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Cranioplasty following decompressive craniectomy (DC) has a primary complication when using the autologous bone: aseptic bone resorption (ABR). So far, risk factors such as age, number of fragments, and hydrocephalus have been identified but a thorough understanding of the underlying pathophysiology is still missing. The aim of this osteopathological investigation was to gain a better understanding of the underlying processes. Clinical data of patients who underwent surgical revision due to ABR was collected. Demographics, the time interval between craniectomy and cranioplasty, and endocrine serum parameters affecting bone metabolism were collected. Removed specimens underwent qualitative and quantitative histological examination. Two grafts without ABR were examined as controls. Compared to the controls, the typical layering of the cortical and cancellous bone was largely eliminated in the grafts. Histological investigations revealed the coexistence of osteolytic and osteoblastic activity within the necrosis. Bone appositions were distributed over the entire graft area. Remaining marrow spaces were predominantly fibrotic or necrotic. In areas with marrow cavity fibrosis, hardly any new bone tissue was found in the adjacent bone, while there were increased signs of osteoclastic resorption. Insufficient reintegration of the flap may be due to residual fatty bone marrow contained in the bone flap which seems to act as a barrier for osteogenesis. This may obstruct the reorganization of the bone structure, inducing aseptic bone necrosis. Following a path already taken in orthopedic surgery, thorough lavage of the implant to remove the bone marrow may be a possibility, but will need further investigation. [ABSTRACT FROM AUTHOR]

Artifacts in computed tomography (CT) and magnetic resonance imaging (MRI) due to titanium implants in spine surgery are known to cause difficulties in follow-up imaging, radiation planning, and precise dose delivery in patients with spinal tumors. Carbon fiber–reinforced polyetheretherketon (CFRP) implants aim to reduce these artifacts. Our aim was to analyze susceptibility artifacts of these implants using a standardized in vitro model. Titanium and CFRP screw-rod phantoms were embedded in 3% agarose gel. Phantoms were scanned with Siemens Somatom AS Open and 3.0-T Siemens Skyra scanners. Regions of interest (ROIs) were plotted and analyzed for CT and MRI at clinically relevant localizations. CT voxel–based imaging analysis showed a significant difference of artifact intensity and central overlay between titanium and CFRP phantoms. For the virtual regions of the spinal canal, titanium implants (ti) presented − 30.7 HU vs. 33.4 HU mean for CFRP (p < 0.001), at the posterior margin of the vertebral body 68.9 HU (ti) vs. 59.8 HU (CFRP) (p < 0.001) and at the anterior part of the vertebral body 201.2 HU (ti) vs. 70.4 HU (CFRP) (p < 0.001), respectively. MRI data was only visually interpreted due to the low sample size and lack of an objective measuring system as Hounsfield units in CT. CT imaging of the phantom with typical implant configuration for thoracic stabilization could demonstrate a significant artifact reduction in CFRP implants compared with titanium implants for evaluation of index structures. Radiolucency with less artifacts provides a better interpretation of follow-up imaging, radiation planning, and more precise dose delivery. [ABSTRACT FROM AUTHOR]

Bioluminescence imaging of single cells is often complicated by the requirement of exogenous luciferins that can be poorly cellpermeable or produce high background signal. Bacterial bioluminescence is unique in that it uses reduced flavin mononucleotide as a luciferin, which is abundant in all cells, making this system purely genetically encodable by the lux operon. Unfortunately, the use of bacterial bioluminescence has been limited by its low brightness compared with other luciferases. Here, we report the generation of an improved lux operon named ilux with an approximately sevenfold increased brightness when expressed in Escherichia coli; ilux can be used to image single E. coli cells with enhanced spatiotemporal resolution over several days. In addition, since only metabolically active cells produce bioluminescent signal, we show that ilux can be used to observe the effect of different antibiotics on cell viability on the single-cell level. [ABSTRACT FROM AUTHOR]

Contents To support conservation strategies in wild species, simple but highly reproducible procedures of sperm cryopreservation are required for an application under field conditions. We used epididymal sperm of the domestic cat to optimize a sperm freezing procedure for felid species, particularly questioning the demand for sperm cooling to 4°C. We equilibrated sperm during slow cooling to only 15 or 10°C in a Tes-Tris-fructose extender with final concentrations of 4.7% (v/v) glycerol and 10% (v/v) of the water-soluble fraction of hen's egg yolk (low-density lipoproteins). Subsequently, sperm were frozen over liquid nitrogen. Total and progressive motility (mean ± SD) after thawing was 60.7 ± 8.6% and 53.9 ± 9.6% in samples cooled to 15°C or 61.6 ± 9.5% and 55.3 ± 9.9% in samples cooled to 10°C. Therefore, a one-step addition of glycerol to sperm at room temperature together with the freezing extender, the use of cryovials (loaded with diluted sperm aliquots of 300 μl), an equilibration period of 40 min comprising slow cooling to 15°C at a rate of approximately −0.14 K/min before rapid freezing over liquid nitrogen, yielded satisfying results. Cooling, freezing and thawing rates were exactly characterized as a prerequisite for further optimization and to provide a repeatable protocol to other practitioners. [ABSTRACT FROM AUTHOR]

Abstract: During a routine examination of 130 horse sera from 13 herds in Thuringia one TBEV antibody positive serum – with a very high titre – could be detected. The horse had been bought from a holding in Bavaria, and was reported to have clinical signs that may have been caused by a TBEV infection. To identify the source of the suspected TBEV infection, ticks from the surroundings of the barn in Thuringia as well as horse sera and ticks from two herds in Bavaria were examined. In the holding in Bavaria, where the horse was kept before, two out of ten horse sera were found to be TBEV antibody positive (20%), in a second herd nearby five out of 15 horse sera were TBEV antibody positive (30%), and in one serum TBEV-RNA could be detected. In addition, at both Bavarian sites, two different TBEV strains were detected in ticks collected in the vicinity of the respective holdings and in the surrounding areas. In contrast, no TBEV-RNA could be found in ticks collected in Thuringia. The suitability of horses as sentinels for the detection of natural TBEV foci supported by subsequent, targeted tick collection as well as the clinical importance of TBEV infection in horses are discussed. [Copyright &y& Elsevier]

This pilot, double-blind, placebo-controlled, randomized, escalating dose trial explored the safety and efficacy of tideglusib, an inhibitor of glycogen synthase kinase-3, in Alzheimer's disease (AD) patients. Thirty mild-moderate AD patients on cholinesterase inhibitor treatment were administered escalating doses (400, 600, 800, 1,000 mg) of tideglusib or placebo (ratio 2 : 1) for 4, 4, 6, and 6 weeks, respectively. The primary objective was to evaluate the safety and tolerability of tideglusib with strict criteria for drug escalation or withdrawal. Mini-Mental Status Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog+), word fluency, Geriatric Depression Scale (GDS), and a final Global Clinical Assessment (GCA) were assessed as secondary objectives. Treatment was well tolerated. Adverse events were as frequent in active and placebo groups, except for some moderate, asymptomatic, and fully reversible increases (>2.5 × ULN) of serum transaminases in 6 active cases (p = 0.001). Tideglusib produced positive trends in MMSE, ADAS-cog, GDS, and GCA without statistical significance in this small sample. Responders in MMSE were significantly higher in the active group (p = 0.05). Patients escalated up to 1000 mg/day had a benefit of 1.68 points in the MMSE and 4.72 points in the ADAS-cog+ when compared to placebo. This small pilot study provides valuable safety and efficacy estimates for the treatment of AD patients with tideglusib, currently being confirmed in a larger clinical trial. Due to escalating doses and the small sample size, this trial provides insufficient evidence to support or reject a benefit of tideglusib in AD. [ABSTRACT FROM AUTHOR]

Abstract: In order to deposit thin films on a substrate several techniques can be used, e.g. chemical vapour deposition, atomic layer deposition or sputter deposition, depending on their specific advantages and disadvantages due to the related application. A significant parameter is the energy incident upon the substrate by the specific technique, especially when the heat capacitance of the substrate is low. Within this paper we analyse the energy transported into a thin wire (few 10μm in diameter) during a dynamic inline aluminium sputter process in a cylindrical magnetron source. The evoked heating is important for the tensile strength of the wire and uniformity of the sputtered layer. Therefore, mathematical models were created to estimate the energy input into the wire supported by monte-carlo-simulations of the sputtering process using the TRIM-simulation (Transport and Range of Ions in Matter). Measurements with a Langmuir probe and the corresponding deposition rate were used to quantify these models, showing that at an aluminium coating process of a gold wire, the significant energy input is only due to electrons and ions of the processing gas (argon). Using the heat equation based on the sputtering apparatus'' parameters, it was also possible to determine the energy input into the wire with in situ electrical resistance measurements. Both methods did show similar results, whereby the resistance results were more stable. The determined energy input made it possible to calculate the temperature profile during the wire-coating process which can be useful for estimations about film diffusion and process optimisation. [Copyright &y& Elsevier]

Two luminescent ruthenium complexes containing tripod-type end groups linked through a rigid spacer to a phenanthroline derivative, able to confer an axial geometry to the complexes, are described. One of the compounds is functionalized with thioacetate groups in order to link the metal complex to metallic surfaces. The photophysical and electrochemical behavior of the complexes are studied in solution and on conductive substrates and, furthermore, self-assembled monolayers are investigated in a junction using gold and an indium gallium eutectic, as electrodes, and by time-resolved confocal microscopy. The results show that the complexes form very stable and well-ordered monolayers because of the tripod system, which can anchor the complex almost perpendicular to the surfaces. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2010; 16: 238–244 Tick-borne encephalitis (TBE) is recognized as the most important viral tick-borne zoonosis in 27 countries in Europe. In this study, ticks were collected in Germany from two non-risk areas in the states of Saxony-Anhalt and Mecklenburg-Western Pomerania, where several single human TBE cases have occurred in recent years. Ticks were also collected from a region in Thuringia, known to be a former risk area for TBE virus (TBEV), where numerous human cases were reported between 1960 and 1975. Detection of TBEV RNA was conducted by real-time RT-PCR. No TBEV was detected in any field-collected ticks. However, ticks were also collected from volunteers living in Bavaria. Three of 239 ticks from this collection were positive for TBEV genome and two genetically distinct TBEV strains were detected and characterized. [ABSTRACT FROM AUTHOR]

Oral viridans streptococci are a reservoir of resistance genes for pathogens. Through prolonged exposure, long-acting macrolides (e.g., azithromycin) may induce the resistance of the commensals to macrolides more frequently than macrolides with a shorter half-life (e.g., clarithromycin). In a prospective, randomized, evaluator-blinded trial in healthy volunteers receiving standard courses of either azithromycin ( n = 20) or clarithromycin ( n = 20), we compared the susceptibility of oral viridans streptococci to macrolides over a period of 12 weeks. There was a significant temporal increase in the numbers of resistant isolates in both groups ( p < 0.0005 at week 1). The proportion of macrolide-resistant isolates over time was significantly higher following azithromycin treatment ( p = 0.0005), but returned to baseline values until week 12 in both groups. Temporal differential effects of azithromycin and clarithromycin on the induction of resistance were observed and need to be investigated regarding their effect on co-colonizing pathogens. [ABSTRACT FROM AUTHOR]

This paper presents a model of acoustic wave propagation in unconsolidated marine sediment, including compaction, using a concept of a simplified sediment structure, modeled as a binary grain-size sphere pack. Compressional- and shear-wave velocities and attenuation follow from a combination of Biot’s model, used as the general framework, and two viscoelastic extensions resulting in complex grain and frame moduli, respectively. An effective-grain model accounts for the viscoelasticity arising from local fluid flow in expandable clay minerals in clay-bearing sediments. A viscoelastic-contact model describes local fluid flow at the grain contacts. Porosity, density, and the structural Biot parameters (permeability, pore size, structure factor) as a function of pressure follow from the binary model, so that the remaining input parameters to the acoustic model consist solely of the mass fractions and the known mechanical properties of each constituent (e.g., carbonates, sand, clay, and expandable clay) of the sediment, effective pressure, or depth, and the environmental parameters (water depth, salinity, temperature). Velocity and attenuation as a function of pressure from the model are in good agreement with data on coarse- and fine-grained unconsolidated marine sediments. [ABSTRACT FROM AUTHOR]

Velocities and attenuation of compressional (50 kHz) and shear waves (100 kHz) in two deep-sea sediment samples are investigated as a function of effective pressure up to 20 MPa with simultaneous measurement of porosity, density, and permeability. In both samples, the compressional-wave velocities show a strong increase with pressure, ranging from 1683 m/s at 1 MPa to 2128 m/s at 20 MPa in a silty clay and from 1840 m/s to 2462 m/s in a foraminiferal mud. Shear wave propagation is strongly restricted at pressures below 4 and 9 MPa in the respective sample, indicating a structural change in the sediment material at critical porosity values of 0.430 and 0.397, respectively. The compressional-wave attenuation, in terms of 1/QP, varies between 0.03 and 0.08, and 0.04 and 0.07, respectively. A result previously not reported in laboratory studies is a maximum in 1/QP as a function of effective pressure observed in both samples. The shear-wave attenuation is nearly constant as a function of pressure, having average values of about 0.07. The maximum of compressional-wave attenuation occurs at the respective critical porosity for each sample. Velocities and attenuation from this experiment exhibit a systematic pattern in a QP/QS vs (VP/VS)² representation. [ABSTRACT FROM AUTHOR]

Both cynomolgus and rhesus monkeys are utilized in chemical toxicity screening and drug development studies by industry and government laboratories. Along with better utilization of their tissue for in vivo studies, it would be advantageous if the tissue could be cold-preserved or cryopreserved for future in vitro experimentation. Therefore, livers were excised from control monkeys and precision-cut tissue slices were prepared. The objective of this study was twofold: to compare cold-preservation solutions ( V-7 and Viaspan) and to compare controlled-rate and vitrification cryopreservation protocols. Monkey liver slices were cold-stored in V-7 or Viaspan preservation solutions for 7 days. V-7 maintained slice viability for 5 days whereas Viaspan maintained slice viability for 1 day. In the controlled-rate freezing procedure, slices were exposed to 10% dimethyl sulfoxide and 90% fetal calf serum (FCS); cooled at the rate of 0.5°C, 1°C, or 12°C per min to -70°C; then placed into liquid nitrogen. Vitrification was accomplished by exposing slices stepwise to increasing concentrations of 1,2-propanediol (1.2, 2.4, and 4 M) in FCS with direct submersion into liquid nitrogen. In both protocols, slices were rewarmed quickly to 37°C and then incubated in FCS for 4 h. Three viability parameters were used to measure slice viability - retention of potassium, leakage of lactate dehydrogenase, and synthesis of protein. Liver slices cryopreserved at a rate of 0.5°C per min and vitrified successfully retained 80 to 90% of their viability. These results confirm the feasibility of functional cold preservation and cryopreservation protocols for monkey liver slices that would allow for a more efficient use of monkey tissue. [ABSTRACT FROM AUTHOR]

Background and purpose: To simulate patient-level costs, analyze the economic potential of telemedicine-based mobile stroke units for acute prehospital stroke care, and identify major determinants of cost-effectiveness, based on two recent prospective trials from the United States and Germany. Methods: A Markov decision model was developed to simulate lifetime costs and outcomes of mobile stroke unit. The model compares diagnostic and therapeutic pathways of ischemic stroke, hemorrhagic stroke, and stroke mimic patients by conventional care or by mobile stroke units. The treatment outcomes were derived from the B_PROUD and the BEST-mobile stroke unit trials and further input parameters were derived from recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. A lifetime horizon based on the US healthcare system was adopted to evaluate different cost thresholds for mobile stroke unit and the resulting cost-effectiveness. Willingness-to-pay thresholds were set at 1x and 3x gross domestic product per capita, as recommended by the World Health Organization. Results: In the base case scenario, mobile stroke unit care yielded an incremental gain of 0.591 quality-adjusted life years per dispatch. Mobile stroke unit was highly cost-effective up to a maximum average cost of 43,067 US dollars per patient. Sensitivity analyses revealed that MSU cost-effectiveness is mainly affected by reduction of long-term disability costs. Also, among other parameters, the rate of stroke mimics patients diagnosed by MSU plays an important role. Conclusion: This study demonstrated that mobile stroke unit can possibly be operated on an excellent level of cost-effectiveness in urban areas in North America with number of stroke mimic patients and long-term stroke survivor costs as major determinants of lifetime cost-effectiveness. [ABSTRACT FROM AUTHOR]

Two types of small-aspect-ratio slot jets were investigated. An orifice slot jet with a 3:1 aspect ratio was shown to have features similar to an elliptic jet with a well-designed contraction. A larger spreading rate and enhanced turbulent mixing, relative to a circular jet, can be obtained using this orifice nozzle, which is advantageous for many practical applications. By adding a conical contraction to the slot jet (tapered slot jet) the characteristics were totally altered. The axes switching, typical to an elliptic jet, did not occur and the spreading rate at the major axis plane was larger than at the minor axis plane. The turbulence amplification in the initial core region was higher than both in the circular and elliptic jets. The transition from the conical contraction of the nozzle to the slot shape of the outlet section produced three-dimensional vortical structures. These structures interacted with the asymmetric vortices shed from this noncircular configuration to enhance the small scale turbulence in the core region as well as in the jet circumference. The large spreading rate of the two configurations of slot jets is beneficial to increase the bulk mixing with the surrounding fluid through entrainment. The augmented turbulence level of the tapered slot jet is important for reacting flows where small scale mixing is required. [ABSTRACT FROM AUTHOR]

Presents a study on a different spatial filtering velocimeter. Utilization of a common charge-coupled device (CCD) as spatial filter for one-component velocity measurements; Basis of velocity estimation.

Objective: To report an outbreak of follicular conjunctivitis in a group of sheep diagnosed with Anaplasma spp., without any other co‐infection. Animals Studied: In all, 18 animals from a sheep head, males and females, from eight months to four years of age, were assessed for follicular conjunctivitis. Procedures: The procedures performed included general physical and ophthalmological examinations; PCR evaluation for infectious agents; analysis of hematological parameters, microbiological tests of ocular swabs, coproparasitological examination, histopathological examination of conjunctival biopsy. Results: All 18 animals had uni‐ or bilateral follicular conjunctivitis, and one animal also had unilateral uveitis. The results of microbiological analyzes were negative for Moraxella spp., Staphylococcus spp., and Pseudomonas spp., and PCR analysis results were negative for Chlamydia spp., Mycoplasma spp., and Toxoplasma gondii. Anemia, thrombocytopenia, lymphocytosis, and an inclusion body in some erythrocytes, compatible with Anaplasma and PCR analysis for Anaplasma spp. were positive. Conclusion: Anaplasmosis may be associated with follicular conjunctivitis in sheep and should be included in the differential diagnosis list and investigated in cases of conjunctivitis in herds. [ABSTRACT FROM AUTHOR]

Bioluminescence-based imaging of living cells has become an important tool in biological and medical research. However, many bioluminescence imaging applications are limited by the requirement of an externally provided luciferin substrate and the low bioluminescence signal which restricts the sensitivity and spatiotemporal resolution. The bacterial bioluminescence system is fully genetically encodable and hence produces autonomous bioluminescence without an external luciferin, but its brightness in cell types other than bacteria has, so far, not been sufficient for imaging single cells. We coexpressed codon-optimized forms of the bacterial luxCDABE and frp genes from multiple plasmids in different mammalian cell lines. Our approach produces high luminescence levels that are comparable to firefly luciferase, thus enabling autonomous bioluminescence microscopy of mammalian cells. [ABSTRACT FROM AUTHOR]

Compared with localization schemes solely based on evaluating patterns of molecular emission, the recently introduced single molecule localization concept called MINFLUX and the fluorescence nanoscopies derived from it require up to orders of magnitude fewer emissions to attain single-digit nanometer resolution. Here, we demonstrate that the lower number of required fluorescence photons enables MINFLUX to detect molecular movements of a few nanometers at a temporal sampling of well below 1 millisecond. Using fluorophores attached to thermally fluctuating DNA strands as model systems, we demonstrate that measurement times as short as 400 microseconds suffice to localize fluorescent molecules with ∼2-nm precision. Such performance is out of reach for popular camera-based localization by centroid calculation of emission diffraction patterns. Since theoretical limits have not been reached, our results show that emerging MINFLUX nanoscopy bears great potential for dissecting the motions of individual (macro)molecules at hitherto-unattained combinations of spatial and temporal resolution. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to identify the impact of different surgical strategies on the incidence of C5 palsy. Background: Degenerative cervical spinal stenosis is a steadily increasing morbidity in the ageing population. Postoperative C5 nerve root palsy is a common complication with severe impact on the patients´ quality of life. Methods: We identified 1708 consecutive patients who underwent cervical decompression surgery due to degenerative changes. The incidence of C5 palsy and surgical parameters including type and level of surgery were recorded to identify predictors for C5 nerve palsy. Results: The overall C5 palsy rate was 4.8%, with 18.3% of cases being bilateral. For ACDF alone the palsy rate was low (1.13%), compared to 14.0% of C5 palsy rate after corpectomy. The risk increased with extension of the procedures. Hybrid constructs with corpectomy plus ACDF at C3-6 showed significantly lower rates of C5 palsy (10.7%) than corpectomy of two vertebrae (p = 0.005). Multiple regression analysis identified corpectomy of C4 or C5 as a significant predictor. We observed a lower overall incidence for ventral (4.3%) compared to dorsal (10.9%) approaches (p<0.001). When imaging detected a postoperative shift of the spinal cord at index segment C4/5, palsy rate increased significantly (33.3% vs. 12.5%, p = 0.034). Conclusions: Extended surgical strategies, such as dorsal laminectomies, multilevel corpectomies and procedures with extensive spinal cord shift were shown to display a high risk of C5 palsy. The use of extended procedures should therefore be employed cautiously. Switching to combined surgical methods like ACDF plus corpectomy can reduce the rate of C5 palsy. [ABSTRACT FROM AUTHOR]

We introduce MINFLUX, a concept for localizing photon emitters in space. By probing the emitter with a local intensity minimum of excitation light, MINFLUX minimizes the fluorescence photons needed for high localization precision. In our experiments, 22 times fewer fluorescence photons are required as compared to popular centroid localization. In superresolution microscopy, MINFLUX attained ~1-nanometer precision, resolving molecules only 6 nanometers apart. MINFLUX tracking of single fluorescent proteins increased the temporal resolution and the number of localizations per trace by a factor of 100, as demonstrated with diffusing 30 S ribosomal subunits in living Escherichia coli . As conceptual limits have not been reached, we expect this localization modality to break new ground for observing the dynamics, distribution, and structure of macromolecules in living cells and beyond. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cervical cancer causes over 4000 deaths yearly in the United States, although highly preventable through vaccination, screening, and early treatment. We aimed to determine demographic correlates for cervical cancer in North Carolina to identify target populations for interventions and to create a framework for state-level analyses. METHOD: Data on all reported invasive cervical cancer cases from 1998 to 2007 were obtained from the North Carolina Central Cancer Registry. Age-adjusted incidence and mortality rates were estimated using population data from the National Center for Health Statistics. RESULTS: Cervical cancer incidence and mortality rates varied greatly by county and were inversely associated with county prosperity. Hispanic women had the highest incidence rate, black women the highest mortality rate, although white women accounted for most cases. Incidence rates remained fairly steady above age 35 and mortality rates steadily increased with age. A later stage at diagnosis was more common for older women and for women without private insurance. CONCLUSION: Registry-based assessment illustrates the economic, racial, and age disparities associated with cervical cancer. This localized focus on demographic correlates is an important step toward eliminating this preventable disease and offers a template for cervical cancer prevention programs in other states. [ABSTRACT FROM AUTHOR]

Habitat selection in ungulates should ensure access to abundant forage of sufficiently high quality. Species living in rugged mountain areas have to face nutritional bottlenecks regularly and should show particularly sophisticated habitat selection behaviour. However, patterns and mechanisms of such adaptations remain little studied. We analysed habitat selection and its seasonal variability of 10 GPS-collared red deer Cervus elaphus living in a topographically challenging landscape of the Swiss Alps. We hypothesised that resource selection by red deer was scale-dependent and predicted that scale-dependence would vary among seasons in relation to seasonal changes of available forage biomass and quality, which we sampled across the entire study area of 250 km2. The studied population of Alpine red deer undertook altitudinal migrations and showed scale-dependent habitat selection that was strongest in winter and declined through spring and summer. Selection occurred mostly at the larger (landscape/home-range location) scale and less so at the smaller (within home-range) scale. Topographic parameters were selected mainly at the landscape scale and mostly in winter. About 70% of all instances of preference for habitat parameters were associated with above-average forage characteristics, represented mostly by higher crude protein content, in a few cases also by higher biomass or both. The overall pattern of space use by red deer characterised by migration and seasonal habitat selection was therefore closely linked to the quality of food resources, although some trade-offs with avoiding human disturbance may also have been involved. [ABSTRACT FROM AUTHOR]

The generalized shooting method, previously developed for the analysis of spatial instability modes of arbitrary shape jets, is applied to incompressible jets with triangular core regions of constant flow. The instability modes of these jets are classified, and calculations are carried out for spatial growth rates, phase velocities, and velocity fluctuation eigenfunctions of three fundamental and two overtone modes. All of the calculated eigenfunctions show negligible velocity fluctuations at the triangle vertices, in good correlation with experimental findings. [ABSTRACT FROM AUTHOR]

Background: Multiple Sclerosis (MS) is an autoimmune-mediated disease of the central nervous system. Experimental data suggest a role of intestinal microbiota and microbial products such as short-chain fatty acids (SCFAs) in the pathogenesis of MS. A recent clinical study reported beneficial effects (mediated by immunomodulatory mechanisms) after oral administration of the SCFA propionate in MS patients. Based on available evidence, we investigated whether SCFAs and the fecal inflammation marker calprotectin are altered in MS. Methods: 76 subjects (41 patients with relapsing–remitting MS and 35 age-matched controls) were investigated in this case–control study. All subjects underwent clinical assessment with established clinical scales and provided fecal samples for a quantitative analysis of fecal SCFA and fecal calprotectin concentrations. Fecal markers were compared between MS patients and controls, and were analyzed for an association with demographic as well as clinical parameters. Results: Median fecal calprotectin concentrations were within normal range in both groups without any group-specific differences. Fecal SCFA concentrations showed a non-significant reduction in MS patients compared to healthy subjects. Female subjects showed significantly reduced SCFA concentrations compared to male subjects. Conclusions: In our cohort of MS patients, we found no evidence of an active intestinal inflammation. Yet, the vast majority of the investigated MS patients was under immunotherapy which might have affected the outcome measures. The sex-associated difference in fecal SCFA concentrations might at least partially explain female predominance in MS. Large-scale longitudinal studies including drug-naïve MS patients are required to determine the role of SCFAs in MS and to distinguish between disease-immanent effects and those caused by the therapeutic regime. [ABSTRACT FROM AUTHOR]

The article demonstrates the controllable growth and field-effect property of aligned monolayer to multilayer microstripes of a prototype organic semiconductor through various pulling speed using the dip-coating process. The study shows the decrease of molecular layers due to the increased pulling speed. It finds out that field effect cannot be detected in monolayer stripes due to its amorphous character.

Background IgE-mediated allergy is a common disease characterized by a harmful immune response towards otherwise harmless environmental antigens. Induction of specific immunological non-responsiveness towards allergens would be a desirable goal. Blockade of costimulatory pathways is a promising strategy to modulate the immune response in an antigen-specific manner. Recently, OX40 ( CD134) was identified as a costimulatory receptor important in Th2-mediated immune responses. Moreover, synergy between OX40 blockade and 'conventional' costimulation blockade (anti- CD40L, CTLA4Ig) was observed in models of alloimmunity. Objective We investigated the potential of interfering with OX40 alone or in combination with CD40/ CD28 signals to influence the allergic immune response. Methods The OX40 pathway was investigated in an established murine model of IgE-mediated allergy where BALB/c mice are repeatedly immunized with the clinically relevant grass pollen allergen Phl p 5. Groups were treated with combinations of anti- OX40L, CTLA4Ig and anti- CD40L. In selected mice, Tregs were depleted with anti- CD25. Results Blockade of OX40L alone at the time of first or second immunization did not modulate the allergic response on the humoral or effector cell levels but slightly on T cell responses. Administration of a combination of anti- CD40L/ CTLA4Ig delayed the allergic immune response, but antibody production could not be inhibited after repeated immunization even though the allergen-specific T cell response was suppressed in the long run. Notably, additional blockade of OX40L had no detectable supplementary effect. Immunomodulation partly involved regulatory T cells as depletion of CD25+ cells led to restored T cell proliferation. Conclusions and Clinical Relevance Collectively, our data provide evidence that the allergic immune response towards Phl p 5 is independent of OX40L, although reduction on T cell responses and slightly on the asthmatic phenotype was detectable. Besides, no relevant synergistic effect of OX40L blockade in addition to CD40L/ CD28 blockade could be detected. Thus, the therapeutic potential of OX40L blockade for IgE-mediated allergy appears to be ineffective in this setting. [ABSTRACT FROM AUTHOR]

This pilot, double-blind, placebo-controlled, randomized, escalating dose trial explored the safety and efficacy of tideglusib, an inhibitor of glycogen synthase kinase-3, in Alzheimer's disease (AD) patients. Thirty mild-moderate AD patients on cholinesterase inhibitor treatment were administered escalating doses (400, 600, 800, 1,000 mg) of tideglusib or placebo (ratio 2 : 1) for 4, 4, 6, and 6 weeks, respectively. The primary objective was to evaluate the safety and tolerability of tideglusib with strict criteria for drug escalation or withdrawal. Mini-Mental Status Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog+), word fluency, Geriatric Depression Scale (GDS), and a final Global Clinical Assessment (GCA) were assessed as secondary objectives. Treatment was well tolerated. Adverse events were as frequent in active and placebo groups, except for some moderate, asymptomatic, and fully reversible increases (>2.5 × ULN) of serum transaminases in 6 active cases (p = 0.001). Tideglusib produced positive trends in MMSE, ADAS-cog, GDS, and GCA without statistical significance in this small sample. Responders in MMSE were significantly higher in the active group (p = 0.05). Patients escalated up to 1000 mg/day had a benefit of 1.68 points in the MMSE and 4.72 points in the ADAS-cog+ when compared to placebo. This small pilot study provides valuable safety and efficacy estimates for the treatment of AD patients with tideglusib, currently being confirmed in a larger clinical trial. Due to escalating doses and the small sample size, this trial provides insufficient evidence to support or reject a benefit of tideglusib in AD. [ABSTRACT FROM AUTHOR]

Background Development of antigen-specific preventive strategies is a challenging goal in IgE-mediated allergy. We have recently shown in proof-of-concept experiments that allergy can be successfully prevented by induction of durable tolerance via molecular chimerism. Transplantation of syngeneic hematopoietic stem cells genetically modified to express the clinically relevant grass pollen allergen Phl p 5 into myeloablated recipients led to high levels of chimerism (i.e. macrochimerism) and completely abrogated Phl p 5-specific immunity despite repeated immunizations with Phl p 5. Objective It was unclear, however, whether microchimerism (drastically lower levels of chimerism) would be sufficient as well which would allow development of minimally toxic tolerance protocols. Methods Bone marrow cells were transduced with recombinant viruses integrating Phl p 5 to be expressed in a membrane-anchored fashion. The syngeneic modified cells were transplanted into non-myeloablated recipients that were subsequently immunized repeatedly with Phl p 5 and Bet v 1 (control). Molecular chimerism was monitored using flow cytometry and PCR. T cell, B-cell and effector-cell tolerance were assessed by allergen-specific proliferation assays, isotype levels in sera and RBL assays. Results Here we demonstrate that transplantation of Phl p 5-expressing bone marrow cells into recipients having received non-myeloablative irradiation resulted in chimerism persisting for the length of follow-up. Chimerism levels, however, declined from transient macrochimerism levels to persistent levels of microchimerism (followed for 11 months). Notably, these chimerism levels were sufficient to induce B-cell tolerance as no Phl p 5-specific IgE and other high affinity isotypes were detectable in sera of chimeric mice. Furthermore, T-cell and effector-cell tolerance were achieved. Conclusions and Clinical Relevance Low levels of persistent molecular chimerism are sufficient to induce long-term tolerance in IgE-mediated allergy. These results suggest that it will be possible to develop minimally toxic conditioning regimens sufficient for low level engraftment of genetically modified bone marrow. [ABSTRACT FROM AUTHOR]

Abstract: There is an increasing need and interest in including indicators of landscape fragmentation in monitoring systems of sustainable landscape management. Landscape fragmentation due to transportation infrastructure and urban development threatens human and environmental well-being by noise and pollution from traffic, reducing the size and viability of wildlife populations, facilitating the spread of invasive species, and impairing the scenic and recreational qualities of the landscape. This paper provides the rationale, method, and data for including landscape fragmentation in monitoring systems, using as an example the Swiss Monitoring System of Sustainable Development (Monet). We defined and compared four levels of fragmentation analysis, or fragmentation geometries (FGs), each based on different fragmenting elements, e.g., only anthropogenic, or combinations of anthropogenic and natural elements. As each FG has specific strengths and weaknesses, the most appropriate choice of FG depends on the context and objectives of a study. We present data on the current degree of landscape fragmentation for the five ecoregions and 26 cantons in Switzerland for all four FGs. Our results show that the degree of landscape fragmentation as quantified by the effective mesh size method is strongly supported by the postulates and indicator selection criteria of Monet, and we identify the most suitable FG focusing on the land area below 2100m (e.g., excluding lakes) and allowing for an equitable comparison of fragmentation degrees among regions that differ in area covered by lakes and high mountains. For a more detailed analysis of landscape fragmentation in the context of environmental impact assessments and strategic environmental assessments, a combination of all four FGs may provide a more informative tool than any single FG. [Copyright &y& Elsevier]

Single subject and group analyses (n = 12) showed that the eyes-open and eyes-closed states in complete darkness considerably and consistently differ in the patterns of associated brain activation in fMRI. During nonchanging external stimulation, ocular motor and attentional systems were activated when the eyes were open; the visual, somatosensory, vestibular, and auditory systems were activated when the eyes were closed. These data suggest that there are two different states of mental activity: with the eyes closed, an “interoceptive” state characterized by imagination and multisensory activity and with the eyes open, an “exteroceptive” state characterized by attention and ocular motor activity. Our study also shows that the chosen baseline condition may have a considerable impact on activation patterns and on the interpretation of brain activation studies. [Copyright &y& Elsevier]

The authors describe the experimental observation of negative group velocity propagation of sound waves through an asymmetric loop filter. The characteristics of the filter are established using impulse response and direct tunneling of narrow bandwidth Gaussian pulses. The results confirm recent theoretical predictions that faster-than-light group velocity propagation of sound is possible. Further, the results show that the spectral rephasing achieved in a loop filter is sufficient to produce negative group velocities independent of the phase velocity of the spectral components themselves. Thus, superluminal propagation is realized despite almost six orders of magnitude difference between the speeds of sound and light. [ABSTRACT FROM AUTHOR]