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Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P =.23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P

Background: To determine the role of sub-retinal fluid in age-related macular degeneration concerning the long-term incidence of macular atrophy and clinical outcomes in eyes treated with anti-vascular endothelial growth factor therapy using a treat & extend regimen. Methods: All patients with[for full text, please go to the a.m. URL], 7th International Symposium on AMD: Age-related Macular Degeneration - Understanding Pathogenetic Mechanisms of Disease

Fragestellung: Subretinale Flüssigkeit wird vielen Studien zur neovaskulären AMD als protektiver Faktor gegen makuläre Atrophie diskutiert. Allerdings fehlen Langzeitdaten, um dies zu bestätigen. Methoden: Alle Augen, die zwischen 2014 und 2016 an der Universitäts-Augenklinik[zum vollständigen Text gelangen Sie über die oben angegebene URL], 32. Jahrestagung der Retinologischen Gesellschaft

We report inelastic neutron scattering experiments in Ca2Y2Cu5O10 and map out the full one magnon dispersion which extends up to a record value of 53 meV for frustrated ferromagnetic (FM) edge-sharing CuO2 chain (FFESC) cuprates. A homogeneous spin-1/2 chain model with a FM nearest-neighbor (NN), an antiferromagnetic (AFM) next-nearest-neighbor (NNN) inchain, and two diagonal AFM interchain couplings (ICs) analyzed within linear spin-wave theory (LSWT) reproduces well the observed strong dispersion along the chains and a weak one perpendicularly. The ratio R=|J_{a2}/J_{a1}| of the FM NN and the AFM NNN couplings is found as ~0.23, close to the critical point Rc=1/4 which separates ferromagnetically and antiferromagnetically correlated spiral magnetic ground states in single chains, whereas Rc>0.25 for coupled chains is considerably upshifted even for relatively weak IC. Although the measured dispersion can be described by homogeneous LSWT, the scattering intensity appears to be considerably reduced at ~11.5 and ~28 meV. The gap-like feature at 11.5 meV is attributed to magnon-phonon coupling whereas based on DMRG simulations of the dynamical structure factor the gap at 28 meV is considered to stem partly from quantum effects due to the AFM IC. Another contribution is ascribed to the intrinsic superstructure from the distorting incommensurate pattern of CaY cationic chains adjacent to the CuO2 ones. It gives rise to non-equivalent CuO4 units and Cu-O-Cu bond angles Phi and a resulting distribution of all exchange integrals. The J's fitted by homogeneous LSWT are regarded as average values. The record value of the FM NN integral J1=24 meV among FFESC cuprates can be explained by a non-universal Phi (not 90 deg.) and Cu-O bond length dependent anisotropic mean direct FM Cu-O exchange K_{pd}~120 meV. Enhanced K_{pd} values are also needed to compensate a significant AFM J_{dd} > ~6 meV., 36 pages

Hintergrund: Der horizontale Durchmesser der vitreomakulären Anheftungsfläche ist ein wichtiger Parameter im Rahmen des vitreomakulären Traktionssyndroms (VMT-Syndroms): er unterteilt definitionsgemäße zwischen „fokaler“ und „breiter“ VMT und korreliert[zum vollständigen Text gelangen Sie über die oben angegebene URL], 90. Versammlung des Vereins Rhein-Mainischer Augenärzte

Zielsetzung: Analyse von Therapieerfolg und Nebenwirkungen der Ocriplasmin Behandlung bei vitreomakulärer Traktion (VMT) mit oder ohne durchgreifendes Makulaforamen (MF) im klinischen Alltag. Methode: Monozentrische, retrospektive, konsekutivve Fallserie von 85 Augen von 84 Patienten, die eine[zum vollständigen Text gelangen Sie über die oben angegebene URL], 30. Internationaler Kongress der Deutschen Ophthalmochirurgen

Hintergrund: Augen mit Makulaschichtforamen (MSF) zeigen neben einer Makulaschichtforamen-assoziierten epiretinalen Proliferation (engl. lamellar hole-associated epiretinal proliferation, LHEP) auch konventionelle epiretinale Membranen (ERM). Ziel dieser Studie war deshalb die Untersuchung von traktiven[zum vollständigen Text gelangen Sie über die oben angegebene URL], 30. Internationaler Kongress der Deutschen Ophthalmochirurgen

The Early Iron Age Hallstatt C period in Northwest and Central Europe is marked by the emergence of monumental tumuli with lavish burials, some of which are known as chieftain’s or princely graves. This new burial rite reflects one of the most noteworthy developments in Early Iron Age Europe: the rise of a new and elaborate way of elite representation north of the Alps.These sumptuous burials contain beautiful weaponry, bronze vessels and extravagantly decorated wagons and horse-gear. They reflect long-distance connections in material culture and elite (burial) practices across the breadth of Northwest and Central Europe. Research into this period, however, tends to be regionally focused and poorly accessible to scholars from other areas – language barriers in particular are a hindering factor.In an attempt to overcome this, Connecting Elites and Regions brings together scholars from several research traditions and nations who present regional overviews and discussions of elite burials and material culture from all over Northwest and Central Europe. In many cases these are the first overviews available in English and together they make regional research accessible to a wider audience. As such this volume contributes to and hopes to stimulate research on the Early Iron Age Hallstatt C period on a European scale.

Der Beitrag erläutert die VDI/VDE-Richtlinie 3693 zu den Themen Modellarten und Glossar (Blatt 1) und gibt einen Ausblick auf die Erarbeitung der Folgeblätter. Die Chancen, Gründe und Erfolgsfaktoren bei der Einführung der virtuellen Inbetriebnahme (VIBN) und die erste Ergebnisse (Best Practice) anhand der Projektphasen eines VIBN-Projektes werden vorgestellt. Auf die Herausforderungen und bestehenden Grenzen der VIBN auf Grund des Einsatzes von Simulationsmodellen wird hingewiesen. Die Rollen der Automatisierungstechnik und des Anlagenbaus werden beschrieben.

Hintergrund: Augen mit Makulaschichtforamen (MSF) zeigen neben einer konventionellen epiretinalen Membran (ERM) häufig auch eine Makulaschichtforamen assoziierte epiretinale Proliferation (engl. lamellar hole-associated epiretinal proliferation, LHEP). Ziel dieser Studie war deshalb die Untersuchung[zum vollständigen Text gelangen Sie über die oben angegebene URL], Jahrestagung der Vereinigung Bayerischer Augenärzte BayOG 2016|49. Weihnachtssitzung der Münchner Ophthalmologischen Gesellschaft MOG 2016

Insect odorant receptors (ORs) are 7-transmembrane receptors with inverse membrane topology. They associate with the conserved ion channel Orco. As chaperon, Orco maintains ORs in cilia and, as pacemaker channel, Orco controls spontaneous activity in olfactory receptor neurons. Odorant binding to ORs opens OR-Orco receptor ion channel complexes in heterologous expression systems. It is unknown, whether this also occurs in vivo. As an alternative to this ionotropic transduction, experimental evidence is accumulating for metabotropic odor transduction, implicating that insect ORs couple to G-proteins. Resulting second messengers gate various ion channels. They generate the sensillum potential that elicits phasic-tonic action potentials (APs) followed by late, long-lasting pheromone responses. Because it is still unclear how and when Orco opens after odor-OR-binding, we used tip recordings to examine in vivo the effects of the Orco antagonist OLC15 and the amilorides MIA and HMA on bombykal transduction in the hawkmoth Manduca sexta. In contrast to OLC15 both amilorides decreased the pheromone-dependent sensillum potential amplitude and the frequency of the phasic AP response. Instead, OLC15 decreased spontaneous activity, increased latencies of phasic-, and decreased frequencies of late, long-lasting pheromone responses Zeitgebertime-dependently. Our results suggest no involvement for Orco in the primary transduction events, in contrast to amiloride-sensitive channels. Instead of an odor-gated ionotropic receptor, Orco rather acts as a voltage- and apparently second messenger-gated pacemaker channel controlling the membrane potential and hence threshold and kinetics of the pheromone response.

Hintergrund: Die Kultivierung von humanen epiretinalen Membranen war bisher selten erfolgreich. Ziel der Studie war ein neues Modell zu entwickeln, das die Kultivierung von chirurgisch gewonnenen epiretinalen Membranen nach Vitrektomie erlaubt und eine funktionelle Untersuchung der epiretinalen Zellen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 29. Jahrestagung der Retinologischen Gesellschaft

Purpose: To describe immunocytochemical and ultrastructural characteristics of vitreomacular traction associated with epiretinal membranes at the vitreomacular interface in non-neovascular age-related macular degeneration (AMD), to correlate with optical coherence tomography (OCT) findings and clinical[for full text, please go to the a.m. URL], 29. Jahrestagung der Retinologischen Gesellschaft

The work on Autonomic Road Transport Support (ARTS) presented here aims at\ud meeting the challenge of engineering autonomic behavior in Intelligent Transportation\ud Systems (ITS) by fusing research from the disciplines of traffic engineering\ud and autonomic computing. Ideas and techniques from leading edge artificial intelligence\ud research have been adapted for ITS over the last years. Examples include\ud adaptive control embedded in real time traffic control systems, heuristic algorithms\ud (e.g. in SAT-NAV systems), image processing and computer vision (e.g. in automated\ud surveillance interpretation). Autonomic computing which is inspired from the\ud biological example of the body’s autonomic nervous system is a more recent development.\ud It allows for a more efficient management of heterogeneous distributed\ud computing systems. In the area of computing, autonomic systems are endowed\ud with a number of properties that are generally referred to as self-X properties,\ud including self-configuration, self-healing, self-optimization, self-protection and more\ud generally self-management. Some isolated examples of autonomic properties such\ud as self-adaptation have found their way into ITS technology and have already proved\ud beneficial. This edited volume provides a comprehensive introduction to Autonomic\ud Road Transport Support (ARTS) and describes the development of ARTS systems. It\ud starts out with the visions, opportunities and challenges, then presents the foundations\ud of ARTS and the platforms and methods used and it closes with experiences\ud from real-world applications and prototypes of emerging applications. This makes\ud it suitable for researchers and practitioners in the fields of autonomic computing,\ud traffic and transport management and engineering, AI, and software engineering.\ud Graduate students will benefit from state-of-the-art description, the study of novel\ud methods and the case studies provided.

Noch zum Beginn des letzten Jahrhunderts war die Tuberkulose auch in Deutschland eine sehr häufige Erkrankung. Durch Präventionsmaßnahmen und ein besseres Krankheitsverständnis wurde sie ein immer seltener in unserer Gesellschaft und ist daher aus dem Fokus der differenzialdiagnostischen Erwägungen gerückt. Jedoch ist aufgrund der zunehmenden Globalisierung eine Wiederzunahme dieser Infektionskrankheit zu beobachten. Im folgenden Fall stellte sich eine 37-jährige Patientin (K. R.) mit einer hartnäckigen Mittelohr- und Rachenentzündung im September 2014 in der Sprechstunde vor. Bei der Inspektion des Nasenrachens zeigte sich eine fibrinbelegte Raumforderung. Zusätzliche bestand ein Paukenerguss links, so dass als Verdachtsdiagnose ein Nasenrachenkarzinom im Raum stand. Es erfolgte eine Nasenrachenbiopsie sowie eine Parazentese mit Paukendrainage links. In der Schnellschnittuntersuchung zeigte sich eine epitheloidzellige Entzündung. Seitens des Pathologen wurde der Verdacht auf eine Sarkoidose geäußert. Da die Patientin seit Jahren in Thailand lebt und arbeitet wurde auch eine spezifische Erkrankung in Betracht gezogen. Im daraufhin durchgeführten CT-Thorax fanden sich kleinfleckige Veränderungen im Bereich der linken Lungenspitze als Hinweis auf eine mögliche Tuberkulose, woraufhin eine Verlegung in eine Lungenfachklinik erfolgte. Weder im Sputum, Ohrsekret, Gewebe bzw. in der PCR konnte zunächst Mycobacterium tuberculosis nachgewiesen werden. Erst in der daraufhin angelegten Kultur wurde Mycobacterium tuberculosis sowohl im Mittelohrsekret als auch Sputum nachgewiesen. Bei epitheloidzelligen Entzündungen im Kopf- und Halsbereich, auch wenn keine typische Verkäsung vorliegt, sollte Differenzialdiagnostisch immer an eine primäre bzw. postprimäre Tuberkulose gedacht werden. Der Erstautor gibt keinen Interessenkonflikt an., GMS Current Posters in Otorhinolaryngology - Head and Neck Surgery; 11:Doc082; ISSN 1865-1038

Topological insulators are characterized by Dirac cone surface states with electron spins aligned in the surface plane and perpendicular to their momenta. Recent theoretical and experimental work implied that this specific spin texture should enable control of photoelectron spins by circularly polarized light. However, these reports questioned the so far accepted interpretation of spin-resolved photoelectron spectroscopy. We solve this puzzle and show that vacuum ultraviolet photons (50-70 eV) with linear or circular polarization probe indeed the initial state spin texture of Bi$_2$Se$_3$ while circularly polarized 6 eV low energy photons flip the electron spins out of plane and reverse their spin polarization. Our photoemission calculations, considering the interplay between the varying probing depth, dipole selection rules and spin-dependent scattering effects involving initial and final states explain these findings, and reveal proper conditions for light-induced spin manipulation. This paves the way for future applications of topological insulators in opto-spintronic devices., Comment: Submitted for publication (2013)

Aussagen über den großtechnisch maximal erreichbaren Trockenrückstand (TR) vom Dickstoff durch Abtrennung des freien Wasseranteils mittels maschineller Fest/Flüssig-Trennung mit Dekanterzentrifugen bzw. Kammerfilterpressen sind nach ATV-DVWK-Regelwerk Merkblatt 366 mithilfe des Parameters TR(A) innerhalb eines Toleranzbereiches von +-15 g/l möglich. Die Bestimmung dieses Kennwertes ist messtechnisch aber sehr aufwendig und daher nur für einzelne Untersuchungspunkte realisierbar. Ziel der Untersuchungen ist deshalb die Ableitung eines Modellansatzes zur Vorhersage des unter den aktuellen Betriebszuständen erzielbaren TR vom Dickstoff nach der maschinellen Fest/Flüssig-Trennung. Die verwendeten Kennwerte zur Vorhersage des TR vom Dickstoff beschränken sich dabei nicht nur auf einfach zu charakterisierende Eigenschaften, die routinemäßig unter Verantwortung der Kläranlage analysiert werden, sondern beinhalten bspw. auch integrale Parameter aus Messungen der Partikelgrößenverteilung. So konnte mit Kenntnis der Eigenschaften TR, Glühverlust und Glührückstand anaerob stabilisierter Faulschlämme kommunaler Kläranlagen unter Anwendung des dargestellten Modellansatzes der mit einer Becherzentrifuge erzielbare TR innerhalb des Toleranzbereiches von +-15 g/ vorhergesagt werden. Weiterhin sind die im Labormaßstab gewonnenen Ergebnisse mithilfe eines aggregatspezifischen Übertragungsfaktors auf ein großtechnisches Entwässerungsaggregat übertragbar.

OBJECTIVE High-dose methylprednisolone (MP) is used to treat acute spinal cord injury (ASCI). The objective of the present study was to determine the pharmacokinetics of the pro-drug methylprednisolone hemisuccinate (MPHS) and MP in accident victims with ASCI. METHODS The patients (n = 26) were treated with a bolus intravenous loading dose of 30 mg/kg MPHS within 2 h after injury and this was followed by a maintenance infusion of 5.4 mg/kg/h up to 24 h. Blood, CSF and saliva samples were collected up to 48 h after the initial dose and the samples were analyzed by HPLC. Concentration-time data of MPHS and MP were analyzed using population pharmacokinetic analysis with NONMEM software. RESULTS MPHS and MP could be monitored in plasma and CSF. MP but not MPHS was present in saliva. High variability was seen in the MPHS levels in CSF. The pharmacokinetics of the pro-drug and the metabolite were adequately described by a 2-compartment model with exponential distribution models assigned to the interindividual and the residual variability. At steady state, the average measured MP concentration in plasma was 12.3+/-7.0 microg/ml and 1.74+/-0.85 microg/ml in CSF. The CSF levels of MP could be modeled as a part of the peripheral compartment. CONCLUSION This study demonstrated that CSF concentrations of MP were sufficiently high after i.v. administration and reflected the concentrations of unbound drug in plasma. Salivary levels of MP were about 32% of the plasma level and may serve as an easily accessible body fluid for drug level monitoring.

The thermal remagnetization (TR), i.e. the reentrance of magnetization upon heating in a steady-field demagnetized sample, is a common feature to the four types of polycrystalline permanent magnets, mainly utilized for practical purposes, i.e. barium ferrites, SmCo5, Sm2Co17 and NdFeB magnets. The effect is small for pinning controlled and large for nucleation controlled magnets. The effect is strongly dependent on the demagnetization factor and may reach nearly 100 per cent in SmCo5 samples measured in a closed circuit. The TR is very sensitive to a small superimposed steady field. The maximum effect and the position of the peak is dependent on the initial temperature. The direction of the TR is correlated with the temperature coefficient of the coercivity, resulting in a inverse TR in barium ferrite. The susceptibility of the thermally remagnetized samples is increased. Repeated cycles of steady-field demagnetization followed by heating result in the same TR. The phenomenology of TR and ITR is explained by means of a model taking into account both the internal field fluctuations due to grain interactions and the decay of single domain grains into multi-domain state. By taking the measured temperature dependencies of the coercivity and the saturation magnetization the theory is able to reproduce the experiments very well, allowing to determine the width of the field fluctuations, the width of the switching field distribution and an internal demagnetization factor as characteristics of the materials by fitting., 26 pages, 29 figures, 3 tables Contribution to the book-project: "Recent Research Developments In Magnetism And Magnetic Materials" by Transworld Research Network

4 pp. (2002)., The Photo Injector Test facility at DESY Zeuthen (PITZ) was built to develop electron sources for the TESLA Test Facility Free Electron Laser and future linear colliders. The main goal is to study the production of minimum transverse emittance beams with short bunch length at medium charge (∼1 nC). The facility includes a 1.5 cell L-band cavity with coaxial RF coupler, a solenoid for space charge compensation, a laser capable to generate long pulse trains, an UHV photo cathode exchange system, and different diagnostics tools. Besides an overview of the facility, its main components and their commissioning, this contribution will concentrate on the first measurements at PITZ with photoelectrons. This will include measurements of the transverse and longitudinal laser profile, charge and quantum efficiency, momentum and momentum spread, transverse electron beam profiles at different locations and first results on transverse emittance.

Based on the special properties of Liouville eigenoperators a perturbation theory for the partition sum is given. It is applicable for any temperature and includes the case of degenerate Hamiltonians. To demonstrate the reliability of the method, the second order correction to the atomic limit grand canonical potential of the Hubbard model is calculated and compared to results known from the literature., Comment: 22 pages, latex, needs PSTricks-macro from Princeton University, new version with some minor corrections of mistyped formulas

Microbial food webs represent an important part of the carbon flow in tideless eutrophic estuaries of the Baltic Sea. Results from three different localities are presented: - the shallow eutrophic Darss-Zingst estuary - the waste water influenced eutrophic Warnow river estuary - the eutrophic freshwater region of the Warnow river. In all ecosystems investigated the detritus is an integral carbon source. Bacteria are the main heterotrophic biomass component. Changes in interactions are analyzed up to eight weeks in field mesocosms and lab microcosms. The observed developments are caused by bottom-up and top-down mechanisms in the microbial food web.

30 Patienten mit histologisch gesichertem malignen Schwannom wurden untersucht. In funf Fallen handelte es sich um entartete Neurofibrome bei M. Recklinghausen, ansonsten um solitare maligne Schwannome. Das computertomographische Erscheinungsbild maligner Schwannome ist uneinheitlich. Form, Binnenstruktur und Absorptionsverhalten konnen in weiten Grenzen variieren. Auffallend viele maligne Schwannome erfullen eher die computertomographischen Kriterien benigner Tumoren. Insgesamt finden sich weder fur solitare noch fur M. Recklinghausen assoziierte maligne Schwannome, weder fur die Primartumoren noch fur die Rezidive charakteristische morphologische Merkmale. Eine verlasliche Aussage zur Dignitat ist nur in einem Teil der Falle moglich. Thirty patients with histologically confirmed malignant Schwannomas were examined. In five patients the lesions were malignant neurofibromas, as part of von Recklinghausen's disease, the others were solitary malignant Schwannomas. CT appearances of malignant Schwannomas are variable. Shape, structure and attenuation vary considerably. Most malignant Schwannomas present with the CT criteria of benign tumours. Altogether neither the solitary Schwannomas, nor those associated with von Recklinghausen's disease show specific diagnostic features, whether for the primary tumour or for recurrences. Reliable information on the nature of these lesions is possible in a few cases only.

Oropharyngeal suctioning prior to extubation aims to minimize postextubation tracheal soiling from remaining fluid. We investigated the amount and nature of any fluid remaining after such suctioning and contributing factors.ASA I - III patients undergoing elective surgery under general anesthesia with endotracheal intubation participated in this prospective observational pilot study. Following oropharyngeal suctioning immediately prior to extubation, a dedicated port of the endotracheal tube (TaperGuard Evac™ Endotracheal Tube) was aspirated. The amount and pH of residual fluid was recorded. Data collection included age, sex, body mass index, comorbidities, ASA status, procedure type and duration. The Chi-Square, Wilcoxon Rank-Sum, t-tests, and univariate regression analysis were used as appropriate.Ninety-eight patients completed the study. The mean aspirated volume in 38 (38.8%) patients was 0.9 ± 1.3 mL and sixty patients (61.2%) had no aspirate. A body mass index of ≥ 30 kg/m2 was associated with the presence of fluid (P=0.03), and a higher volume (P=0.03). The fluid pH was 7 ± 0.81 (mean ± SD). A duration of surgery ≥ 120 minutes predicted a lower pH.The prevalence and amount of residual fluid after oropharyngeal suctioning was low and likely clinically insignificant. A higher body mass index was associated with a higher incidence and volume of residual fluid. Longer procedure duration determined a slightly lower pH, with a mildly acidic pH range. The possibility of a lower fluid pH after prolonged surgery contributing to postoperative sore throat via mucosal irritation warrants investigation.

TNF-α, inducible NO synthase (iNOS), and ICAM-1 are considered to be key proteins in the inflammatory response of most tissues. We tested the hypothesis that cell walls of Streptococcus pneumoniae (PCW), the most common cause of adult bacterial meningitis, induce TNF-α, iNOS, and ICAM-1 expression in rat primary brain microvascular endothelial cell cultures. We detected TNF-α mRNA by RT-PCR already 1 h after stimulation with PCW, while TNF-α protein peaked at 4 h (9.4 ± 3.6 vs 0.1 ± 0.1 pg/μg protein). PCW induced iNOS mRNA 2 h after stimulation, followed by an increase of the NO degradation product nitrite (18.1 ± 4 vs 5.8 ± 1.8 at 12 h; 18.1 ± 4 vs 5.8 ± 1.8 pmol/μg protein at 72 h). The addition of TNF-α Ab significantly reduced nitrite production to 62.2 ± 14.4% compared with PCW-stimulated brain microvascular endothelial cells (100%). PCW induced the expression of ICAM-1 (measured by FACS), which was completely blocked by TNF-α Ab (142 ± 18.6 vs 97.5 ± 12.4%; 100% unstimulated brain microvascular endothelial cells). Cerebral endothelial cells express TNF-α mRNA as well as iNOS mRNA and release the bioactive proteins in response to PCW. PCW-induced NO production is mediated in part by an autocrine pathway involving TNF-α, whereas ICAM-1 expression is completely mediated by this autocrine loop. By these mechanisms, cerebral endothelial cells may regulate critical steps in inflammatory blood-brain-barrier disruption of bacterial meningitis.

The metacognition of needing to control thoughts has been implicated in eating disorders (EDs)—specifically, in association with the drive for thinness and over-control. To date, it has yet to be investigated longitudinally in ED outpatients undergoing CBT-based treatment. The current study aims to examine whether endorsing a need to control thoughts undergoes modifications during CBT-based treatment for EDs and whether its modification correlates with treatment response in terms of reduced ED symptomatology. Seventy female ED outpatients (34 with AN, 29 with BN, 7 with OSFED) were assessed at baseline and at the end of treatment with the Metacognitions Questionnaire (MCQ), the Eating Attitudes Test (EAT-40), and the General Health Questionnaire (GHQ). Post-treatment, significant reductions were observed in MCQ-need to control thoughts. Using hierarchical linear regression analyses such decreases significantly explained the variance in observed reductions in EAT-oral control and to a lesser extent, reductions in EAT-bulimia and food preoccupation and EAT-dieting. These results underscore the importance of metacognitive change in EDs and the potential utility of CBT-based treatment in its modification. Improving ED outcomes may warrant broadening the therapeutic target of over-control and a sense of loss of control beyond dysfunctional eating behaviors to include maladaptive metacognitions that concern the need to control thoughts.

Helmet CPAP (H-CPAP) has been recommended in many guidelines as a noninvasive respiratory support during COVID-19 pandemic in many countries around the world. It has the least amount of particle dispersion and air contamination among all noninvasive devices and may mitigate the ICU bed shortage during a COVID surge as well as a decreased need for intubation/mechanical ventilation. It can be attached to many oxygen delivery sources. The MaxVenturi setup is preferred as it allows for natural humidification, low noise burden, and easy transition to HFNC during breaks and it is the recommended transport set-up. The patients can safely be proned with the helmet. It can also be used to wean the patients from invasive mechanical ventilation. Our article reviews in depth the pathophysiology of COVID-19 ARDS, provides rationale of using H-CPAP, suggests a respiratory failure algorithm, guides through its setup and discusses the issues and concerns around using it.

Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Background: Research on which specific maladaptive cognitions characterize eating disorders (ED) is lacking. This study explores irrational beliefs (IBs) in ED patients and controls and the association between IBs and ED-specific and non-specific ED symptomatology and cognitive reappraisal. Methods: 79 ED outpatients with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorders and 95 controls completed the Attitudes and Beliefs Scale-2 (ABS-2) for IBs. ED outpatients also completed the Eating Disorder Inventory-3 (EDI-3) for ED-specific (EDI-3-ED Risk) and non-specific (EDI-3-General Psychological Maladjustment) symptomatology; General Health Questionnaire (GHQ) for general psychopathology; Emotion Regulation Questionnaire (ERQ) for cognitive reappraisal. Results: Multivariate analysis of variance with post hoc comparisons showed that ED outpatients exhibit greater ABS-2-Awfulizing, ABS-2-Negative Global Evaluations, and ABS-2-Low Frustration Tolerance than controls. No differences emerged between ED diagnoses. According to stepwise linear regression analyses, body mass index (BMI) and ABS-2-Awfulizing predicted greater EDI-3-ED Risk, while ABS-2-Negative Global Evaluations and GHQ predicted greater EDI-3-General Psychological Maladjustment and lower ERQ-Cognitive Reappraisal. Conclusion: Awfulizing and negative global evaluation contribute to better explaining ED-specific and non-specific ED symptoms and cognitive reappraisal. Therefore, including them, together with BMI and general psychopathology, when assessing ED patients and planning cognitive–behavioral treatment is warranted.

The aim of this work was to attempt to clarify the relationship between eveningness preferences and eating behaviour. In a survey a sample of 270 females (146 recruited in a treatment centre for eating disorders and 124 control) was administered the reduced version of the morningness–eveningness questionnaire (MEQr) and the eating disorder inventory 2 (EDI-2). A significant higher percentage of evening-type in patient versus control group was observed. About 46 patients who participated in the survey were enrolled in a further prospective study. A significant regression of symptomatology as scored by EDI-2 corresponded to a significant increase in MEQr scores (i.e. shift towards morningness). We concluded that altered eating behaviours could modulate circadian preference. The results are discussed in relation to possible applications for clinical treatment.

Advanced urban traffic control systems are often based on feed-back algorithms. They use road traffic data which has been gathered from a couple of minutes to several years. For instance, current traffic control systems often operate on the basis of adaptive green phases and flexible co-ordination in road (sub) networks based on measured traffic conditions. However, these approaches are still not very efficient during unforeseen situations such as road incidents when changes in traffic are requested in a short time interval. For such anomalies, we argue that systems are needed that can sense, interpret and deliberate with their actions and goals to be achieved, taking into consideration continuous changes in state, required service level and environmental constraints. The requirement of such systems is that they can plan and act effectively after such deliberation, so that behaviourally they appear self-aware. This chapter focuses on the design of a generic architecture for auto- nomic urban traffic control, to enable the network to manage itself both in normal operation and in unexpected scenarios. The reasoning and self- management aspects are implemented using automated planning techniques inspired by both the symbolic artificial intelligence and traditional control engineering.Preliminary test results of the plan generation phase of the architecture are considered and evaluated.

This paper presents case study information on the geochemical and mineralogical nature of tailing materials generated at Savannah Nickel Mine in the Kimberley region of Western Australia (WA). The mine is an underground operation, and tailings generated from processing ore are stored at an above-ground valley fill Tailings Storage Facility (TSF). Various studies have shown that leaving the tailings in situ at mine closure and using a cover system will produce a sustainable environmental outcome, and the mine operator has recently received regulatory approval to increase the capacity of the TSF and implement this closure strategy Over the past decade, geochemical and mineralogical studies have demonstrated that the geochemical behaviour of the tailings in the TSF is much more benign than initially predicted. Despite containing almost 30% pyrrhotite, the tailings generate only a fraction of the acidity predicted by classical static geochemical test techniques, and the rate of acidity generation is more than compensated by the inherent non-carbonate acid neutralising capacity available from specific silicate minerals within the tailings matrix. The mine operator now has a very good understanding of the geochemistry of the tailings, although geochemical, mineralogical and other related studies are continuing, moving towards mine closure. Refereed/Peer-reviewed

OBJECTIVE: Positive functioning is widely neglected in research on eating disorders (EDs). The aim of this exploratory study was to assess psychological well-being (PWB) in out-patients with ED and in controls. METHOD: The authors assessed PWB in 245 out-patients with EDs [105 with bulimia nervosa (BN), 57 with anorexia nervosa (AN), and 83 with binge eating disorder (BED) who met DSM-IV-TR] and 60 controls. They tested whether PWB was associated with eating attitude test (EAT) scores and if such associations differed among ED groups while taking into account confounding variables. RESULTS: Significant differences between groups in all PWB scales were found. While individuals with BN reported significantly lower scores in all PWB dimensions than healthy controls, patients with BED scored significantly lower than controls in PWB autonomy, environmental mastery, and self-acceptance scales. Patients with AN showed similar scores to controls in all PWB dimensions, except for positive relationships and self-acceptance. In all ED groups, most PWB dimensions resulted significantly and negatively associated with EAT scales, except for AN where oral control was found to positively correlate with a high sense of purpose in life. All results were maintained even after adjusting for possible confounding variables. DISCUSSION: Patients with EDs reported an impairment in PWB. The paucity of PWB was not necessarily dependent on the presence of high levels of psychological distress and on the severity of the disorder. Such assessments may therefore yield a more comprehensive evaluation in this clinical population.

This paper focuses on a case study at a base metal mine located in a trop ical semi-arid ar ea of Western Australia (WA). It is demonstrated that understanding the geochemical nature of the mine tailings forms an integral part of innovative management strategies developed throughout the life-of-mine (LaM) when planning for mine closure. The tailings are currently stored at an above-ground valley fill tailings storage facility (TSF) and one option for long-term management under consideration is leaving the tailings ill situ at mine closure and covering using the concept of an enhanced 'store and release' cover system. Extensive geochemical and mineralogical studies have found that the geochemical behaviour of the tailings in the TSF is significant ly more benign than initially predicted . The sulfide content of the tailings is primarily pyrrhotite, which can be acid-forming, acid-neutral or acid-consuming depending on a number of factors including redox conditions. Tailings pore water at depth is pH neutral with excess alkalinity, low concentrations of dissolved metals and elevated sulfate concentration. Recent geochemical tests on tailings samples indicate that a reduction in the acid potential and a corresponding increase in the neutralising potential of the tailings, through partial removal of pyrrhotite at the ore processing stage, has the potential to further reduce the long-term risk of potential impact to the environment from any TSF seepage.The current work program investigates whether partial removal of pyrrhotite is feasible and secondly, whether this approach is necessary to produce a significantly better outcome at mine closure.

Un processo di valutazione accurato è fondamentale per la progettualità di un intervento di cura che voglia definirsi efficace e basato “su evidenze scientifiche”. La natura multifattoriale che lega i fattori biologici, psicologici esociali all’esordio e al mantenimento dei DCA, l’ampia gamma di quadri sub-sindromici attraverso i quali, dalla patologia più conclamata, si sfuma fino alle variegate espressioni della “normalità” del comportamento alimentare, l’elevatissimo grado di comorbilità con altri disturbi psichiatrici del DSM-IV-TR (Diagnostic and Statistical Criteria for Mental Disorder, Four Edition,Text Revised (APA, 1994) (in particolare dell’area ansiosa e dell’umore) e con altre patologie più squisitamente mediche rendono complessa la delimitazione e descrizione degli ambiti di valutazione di maggiore rilevanza clinica per il trattamento di questa popolazione. In questo capitolo sono descritti i più importanti strumenti psicometrici per la rilevazione precoce e la formulazione diagnostica dei DCA e del loro trattamento in un setting di cura interdisciplinare psico-nutrizionale.

Die angeborene Immunität ist in der Lage, Pathogene schon beim erstmaligen Eindringen zu erkennen und zu bekämpfen. Haupteffektoren der schnellen, angeborenen Immunantwort sind Makrophagen und polymorphkernige neutrophile Granulozyten. Diese erkennen und phagozytieren Pathogene und koordinieren die weitere Immunantwort durch die Freisetzung von inflammatorischen Mediatoren und Zytokinen. Die Erkennung mikrobieller Bestandteile, wie Lipopolysaccharid (LPS) Gram-negativer Bakterien bzw. Peptidoglykan (PG) und Lipoteichonsäuren (LTA) Gram-positiver Bakterien, führt zur Aktivierung von unterschiedlichen Proteinkinasen, des Transkriptionsfaktors NF-(B und zur Freisetzung von Zytokinen. Mitglieder der Toll-Proteinfamilie, sogenannte Toll-like-Rezeptoren (TLR), wurden kürzlich als Rezeptoren auf Immunzellen identifiziert, die für die Erkennung solcher mikrobieller Bestandteile verantwortlich sind. Während TLR-4 der LPS-Erkennung dient, und TLR-2 und -6 verschiedene Liganden von Gram-positiven Bakterien binden, blieb die Frage der Erkennung von LTA und verwandten Glykolipiden strittig. Sowohl TLR-2 als auch TLR-4 wurden für diese Rolle diskutiert. Zielsetzung dieser Arbeit war, die Rolle von TLRs in der LTA- und Glykolipid-Erkennung zu untersuchten. Glykolipide von zwei eng verwandten Treponemen-Spezies, T. maltophilum (TM) und T. brennaborense (TB), sowie neuartig aufgereinigte Lipoteichonsäuren von Staphylococcus aureus (SA) und Bacillus subtilis (BS) wurden eingesetzt, um die nukleäre Translokation von NF-(B in verschiedenen Zellsystemen zu induzieren. Diese Zellstimulationsexperimente wurden mit verschiedenen TLR-2-negativen Zellinien sowie mit Peritonealexsudatzellen TLR-4-defizienter C3H/HeJ-Mäuse durchgeführt. Weitere Informationen lieferten TLR-2-Überexpressions-Experimente sowie Zellstimulationen unter Verwendung von anti-TLR-4-Antikörpern. Die Aktivierung von NF-(B wurde anhand von Gelshifts nachgewiesen. Mit der Überexpression von dominant-negativen Mutanten verschiedener Moleküle der Signalkaskade, mit Kinase-Hemmstoffen und mit Western Blots wurden die intrazellulären Signaltransduktionswege untersucht. Für Glykolipide von T. maltophilum und beide verwendeten Lipoteichonsäuren ließ sich eine klare TLR-2-Abhängigkeit in der Aktivierung von NF-(B und der Induktion von proinflammatorischen Zytokinen zeigen. Die Glykolipide von T. brennaborense hingegen waren überraschender Weise gleichzeitig auch TLR-4-Liganden. Beide untersuchten Glykolipide sowie beide LTAs aktivierten einen Signalweg unter Einbeziehung des Adaptermoleküls MyD88 und der NF-(B-induzierenden Kinase (NIK). Des weiteren konnte der Einfluß der MAP-Kinasen p42/44 und p38 auf die Treponema-Glykolipid- und LPS-induzierte TNF-(-Ausschüttung dargestellt werden. Zusammenfassend zeigen diese Ergebnisse, daß TLR-2 der Hauptrezeptor von Lipoteichonsäuren ist, und TLR-2 und -4 beide Rezeptoren der Treponema-Glykolipide sein können. Diese Ergebnisse sollten dazu beitragen, die molekularen Grundlagen der Reaktionen des Immunsystems auf Gram-positive Bakterien und Treponemen zu verstehen. The innate immune response to microbial pathogens is able to protect the host after a first pathogen contact. This immediate immune response is largely mediated by macrophages and neutrophils. They recognize and phagocytose pathogens, and coordinate host responses by secreting inflammatory mediators, such as cytokines. The recognition of lipopolysaccharide (LPS) of Gram-negative bacteria, or peptidoglycan (PG) and lipoteichoic acids (LTAs) of Gram-positive bacteria leads to the induction of protein-kinases, the transcription factor NF-(B, and subsequently the release of proinflammatory cytokines. Recently, members of the Toll-protein-family, the so-called Toll-like receptors (TLRs) have been found to be involved in immune cell activation by microbial products. While TLR-4 has been identified as the transmembrane signal transducer for LPS, and TLR-2 and -6 for different ligands originating from Gram-positive bacteria, the molecular basis of recognition of lipoteichoic acids and related glycolipids has not been completely understood: Both, TLR-4 and -2 have been postulated as receptors. In order to determine the role of TLRs in immune cell activation by Treponema glycolipids and LTAs experiments involving TLR-2-negative cell lines, macrophages from TLR-4-deficient C3H/HeJ-mice, cells overexpression TLR-2, and inhibitory TLR-4 antibodies were performed. The induction of NF-(B was assessed by electrophoretic mobility shift assays. Glycolipids of two related Treponema species, T. maltophilum (TM) and T. brennaborense (TB), and LTAs from Staphylococcus aureus (SA) and Bacillus subtilis (BS) were investigated for induction of nuclear translocation of NF-(B in different cell systems. Glycolipids from T. maltophilum and both LTAs studied revealed TLR-2-dependency in induction of NF-(B and proinflammatory cytokines. Surprisingly, glycolipids from T. brennaborense were found to be TLR-4-ligands. Furthermore an involvement of the signaling molecules MyD88 and NIK in cell stimulation by LTAs and glycolipids was revealed by dominant-negative overexpression experiments. The induction of TNF-( by Treponema glycolipids furthermore was dependent on activation of MAP kinases p42/44 and p38, as indicated by specific kinase inhibitors. Tyrosinephosporylation of the p42/44 kinase induced by Treponema glycolipids were detected by western blots. In summary, the results presented here indicate that TLR-2 is the main receptor for LTAs. Both TLR-2 and -4 serve as receptors for Treponema glycolipids. These results may potentially contribute to explain immune responses to Gram-positive bacteria and treponemes.