Search

This work analyzes the appearance of wide-spread deka-MeV solar energetic proton (SEP) events, in particular the arrival of the first protons within ≈ 4.5 – 45 MeV measured at Earth–Sun L1, and their relationship with their relative solar source longitude. The definition of "wide-spread SEP event" for this study refers to events that are observed as a 25 MeV proton intensity increase at near 1 AU locations that are separated by at least 130∘ in solar longitude. Many of these events are seen at all three of the spacecraft, STEREO (Solar-Terrestrial Relations Observatory) A, STEREO B, and SOHO (Solar and Heliospheric Observatory), and may therefore extend far beyond 130∘ in longitude around the Sun. A large subset of these events have already been part of a study by Richardson et al. (Solar Phys., 289, 3059, 2014). The event source region identifications draw from this study; more recent events have also been added. Our focus is on answering two specific questions: (1) What is the maximum longitude over which SEP protons show energy dispersion, i.e., a clear sign of arrival of higher-energy protons before those of lower energy? (2) What implications can be drawn from the ensemble of events observed regarding either direct magnetic connectivity to shocks and/or cross-field transport from the site of the eruption in the onset phase of the event? [ABSTRACT FROM AUTHOR]

Rare-event search experiments located on-surface, such as short-baseline reactor neutrino experiments, are often limited by muon-induced background events. Highly efficient muon vetos are essential to reduce the detector background and to reach the sensitivity goals. We demonstrate the feasibility of deploying organic plastic scintillators at sub-Kelvin temperatures. For the NUCLEUS experiment, we developed a cryogenic muon veto equipped with wavelength shifting fibers and a silicon photo multiplier operating inside a dilution refrigerator. The achievable compactness of cryostat-internal integration is a key factor in keeping the muon rate to a minimum while maximizing coverage. The thermal and light output properties of a plastic scintillation detector were examined. We report first data on the thermal conductivity and heat capacity of the polystyrene-based scintillator UPS-923A over a wide range of temperatures extending below one Kelvin. The light output was measured down to 0.8 K and observed to increase by a factor of 1.61 ± 0.05 compared to 300 K. The development of an organic plastic scintillation muon veto operating in sub-Kelvin temperature environments opens new perspectives for rare-event searches with cryogenic detectors at sites lacking substantial overburden. [ABSTRACT FROM AUTHOR]

The NUCLEUS experiment aims at measuring the coherent elastic scattering of nuclear reactor antineutrinos off nuclei using cryogenic calorimeters. Operating at an overburden of 3 m.w.e., muon-induced backgrounds are expected to be dominant. It is therefore essential to develop an efficient muon veto, with a detection efficiency of more than 99 %. This will be realized in NUCLEUS through a compact cube assembly of plastic scintillator panels. In order to prevent a large unshielded area where the cryostat intersects the shielding arrangement without unnecessarily increasing the induced detector dead time, a novel concept has been investigated, featuring a plastic scintillator-based active muon veto operating inside the NUCLEUS cryostat at sub-Kelvin temperatures. The verification of the key physical aspects of this cryogenic muon veto detector led to the first reported measurements of organic plastic scintillators at sub-Kelvin temperatures. The functionality of the principal scintillation process of organic plastic scintillators at these temperatures has been confirmed. On the basis of these findings, a disk-shape plastic scintillator equipped with wavelength shifting fibers and a silicon photomultiplier to guide and detect the scintillation light has been developed. The NUCLEUS cryogenic muon veto will be the first of its kind to be operated at sub-Kelvin temperatures. [ABSTRACT FROM AUTHOR]

Thanks to dedicated long-term missions like Voyager and GOES over the past 50 years, much insight has been gained on the activity of our Sun, the solar wind, its interaction with the interstellar medium, and, thus, about the formation, the evolution, and the structure of the heliosphere. Additionally, with the help of multi-wavelength observations by the Hubble Space Telescope, Kepler, and TESS, we not only were able to detect a variety of extrasolar planets and exomoons but also to study the characteristics of their host stars, and thus became aware that other stars drive bow shocks and astrospheres. Although features like, e.g., stellar winds, could not be measured directly, over the past years several techniques have been developed allowing us to indirectly derive properties like stellar mass-loss rates and stellar wind speeds, information that can be used as direct input to existing astrospheric modeling codes. In this review, the astrospheric modeling efforts of various stars will be presented. Starting with the heliosphere as a benchmark of astrospheric studies, investigating the paleo-heliospheric changes and the Balmer H α projections to 1 pc , we investigate the surroundings of cool and hot stars, but also of more exotic objects like neutron stars. While pulsar wind nebulae (PWNs) might be a source of high-energy galactic cosmic rays (GCRs), the astrospheric environments of cool and hot stars form a natural shield against GCRs. Their modulation within these astrospheres, and the possible impact of turbulence, are also addressed. This review shows that all of the presented modeling efforts are in excellent agreement with currently available observations. [ABSTRACT FROM AUTHOR]

Introduction: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. Patients and methods: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. Results: In total, 435 cancer patients were included in our analysis. Commonest age category was 76–85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. Conclusion: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions. [ABSTRACT FROM AUTHOR]

Purpose: Automated spectral domain optical coherence tomography (SD-OCT) segmentation algorithms currently do not perform well in segmenting individual intraretinal layers in eyes with Stargardt disease (STGD). We compared selective B-scan segmentation strategies for generating mean retinal layer thickness and preserved area data from SD-OCT scans in patients with STGD1.Methods: Forty-five eyes from 40 Stargardt patients were randomly selected from the ongoing Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. All eyes underwent SD-OCT using a standard macular volume consisting of 1024 × 49 equally spaced B-scans within a 20 × 20 degree field centered on the fovea. All 49 B-scans were segmented manually to quantify total retina, outer nuclear layer (ONL), photoreceptor inner segments, photoreceptor outer segments (OS), and retinal pigment epithelial layer (RPE). Mean thickness and total area were generated using all 49 B-scans (spaced 122 μm apart), 25 B-scans (every other B-scan, spaced 240 μm apart), 17 B-scans (every third scan, 353 μm apart), and 13 B-scans (every fourth scan, 462 μm apart), as well as by using an "adaptive" method where a subset (minimum 25 B-scans) of B-scans that the grader deemed as significantly different from adjacent B-scans were utilized. Mean absolute and percentage errors were calculated for macular thickness and area of different retinal layers for the different B-scan subset selection strategies relative to using all 49 B-scans, which was considered the reference or ground truth.Results: Mean thickness and area measurements were significantly different for any regularly spaced reduction in B-scan density relative to the ground truth. When an adaptive approach was applied using a minimum of half the scans, the differences relative to ground truth were no longer significantly different. The mean percent differences for the area and thicknesses of the various layers ranged from 0.02 to 33.66 (p < 0.05 for all comparisons) and 0.44 to 7.24 (p > 0.05) respectively.Conclusion: Manual segmentation of a subset of B-scans using an adaptive strategy can yield thickness and area measurements of retinal sublayers comparable to the reference ground truth derived from using all B-scans in the volume. These results may have implications for increasing the efficiency of SD-OCT grading strategies in clinical trials for STGD and other related macular degenerative disorders. [ABSTRACT FROM AUTHOR]

The Physics Department of the Technical University of Munich operates a shallow underground detector laboratory in Garching, Germany. It provides ∼160m2 of laboratory space which is shielded from cosmic radiation by ∼6m of gravel and soil, corresponding to a shielding of ∼15m.w.e.. The laboratory also houses a cleanroom equipped with work- and wetbenches, a chemical fumehood as well as a spin-coater and a mask-aligner for photolithographic processing of semiconductor detectors. Furthermore, the shallow underground laboratory runs two high-purity germanium detector screening stations, a liquid argon cryostat and a 3He-4He dilution refrigerator with a base temperature of ≤12-14mK. The infrastructure provided by the shallow laboratory is particularly relevant for the characterization of CaWO4 target crystals for the CRESST-III experiment, detector fabrication and assembly for rare event searches. Future applications of the laboratory include detector development in the framework of coherent neutrino nucleus scattering experiments (ν-cleus) and studying its potential as a site to search for MeV-scale dark matter with gram-scale cryogenic detectors. [ABSTRACT FROM AUTHOR]

In this review, an overview of the recent history of stochastic differential equations (SDEs) in application to particle transport problems in space physics and astrophysics is given. The aim is to present a helpful working guide to the literature and at the same time introduce key principles of the SDE approach via 'toy models'. Using these examples, we hope to provide an easy way for newcomers to the field to use such methods in their own research. Aspects covered are the solar modulation of cosmic rays, diffusive shock acceleration, galactic cosmic ray propagation and solar energetic particle transport. We believe that the SDE method, due to its simplicity and computational efficiency on modern computer architectures, will be of significant relevance in energetic particle studies in the years to come. [ABSTRACT FROM AUTHOR]

This paper summarizes the results obtained by the team 'Heliosheath Processes and the Structure of the Heliopause: Modeling Energetic Particles, Cosmic Rays, and Magnetic Fields' supported by the International Space Science Institute (ISSI) in Bern, Switzerland. We focus on the physical processes occurring in the outer heliosphere, especially at its boundary called the heliopause, and in the local interstellar medium. The importance of magnetic field, charge exchange between neutral atoms and ions, and solar cycle on the heliopause topology and observed heliocentric distances to different heliospheric discontinuities are discussed. It is shown that time-dependent, data-driven boundary conditions are necessary to describe the heliospheric asymmetries detected by the Voyager spacecraft. We also discuss the structure of the heliopause, especially due to its instability and magnetic reconnection. It is demonstrated that the Rayleigh-Taylor instability of the nose of the heliopause creates consecutive layers of the interstellar and heliospheric plasma which are magnetically connected to different sources. This may be a possible explanation of abrupt changes in the galactic and anomalous cosmic ray fluxes observed by Voyager 1 when it was crossing the heliopause structure for a period of about one month in the summer of 2012. This paper also discusses the plausibility of fitting simulation results to a number of observational data sets obtained by in situ and remote measurements. The distribution of magnetic field in the vicinity of the heliopause is discussed in the context of Voyager measurements. It is argued that a classical heliospheric current sheet formed due to the Sun's rotation is not observed by in situ measurements and should not be expected to exist in numerical simulations extending to the boundary of the heliosphere. Furthermore, we discuss the transport of energetic particles in the inner and outer heliosheath, concentrating on the anisotropic spatial diffusion diffusion tensor and the pitch-angle dependence of perpendicular diffusion and demonstrate that the latter can explain the observed pitch-angle anisotropies of both the anomalous and galactic cosmic rays in the outer heliosheath. [ABSTRACT FROM AUTHOR]

We study the temporal intensity profile, or pulse shape, of cosmic ray ground-level enhancements (GLEs) by calculating the rise (τr) and decay (τd) times for a small subset of all available events. Although these quantities show very large inter-event variability, a linear dependence of τd ≈ 3.5τr is found. We interpret these observational findings in terms of an interplanetary transport model, thereby including the effects of scattering (in pitch-angle) as these particles propagate from (near) the Sun to Earth. It is shown that such a model can account for the observed trends in the pulse shape, illustrating that interplanetary transport must be taken into account when studying GLE events, especially their temporal profiles. Furthermore, depending on the model parameters, the pulse shape of GLEs may be determined entirely by interplanetary scattering, obscuring all information regarding the initial acceleration process, and hence making a classification between impulsive and gradual events, as is traditionally done, superfluous. [ABSTRACT FROM AUTHOR]

The CRESST-II (Cryogenic Rare Event Search with Superconducting Thermometers) experiment, whose second phase has been successfully finished in summer 2015, aims at the direct detection of dark matter particles. The intrinsic radiopurity of CaWO $$_4$$ crystals, the capability to reject recoil events from alpha-surface contamination, and the energy threshold were significantly improved compared to previous runs of the experiment. A moderate exposure of 29 kg-days acquired by one $$\sim $$ 250 g CaWO $$_4$$ detector provides competitive limits on the spin-independent dark matter particle-nucleon cross section and probes a new region of parameter space for dark matter particle masses below 3 GeV/c $$^2$$ . The potential for low-mass dark matter particle search can be further exploited by a new detector design planned for CRESST-III. We describe the experimental strategy for the near future and give projections for the sensitivity. [ABSTRACT FROM AUTHOR]

CRESST-II is a direct dark matter experiment that uses scintillating calorimeters to detect WIMP-induced nuclear scatter processes. Heat and light signals are read out with tungsten transition edge sensors (TESs) that are optimized toward their sensitivity to non-thermal phonons. The usage of superconducting thin film structures (e.g., aluminum) serving as phonon collectors to increase the collection area for this signal component is an approach to improve the sensitivity of the TES. The performance of the phonon collectors depends on the material properties and the quality achieved in the production process. We optimized the size of the phonon collectors for the given quality of CRESST-II light detectors. The diffusion lengths measured in this work are $$\mathcal {O}$$ (1 mm) and show a strong correlation to the Residual Resistivity Ratio of the respective films. First tests of CRESST-II light detectors with larger as well as thicker phonon collectors individually show improvements in the measured pulse height of 30 %. [ABSTRACT FROM AUTHOR]

Introduction: In the time of increasing resistance and paucity of new drug development there is a growing need for strategies to enhance rational use of antibiotics in German and Austrian hospitals. An evidence-based guideline on recommendations for implementation of antibiotic stewardship (ABS) programmes was developed by the German Society for Infectious Diseases in association with the following societies, associations and institutions: German Society of Hospital Pharmacists, German Society for Hygiene and Microbiology, Paul Ehrlich Society for Chemotherapy, The Austrian Association of Hospital Pharmacists, Austrian Society for Infectious Diseases and Tropical Medicine, Austrian Society for Antimicrobial Chemotherapy, Robert Koch Institute. Materials and methods: A structured literature research was performed in the databases EMBASE, BIOSIS, MEDLINE and The Cochrane Library from January 2006 to November 2010 with an update to April 2012 (MEDLINE and The Cochrane Library). The grading of recommendations in relation to their evidence is according to the AWMF Guidance Manual and Rules for Guideline Development. Conclusion: The guideline provides the grounds for rational use of antibiotics in hospital to counteract antimicrobial resistance and to improve the quality of care of patients with infections by maximising clinical outcomes while minimising toxicity. Requirements for a successful implementation of ABS programmes as well as core and supplemental ABS strategies are outlined. The German version of the guideline was published by the German Association of the Scientific Medical Societies (AWMF) in December 2013. [ABSTRACT FROM AUTHOR]

The cryogenic dark matter experiment CRESST-II aims at the direct detection of WIMPs via elastic scattering off nuclei in scintillating CaWO $$_4$$ crystals. We present a new, highly improved, detector design installed in the current run of CRESST-II Phase 2 with an efficient active rejection of surface-alpha backgrounds. Using CaWO $$_4$$ sticks instead of metal clamps to hold the target crystal, a detector housing with fully-scintillating inner surface could be realized. The presented detector (TUM40) provides an excellent threshold of $${\sim }0.60$$ keV and a resolution of $$\sigma \,{\approx }\,0.090$$ keV (at 2.60 keV). With significantly reduced background levels, TUM40 sets stringent limits on the spin-independent WIMP-nucleon scattering cross section and probes a new region of parameter space for WIMP masses below 3 GeV/c $$^2$$ . In this paper, we discuss the novel detector design and the surface-alpha event rejection in detail. [ABSTRACT FROM AUTHOR]

Fractionated ionizing radiation combined with surgery or hormone therapy represents the first-choice treatment for medium to high-risk localized prostate carcinoma. One of the main reasons for the failure of radiotherapy in prostate cancer is radioresistance and further dissemination of surviving cells. In this study, exposure of four metastasis-derived human prostate cancer cell lines (DU145, PC-3, LNCaP and 22RV1) to clinically relevant daily fractions of ionizing radiation (35 doses of 2 Gy) resulted in generation of two radiation-surviving populations: adherent senescent-like cells expressing common senescence-associated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2 and Nanog. While a subset of the radiation-surviving adherent cells resumed proliferation shortly after completion of the irradiation regimen, the non-adherent cells started to proliferate only on their reattachment several weeks after the radiation-induced loss of adhesion. Like the parental non-irradiated cells, radiation-surviving re-adherent DU145 cells were tumorigenic in immunocompromised mice. The radiation-induced loss of adhesion was dependent on expression of Snail, as siRNA/shRNA-mediated knockdown of Snail prevented cell detachment. On the other hand, survival of the non-adherent cells required active Erk signaling, as chemical inhibition of Erk1/2 by a MEK-selective inhibitor or Erk1/2 knockdown resulted in anoikis-mediated death in the non-adherent cell fraction. Notably, whereas combined inhibition of Erk and PI3K-Akt signaling triggered cell death in the non-adherent cell fraction and blocked proliferation of the adherent population of the prostate cancer cells, such combined treatment had only marginal if any impact on growth of control normal human diploid cells. These results contribute to better understanding of radiation-induced stress response and heterogeneity of human metastatic prostate cancer cells, document treatment-induced plasticity and phenotypically distinct cell subsets, and suggest the way to exploit their differential sensitivity to radiosensitizing drugs in overcoming radioresistance. [ABSTRACT FROM AUTHOR]

The CRESST experiment aims at a direct detection of WIMP dark matter (DM) using scintillating CaWO $$_4$$ crystals operated as phonon detectors at mK temperatures. An important feature of the experiment is the active background discrimination technique exploiting the different light outputs depending on the kind of particle interaction. The reduced light yield of nuclear recoils compared to electron recoils is quantified by quenching factors (QFs). The precise measurement of the QFs and thus the identification of the individual recoiling nucleus in the multi-target material CaWO $$_4$$ is crucial for neutron background discrimination and assuming a positive DM signal would allow to a certain extent WIMP-mass spectroscopy. At the Munich tandem accelerator a dedicated neutron scattering facility has been set up to measure the QFs of CaWO $$_4$$ , in particular that of tungsten, at mK temperatures. Monoenergetic neutrons (11 MeV) produced by the accelerator are scattered off a CRESST-like detector module that is operated in a dilution refrigerator. In this setup, the recoiling nucleus (O, Ca and W) is identified by time-of-flight measurement in liquid-scintillator detectors placed at fixed scattering angles. The QF of W could be determined with unprecedented accuracy at mK temperatures and under realistic measurement conditions: $$QF_W=0.0196\pm 0.0022$$ (preliminary value). [ABSTRACT FROM AUTHOR]

The recent 2009 solar-minimum period was characterized by a record-setting high Galactic cosmic-ray flux observed at Earth. This, along with the unexpected low heliospheric magnetic-field magnitude, caused this period to be characterized as unusual compared with previous minimum epochs. In this work, selected solar-activity proxies and corresponding cosmic-ray observations for the past five solar cycles are compared with each other, and we identify those that showed unusual behaviour during the 2009 solar-minimum modulation period. Using a state-of-the-art numerical-modulation model, the proton-intensity spectra for the past solar minima are reproduced to establish which of the transport processes might be considered the main cause of this unusually high cosmic-ray flux. It is found that diffusion was more prominent during 2009 so that drift effects on the modulation of cosmic rays in the heliosphere were less evident than during previous solar-polarity epochs. However, particle drifts still occurred and because of these drift effects, the proton spectrum is predicted to be even higher during the coming A>0 solar-minimum period. [ABSTRACT FROM AUTHOR]

Scintillating CaWO $$_4$$ single crystals are a promising multi-element target for rare-event searches and are currently used in the direct dark matter experiment CRESST (Cryogenic Rare Event Search with Superconducting Thermometers). The relative light output of different particle interactions in CaWO $$_4$$ is quantified by quenching factors (QFs). These are essential for an active background discrimination and the identification of a possible signal induced by weakly interacting massive particles (WIMPs). We present the first precise measurements of the QFs of O, Ca and W at mK temperatures by irradiating a cryogenic detector with a fast neutron beam. A clear energy dependence of the QF of O and, less pronounced, of Ca was observed for the first time. Furthermore, in CRESST neutron-calibration data a variation of the QFs among different CaWO $$_4$$ single crystals was found. For typical CRESST detectors the QFs in the region-of-interest (10-40 keV) are $$\hbox {QF}_\mathrm{O}^\mathrm{ROI}=(11.2\pm 0.5)$$ %, $$\hbox {QF}_\mathrm{Ca}^\mathrm{ROI}=(5.94\pm 0.49)$$ % and $$\hbox {QF}_\mathrm{W}^\mathrm{ROI}=(1.72\pm 0.21)$$ %. The latest CRESST data (run32) is reanalyzed using these fundamentally new results on light quenching in CaWO $$_4$$ having moderate influence on the WIMP analysis. Their relevance for future CRESST runs and for the clarification of previously published results of direct dark matter experiments is emphasised. [ABSTRACT FROM AUTHOR]

Purpose: Simple, valid, and evidence-based indicators to measure the quality of antimicrobial prescribing in acute-care hospitals are urgently needed and increasingly requested by policymakers. The aim of this study was to develop new consensus quality indicators (QIs) for hospital antibiotic stewardship (ABS) and infection management which will be further evaluated for internal quality management and external quality assessment in Germany. Methods: Based on an extensive literature review, the Austrian-German hospital ABS Guideline Committee and selected members of the German ABS Expert Network discussed and drafted a list of 99 potential indicators for hospitals that reflect structural prerequisites for ABS (35 items), ABS core activities (18 items), additional ABS measures (5 items), and process of care indicators (both generic and disease-specific-12 and 29 items, respectively). Questionnaires were mailed to German ABS experts and healthcare professionals with further education in ABS. Participants scored (on a nine-point Likert scale) relevance (clinical, ecological/resistance, economical/expenses) and presumed practicability (six categories: clarity of definition, effort to collect data, barrier to implementation, verifiability, suitability for external quality assessment, quality gap), taking into account their local work environment. The scores were processed according to the RAND/UCLA appropriateness method, and QIs were judged relevant if the median (clinical + ecological and/or economical) scores were >6. The indicators thus assessed to be potentially relevant were then filtered according to their practicability. Highly relevant QIs with borderline practicability scores and items with disagreements and overlapping areas were re-discussed in a final multidisciplinary panel consensus workshop convened in November 2012. Results: Of the 340 questionnaires that were mailed, 75 questionnaires were completed and returned. Of 99 initially proposed items, 32 were excluded due to insufficient scores. Of the remaining 67 items, 21 structural and 21 process of care QIs were finally selected, including four QIs with high clinical and ecological but limited economical relevance, and three QIs with high clinical and economical but limited ecological relevance. Among the selected QIs, efforts to collect data and implementation barriers were scored as suboptimal in many cases. Conclusions: A catalog of consensus structural and process of care ABS-QIs was established. These should undergo further pilot and feasibility studies in the German hospital healthcare sector. The panelists were most critical regarding resource use/complexity issues and presumed implementation barriers. How this may limit applicability of QIs remains to be determined. [ABSTRACT FROM AUTHOR]

Objectives: Early broad-spectrum antimicrobial treatment reduces mortality in patients with septic shock. In a multicenter, prospective observational study, we explored whether delayed appropriate antimicrobial therapy (AAT) influences outcome in Staphylococcus aureus bloodstream infection (SAB). Methods: Two hundred and fifty-six patients with SAB from ten German study centers were enrolled and followed for 3 months. Predisposing factors, clinical features, diagnostic procedures, antimicrobial therapy, and outcome were recorded. The appropriateness of antimicrobial therapy was judged by a trained physician based on in vitro activity, dosage, and duration of therapy. Therapy was considered to be delayed when more than 24 h elapsed between the first positive blood culture and the start of appropriate therapy. The association of delayed therapy with overall mortality and SAB-related events (i.e., attributable mortality or late SAB-related complications) was assessed by crosstabulation and propensity score-based logistic regression. Results: One hundred and sixty-eight patients received AAT during their hospital stay, of whom 42 (25 %) received delayed AAT. The overall mortality and the occurrence of severe sepsis or septic shock were lower in patients with delayed AAT, pointing towards confounding by indication. Adjusted 90-day mortality (adjusted odds ratio [OR] 0.91, 95 % confidence interval [CI] [0.39-2.13], p 0.82) and SAB-related events (adjusted OR 1.46, 95 % CI [0.47-4.51], p 0.52) also failed to show a significant impact of delayed AAT on outcome. Conclusion: In patients with SAB, early AAT may not improve survival. However, confounding by indication is a major challenge when analyzing and interpreting observational studies on the impact of delayed AAT. [ABSTRACT FROM AUTHOR]

The light yield of scintillating crystals which is quantified by light Quenching Factors (QFs) strongly depends on the kind of interaction in the crystal. For Dark Matter experiments like CRESST the precise knowledge of QFs is crucial for the discrimination of background events from possible WIMP signals. At the tandem accelerator of the Maier-Leibnitz-Laboratorium (MLL) in Garching a low-temperature scattering facility was set up, which in its current phase aims at the determination of the QFs of O, Ca, and W in CaWO crystals as used in the CRESST experiment. A CRESST detector module consists of a 300 g CaWO target crystal operated as a phonon detector and a separate silicon-on-sapphire (SOS) light detector to detect the corresponding scintillation light simultaneously. In order to disentangle the light yield corresponding to O, Ca and W recoils, monoenergetic neutrons (11 MeV) produced by the accelerator are scattered off an especially developed CRESST-like detector module, which is operated at mK temperatures in a dilution refrigerator. Arrays of liquid-scintillator detectors placed at fixed scattering angles allow one to identify the recoiling nuclei by a neutron time-of-flight measurement. The unique facility is suited for the characterization of different detector materials and will be a powerful tool also for the future multi-material experiment EURECA. We report on the experimental approach, the low-temperature setup and present first results. [ABSTRACT FROM AUTHOR]

Drifts are one of the major cosmic ray modulation mechanisms in the heliosphere. Three types of drifts occur in the background heliospheric magnetic field, namely curvature, gradient and current sheet drifts. The last component occurs because of the switch in magnetic field polarity across the heliospheric current sheet and is the main topic of study. We discuss and implement a new approach to model drifts in a numerical modulation model. The model employs stochastic differential equations to solve the relevant transport equation in five (three spatial, energy and time) dimensions. What is of interest is the fact that the model can handle current sheet tilt angles up to the theoretical maximum of α=90° and still remain numerically stable. We use the additional insights gained from the numerical model to investigate the effectiveness of drifts along the current sheet by examining the relationship between the current sheet path length and the cosmic ray propagation time. It is found that diffusion can disrupt the drift process very effectively, leading to diffusive short circuiting of the current sheet by the cosmic rays. [ABSTRACT FROM AUTHOR]

There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.Cancer Gene Therapy (2006) 13, 1072–1081. doi:10.1038/sj.cgt.7700981; published online 28 July 2006 [ABSTRACT FROM AUTHOR]

Problemstellung: Bericht über einen Patienten, der im postoperativen Verlauf nach radiärer Optikoneurotomie (RON) einen Gesichtsfelddefekt sowie ein zystoides Makulaödem entwickelte. Patienten und Methode: Die RON ist ein neues Verfahren zur operativen Behandlung der Zentralvenenthrombose, das von Opremcak eingeführt wurde. Wir berichten über einen 32-jährigen Patienten, der sich mit einer einseitigen, akut aufgetretenen Zentralvenenthrombose bei uns vorgestellt hatte. Nach Ursachenabklärung und ausführlicher Diskussion wurde bei diesem Patienten eine radiäre Optikoneurotomie (RON) durchgeführt. Dabei wurde im Rahmen einer Parsplana-Vitrektomie (ppV) nach der Induktion einer hinteren Glaskörperabhebung im nasalen Bereich der Papilla nervi optici mit einem speziellen intraokulären Stilett eine radiäre Inzision vorgenommen. Der intraoperative und unmittelbar postoperative Verlauf war komplikationslos. Ergebnisse: Im Laufe der postoperativen Nachbeobachtungszeit von 6 Monaten entwickelte sich ein zystoides Makulaödem, das von einer massiven epiretinalen Gliose begleitet war. Ebenfalls entwickelte sich ein nasaler Nervenfaserbündeldefekt, der im Goldmann-Gesichtsfeld in seiner Entwicklung dokumentiert werden konnte. Schlussfolgerung: Bei jungen Patienten kann sich nach RON ein zystoides Makulaödem mit epiretinaler Gliose entwickeln. Im vorliegenden Fall kann jedoch nicht ausgeschlossen werden, dass sich dieses zystoide Makulaödem unabhängig vom operativen Eingriff ebenfalls entwickelt hätte. Dagegen ist der Gesichtsfelddefekt von Lokalisation und Ausprägung her korrespondierend zu der Inzisionsstelle der RON und muss als schwere Komplikation nach diesem invasiven Verfahren angesehen werden. Purpose: To report on a patient that developped a visual field defect and a cystoid macular edema after radial optic neuropathy (RON). Patient and method: RON is a new procedure that was introduced by Opremcak for surgical management of central retinal vein occlusion (CRVO). We report on a 32-year old male patient, who was referred with a unilateral acute CRVO. A RON was performed in a typical way after induction of a posterior hyloid detachment. The intraoperative and immediate postoperative period was uneventful. Results: Within 6 months after surgery a cystoid macular edema developed, which was accompanied by a massive macular pucker. Parallely a nerve fiber bundle layer defect developed which could be well documented in the visual field examinations by Goldmann perimetry. Conclusion: After RON a cystoid macular edema with epiretinal membranes may develop, especially in young patients. However, it is conceivable that this macular pucker would have also developed following the CRVO without a RON-intervention. The visual field defect is corresponding to the incision site of RON and hence is attributable to the procedure itself and must be seen as a severe complication of RON. [ABSTRACT FROM AUTHOR]

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In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1x106 CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided =grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of =grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.Bone Marrow Transplantation (2003) 31, 121-128. doi:10.1038/sj.bmt.1703803 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine long-term safety and efficacy for weight loss of an herbal Ma Huang and Kola nut supplement (90/192 mg/day ephedrine alkaloids/caffeine). DESIGN: Six-month randomized, double-blind placebo controlled trial. SUBJECTS: A total of 167 subjects (body mass index (BMI) 31.8±4.1 kg/m²) randomized to placebo (n=84) or herbal treatment (n = 83) at two outpatient weight control research units. MEASUREMENTS: Primary outcome measurements were changes in blood pressure, heart function and body weight. Seco'ndary variables included body composition and metabolic changes. RESULTS: By last observation carried forward analysis, herbal vs placebo treatment decreased body weight (-5.3±5.0 vs -2.6±3.2 kg, P < 0.001), body fat (-4.3 ± 3.3 vs -2.7±2.8 kg, P=0.020) and LDL-cholesterol(-8±20 vs 0±17mg/dl, P=0.013), and increased HDL-cholesterol (+2.7±5.7 vs -0.3±6.7mg/dl, P=0.004). Herbal treatment produced small changes in blood pressure variables (+3 to -5 mmHg, P ≤ 0.05), and increased heart rate (4 ± 9 vs -3 ± 9 bpm, P < 0.001), but cardiac arrhythmias were not increased (P > 0.05). By self-report, dry mouth (P < 0.01), heartburn (P < 0.05), and insomnia (P < 0.01 ) were increased and diarrhea decreased (P < 0.05). Irritability, nausea, chest pain and palpitations did not differ, nor did numbers of subjects who withdrew. CONCLUSION: In this 6-month placebo-controlled trial, herbal ephedra/caffeine (90/192 mg/day) promoted body weight and body fat reduction and improved blood lipids without significant adverse events. [ABSTRACT FROM AUTHOR]

AIM:: To explore the relationship between smoking and dieting in a cross-sectional nationally representative sample of young adolescents. METHODS:: Smoking was assessed by serum cotinine concentrations in 1132 adolescents aged 12–18 y enrolled in the NHANES III study. Information on adolescents' weight loss attempts were obtained by questionnaire. Normal weight was defined as a body mass index (BMI) less than the 85th percentile for age and gender. Overweight was defined as a BMI equal to or greater than the 85th percentile for age and gender. Nutritional intake was assessed with a 24 h recall and food frequency questionnaire. RESULTS:: There was a two-fold increase in smoking among normal-weight adolescent girls who reported trying to lose weight (23.7% vs 12.6%, P<0.01). In contrast, prevalence of smoking was similar among overweight adolescent girls who tried to lose weight compared to those who did not (15.8% vs 14.1%, P=0.76). Similar trends were observed in boys. However, overweight boys who were trying to lose weight were less likely to smoke than overweight boys who were not trying to lose weight (9.8% vs 24.5%, P<0.05). There were no differences in body weight, BMI, caloric intake or fat intake among smokers and non-smokers. However, smokers reported eating less fruit and vegetables compared to non-smokers, and were over five times more likely to drink alcohol compared to non-smokers (odds ratio: ≥1×/month, 5.28 (3.82–7.28), ≥4×/month, 5.29 (3.58–7.82). CONCLUSION:: Tobacco use is common among normal weight adolescents trying to lose weight. Tobacco use is also associated with a cluster of other unhealthy dietary practices in adolescents.International Journal of Obesity (2001) 25, 1381–1385 [ABSTRACT FROM AUTHOR]

The development of hepatic veno-occlusive disease following bone marrow transplantation is associated with high-dose combination cytoreductive therapy. Experimental models have suggested that drug-induced injury to hepatic sinusoidal endothelial cells is involved in the pathogenesis of this syndrome. Hyaluronic acid is a polysaccharide that is metabolized, almost exclusively, by hepatic sinusoidal endothelial cells. The aim of the present study was to evaluate serum hyaluronic acid as a marker for endothelial cell injury in patients with veno-occlusive disease following bone marrow transplantation. Hyaluronic acid was measured in sera from patients with and without veno-occlusive disease using an enzyme-linked protein binding assay. Mean peak serum hyaluronic acid levels were significantly greater in patients who had a diagnosis of VOD compared to those transplant patients who did not, 1173.4 ± 982.9 vs 444.9 ± 735.6 ng/ml (P = 0.01). Serial serum samples obtained from a separate cohort of patients also demonstrated that serum hyaluronic acid levels were higher in patients with moderate or severe veno-occlusive disease compared to those with none or mild disease at days 7, 17 and 25 following transplantation (greatest difference at day 25: 366 ± 327 vs126 ± 151, P = 0.01). Serum hyaluronic acid levels are increased in veno-occlusive disease and increase over time in patients with severe disease. Further studies are required to determine if elevated serum hyaluronic acid levels are due to decreased clearance by injured hepatic sinusoidal endothelial cells or increased production from early hepatic fibrogenesis associated with the acute liver injury. Bone Marrow Transplantation (2001) 27, 635–639. [ABSTRACT FROM AUTHOR]

Objectives: To determine outcome and changes in health-related quality of life (QOL) in medical intensive care patients.Design and Setting: Prospective comparison of QOL before and 6 months after intensive care unit (ICU) admission in a 12-bed noncoronary medical ICU of a university hospital.Patients: All 325 consecutively admitted adult patients who spent at least 24 h on the ICU were eligible.Measurements and Results: QOL measurements were collected before and 6 months after ICU admission. Comorbidity classified by the Charlson index was 2.44 +/- 1.96. Mean stay in the ICU was 10.4 +/- 15.1 days, mean Acute Physiology and Chronic Health Evaluation II score was 23 +/- 10. Cumulative mortality was: ICU 24 %, hospital 34 %, 6 months 43 %. Relative to baseline, follow-up interviews of 185 survivors revealed no significant changes in the overall QOL score (p = 0.93). The subscales basic physiological activities (p = 0.07) and normal daily activities (p = 0.15) showed a nonsignificant deterioration. A significant improvement was noted for the domain emotional state (p = 0.013).Conclusions: Six months after admission to a medical ICU most survivors had regained their preadmission health-related QOL. Multivariate analysis showed that preadmission QOL, age, and severity of illness were most strongly associated with follow-up QOL. Of the survivors 86 % were living at home, and all but one of those previously in employment had returned to their former work. Most patients (94%) would undergo ICU treatment again if necessary. [ABSTRACT FROM AUTHOR]

Objectives: To investigate changes in the use of PTCA application in respect to morbidity, gender, region and age, and to investigate the morbidity as related to geographical variation.Study design: Retrospective record linkage study.Setting: All hospitals and cardiological centres (n=156) which performed the Minimum Basic Data Set (MBDS).Patients: All Austrian residents who were diagnosed for myocardial infarction, coronary heart disease or angina pectoris in 1993–1995 (1993: n=73.077; 1994: n=80.173; 1995: n=84.896).Measurements and main results: The intervention rate (IR=PTCA/indication) increased from 0.03–0.04 (33%) between 1993 and 1995 with differences in genders (males: 24%, females: 27.7%) and regions (Vorarlberg: -7.5%, Burgenland: 65.3%). Male morbidity started to increase at about 60 y and female morbidity at about 70 y. Morbidity as a demand factor did not correlate with PTCA application. The intervention rate was significantly lower for females in Austria in general (P<0.001) as it was in every Federal State (P<0.001). This pattern was constant during 1993–1995 with the highest difference in Salzburg and the lowest in Styria. Austrian men were about three times more likely to have received PTCA application than women (crude Odds Ratio=2.8, 95% CI=2.6–3, P-value <0.001). Logistic regression modelling revealed age as main confounder (adjusted Odds Ratio=1.36, 95% CI=1.31–1.42, P<0.001). The ≥5% intervention rate peak was between 30–75 y for males and between 30–65 y for females whereas morbidity of ≥1% started for males at about 50 y and for females at about 60 y. Marked geographical differences of the intervention rate were observed (Upper Austria, Salzburg IR=0.07, Styria IR=0.02) but could not be explained by the demand factor morbidity (Pearson’s correlation coefficients 1993: 0.039, P=0.71; 1994: 0.155, P=0.133; 1995: 0.087, P=0.399).Conclusions: The highest intervention... [ABSTRACT FROM AUTHOR]

AIM: To explore the relationship between self-reported weight and height to actual weight and height in a crosssectional nationally representative sample of young adolescents. METHODS: Weights and heights were obtained on 1932 adolescents aged 12-16y enrolled in the NHANES III study. Self-reported weights and heights were available on 1657 of the adolescents (86%). RESULTS: Correlation between self-reported weight and actual weight ranged between 0.87 and 0.94, depending on gender or race. However, self-reported weights were significantly lower than measured weights among girls, compared to boys (P< 0.001). Correlation between self-reported height and actual height ranged from 0.82-0.91. There were no differences in the accuracy of self-reported heights among boys and girls or racial groups. Differences between actual weight and self-reported weight were significantly greater for obese children compared with nonobese children (P < 0.001). Nevertheless, the use of self-reported weight and height resulted in the correct classification of weight status in 94% of children. As a result, small differences in self-reported weights and heights had no impact in assessing obesity related morbidities. CONCLUSION: Influences of gender and racial biases in reporting of weight and height were relatively small. Selfreported heights and weights were extremely reliable for the predicting obesity related morbidities and behaviours. [ABSTRACT FROM AUTHOR]

Many children with esophagitis demonstrate histological changes without gross evidence of esophagitis by esophagoscopy. The effect of omeprazole on the histological healing of esophagitis in children is unknown. Therefore, the aim of this study was to determine the effect of omeprazole on refractory histological esophagitis in pediatric patients. Eighteen patients with histological evidence of esophagitis and recurrent symptoms despite therapy with H2-receptor antagonists and prokinetic agents were prospectively treated with omeprazole. Dosing was adjusted by monitoring intragastric pH, and esophagoscopy was repeated after 8-12 weeks of omeprazole treatment. Two patients did not complete the study due to either worsening symptoms or hypergastrinemia. Of the remaining patients, 76% were asymptomatic with omeprazole treatment and 24% reported improvement in their symptoms. Approximately 40% demonstrated complete histological healing of their esophagitis. Three patients (17%) had persistent elevations in serum gastrin levels while on omeprazole treatment, which was associated with both younger patient age and higher omeprazole dosing; however, all elevated gastrin levels returned to normal after discontinuation of the medication. All patients had recurrence of their symptoms after completing a course of omeprazole, even patients with complete histological healing. Omeprazole is efficacious in treating children with esophagitis refractory to H2-receptor antagonist and prokinetic agents. However, none of the patients were able to discontinue acid suppressive therapy even after documented healing of their esophagitis. [ABSTRACT FROM AUTHOR]

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450–480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes ( > 1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations. [ABSTRACT FROM AUTHOR]

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In arena experiments with the walking fruit fly, we found a remarkable persistence of orientation toward a landmark that disappeared during the fly's approach. The directional stability achieved by `after-fixation' allows a fly to continue pursuit under natural conditions, where a selected target is frequently concealed by surrounding structures. The persistence of after-fixation was investigated in Buridan's paradigm, where a fly walks persistently back and forth between two inaccessible landmarks. Upon disappearance of a selected target, the flies maintained their intended course for more than 15 body lengths of approximately 2.5 mm in about 50% of the trials. About 13% even exceeded 75 body lengths. About 88% of the approaches clustered in equal portions around peaks at 2.4 s and 8.6 s. About 12% of the approaches persisted even longer. In contrast, a single peak at about 2.2 s is sufficient to describe the persistence of orientation in a random walk. The ability to pursue an invisible landmark is disturbed neither by a transient angular deviation from the course toward this landmark, when this target disappeared, nor by a distracting second landmark. Accordingly, after-fixation seems to require an internal representation of the direction toward the concealed target, and idiothetical course control to maintain this direction. [ABSTRACT FROM AUTHOR]

Leg coordination of Drosophila melanogaster was studied using frame-by-frame film analysis. Results are compared to those for other walking insects and their relevance in screens for locomotor mutants is discussed. [ABSTRACT FROM AUTHOR]

The π N charge-exchange forward scattering amplitude has been recalculated, using the most recent total cross section data, charge independence and the forward dispersion relation. In general the prediction agrees rather well with the data, but there are several discrepancies which are considerably larger than the errors. Some of these discrepancies follow from the fact that a structure at small ¦ t¦ has been ignored in the extrapolation. - The new fit gives an accurate value for the subtraction constant of the integral. It agrees with the evaluation of the unsubtracted integral at threshold, if, at high energies, the Regge behaviour for σ(π p)-σ(π p) is inserted. This result favours the validity of Pomeranchuk's theorem. - An improved value for f cannot be obtained at present because of the uncertainty following from charge-dependent effects at low energies. [ABSTRACT FROM AUTHOR]

The total cross sections up to 65 GeV/c and the experimental real parts of the isospin even πN forward amplitude are compatible with the dispersion relation. However the arguments which led to the introduction of the P′ Regge pole ( α≈0.5) are not valid. The data are compatible with the existence of the integral in Lehmann's sum rule, which implies a finite real part D(∞) at infinity. - The isospin odd combination σ is still consistent with the reggeized ρ-exchange model and with Pomeranchuk's theorem. [ABSTRACT FROM AUTHOR]

It is shown that the assumption of an unsubtracted fixed- t dispersion relation for the isospin even πN amplitude A is compatible with all data. The prediction for the subtraction function agrees reasonably well with independent determinations. The assumption has the consequence that the ratio of the s-channel helicity flip and non flip amplitudes vanishes in the high energy limit. [ABSTRACT FROM AUTHOR]