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The aim of this study was to ascertain whether dynamic cerebral autoregulation (CA) in the middle cerebral artery (MCA) is disturbed by cerebral infarctions outside the MCA territory.

A patient’s respiratory rate is one of the critical vital signs that is a determinant of patient well-being. However, it is all too often neglected or misreported by health care professionals. This study presents the design, build and testing of a low-cost, portable monitor to facilitate accurate reporting of respiratory rate. The monitor comprised a thermistor-based transducer to capture the breath cycle of patients based on the temperature differential created across the thermistor. The signal was conditioned and processed such that the signal could be analysed to identify the peaks and ultimately determine the respiratory rate. For a total cost at the time of development of less than C40, the integrated system demonstrated a modest average error of 5.6% across a range of different ambient temperatures, rate and depth of breathing, and orifice of breathing. This is comparable with other commercial and custom devices. The presented monitor may be of interest for use in an emergency room or clinical setting, especially in severely resource-constrained countries.

In this study, we utilize the SMASH transport model to explore the generation of global angular momentum in heavy-ion collisions. Our results corroborate previous models, highlighting a pronounced peak in angular momentum transfer during mid-central collisions at b = 4 - 6 fm across √SNN = 2:41 - 200 GeV. Additionally, we thoroughly investigate the impact of system size and centrality on angular momentum. Intriguingly, we observe a distinct trend towards higher relative angular momentum transfer in smaller systems and more central collisions. To address local angular momentum conservation intricacies, we propose tailored setups for varying energy regimes, relying on the test particle method and Fermi motion treatment.

A one-day Nordic Concrete Research workshop on “Accelerated freeze-thaw testing of concrete” attracted approx. 30 participants. The workshop included presentations on various aspects, such as observed frost damage in the field and the importance of the temperature curve during testing as well as other interactions with the surroundings of the concrete. The workshop also included examples of recent research, which can improve our knowledge about the frost damage mechanism and therefore provide input to improving the standardised test methods. The present paper is a summary of the nine presentations and the discussion arising from the presentations.

Graphene flakes acting as photonic nanoantennas may sustain strong electromagnetic field localization and enhancement. To exploit the field enhancement, quantum emitters such as atoms or molecules should be positioned in such close proximity to the flake that electron tunneling might influence the optical and electronic properties of the system. However, tunneling is usually not considered if the optical coupling mechanism between quantum emitters and nanoantennas is at focus. This work presents a framework for describing the electron dynamics in hybrid systems consisting of graphene nanoflakes coupled both electronically and optically to adatoms and subject to external illumination. Our framework combines the single-particle tight-binding approach with a nonlinear master equation formalism that captures both optical and electronic interactions. We apply the framework to demonstrate the impact of electron tunneling between the adatom and the flake on emblematic quantum optical phenomena: degradation of coherent Rabi oscillations and quenching of Purcell spontaneous emission enhancement in two-level adatoms in proximity of triangular graphene nanoflakes.

Autologous plasma proteins can be used to fabricate patient specific cardiovascular implants but need to be cross-linked to increase their mechanical strength and reduce water solubility. Glutaraldehyde is the state-of-the-art solution but its reaction products have been shown to be cytotoxic and pro-inflammatory. In this work, it has been shown, that cross-linking of plasma proteins with biocompatible alternatives to glutaraldehyde is possible. This was achieved by identifying four candidate substances (thrombin, transglutaminase, genipin, EDC) from current literature and investigating their ability to cross-link porcine plasma proteins in vitro. The degree of crosslinking was examined using calorimetric (DSC) and spectroscopic (FTIR, Raman) methods, mapping the influence of cross-linking on the denaturation temperature and primary amino-group content of the proteins. It could be shown that thrombin, genipin and EDC are able to cross-link plasma proteins to a satisfactory degree and thus represent useful alternatives to glutaraldehyde. Transglutaminase, on the other hand, could not sufficiently cross-link the plasma proteins and was therefore ruled out as an alternative.

Sublingual haematoma is a rare complication of anticoagulants and can be life-threatening. As the number of prescribed anticoagulants is increasing, the incidence of complications of these drugs will continue to increase. A report of a sublingual haematoma in an elderly patient with chronic atrial fibrillation treated with edoxban (Lixiana ©, Daiichi Sankyo Europe GmbH, München, Germany) is reported. A 90-year male presented at the emergency department with an obstructed upper airway due to a sublingual haematoma. The patient received tranexamic acid, prothrombin complex, and fresh frozen plasma. After fiberoptic nasal intubation, the patient was monitored in the intensive care unit. After four days, the patient was extubated, and after six days, the swelling resolved completely. Complications of anticoagulants are rare but can be life-threatening. Recognition of an endangered airway and reversing the effects of the anticoagulant are essential. Surgical evacuation of the haematoma could be considered but is not necessary.

This edition of the European Conference on Neutron Scattering, which is held every four years, took place in Garching, Germany and gathered over 500 people from all areas of neutron science. From new source or instrumental concepts to fundamental physics, and chemistry, all areas of this community were represented. Lively discussions in the lecture halls, poster areas,and social events around this conference contributed to a very fruitful exchange of new ideas.

Neutron detection by MWPC based on 10B4C coatings can surpass in performance the one utilising 3He-gas in terms of position resolution and count rate capability at similar detection efficiency [13]. The use of m2-size foils coated by 10B4C demands the development of a mechanical concept to avoid deformations of the neutron sensitive surface due to their own weight and the electrostatic forces resulting from high voltage for operation. To preserve a flat shape of the converter, a pressure gradient is applied between its both sides [4]. The design shall allow a stacking of detection modules consisting of sequenced elements [converter/x-y-multi-wire planes/converter] in few mm proximity. A multiple stacking of the detector modules is needed to accumulate a sufficient high detection efficiency for diffraction with thermal neutrons over the entire detector [2]. The MWPC is planned to have fifteen detection modules corresponding to an efficiency equivalent of 30 converters coated with 1.2 µm of 10B4C. Efficiency simulations of a converter coating thickness-profile from 0.6 µm up to 1.2 µm prognoses a conversion rate up to 50 % for thermal neutrons and the presented design parameters of the 1-m2 MWPC allow a position resolution of 2 mm.

The existence of a set of stable proton-rich nuclei - the p nuclei - cannot be explained via neutron-capture reactions. Therefore, another mechanism has to exist in order to explain their origin, the most probable, especially at high masses, being photodisintegration reactions. This gives rise to the γ process. Since most photodisintegration reactions involved in the process are not experimentally accessible, reliable statistical model calculations are needed to predict cross sections and reaction rates. To improve these calculations nuclear input parameters need to be constrained and a large experimental database is needed. Via comparison of experimental data to theoretical predictions different models can be tested and constrained. In order to study the 87Rb(p,γ)88Sr reaction, for which previously no experimental data have been available, an in-beam experiment at at the University of Cologne’s high-efficiency HPGe γ-ray spectrometer HORUS was performed. Proton beams with energies between Ep = 2000 to 5000 keV reaching deep into the Gamow window of the reaction were provided by the 10 MV FN Tandem accelerator. Cross-section values at six proton beam energies were determined. The experimental results are in good agreement with statistical model calculations. The obtained results are the first experimental cross-section values for the87Rb(p,γ)88Sr reaction and help to constrain the nuclear physics input for statistical model calculations.

Super-resolution structured illumination microscopy (SR-SIM) can be conducted at video-rate acquisition speeds when combined with high-speed spatial light modulators and sCMOS cameras, rendering it particularly suitable for live-cell imaging. If, however, three-dimensional (3D) information is desired, the sequential acquisition of vertical image stacks employed by current setups significantly slows down the acquisition process. In this work, we present a multiplane approach to SR-SIM that overcomes this slowdown via the simultaneous acquisition of multiple object planes, employing a recently introduced multiplane image splitting prism combined with high-speed SIM illumination. This strategy requires only the introduction of a single optical element and the addition of a second camera to acquire a laterally highly resolved 3D image stack. We demonstrate the performance of multiplane SIM by applying this instrument to imaging the dynamics of mitochondria in living COS-7 cells.

Clinical laboratory analyses are essential part of critical care. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19)-confirmed cases were doubling in Germany every 3 days during March 2020. Health care systems are preparing for an epidemic crisis.

The atomistic structure and dynamics obtained from molecular dynamics (MD) simulations with the example of TIP3P (rigid and flexible) and TIP4P/2005 (rigid) water is compared to neutron and X-ray scattering data at ambient conditions. Neutron and X-ray diffractograms are calculated from the simulations for four isotopic substitutions as well as the incoherent intermediate scattering function for neutrons. The resulting curves are compared to each other and to published experimental data. Differences between simulated and measured intermediate scattering functions are quantified by fitting an analytic model to the computed values. The sensitivity of the scattering curves to the parameters of the MD simulations is demonstrated on the example of two parameters, bond length and angle.

The astrophysical p process unites all processes that have been introduced to explain the abundance of a group of 30 to 35 neutron-deficient nuclei which are referred to as p nuclei. In general, these p processes include large networks of nuclear reactions and a complete understanding of the individual reaction rates is required to describe the abundance of the p nuclei qualitatively and quantitatively. In many cases the involved nuclear reactions are not accessible in the laboratory, either due to their low cross sections or because they involve unstable or exotic isotopes. For those purposes, the motivation of cross-section measurements performed at the University of Cologne is twofold: First, experimentally constrained reaction rates are of direct relevance for nucleosynthesis network calculations. And second, experimental cross-section values are required to test existing theoretical descriptions and to improve their predictive power. In this work, we present the experimental setups and methods that are used to measure nuclear cross-sections at very low sensitivities and we show a detailed overview of proton-and α-induced reactions that have been measured in Cologne in the last decade.

Abstract: Glasses doped either with chromium or manganese or with both chromium and manganese were melted from the raw materials and studied by UV–vis–NIR spectroscopy. The measurements were carried out at temperatures in the range from 25 to 800°C. In the glasses doped with only one transition metal oxide, the intensity of the absorption lines decreases and the full width at half maximum increases with increasing temperatures. Simultaneously, the peaks were shifted to larger wave numbers. In glasses doped with both chromium and manganese, the same behaviour was observed up to a temperature of 600°C. At larger temperatures, the absorption band at 27500cm−1 due to Cr6+ increases again, while the absorption band at 20300cm−1 caused by Mn3+ decreases more strongly than in glasses solely doped with manganese. The behaviour observed was explained by the redox reaction Cr6+ +3Mn2+ ⇄Cr3+ +3Mn3+ which is shifted to the left while increasing the temperature. [Copyright &y& Elsevier]

A major challenge in cardiovascular tissue engineering is the fabrication of scaffolds, which provide appropriate morphological and mechanical properties while avoiding undesirable immune reactions. In this study electrospinning was used to fabricate scaffolds out of blood proteins for cardiovascular tissue engineering. Lyophilised porcine plasma was dissolved in deionised water at a final concentration of 7.5% m/v and blended with 3.7% m/v PEO. Electrospinning resulted in homogeneous fibre morphologies with a mean fibre diameter of 151 nm, which could be adapted to create macroscopic shapes (mats, tubes). Cross-linking with glutaraldehyde vapour improved the long-term stability of protein based scaffolds in comparison to untreated scaffolds, resulting in a mass loss of 41% and 96% after 28 days of incubation in aqueous solution, respectively.

One of the greatest challenges in cardiovascular tissue engineering is to develop vascular grafts with properties similar to autologous vessels. A promising approach is the fabrication of scaffolds from biodegradable polymers by electrospinning. Unstructured vascular subs possess a weak dimensional stability resulting in lumen collapse when subjected to bending stress. In order to examine different structured grafts, a standardised test method is required. A manual test method, designed in a former study, was adopted in terms of standardisation and automation. Therefore, a control system was programmed to regulate the required electronics. The electronic circuit was then developed and put into service. To fix samples into the test bench a new sample holder and a new collector for electrospinning were designed. Subsequently, a validation showed the new systems’ improved functionality compared to the former test bench. The samples were manufactured with the new collector. They could be fixed to the sample holder with high repeatability. The demand for vascular grafts with biological and mechanical properties similar to autologous vessels requires a standardised test method to examine bendability. The new test system enables the scaffolds to be examined regarding bendability with low personal expense and a simultaneously high degree of reproducibility. In addition, the new collector geometry can be easily adapted to higher or lower inner diameters. Hence, a new sample geometry was developed within this work.

Green manures have become an important option for recycling nutrients in organic cropping. However, its benefits are often not obtained in the short term. In this context, the study aimed to determine whether the use of cover crops during winter can contribute to N provision in the following spring, in the beginning of the growth of young grapevines. The winter green manure species white lupin (Lupinus albus), forage pea (Pisum arvense), common vetch (Vicia sativa), hairy vetch (Vicia villosa), triticale (Triticale hexaploide), oat (Avena sativa), ryegrass (Lollium multiflorum) and forage turnip (Brassica rapa) were grown until flowering in 4 L pots and fertilized with ammonium sulfate enriched at 10% with 15N atoms. In the following spring, grapevines cv. Niagara Rosada (Vitis labrusca) grafted on two different rootstocks (IAC-572 ‘Jales’ and IAC 766 ‘Campinas’) were planted in 14 L pots where it was superficially applied one of the five different sources of N. The green manure species employed as N source were forage pea (Pisum arvense), common vetch (Vicia sativa), hairy vetch (Vicia villosa) and oat (Avena sativa). The soil surface was covered with the dry matter from the green manure species (3g dry matter pot-1) or fertilized with ammonium sulfate enriched at 2% with 15N atoms. The results demonstrated that the oat plants showed the highest dry matter content (11.68 g pot-1). The species forage pea, hairy vetch and common vetch had the lowest C/N ratios, with values of 16, 16 and 18, respectively. Hairy vetch was the most efficient (255.1 mg pot-1) for the accumulation of N and oat plants showed the highest N uptake from the mineral fertilizer. The N uptake and accumulation by the ‘Niagara Rosada’ grapevines varied according to N source and rootstock. Grapevines accumulated N in higher amounts from mineral fertilizer, followed by the N from leguminous species and then lower quantities from the oat plants. Grapevines grafted on the IAC-572 ‘Jales’ rootstock accumulated higher amounts of N than those grafted on IAC-766 ‘Campinas’, probably due its higher vigor and, consequently, better soil exploration by the roots. Despite of the rootstock, between the green manure species, the N from forage peas was the most recovered by the grapevines cv. Niagara Rosada, attaining 30.8%, while common vetch 23.1%, hairy vetch 19.0%, and oat only 5.2%.

The determination of the current driven by electron cyclotron waves is usually performed employing ray/beam tracing codes, which require as an input the magnetic equilibrium, the electron density and the electron temperature profiles on one side and the beam injection parameters on the other. In the frame of systems-code applications, however, a different approach is needed, as some of the required input quantities are not available. Here, a procedure to evaluate the achievable ECCD efficiency for given global reactor parameters is proposed. It relies on a single numerical evaluation of the current drive efficiency (based on the adjoint method and including momentum-conserving corrections) for suitably chosen input values. The results are shown to be in good agreement with the full numerical optimization of the ECCD efficiency for a number of reactor-relevant scenarios. As described in this paper, this approach does not include the effect of parasitic absorption from higher cyclotron harmonics, which becomes important starting from electron temperatures of the order of 30 keV.

Weedy sunflowers have been officially reported in South-Western France in 2004. They display a combination of phenotypic traits of the wild and domesticated forms of the species and infest between 15 and 20% of fields of sunflower crop in this area, although at variable levels. When the infestation is strong, it affects seed yield and oil quality. Molecular studies showed that weedy sunflowers most probably resulted from accidental crop-wild hybridization during the seed production process and from the introduction of the resulting hybrids into commercial seed lots. Multiple independent introductions were at the source of the number of infested fields observed nowadays. The temporal dynamics of the infestation of a field and the detailed conditions for its success remain largely unknown. The flowering synchrony between crops and weeds is substantial, even if a variable fraction of the weeds (15-55%) flower completely outside the crop flowering period. Molecular survey of adult weedy plants and their progenies showed that crop-toweed gene flow occurs, at a rate that can reach 35 %on average, at the peak of the crop flowering period. We draw perspectives on the durability of herbicide-tolerant sunflower varieties as a solution to control these weeds, and call for more studies tackling weed management from an evolutionary lens.

An important element of the process of aircraft certification is the demonstration of the crashworthiness of the structure in the event of an emergency landing on water, also referred to as ditching. Novel numerical simulation methods that incorporate the interaction between fluid and structure open up a promising way to model ditching in full scale. This study presents a numerical framework for the simulation of ditching on a high–fidelity level. A partitioned approach that combines a finite volume hydrodynamic fluid solver as well as an finite element structural solver is implemented using a Python-based distributed coupling environment [1]. High demands are placed both on the fluid and the structural solver. The fluid solver needs to account for hydrodynamic effects such as cavitation in order to correctly compute the ditching loads acting on the aircraft structure. In the structural model, the highly localized damage induces nonlinearities and large differences in model scale. In order to reduce the computational effort a reduced order model is used to model the failure of fuselage frames. The fluid-structure coupling requires an explicit coupling scheme. It is shown that the standard Dirichlet-Neumann approach exhibits unstable behaviour if a strong added-mass effect is present, as is the case in aircraft ditching. This indicates a need for methods other than the standard Dirichlet-Neumann approach [2].

The goal of SecondHands, a H2020 project, is to design a robot that can offer help to a maintenance technician in a proactive manner. The robot is to act as a second pair of hands that can assist the technician when he is in need of help. In order for the robot to be of real help to the technician, it needs to understand his needs and follow his commands. Interaction via speech is a crucial part of this. Due to the nature of the situation in which the interactions take place, often the technician needs to speak to the robot when under stress performing strenuous physical labor, the classical turn based interaction schemes need to be transformed into dialogue systems that perform stream processing, anticipating user intentions, correcting itself as more information become available, in order to be able to respond in a rapid manner. In order to meet these demands, we are developing low-latency streaming based automatic speech recognition systems in combination with recurrent neural network based Natural Language Understanding systems that perform slot filling and intent recognition in order for the robot to provide assistance in a rapid manner, that can be partly based on speculative classifications that are then being refined as more speech becomes available.

V-band clamp joints are used in a wide range of applications to connect circular flanges, for ducts, pipes and the turbocharger housing. Previous studies and research on V-bands are either purely empirical or analytical with limited applicability on the variety of V-band design and working conditions. In this paper models of the V-band are developed based on the classical theory of solid mechanics and the finite element method to study the behaviour of theV-bands under axial loading conditions. The good agreement between results from the developed FEA and the classical model support the suitability of the latter to modelV-band joints with diameters greater than 110mm under axial loading. The results from both models suggest that the axial stiffness for thisV-band cross section reaches a peak value for V-bands with radius of approximately 150 mmacross a wide range of coefficients of friction. Also, it is shown that the coefficient of friction and the wedge angle have a significant effect on the axial stiffness of V-bands.

Neste trabalho estudou-se a viabilidade econômica de um plantio de teca (Tectona grandis L.f.) submetido a desbastes. Foram utilizados os seguintes critérios de análise econômica de projetos: valor presente líquido, benefício (custo) periódico equivalente, taxa interna de retorno e valor esperado da terra. A taxa de desconto utilizada foi de 10% a.a. Os indicadores demonstraram a viabilidade econômica do plantio da teca, conforme as condições estabelecidas na análise. O plantio será inviável se houver redução maior que 25% nas receitas ou aumento superior a 35% nos custos, sendo, portanto, mais sensível às variações na redução de receitas que às variações no aumento de custos.

Investigou-se o período mínimo de colheitas sucessivas necessário para avaliação do desempenho de cultivares de cacau. Os cultivares locais não-melhorados 'Maranhão', 'Pará' e 'Parazinho', juntamente com os cultivares melhorados 'ICS 1' polinização livre e híbrido comercial, foram avaliados em quadrado latino 5 x 5 com parcelas de 196 plantas, durante dez anos (1984-93). O número de frutos sadios por planta (NFSP) e o peso de sementes úmidas por hectare (PSUH) e por fruto (PSUF) foram os componentes de produção avaliados. A análise dos coeficientes de correlação entre produções anuais e acumuladas no decênio mostrou a necessidade da combinação dos primeiros seis e oito anos de colheitas sucessivas para NFSP e PSUH, respectivamente, para avaliação dos cultivares. A ampla variabilidade e o desempenho superior no pós-clímax (1989-93) e a tendência de os cultivares interagirem com os anos no pré-clímax indicaram que a avaliação deve ser conduzida em cacaueiros cultivados em Linhares somente após o oitavo ano de cultivo.

Matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS) is usually used for the analyses of proteins carbohydrates and oligonucleotides. In spite of the number of advantages that MALDI-TOF MS exhibits for lipid analysis, this method has not often been applied in this field. In this paper we have extended our previous studies on the suitability of MALDI-TOF MS for the investigation of changes in the content of lipid-derived second messengers in organic extracts of human neutrophils. Qualitative differences in the lysophospholipid composition in organic extracts of the human neutrophils under different stimulation conditions could be easily observed by MALDI-TOF MS. Although there are still some methodological problems to be solved before this method can be routinely applied for the quantification of different lipid classes in complex biological mixtures (such as organic extracts of human neutrophils) it is shown here that MALDI-TOF MS possesses the capability to be used as a simple screening method for the investigation of the content of lipid-derived second messengers and of signalling pathways in cells.

O uso da irrigação em pastagens é uma realidade fundamentada na experiência empírica de produtores, devido à falta de bases científicas definidas sobre o assunto. O trabalho visou avaliar a produtividade do capim Mombaça (Panicum maximum Jacq. cv. Mombaça) manejado em pastejo rotacionado, sob sistema de irrigação e as principais variáveis climáticas responsáveis pelo acúmulo de massa de forragem. O experimento foi conduzido sob irrigação por aspersão tipo pivô central, de julho a dezembro de 1998, em região de cerrado (Latossolo Vermelho-Amarelo) em São Desidério, BA. Foi quantificada a massa de forragem da pastagem aos 30 dias de crescimento e antes do pastejo e desenvolvidos modelos matemáticos que relacionam a produção de forragem a variáveis climáticas. A produção e a taxa de acúmulo de matéria seca da pastagem, ao longo do período de inverno não apresentaram diferenças significativas. Na primavera, houve tendência de aumento em ambas, com maiores produções obtidas no período final de avaliação. As menores taxas de acúmulo durante a primavera foram observadas nos primeiros piquetes, coincidindo com a ocorrência de baixas temperaturas durante o período de descanso. Com a elevação da temperatura mínima, a produção forrageira entrou em fase de acúmulo crescente. A produção de forragem, durante a primavera, foi superior à do inverno, apresentando incrementos em função da maior temperatura mínima do ar, do período de descanso e da área foliar inicial. As principais variáveis climáticas responsáveis pela produção da forragem foram temperatura mínima do ar e disponibilidade de água no solo.

Das geriatrische Schulungsprogramm Casaplus der MedicalContact AG bietet bereits seit 2007 telefonische Gesundheitscoachings für multimorbide geriatrische Versicherte, von dem bereits ca. 30.000 Versicherte profitiert haben. Die erfolgskritischen Faktoren für ein solches Programm sind die risikobasierte Identifikation der geeigneten Kandidat:innen, die Teilnehmergewinnung sowie die individuelle Betreuung durch speziell ausgebildete medizinische Fachkräfte. Seit 2017 wird das Casaplus-Programm gemeinsam mit der VIACTIV-Krankenkasse und der DCC Risikoanalytik GmbH um KI-basierte Komponenten sowohl bei der Prädiktion von beeinflussbaren Risiken im Rahmen der Identifikation als auch bei der Nutzung risikoadjustierter Propensity Scores im Rahmen der Evaluation zum smartCasaplus-Coaching weiterentwickelt. Die aktuellen Evaluationsergebnisse der VIACTIV-Krankenkasse zeigen, dass damit unter Berücksichtigung der Zuweisungseffekte und Programmkosten ein Return-on-Invest von 1,7 im Mittel über die ersten 4 Programmjahre erreicht wird.

Abstract Background During the extremely challenging 4,487 km ultramarathon TransEurope-FootRace 2009, runners showed considerable reduction of body weight. The effects of this endurance run on brain volume changes but also possible formation of brain edema or new lesions were explored by repeated magnetic resonance imaging (MRI) studies. Methods A total of 15 runners signed an informed consent to participate in this study of planned brain scans before, twice during, and about 8 months after the race. Because of dropouts, global gray matter volume analysis could only be performed in ten runners covering three timepoints, and in seven runners who also had a follow-up scan. Scanning was performed on three identical 1.5 T Siemens MAGNETOM Avanto scanners, two of them located at our university. The third MRI scanner with identical sequence parameters was a mobile MRI unit escorting the runners. Volumetric 3D datasets were acquired using a magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence. Additionally, diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR) imaging was performed. Results Average global gray matter volume as well as body weight significantly decreased by 6% during the race. After 8 months, gray matter volume returned to baseline as well as body weight. No new brain lesions were detected by DWI or FLAIR imaging. Conclusions Physiological brain volume reduction during aging is less than 0.2% per year. Therefore a volume reduction of about 6% during the 2 months of extreme running appears to be substantial. The reconstitution in global volume measures after 8 months shows the process to be reversible. As possible mechanisms we discuss loss of protein, hypercortisolism and hyponatremia to account for both substantiality and reversibility of gray matter volume reductions. Reversible brain volume reduction during an ultramarathon suggests that extreme running might serve as a model to investigate possible mechanisms of transient brain volume changes. However, despite massive metabolic load, we found no new lesions in trained athletes participating in a multistage ultramarathon. See related commentary http://www.biomedcentral.com/1741-7015/10/171

Abstract Background Medications are frequently prescribed outside their regulatory approval (off-label) by physicians particularly where appropriate therapies are not available. However, the risk/benefit ratio of drugs in off-label use needs to be critically appraised because it may differ from approved on-label usage. Therefore, an extensive exploration of current evidence on clinical data is well-advised. The objective of this study was to develop a search strategy that facilitates detection of the off-label drug use documents in EMBASE via OvidSP. Methods We constructed two sets of gold standards from relevant records to off-label drug use by a sensitive search of MEDLINE and EMBASE. Search queries, including search words and strings, were conceived based on definition of off-label use of medications as well as text analysis of 500 randomly selected relevant documents. The selected terms were searched in EMBASE (from 1988 to 2011) and their retrieval performance was compared with the gold standards. We developed a sensitivity-maximizing, and a sensitivity- and precision-maximizing search strategy. Results From 4067 records relevant to off-label drug use in our full gold standard set, 3846 records were retrievable from EMBASE. “off label*.af.” was the most sensitive single term (overall sensitivity 77.5%, sensitivity within EMBASE 81.9%, precision 88.1%). The highest sensitive search strategy was achieved by combining 36 search queries with overall sensitivity of 94.0% and precision of 69.5%. An optimal sensitive and precise search strategy was yielded precision 87.4% at the expense of decreasing overall sensitivity to 89.4%. Conclusion We developed highly sensitive search strategies to enhance the retrieval of studies on off-label drug use in OvidSP EMBASE.

Abstract Infiltration of Ly6Chi monocytes from the blood is a hallmark of viral encephalitis. In mice with lethal encephalitis caused by West Nile virus (WNV), an emerging neurotropic flavivirus, inhibition of Ly6Chi monocyte trafficking into the brain by anti-very late antigen (VLA)-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice, with subsequent sterilizing immunity. This treatment had no effect on viral titers but appeared to be due to inhibition of Ly6Chi macrophage immigration. Although macrophages isolated from the infected brain induced WNV-specific CD4+ T-cell proliferation, T cells did not directly contribute to pathology, but are likely to be important in viral control, as antibody-mediated T-cell depletion could not reproduce the therapeutic benefit of anti-VLA-4. Instead, 70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (NO). Furthermore, aminoguanidine-mediated inhibition of induced NO synthase activity in infiltrating macrophages significantly prolonged survival, indicating involvement of NO in the immunopathology. These data show for the first time the therapeutic effects of temporally targeting pathogenic NO-producing macrophages during neurotropic viral encephalitis.

Abstract Microarrays are routine tools for transcript profiling, and genomic tiling arrays such as the Arabidopsis AGRONOMICS1 arrays have been found to be highly suitable for such experiments because changes in genome annotation can be easily integrated at the data analysis level. In a transcript profiling experiment, RNA labeling is a critical step, most often initiated by oligo-dT-primed reverse transcription. Although this has been found to be a robust and reliable method, very long transcripts or non-polyadenylated transcripts might be labeled inefficiently. In this study, we first provide data handling methods to analyze AGRONOMICS1 tiling microarrays based on the TAIR10 genome annotation. Second, we describe methods to easily quantify antisense transcripts on such tiling arrays. Third, we test a random-primed RNA labeling method, and find that on AGRONOMICS1 arrays this method has similar general performance as the conventional oligo-dT-primed method. In contrast to the latter, however, the former works considerably better for long transcripts and for non-polyadenylated transcripts such as found in mitochondria and plastids. We propose that researchers interested in organelle function use the random-primed method to unleash the full potential of genomic tiling arrays.

Abstract Background Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure. Methods A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay. Discussion The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure. Trial Registration Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909

Abstract Background Interferon beta (IFNβ) and glatiramer acetate (GA) are administered by subcutaneous (SC) or intramuscular (IM) injection. Patients with multiple sclerosis (MS) often report injection-site reactions (ISRs) as a reason for noncompliance or switching therapies. The aim of this study was to compare the proportion of patients on different formulations of IFNβ or GA who experienced ISRs and who switched or discontinued therapy because of ISRs. Methods The Swiss MS Skin Project was an observational multicenter study. Patients with MS or clinically isolated syndrome who were on the same therapy for at least 2 years were enrolled. A skin examination was conducted at the first study visit and 1 year later. Results The 412 patients enrolled were on 1 of 4 disease-modifying therapies for at least 2 years: IM IFNβ-1a (n = 82), SC IFNβ-1b (n = 123), SC IFNβ-1a (n = 184), or SC GA (n = 23). At first evaluation, ISRs were reported by fewer patients on IM IFNβ-1a (13.4%) than on SC IFNβ-1b (57.7%; P < 0.0001), SC IFNβ-1a (67.9%; P < 0.0001), or SC GA (30.4%; P = not significant [NS]). No patient on IM IFNβ-1a missed a dose in the previous 4 weeks because of ISRs, compared with 5.7% of patients on SC IFNβ-1b (P = 0.044), 7.1% of patients on SC IFNβ-1a (P = 0.011), and 4.3% of patients on SC GA (P = NS). Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy. Similar patterns were observed at 1 year. Conclusions Patients on IM IFNβ-1a had fewer ISRs and were less likely to switch therapies than patients on other therapies. This study may have implications in selecting initial therapy or, for patients considering switching or discontinuing therapy because of ISRs, selecting an alternative option.

Abstract Background Plant hormones play a pivotal role in several physiological processes during a plant's life cycle, from germination to senescence, and the determination of endogenous concentrations of hormones is essential to elucidate the role of a particular hormone in any physiological process. Availability of a sensitive and rapid method to quantify multiple classes of hormones simultaneously will greatly facilitate the investigation of signaling networks in controlling specific developmental pathways and physiological responses. Due to the presence of hormones at very low concentrations in plant tissues (10-9 M to 10-6 M) and their different chemistries, the development of a high-throughput and comprehensive method for the determination of hormones is challenging. Results The present work reports a rapid, specific and sensitive method using ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem spectrometry (UPLC/ESI-MS/MS) to analyze quantitatively the major hormones found in plant tissues within six minutes, including auxins, cytokinins, gibberellins, abscisic acid, 1-amino-cyclopropane-1-carboxyic acid (the ethylene precursor), jasmonic acid and salicylic acid. Sample preparation, extraction procedures and UPLC-MS/MS conditions were optimized for the determination of all plant hormones and are summarized in a schematic extraction diagram for the analysis of small amounts of plant material without time-consuming additional steps such as purification, sample drying or re-suspension. Conclusions This new method is applicable to the analysis of dynamic changes in endogenous concentrations of hormones to study plant developmental processes or plant responses to biotic and abiotic stresses in complex tissues. An example is shown in which a hormone profiling is obtained from leaves of plants exposed to salt stress in the aromatic plant, Rosmarinus officinalis.

Abstract Background Lipocalin 2 (Lcn2) is a bacteriostatic factor that may also modulate cellular function, however, little is known concerning the expression or role of Lcn2 in CNS inflammation. Therefore, here we investigated the regulation and possible function of Lcn2 in the CNS following peripheral lipopolysaccharide (LPS) injection in mice. Methods A murine model for systemic endotoxemia was used in this study. Wild type or Lcn2 KO mice (both genotypes C57BL/6 strain) were given either a single or dual, staggered intraperitoneal injections of purified E. coli LPS or vehicle alone. The brain was examined for the expression and location of Lcn2 mRNA and protein and various markers for neuroinflammation were analyzed. Results Although undetectable under physiological conditions, both Lcn2 mRNA and protein were induced to high levels in the brain after LPS injection. By contrast, RNA corresponding to the putative Lcn2 (termed 24p3R) receptor was present at high levels in the normal brain and remained unaltered by LPS injection. Differences between Lcn2 and 24p3R mRNA expression were found at the anatomic and cellular level. Endothelial cells, microglia and the choroid plexus but not neurons were identified as the main cellular sources for Lcn2 mRNA in the CNS. By contrast, 24p3R mRNA was detected in neurons and the choroid plexus only. Lcn2 protein was found to have a similar cellular localization as the corresponding RNA transcripts with the exception that subsets of neurons were also strongly positive. Various inflammatory, glial, and iron handling markers were analyzed and found to have similar alterations between WT and Lcn2 KO animals. Conclusions 1) Lcn2 production is strongly induced in the CNS by systemic LPS injection, 2) in addition to Lcn2 production at key gateways of bacterial entry to the CNS, neurons may be a target for the actions of Lcn2, which is apparently taken up by these cells, and 3) the cellular functions of Lcn2 in the CNS remain enigmatic.

Abstract Background Uncontrollable aversive events are associated with feelings of helplessness and cortisol elevation and are suitable as a model of depression. The high comorbidity of depression and pain symptoms and the importance of controllability in both conditions are clinically well-known but empirical studies are scarce. The study investigated the relationship of pain experience, helplessness, and cortisol secretion after controllable vs. uncontrollable electric skin stimulation in healthy male individuals. Methods Sixty-four male volunteers were randomly assigned to receive 30 controllable (self-administered) or uncontrollable (experimenter-administered) painful electric skin stimuli. Perceived pain intensity (PPI), subjective helplessness ratings, and salivary cortisol concentrations were assessed. PPI was assessed after stress exposure. For salivary cortisol concentrations and subjective helplessness ratings, areas under the response curve (AUC) were calculated. Results After uncontrollable vs. controllable stress exposure significantly higher PPI ratings (P = 0.023), higher subjective helplessness AUC (P < 0.0005) and higher salivary cortisol AUC (P = 0.004, t-tests) were found. Correlation analyses revealed a significant correlation between subjective helplessness AUC and PPI (r = 0.500, P < 0.0005), subjective helplessness AUC and salivary cortisol AUC (r = 0.304, P = 0.015) and between PPI and salivary cortisol AUC (r = 0.298, P = 0.017). Conclusions The results confirm the impact of uncontrollability on stress responses in humans; the relationship of PPI with subjective helplessness and salivary cortisol suggests a cognitive-affective sensitization of pain perception, particularly under uncontrollable conditions.

Abstract Background Receiver operating characteristic (ROC) curves are useful tools to evaluate classifiers in biomedical and bioinformatics applications. However, conclusions are often reached through inconsistent use or insufficient statistical analysis. To support researchers in their ROC curves analysis we developed pROC, a package for R and S+ that contains a set of tools displaying, analyzing, smoothing and comparing ROC curves in a user-friendly, object-oriented and flexible interface. Results With data previously imported into the R or S+ environment, the pROC package builds ROC curves and includes functions for computing confidence intervals, statistical tests for comparing total or partial area under the curve or the operating points of different classifiers, and methods for smoothing ROC curves. Intermediary and final results are visualised in user-friendly interfaces. A case study based on published clinical and biomarker data shows how to perform a typical ROC analysis with pROC. Conclusions pROC is a package for R and S+ specifically dedicated to ROC analysis. It proposes multiple statistical tests to compare ROC curves, and in particular partial areas under the curve, allowing proper ROC interpretation. pROC is available in two versions: in the R programming language or with a graphical user interface in the S+ statistical software. It is accessible at http://expasy.org/tools/pROC/ under the GNU General Public License. It is also distributed through the CRAN and CSAN public repositories, facilitating its installation.