U. auch fur die Herstellung and die Pflege der Sportgerate and -anlagen sowie for Vereinswesen and ehrenamtliche Tatigkeit im Verein.

The magnetic anisotropy in Co films epitaxially grown on Cu(001) is investigated by measuring magneto-optical Kerr hysteresis loops during film growth. As a function of Co thickness the magnetic anisotropy oscillates with a period of 1 monolayer. These oscillations are attributed to the periodic variations of the film morphology alternating between filled and incompletely filled atomic layers. Upon coverage of the Co films with Cu overlayers the anisotropy of the magnetic film is found to oscillate with increasing Cu layer thickness. We relate these oscillations to quantum interferences due to the confinement of electrons in ultrathin films.

Rotation and inversion barriers in N-methylmethanesulfonamide were calculated using restricted Hartree-Fock and MP2 ab initio methods with 6-31G∗ and larger basis sets. The two enantiomeric global minima are separated by a single transition state along the minimum energy path. The intrinsic reaction coordinate combines the two necessary motions: rotation and inversion.

The biosynthesis of the pancreatic lipase inhibitor lipstatin was investigated by fermentation experiments using cultures of Streptomyces toxytricini, which were supplied with soybean oil and a crude mixture of U-13C-lipids obtained from algal biomass cultured with 13CO2. Lipstatin was analyzed by one- and two-dimensional NMR spectroscopy. 13C total correlation spectroscopy and INADEQUATE experiments show that two fatty acid fragments containing 14 and 8 carbon atoms, respectively, are incorporated en bloc into lipstatin. The 14-carbon fragment is preferentially derived from the unsaturated fatty acid fraction, as shown by an experiment with hydrogenated U-13C-lipid mixture, which is conducive to labeling of the 8-carbon moiety but not of the 14-carbon moiety. The data indicate that the lipstatin molecule can be assembled by Claisen condensation of octanoyl-CoA with 3-hydroxy-∆5,8-tetradecanoyl-CoA obtained by β oxidation of linoleic acid. The formation of lipstatin from acetate units by a polyketide-type pathway is ruled out conclusively by these data. The data show that surprisingly clear labeling patterns can be obtained in studies with crude, universally 13C-labeled precursor mixtures that are proffered together with a large excess of unlabeled material. One- and two-dimensional 13C total correlation spectroscopy analyses are suggested as elegant methods for the delineation of contiguously 13C-labeled biosynthetic blocks.

Dysfunctional connectivity within the hippocampal-prefrontal circuit (HC-PFC) is associated with schizophrenia, major depression, and neurodegenerative disorders, and both the hippocampus and prefrontal cortex have dense populations of N-methyl-D-aspartate (NMDA) receptors. Ketamine, a potent NMDA receptor antagonist, is of substantial current interest as a mechanistic model of glutamatergic dysfunction in animal and human studies, a psychotomimetic agent and a rapidly acting antidepressant. In this study, we sought to understand the modulatory effect of acute ketamine administration on functional connectivity in the HC-PFC system of the rat brain using resting-state fMRI. Sprague-Dawley rats in four parallel groups (N=9 per group) received either saline or one of three behaviorally relevant, sub-anesthetic doses of S-ketamine (5, 10, and 25 mg/kg, s.c.), and connectivity changes 15- and 30-min post-injection were studied. The strongest effects were dose- and exposure-dependent increases in functional connectivity within the prefrontal cortex and in anterior-posterior connections between the posterior hippocampus and retrosplenial cortex, and prefrontal regions. The increased prefrontal connectivity is consistent with ketamine-induced increases in HC-PFC electroencephalographic gamma band power, possibly reflecting a psychotomimetic aspect of ketamine's effect, and is contrary to the data from chronic schizophrenic patients suggesting that ketamine effect does not necessarily parallel the disease pattern but might rather reflect a hyperglutamatergic state. These findings may help to clarify the brain systems underlying different dose-dependent behavioral profiles of ketamine in the rat.

Recently, a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology.

The prediction of dopaminergic responsiveness in patients with parkinsonism is desirable for effective treatment strategies. We investigated whether striatal dopamine D2/D3 receptor (D2R) binding assessed by 123I-iodobenzamide SPECT is an independent predictor of dopaminergic responsiveness in patients with parkinsonism. Methods: Seventy-eight patients with clinically suspected atypical parkinsonian syndrome (APS) were prospectively recruited for imaging. To quantify striatal D2R binding, 123I-iodobenzamide SPECT datasets were subjected to an observer-independent, regions-of-interest analysis. A final clinical diagnosis of Lewy-body disease (LBD) or APS was made after a mean follow-up of 12 mo. On the basis of follow-up data, dopaminergic responsiveness was classified as 0 (none), 1 (transient), 2 (sustained mild), or 3 (sustained strong). Uni- and multivariate analyses of the relationship between treatment response, D2R binding, and confounding variables were conducted. Results: Sixty patients with clinically verified LBD (n = 28; 22/28 with Parkinson disease) or APS (n = 32), in whom dopaminergic responsiveness could be assessed (n = 19/13/15/13 in categories 0/1/2/3; 18 were excluded because of insufficient dosing), were included in the statistical analysis. Univariate analyses revealed that a sustained treatment response was significantly associated with higher D2R binding, clinical diagnosis of LBD, lower Hoehn and Yahr scores, and younger age. After multivariate correction of D2R binding for diagnosis, age, symptom duration, Hoehn and Yahr score, and dopaminergic pretreatment, no association was found between D2R binding and treatment response, either in the pooled group or in LBD or APS subgroups. Conclusion: Striatal D2R binding assessed by 123I-iodobenzamide SPECT does not provide additional predictive information about treatment response beyond other clinical variables, most notably the clinical diagnosis.

The title compounds (III) are formed by reaction of thiophosgene with carbonotrithioates or O-ethyldithiocarbonates (I).

van der Waals (vdW) interactions within density functional theory are shown to strongly reduce the distance between manganese phthalocyanine (MnPc) and a Cu(001) surface to that found by x-ray standing wave experiments. Thus, the physisorbed ground state that is predicted within the generalized-gradient approximation formalism is replaced by a chemisorbed ground state once vdW interactions are taken into account. These findings indicate how to systematically obtain the correct theoretical adsorption distance for complex molecules and thus accurately predict the properties of the ensuing molecule/metal interface. The reduction of the experimental work function upon molecular adsorption is satisfactorily accounted for and explained in terms of Friedel-like oscillations of the charge density at the vicinity of the MnPc molecule that change the sign of the charge transfer electric dipole. This shows how vdW interactions can strongly impact charge injection in organic electronic devices. DOI: 10.1103/PhysRevB.87.155418

International audience; Organic semiconductors constitute promising candidates toward large-scale electronic circuits that are entirely spintronics-driven. Toward this goal, tunneling magnetoresistance values above 300% at low temperature suggested the presence of highly spin-polarized device interfaces. However, such spinterfaces have not been observed directly, let alone at room temperature. Thanks to experiments and theory on the model spinterface between phthalocyanine molecules and a Co single crystal surface, we clearly evidence a highly efficient spinterface. Spin-polarised direct and inverse photoemission experiments reveal a high degree of spin polarisation at room temperature at this interface. We measured a magnetic moment on the molecule's nitrogen p orbitals, which substantiates an ab-initio theoretical description of highly spin-polarised charge conduction across the interface due to differing spinterface formation mechanisms in each spin channel. We propose, through this example, a recipe to engineer simple organic-inorganic interfaces with remarkable spintronic properties that can endure well above room temperature

Group V major allergen Phl p 5b of timothy grass pollen induces allergic rhinitis and bronchial asthma in 90% of grass pollen-allergic patients. In addition to its allergenicity ribonuclease activity has recently been attributed to this 29-kDa protein. The allergen was expressed in Escherichia coli and subsequently purified. Spontaneous conversion of these preparations to a mixture of various forms with molecular sizes between 10 and 29 kDa was consistently observed. Surprisingly, crystals could be grown from this heterogenous preparation. Single crystals, redissolved and analyzed by SDS-polyacrylamide gel electrophoresis and immunoblot, yielded one distinct low molecular weight protein, which was identified by amino acid sequencing as the C-terminal 13-kDa portion of the allergen. Histamine release assays with single crystal solutions using basophils of an allergic patient demonstrated allergenicity comparable with that of the holo-allergen. By contrast, RNase activity of the crystallized C-terminal form was 23 times higher than that of the full-length parent allergen. Crystals were used to collect preliminary diffraction data; the space group was evaluated to I4122 with cell dimensions of a = 87.7 A, b = 87.7 A, and c = 59.6 A. We conclude that preferential crystal growth of the 13-kDa form is indicative of a compact conformation of this particular C-terminal portion of the allergen. Thus, we show here that protein crystallization is not only a prerequisite for structural analyses, but it also can provide a unique separation technique to localize the functional domain of a major allergen.

The magnetic anisotropy of Co/Cu(001) films has been investigated by the magneto-optical Kerr effect, both in the pseudomorphic growth regime and above the critical thickness where strain relaxation sets in. A clear correlation between the onset of strain relaxation---as measured by means of reflection high-energy electron diffraction---and changes of the magnetic anisotropy has been found. \textcopyright{} 1996 The American Physical Society.

We describe in vitro tyrosine phosphorylation of the C-terminal 334 amino acids of ras-GTPase-activating protein (ras-GAP)1 that contains the activity domain for ras interaction. To date, there have been no other phosphorylation sites determined than the reported in N-terminal domain of ras-GAP Tyr-460, which is considered to be the major phosphorylation site of ras-GAP. In our assays some differences of the kinetic parameters were observed when the reaction was catalyzed by EGF-R compared to p60c-src. Enzyme specific regulation of activity is associated with autophosphorylation which leads to reduced (in case of EGF-R) or increased (in case of p60c-src) phosphorylation of the C-terminal 334 amino acids of ras-GAP (GAP334). Because of the characteristics of these investigated reactions the phosphorylation of GAP334 seems to be-independent from the presence of SH2 or SH3 domains-triggered off by complex mechanisms different from those regulating the phosphorylation at Tyr-460.

The magnetic anisotropy of Co films grown on stepped Cu(100) substrates is found to oscillate with varying Cu overlayer thickness. We relate these oscillations to the occurrence of quantum well states in the Cu overlayer.

Primary central nervous system (CNS) lymphoma is an aggressive non-Hodgkin lymphoma with poor prognosis. We evaluated pretreatment 18F-FDG PET as a prognostic marker in primary CNS lymphoma. Methods: Forty-two immunocompetent patients with newly diagnosed primary CNS lymphoma who underwent pretreatment 18F-FDG PET were retrospectively analyzed. Baseline status and response to treatment were evaluated by MR imaging. Tumor maximum standardized uptake values were assessed by volume-of-interest analyses using an automatic isocontour definition. A 10-step semiquantitative visual rating system (metabolic imaging lymphoma aggressiveness scale, or MILAS) was used to assess primary CNS lymphoma metabolism as a marker of clinical aggressiveness. Logistic regression, log-rank testing, and multivariable Cox regression were used to investigate the association between 18F-FDG uptake and tumor response and survival. Results: Mean maximum standardized uptake value correlated linearly with MILAS. The distribution of patients according to MILAS (0–9) was 0%, 28.6%, 23.8%, 21.4%, 11.9%, 4.8%, 7.1%, 0%, 0%, and 2.4%. There was no correlation between MILAS and response to treatment. Respective 2- and 5-y survival rates were 52% and 32% for progression-free survival (PFS) and 64% and 50% for overall survival (OS). A cutoff at MILAS 3 was a good separator for PFS (median: 54.7 mo [≤3], 3.8 mo [>3], P = 0.0272) and OS (median: not reached [≤3], 13.8 mo [>3], P = 0.131). In multivariable analyses, increasing MILAS was significantly associated with shorter PFS (hazard ratio, 1.49, P = 0.006) and OS (hazard ratio, 1.43, P = 0.018). Conclusion: Increased pretreatment 18F-FDG uptake may offer new opportunities for baseline risk evaluation in untreated primary CNS lymphoma.

We report a striking sensitivity of the easy magnetization axis in epitaxial Co films upon adsorption of submonolayers of Cu, Ag, Fe, and O if the Cu substrate is a stepped surface slightly miscut from the (100) orientation. All adsorbates cause a switch of the easy axis by 90\ifmmode^\circ\else\textdegree\fi{} within the plane. The key role of this switching phenomenon is played by the atoms at the step sites and their influence on the magnetic surface anisotropy.

The paper presents a philosophy, an architecture and an implementation of a distributed manipulator control system whereby the controllers are to be interconnected by standard LAN-means. MONSUN focusses on manual control in the sense of telepresence systems but also includes semiautonomous operation modes. The application protocols are of prime importance for MONSUN to be an open system. An important finding is that a motorized master arm is of significant help giving natural cues for the limits of the actual working envelope.

The purpose of this paper is to provide a brief summary of developments in NATO nations in order to bring these developments to a wider audience. The basis of the survey provided is the information collated by NATO Research Study Group 15 Computer-Based Assessment of Military Personnel as given in its report to NATO Headquarters in 1993.

Species-conserved (intermediate) phenotypes that can be quantified and compared across species offer important advantages for translational research and drug discovery. Here, we investigate the utility of network science methods to assess the pharmacological alterations of the large-scale architecture of brain networks in rats and humans. In a double-blind, placebo-controlled, cross-over study in humans and a placebo-controlled two-group study in rats, we demonstrate that the application of ketamine leads to a topological reconfiguration of large-scale brain networks towards less-integrated and more-segregated information processing in both the species. As these alterations are opposed to those commonly observed in patients suffering from depression, they might indicate systems-level correlates of the antidepressant effect of ketamine.

287 Background: There is a pressing need for improved imaging biomarkers to identify disease distribution and response in both localized and advanced prostate cancer patients. PSMA-directed imaging is undergoing analytic and clinical validation for these contexts of use. IAB2M is an anti-PSMA recombinant minibody (Mb) derived from huJ591. We have previously reported on 28 pts imaged with IAB2M(Pandit-Taskar et al, SNM 2015). Here we report the lesion targeting and uptake (SUV) of the Mb and correlation with pathology of biopsied lesions on the full complement of the 38 pts examined in this trial. Methods: 38 pts with progressive metastatic PCa received escalating amounts of the Mb (16 pts at 10mg, 16 pts at 20mg, 6 pts at 50mg) in a phase I/IIa trial. All pts underwent standard imaging (SI) using CT, bone scintigraphy (BS), FDG PET, followed by imaging with 5 mCi of IAB2M. Whole body PET/CT scans were performed and evaluated for lesion targeting and SUVmax. Biopsy (bx) locations were selected by a consensus panel prioritized on the basis of: IAB2M & FDG positivity, IAB2M & FDG mismatch, and CT or BS positivity & any PET mismatch. Results: A total of 556 lesions (410 bone, 146 soft tissue) in 38 pts were detected by SI or IAB2M. In bone, IAB2M detected 344 lesions (83.9%), CT 209 (51%), BS 211 (51.5%), and FDG 109 (26.6%). For soft tissue, IAB2M detected 119 (81.5%), CT 83 (56.8%), and FDG 79 (54.1%). The SUV for bone lesions ranged from 2.1-60.4 for 10mg Mb, 1.7- 33 in 20mg Mb, and 2.3-17.5 in 50mg Mb. For soft tissue lesions, SUV range was 3.1-45.4, 2.1-20, and 1.9-13.8 respectively. 28 bxs (13 bone, 15 soft tissue) were obtained from 27 pts; 27 bxs were evaluable (1 was non-diagnostic). 20/27 (74.1%) bxs were pos for PCa; 20/24 (83.3%) IAB2M pos lesions were path pos and 3/3 (100%) IAB2M neg lesions were neg on path. All imaging and path correlated (true pos + true neg) in 23/27 (85.2%) bxs. Conclusions: PET imaging with IAB2M has demonstrated higher lesion detection when compared with SI. IAB2M’s high concordance with path suggests pos findings represent bx confirmed PCa. Further studies to examine biochemically recurrent prostate cancer are planned. Clinical trial information: NCT01923727.

Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects.

Background: Thedevelopmentandmaintenanceofalcoholusedisorders(AUD)have beenhypoth-esized to be associated with an imbalance of glutamate (GLU) homeostasis. White matter (WM) loss,especially in anterior brain regions, has been reported in alcohol dependence, which may involvedisturbances in both myelin and axonal integrity. Frontal lobe dysfunction plays an important role inaddiction, because it is suggested to be associated with the loss of control over substance use. Thisstudy investigated magnetic resonance spectroscopy (MRS)-detectable Glu levels in frontal WM ofnon-treatment-seekingheavydrinkersanditsassociationswithAUDsymptoms.Methods: Single-voxel MR spectra optimized for Glu assessment (TE 80 ms) were acquired at 3Tfrom a frontal WM voxel in a group of heavy drinking, non-treatment-seeking subjects in comparisonwithagroupofsubjectswithonlylightalcoholconsumption.Results: The results corroborate previous findings of increased total choline in heavy drinkingsubjects. A negative association of Glu levels with severity of alcohol dependence and especially loss ofcontrolovertimeandamountofalcoholintakewasobserved.Conclusions: In contrast to the rather unspecific rise in choline-containing compounds, low Glu infrontal WM may be specific for the shift from nondependent heavy drinking to dependence and doesnotreflectasimpleeffectoftheamountofalcoholconsumptionalone.Key Words: Alcohol Dependence, Frontal White Matter, Glutamate, Choline-ContainingCompounds, LossofControl,HeavyDrinking.

PURPOSE: Reconstruction of striatal dopamine transporter (DAT) SPECT is commonly done by filtered back projection (FBP). We investigated if image reconstruction by 3-dimensional ordered-subset expectation maximization (3D-OSEM) with resolution recovery, which has recently become available for clinical routine, provides a relevant improvement. METHODS: I-FP-CIT SPECT studies of 18 patients with normal to severely decreased DAT binding were reconstructed by FBP, 2D-OSEM (without resolution recovery), and 3D-OSEM, each with 2 different filter settings, yielding 3 data set pairs of relatively low and high resolution and noise: FBP with seventh-order Butterworth filter [cutoff frequency, 0.36 Nyquist (FBPlow) and 0.45 Nyquist (FBPhigh)] and OSEM with 8 iterations and 8 subsets (2D-/3D-OSEMlow) and 6 iterations and 16 subsets (2D-/3D-OSEMhigh), each with 8-mm Gaussian filtering. Mean regional counts, variability of counts (coefficient of variation), and binding potential (BPND) were assessed by volume-of-interest analyses of the caudate nucleus, the putamen, and the occipital cortex (reference region). RESULTS: On visual inspection, both 2D- and 3D-OSEM-reconstructed images showed an optimal delineation of striatal structures, whereas variability (noise) of nonspecific cortical I-FP-CIT uptake was lowest (most homogenous) with FBPlow, slightly higher with 2D-/3D-OSEMlow, and notably higher for the other methods. Volume-of-interest analyses revealed no significant differences of counts in the occipital reference region in comparison to FBPlow (reference method). In caudate nucleus, counts and, consequently, BPND values increased significantly with FBPhigh (mean BPND change, +5.2%), 2D-OSEMlow/high (+3.7%/+6.2%), and, most notably, 3D-OSEMlow/high (+11.1%/+14.0%). In the putamen, this effect was less pronounced for FBPhigh (+1.8%) and 3D-OSEMlow/high (+5.6%/+6.8%) and failed to reach statistical significance for 2D-OSEMlow/high (-0.2%/+0.8%). Regression analyses indicated excellent correlations of BPND between FBPlow and all other methods (R > 0.97), with the highest regression slopes for 3D-OSEM (1.12-1.16) followed by FBPhigh (1.04-1.06) and then 2D-OSEM (1.01-1.04). The order of the variability of counts in the occipital cortex was as follows: FBPlow (12.5%), 2D-OSEMlow (13.9%), 3D-OSEMlow (14.2%), FBPhigh (15.1%), 2D-OSEMhigh (17.0%), and 3D-OSEMhigh (17.6%). CONCLUSIONS: Three-dimensional OSEM considerably improves DAT SPECT reconstruction by offering an optimal combination of high-resolution delineation of striatal structures, superior recovery of signal and BPND, and sufficiently homogeneous nonspecific tracer uptake of the reference region.

Lactoferrin was purified from human seminal fluid obtained from the semen bank. The purified samples were saturated with Fe3+ and crystallized by microdialysis method. The crystals belong to orthorhombic space group P21212, with a = 55.9 Angstrom. b = 97.2 Angstrom, c = 156.1 Angstrom and Z = 4. The structure was determined with molecular replacement method and refined to an R factor of 18.7% for all the data to 3.4 Angstrom resolution. The overall structure of seminal lactoferrin is similar to human colostrum lactoferrin. The amino acid sequence of seminal lactoferrin shows that it has one amino acid less than human colostrum lactoferrin and the structure of its N-terminal region is far more ordered than other lactoferrins. The structure of the iron-binding site and its immediate surroundings indicate well defined features.

Assessment of striatal dopamine receptor availability with (18)F-desmethoxyfallypride PET is of high diagnostic utility in parkinsonism. The present study was undertaken to define the optimal clinical scan protocol with regard to quantification accuracy and scan time.Fourteen patients with parkinsonian syndromes underwent (18)F-desmethoxyfallypride PET over 90 min. Volume-of-interest analyses were performed after spatial normalization, with the right and left caudate nuclei and putamina as target regions and the cerebellum as reference region. The estimate of target region binding potential (relative to nondisplaceable radioligand in tissue) (BP(ND)) provided by the 2-step simplified reference tissue model (SRTM2) served as the reference standard. Additional analyses included the multilinear reference tissue model 2 (MRTM2), noninvasive graphical analyses, and single-scan analyses (peak-equilibrium analysis at 35-65 min [PEA]; pseudoequilibrium analysis at 60-90 min [PsEA]).SRTM2 and MRTM2 yielded virtually identical results (mean BP(ND) difference = 0.1% ± 0.5%, r(2) = 1.0). Noninvasive graphical analyses with and without inclusion of the k(2)' term were affected by a small BP(ND) bias (2.5% ± 3.6% and -5.0% ± 6.7%, respectively), although correlations with SRTM2 were still excellent (r(2) = 1.0 and 0.98, respectively). In turn, single-scan analyses suffered from limited precision (PEA, mean BP(ND) bias = 0.7% ± 13.0%, r(2) = 0.90) or a considerable positive bias (PsEA, 19.2% ± 7.1%, r(2) = 0.98). Shortening scan time to 70 and 60 min resulted in an acceptable average BP(ND) change (5% decline) for SRTM2/MRTM2 and graphical analysis with inclusion of the k(2)' term, respectively.Kinetic reference tissue model analyses of (18)F-desmethoxyfallypride PET data offer the least biased results at a well-tolerable scan duration and should thus be pursued whenever possible. Single-scan analyses may be pragmatic alternatives that, however, suffer from a relevant positive bias (PsEA) or limited precision (PEA).

UNLABELLED Paragangliomas and pheochromocytomas are genetically heterogeneous diseases. The purpose of this study was to determine the sensitivity and specificity of PET with 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanin ((18)F-DOPA) for the detection and staging of pheochromocytomas/paragangliomas. Furthermore, we assessed whether the genotypes of pheochromocytomas and paragangliomas correlate with the uptake of (18)F-DOPA. METHODS We retrospectively analyzed 101 consecutive patients who underwent (18)F-DOPA PET or (18)F-DOPA PET/CT for known or suspected pheochromocytomas or paragangliomas. Maximum (18)F-DOPA tumor uptake was quantified relative to uptake in the liver. RESULTS Histopathology, cross-sectional imaging, and follow-up indicated the presence of paragangliomas and pheochromocytomas in 68 patients and the absence of a tumor in 33 patients. The average (18)F-DOPA uptake by paragangliomas and pheochromocytomas, expressed as a tumor-to-liver ratio, was 5.9 ± 5.2. There was no significant difference in uptake among patients with von Hippel Lindau syndrome (VHL; n = 19), succinate dehydrogenase B-D mutation (n = 21), neurofibromatosis type 1 (n = 1), RET (n = 1), no germline mutation (n = 20), or unknown mutation status (n = 6) (P = 0.84). All 8 patients with an SDHD mutation were true-positive on (18)F-DOPA PET. There were 2 cases of false-negative results each in the group with SDHB (2/12) and VHL mutations (2/19) and 1 false-negative result in the subgroup of patients with unknown mutation status (1/6). Overall, (18)F-DOPA PET yielded a sensitivity of 93% and a specificity of 88% for the detection of paragangliomas and pheochromocytomas on a patient basis (positive and negative predictive value, 94% and 85%, respectively). CONCLUSION (18)F-DOPA PET is a sensitive and specific imaging modality for the detection and staging of pheochromocytomas and paragangliomas in different genotypes, including VHL-, SDHB-, and SDHD-mutation carriers, and in patients with no germline mutation.

The overexpression of the folate receptor (FR) in a variety of malignant tumors, along with its limited expression in healthy tissues, makes it an attractive tumor-specific molecular target. Noninvasive imaging of FR using radiolabeled folate derivatives is therefore highly desirable. Given the advantages of positron emission tomography (PET) and the convenience of (68)Ga production, the aim of our study was to develop a new (68)Ga-folate-based radiotracer for clinical application. The chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) was conjugated to folic acid and to 5,8-dideazafolic acid using 1,2-diaminoethane as a spacer, resulting in two novel conjugates, namely, P3246 and P3238, respectively. Both conjugates were labeled with (68/67)Ga. In vitro internalization, efflux, and saturation binding studies were performed using the FR-positive KB cell line. Biodistribution and small-animal PET imaging studies were performed in nude mice bearing subcutaneous KB xenografts. Both conjugates were labeled with (68)Ga at room temperature within 10 min in labeling yields95% and specific activity ~30 GBq/μmol. The K(d) values of (68/67)Ga-P3246 (5.61 ± 0.96 nM) and (68/67)Ga-P3238 (7.21 ± 2.46 nM) showed high affinity for the FR. (68/67)Ga-P3246 showed higher cell-associated uptake in vitro than (68/67)Ga-P3238 (approximately 72 and 60% at 4 h, respectively, P0.01), while both radiotracers exhibited similar cellular retention up to 4 h (approximately 76 and 71%, respectively). Their biodistribution profile is characterized by high tumor uptake, fast blood clearance, low hepatobiliary excretion, and almost negligible background. Tumor uptake was already high at 1 h for both (68)Ga-P3246 and (68)Ga-P3238 (16.56 ± 3.67 and 10.95 ± 2.12% IA/g, respectively, P0.05) and remained at about the same level up to 4 h. Radioactivity also accumulated in the FR-positive organs, such as kidneys (91.52 ± 21.05 and 62.26 ± 14.32% IA/g, respectively, 1 h pi) and salivary glands (9.05 ± 2.03 and 10.39 ± 1.19% IA/g, respectively, 1 h pi). The specificity of the radiotracers for the FR was confirmed by blocking experiments where tumor uptake was reduced by more than 85%, while the uptake in the kidneys and the salivary glands was reduced by more than 90%. Reduction of the kidney uptake was achieved by administration of the antifolate pemetrexed 1 h prior to the injection of the radiotracers, which resulted in an improvement of tumor-to-kidney ratios by more than a factor of 3. In line with the biodistribution results, small-animal PET images showed high uptake in the kidneys, clear visualization of the tumor, accumulation of radioactivity in the salivary glands, and no uptake in the gastrointestinal tract. (68)Ga-P3246 and (68)Ga-P3238 showed very high tumor-to-background contrast in PET images; however, the tumor-to-kidney ratio remained low. The new radiotracers, especially (68)Ga-P3246, are promising as PET imaging probes for clinical application due to their facile preparation and improved in vivo profile as compared to the other folate-based PET radiotracers.

Introduction [ 18 F]desmethoxyfallypride ([ 18 F]DMFP) is a promising tracer for longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by positron emission tomography (PET) in small animal models. We explored the feasibility of [ 18 F]DMFP-PET to image D2R availability in rat models of Huntington's (HD) and Parkinson's disease (PD). Methods Animals received either unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle injections of 6-OHDA to produce the loss of striatal projection neurones or deplete the striatal dopamine, corresponding to established animal models for HD and PD, respectively. Three weeks after lesioning, PET scans were acquired on a microPET Focus 120 system following the tail vein injection of [ 18 F]DMFP. Results [ 18 F]DMFP-PET clearly visualized lesion induced decreases and increases of D2R availability. In vivo estimates of D2R binding and changes thereof gained by pharmacokinetic analyses correlated significantly with D2R density and its change provided by in vitro [ 3 H]raclopride-autoradiography. Conclusions In conclusion, [ 18 F]DMFP-PET is a suitable method for in vivo D2R-assessment in preclinical research, e.g for monitoring cell-based therapies.

Purpose: Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 2[18F]fluoro-2-deoxy-d-glucose (18F-FDG)-PET/computed tomographic (CT) imaging after the initial cycle of neoadjuvant therapy could predict overall survival in these patients. Experimental Design: Thirty-nine patients underwent 18F-FDG-PET/CT before and after one cycle of neoadjuvant therapy. Fifty-six patients underwent end-of-treatment PET. Overall survival was, among others, correlated with changes of SUVpeak and histopathology. Results: One-, two-, and five-year survival rates were 95% ± 3.0%, 86% ± 4.6%, and 68% ± 6.6%, respectively. Median time to death was 30.9 months (mean, 27.7; range, 6.9–50.1). Optimal cutoff values for early and late decreases in SUVpeak (26% and 57%, respectively) were significant predictors of survival in univariate survival analysis [P = 0.041; HR, 0.27; 95% confidence interval (CI), 0.08–0.95 and P = 0.045; HR, 0.31; 95% CI, 0.10–0.98]. Seven of 15 early PET nonresponders but only four of 24 early PET responders died during follow-up (P = 0.068). The only other significant survival predictor was surgical margin positivity (P = 0.041; HR, 3.31; 95% CI, 1.05–10.42). By multivariable analysis, early metabolic response (P = 0.016) and positivity of surgical margins (P = 0.036) remained significant survival predictors. Conclusion: 18F-FDG-PET predicted survival after the initial cycle of neoadjuvant chemotherapy in patients with STS and can potentially serve as an intermediate endpoint biomarker in clinical research and patient care. Clin Cancer Res; 18(7); 2024–31. ©2012 AACR.