[Mechanisms of action and clinical application of diuretics in intensive care medicine]. / Wirkmechanismen und klinische Anwendung von Diuretika in der Intensivmedizin.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

Joint Measurement of the

The PROSPECT and STEREO collaborations present a combined measurement of the pure ^{235}U antineutrino spectrum, without site specific corrections or detector-dependent effects. The spectral measurements of the two highest precision experiments at research reactors are found to be compatible with χ^{2}/ndf=24.1/21, allowing a joint unfolding of the prompt energy measurements into antineutrino energy. This ν[over ¯]_{e} energy spectrum is provided to the community, and an excess of events relative to the Huber model is found in the 5-6 MeV region. When a Gaussian bump is fitted to the excess, the data-model χ^{2} value is improved, corresponding to a 2.4σ significance.

Searching for Hidden Neutrons with a Reactor Neutrino Experiment: Constraints from the STEREO Experiment.

Different extensions of the standard model of particle physics, such as braneworld or mirror matter models, predict the existence of a neutron sterile state, possibly as a dark matter candidate. This Letter reports a new experimental constraint on the probability p for neutron conversion into a hidden neutron, set by the STEREO experiment at the high flux reactor of the Institut Laue-Langevin. The limit is p<3.1×10^{-11} at 95% C.L. improving the previous limit by a factor of 13. This result demonstrates that short-baseline neutrino experiments can be used as competitive passing-through-walls neutron experiments to search for hidden neutrons.

Constraints on Elastic Neutrino Nucleus Scattering in the Fully Coherent Regime from the CONUS Experiment.

We report the best limit on coherent elastic scattering of electron antineutrinos emitted from a nuclear reactor off germanium nuclei. The measurement was performed with the CONUS detectors positioned at 17.1 m from the 3.9 GW_{th} reactor core of the nuclear power plant in Brokdorf, Germany. The antineutrino energies of less than 10 MeV assure interactions in the fully coherent regime. The analyzed dataset includes 248.7 kg d with the reactor turned on and background data of 58.8 kg d with the reactor off. With a quenching parameter of k=0.18 for germanium, we determined an upper limit on the number of neutrino events of 85 in the region of interest at 90% confidence level. This new CONUS dataset disfavors quenching parameters above k=0.27, under the assumption of standard-model-like coherent scattering of the reactor antineutrinos.

Accurate Measurement of the Electron Antineutrino Yield of

We report a measurement of the antineutrino rate from the fission of ^{235}U with the STEREO detector using 119 days of reactor turned on. In our analysis, we perform several detailed corrections and achieve the most precise single measurement at reactors with highly enriched ^{235}U fuel. We measure an IBD cross section per fission of σ_{f}=(6.34±0.06[stat]±0.15[sys]±0.15[model])×10^{-43} cm^{2}/fission and observe a rate deficit of (5.2±0.8[stat]±2.3[sys]±2.3[model])% compared to the model, consistent with the deficit of the world average. Testing ^{235}U as the sole source of the deficit, we find a tension between the results of lowly and highly enriched ^{235}U fuel of 2.1 standard deviations.

Can nature conservation and wood production be reconciled in managed forests? A review of driving factors for integrated forest management in Europe.

Integrated forest management (IFM) can help reconcile critical trade-offs between goals in forest management, such as nature conservation and biomass production. The challenge of IFM is dealing with these trade-offs at the level of practical forest management, such as striving for compromises between biomass extraction and habitat retention. This paper reviews some of the driving factors that influence the integration of nature conservation into forest management. The review was conducted in three steps - a literature review, an expert workshop and an expert-based cooperative analysis. Of 38 driving factors identified, three were prioritised by more of the participants than any of the others: two are socio-cultural factors, identity (how people identify with forest) as well as outreach and education, and one is economic - competitiveness in forest value chains. These driving factors correspond to what are considered in the literature as enablers for IFM. The results reveal that targeted, group-oriented, adaptive and innovative policy designs are needed to integrate nature conservation into forest management. Further, the results reveal that a "one-size-fits-all" governance approach would be ineffective, implying that policy instruments need to consider contextually specific driving factors. Understanding the main driving factors and their overall directions can help to better manage trade-offs between biodiversity conservation and biomass production in European forests.

Reviewing the Use of Resilience Concepts in Forest Sciences.

Purpose of Review: Resilience is a key concept to deal with an uncertain future in forestry. In recent years, it has received increasing attention from both research and practice. However, a common understanding of what resilience means in a forestry context and how to operationalise it is lacking. Here, we conducted a systematic review of the recent forest science literature on resilience in the forestry context, synthesizing how resilience is defined and assessed. Recent Findings: Based on a detailed review of 255 studies, we analysed how the concepts of engineering resilience, ecological resilience and social-ecological resilience are used in forest sciences. A clear majority of the studies applied the concept of engineering resilience, quantifying resilience as the recovery time after a disturbance. The two most used indicators for engineering resilience were basal area increment and vegetation cover, whereas ecological resilience studies frequently focus on vegetation cover and tree density. In contrast, important social-ecological resilience indicators used in the literature are socioeconomic diversity and stock of natural resources. In the context of global change, we expected an increase in studies adopting the more holistic social-ecological resilience concept, but this was not the observed trend. Summary: Our analysis points to the nestedness of these three resilience concepts, suggesting that they are complementary rather than contradictory. It also means that the variety of resilience approaches does not need to be an obstacle for operationalisation of the concept. We provide guidance for choosing the most suitable resilience concept and indicators based on the management, disturbance and application context.

Sterile Neutrino Constraints from the STEREO Experiment with 66 Days of Reactor-On Data.

The reactor antineutrino anomaly might be explained by the oscillation of reactor antineutrinos toward a sterile neutrino of eV mass. In order to explore this hypothesis, the STEREO experiment measures the antineutrino energy spectrum in six different detector cells covering baselines between 9 and 11 m from the compact core of the ILL research reactor. In this Letter, results from 66 days of reactor turned on and 138 days of reactor turned off are reported. A novel method to extract the antineutrino rates has been developed based on the distribution of the pulse shape discrimination parameter. The test of a new oscillation toward a sterile neutrino is performed by comparing ratios of cells, independent of absolute normalization and of the prediction of the reactor spectrum. The results are found to be compatible with the null oscillation hypothesis and the best fit of the reactor antineutrino anomaly is excluded at 97.5% C.L.

Airway-centered interstitial fibrosis - an under-recognized subtype of diffuse parenchymal lung diseases.

Airway centered interstitial fibrosis (ACIF) has been recently suggesed as a rare histological pattern of interstitial lung disease of variable etiology and outcome. It is characterized by fibrosis of the respiratory bronchioles and the peribronchiolar interstitium. We describe the clinical features of 13 patients (7 female, mean age 55 years) with histologically proven ACIF in 12 cases and long-term follow up. In ten patients, exogenous agents could be detected (mould n=5, wood n=2, leather exposure n=1, occupational exposure n=2). Two patients had rheumatoid arthritis and 1 patient suffered from recurrent aspiration. In three patients no associated exposure could be detected. Eight patients were never-smokers, while five were ex- smokers. At time of diagnosis patients presented with a moderate restrictive ventilation impairment and sever reduction in diffusion capacity (VC 61%, TLC 66%, DLCOc-SB 38% pred.). All patients were started on immunosuppressive therapy with steroids which were combined with azathioprine in seven and with mycophenolate mofetil in one patient. Median time of follow up was 52 months (2-127 months). Patients with ACIF due to exogenous agents or associated with RA were stable with immunosuppressive therapy. One patient with idiopathic ACIF showed a progressive deterioration within 29 months despite immunosuppression and died while on a waiting-list for lung transplantation. In our experience ACIF is a rare finding, which is relatively frequently observed in the context of hypersensitivity pneumonitis, aspiration and rheumatoid arthritis, while idiopathic ACIF was a minority. In the majority of patients, ACIF showed a favorable long-term outcome with immunosuppressive therapy. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 218-229).

[Endobronchial Ultrasound Guided Needle Aspiration of a Lung Cyst and Eosinophilic Pneumonia]. / EBUS-Punktion einer Lungenzyste und eosinophile Pneumonie.

We report the case of a young male patient with a solitary pulmonary echinococcus cyst. The diagnosis of Cystic Echinococcosis is based on clinical findings, imaging and serology. In the setting of lung cysts the diagnosis can be difficult, particularly as the sensitivity of the serologic tests is lower compared to liver cysts. Bronchoscopic ultrasound of the cystic lesion and respectively the analysis of the cyst aspirate can lead to the diagnosis. In the present case an eosinophilic pneumonia as the result of the puncture has to be discussed.

[Clinical applications of OCT angiography]. / Klinische Anwendungen der OCT-Angiographie.

BACKGROUND: Optical coherence tomography angiography (OCT-A) allows noninvasive, depth-selective visualization of retinal and choroidal vascular networks by detecting the endoluminal blood flow. This results in three-dimensional high-resolution images which are not possible by regular fluorescein angiography in this spatial resolution. Thus, OCT-A can be used to visualize the microperfusion of retinal and choroidal vessels and their alterations due to diverse pathologies and during the course of therapy. Based on several clinical case reports this article gives an overview of the wide range of applications of OCT-A. METHODS: The OCT-A images were obtained with the Spectralis OCT-2 prototype (Heidelberg Engineering, Heidelberg, Germany). This device provides an increased A scan rate of 70 kHz, which allows the generation of high-resolution OCT volume scans. RESULTS: The areas of application are manifold and include neovascular age-related macular degeneration, diabetic retinopathy, retinal vascular occlusion, inflammatory diseases and telangiectasia of various etiologies. The resulting images and their interpretation differ significantly from regular fluorescein angiography. Knowledge of these differences and of the limitations of this novel diagnostic device are of importance for its clinical application. For certain indications, OCT-A may be used as a substitute for invasive fluorescein angiography and provides more detailed information, particularly due to the absence of blockage phenomena, such as pooling or staining. CONCLUSION: The use of OCT-A allows visualization of the microperfusion of the retinal and choroidal vascular networks and their alterations due to diverse diseases in high resolution and with segmentation of different anatomical layers. The exact interpretation of the three-dimensional OCT-A images and their clinical application are currently under clinical evaluation.

[Technical principles of OCT angiography]. / Technische Grundlagen der OCT-Angiographie.

BACKGROUND: Optical coherence tomography angiography (OCT-A) is a new diagnostic non-invasive method by which the vascular structures of the retina and choroid can be visualized three-dimensionally without need for using fluorescence dyes. The technology of OCT-A is an advancement of the OCT. By means of more powerful software and hardware used for OCT-A not only morphological but also retinal and choroidal vascular perfusion analyses can be performed. In this article, the principles and applications of OCT-A are discussed and compared to other non-invasive diagnostic devices for visualization of the retinal and choroidal blood circulation. METHODS: This article is based on a selective literature review and analyses of own data. RESULTS: The advantages of OCT-A include easy application without the need for mydriasis or intravenous injection of fluorescence dyes and also the exact three-dimensional localization of vascular changes. In the case of retinal pathologies there is a considerable difference between software-assisted automatic segmentation and the real architecture of the retina, which must be taken into consideration in the clinical interpretation. CONCLUSION: Of all noninvasive devices for visualization of the retinal and choroidal circulation, OCT-A is the only one which can already be implemented into the clinical routine. With this novel imaging device retinal and choroidal alterations can be visualized in a depth- selective manner and without masking affects, such as pooling or staining phenomena.

[Trauma and psychological distress in dermatological patients]. / Trauma und psychische Belastung bei dermatologischen Patienten.

BACKGROUND: Although seldom diagnosed, post-traumatic stress disorder (PTSD) has a high prevalence in primary and tertiary care. In a consecutive cross-sectional study, the prevalence of traumatic experiences and the severity of post-traumatic symptoms as well as specific characteristics of traumatized patients in the context of the dermatological treatment were examined. PATIENTS AND METHODS: Standardized questionnaires for assessing general psychopathology (Brief Symptom Inventory, BSI), coping with dermatological diseases (Adjustment to Chronic Skin Diseases Questionnaire, MHF) and diagnosis of trauma (Essen Trauma-Inventory, ETI) were used in 221 patients with different skin diseases. RESULTS: In total, 85.1 % of the patients reported at least one potentially traumatic event in their lives, whereby psychometrically in 8.6 % of the cases the diagnostic criteria for a PTSD were met. Patients with suspected PTSD were more impacted by psychopathology, had more problems in coping with their skin diseases and attributed mental stress as having a greater influence on their skin disease than nontraumatized patients or traumatized patients without suspected PTSD. In addition, cumulative traumatization also leads to increased trauma symptomatology and greater difficulties in coping with skin diseases. CONCLUSION: The results emphasize the impact of a comorbid PTSD on a patient's ability to cope with skin diseases and underline the need for the inclusion of the differential diagnosis PTSD in dermatological treatment settings.

[Pulmonary Tuberculosis--Is Surgery still Necessary?]. / Pulmonale Tuberkulose--ist die Chirurgie noch notwendig?

BACKGROUND: Tuberculosis is still one of the most common infectious diseases along with HIV and malaria and therefore represents a serious problem in the health sector. Due to immigrants and refugees, the disease is also present in Europe. The global increase of multidrug resistant tuberculosis leads to a highly significant and current importance of sufficient therapeutic measures. In recent years, this fact has led to a reevaluation of surgical therapy in the context of an interdisciplinary and multimodal treatment of multidrug resistant tuberculosis. In addition, despite an effective treatment of drug sensitive tuberculosis with antibiotics, there are still indications for surgery in the treatment of tuberculosis. Beside massive hemoptysis as an emergency indication for surgical intervention, secondary complications of tuberculosis such as aspergilloma, chronic hemoptysis, pneumothorax, bronchopleural fistula and destroyed lung remain indications for surgery. CONCLUSION: The indication for surgery should always be made in a multimodal therapeutic approach by an interdisciplinary team, taking patient age and functional analysis into account. Effective antibiotic therapy should be performed before and after surgery in order to achieve a sustained treatment success.

Loss of lamin A function increases chromatin dynamics in the nuclear interior.

Chromatin is organized in a highly ordered yet dynamic manner in the cell nucleus, but the principles governing this organization remain unclear. Similarly, it is unknown whether, and how, various proteins regulate chromatin motion and as a result influence nuclear organization. Here by studying the dynamics of different genomic regions in the nucleus of live cells, we show that the genome has highly constrained dynamics. Interestingly, depletion of lamin A strikingly alters genome dynamics, inducing a dramatic transition from slow anomalous diffusion to fast and normal diffusion. In contrast, depletion of LAP2α, a protein that interacts with lamin A and chromatin, has no such effect on genome dynamics. We speculate that chromosomal inter-chain interactions formed by lamin A throughout the nucleus contribute to chromatin dynamics, and suggest that the molecular regulation of chromatin diffusion by lamin A in the nuclear interior is critical for the maintenance of genome organization.

Limits on spin-dependent WIMP-nucleon cross sections from 225 live days of XENON100 data.

We present new experimental constraints on the elastic, spin-dependent WIMP-nucleon cross section using recent data from the XENON100 experiment, operated in the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 224.6 live days×34 kg of exposure acquired during 2011 and 2012 revealed no excess signal due to axial-vector WIMP interactions with 129Xe and 131Xe nuclei. This leads to the most stringent upper limits on WIMP-neutron cross sections for WIMP masses above 6 GeV/c², with a minimum cross section of 3.5×10(-40) cm² at a WIMP mass of 45 GeV/c², at 90% confidence level.

Dark matter results from 225 live days of XENON100 data.

We report on a search for particle dark matter with the XENON100 experiment, operated at the Laboratori Nazionali del Gran Sasso for 13 months during 2011 and 2012. XENON100 features an ultralow electromagnetic background of (5.3 ± 0.6) × 10(-3) events/(keV(ee) × kg × day) in the energy region of interest. A blind analysis of 224.6 live days × 34 kg exposure has yielded no evidence for dark matter interactions. The two candidate events observed in the predefined nuclear recoil energy range of 6.6-30.5 keV(nr) are consistent with the background expectation of (1.0 ± 0.2) events. A profile likelihood analysis using a 6.6-43.3 keV(nr) energy range sets the most stringent limit on the spin-independent elastic weakly interacting massive particle-nucleon scattering cross section for weakly interacting massive particle masses above 8 GeV/c(2), with a minimum of 2 × 10(-45) cm(2) at 55 GeV/c(2) and 90% confidence level.

Restoration of soman-blocked neuromuscular transmission in human and rat muscle by the bispyridinium non-oxime MB327 in vitro.

The standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and oximes is not sufficiently effective against all types of nerve agents. Alternative therapeutic strategies are required and bispyridinium non-oximes, acting as nicotinic antagonists, were identified as promising compounds. A previous study showed that the di(methanesulfonate) salt of the bispyridinium compound MB327 could restore soman-impaired neuromuscular function in vitro and improve survival of sarin, soman and tabun poisoned guinea pigs in vivo. Here, by using the indirect field stimulation technique, the ability of MB327 to counteract soman-impaired neuromuscular transmission was investigated in human intercostal muscle and rat diaphragm preparations. MB327 restored muscle force in a concentration-dependent manner in both species without reactivating soman-inhibited acetylcholinesterase. The therapeutic effect of MB327 could be washed out, indicating a direct effect at the nicotinic receptor level. Also the ability of MB327 to restore respiratory muscle function could be demonstrated for the first time in rat and human tissue. In combination with previous in vitro and in vivo findings MB327 may be considered a promising compound for the treatment of nerve agent poisoning and further studies are needed to identify optimized drug combinations, concentrations and dosing intervals to provide an effective therapy for OP poisoning.

[Giant hamartoma of the lung]. / Riesiges Hamartom der Lunge.

Hamartomas are the most common benign tumors of the lungs and usually present as solitary intraparenchymal lesions a few centimeters in diameter which are detected radiologically as an incidental finding. This article reports on a case of a giant pulmonary hamartochondroma 29 cm in diameter, which impressed preoperatively and intraoperatively as an extrapulmonary neoplasm. The detection of smaller mesenchymal neoplastic lesions in the lungs and pleura is a further special feature of this case.

Propionic acidemia: neonatal versus selective metabolic screening.

BACKGROUND: Whereas propionic acidemia (PA) is a target disease of newborn screening (NBS) in many countries, it is not in others. Data on the benefit of NBS for PA are sparse. STUDY DESIGN: Twenty PA patients diagnosed through NBS were compared to 35 patients diagnosed by selective metabolic screening (SMS) prompted by clinical findings, family history, or routine laboratory test results. Clinical and biochemical data of patients from 16 metabolic centers in Germany, Austria, and Switzerland were evaluated retrospectively. Additionally, assessment of the intelligent quotient (IQ) was performed. In a second step, the number of PA patients who have died within the past 20 years was estimated based on information provided by the participating metabolic centers. RESULTS: Patients diagnosed through NBS had neither a milder clinical course regarding the number of metabolic crises nor a better neurological outcome. Among NBS patients, 63% were already symptomatic at the time of diagnosis, and <10% of all patients remained asymptomatic. Among all PA patients, 76% were found to be at least mildly mentally retarded, with an IQ <69. IQ was negatively correlated with the number of metabolic decompensations, but not simply with the patients' age. Physical development was also impaired in the majority of patients. Mortality rates tended to be lower in NBS patients compared with patients diagnosed by SMS. CONCLUSION: Early diagnosis of PA through NBS seems to be associated with a lower mortality rate. However, no significant benefit could be shown for surviving patients with regard to their clinical course, including the number of metabolic crises, physical and neurocognitive development, and long-term complications.