Search

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2–31). On day 7, median CIS declined to 6 (range, 1–13); 71% of patients (CI 64–77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3–5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation.

Luminescent solar concentrators (LSCs) are devices that trap a portion of the solar spectrum and funnel it toward photon-harvesting devices. The modeling of LSCs at a quantum chemical level, however, remains a challenge due to the complexity of exciton and photon dynamic modeling. This study examines singlet exciton dynamics occurring within a typical LSC device. To do this, we use a rejection-free kinetic Monte Carlo method to predict diffusion lengths, diffusion coefficients, substrate anisotropy, and average exciton lifetimes of perylene diimide (PDI)- and tetracene-based substrates in the low-concentration scheme. Ab initiorate constants are computed using time-dependent density functional theory-based methods. PDI-type substrates are observed to display enhanced singlet exciton transport properties compared to tetracene. Simulations show that substrates with dipole-aligned chromophores are characterized by anisotropic exciton diffusion, with slightly improved transport properties. Finally, a PDI–tetracene substrate is simulated for both disordered and dipole-aligned chromophore configurations. In this multidopant substrate, transport is predominantly mediated by PDI due to the asymmetry in the transport rates between the two dyes considered. We conclude by discussing the properties of multidopant substrates and how they can impact the design of next-generation LSCs.

Hintergrund: Patienten mit schwerer COVID-19-Erkrankung entwickeln eine hyperferritinämische Inflammation, ein sepsisähnliches Immundysregulationssyndrom. Methode: Retrospektive Kohortenanalyse nach Therapiestratifizierung in einer standortübergreifenden telemedizinischen Fallkonferenz. Frühzeitige, standardisierte Identifizierung von Patienten mit einem Risiko für einen schweren Verlauf (COVID-Inflammation-Score; CIS) und Intubationsvermeidung mit Schwerpunkt auf nichtinvasive Ventilation (NIV) sind Kernelemente des Behandlungsalgorithmus. Patienten mit lebensbedrohlicher Inflammation wurde ein individueller Heilversuch mit dem Immunmodulator Ruxolitinib angeboten. Ergebnisse: Zwischen 04.03.2020 und 26.06.2020 wurden 196 COVID-19-Patienten behandelt. Der Altersmedian (70 Jahre) und die Komorbidität waren im Interstudienvergleich hoch. Die Gesamtmortalität lag bei 17,3 %, wobei bei der Hälfte der verstorbenen Patienten eine A‑priori-Therapielimitierung festgelegt war. Das CIS-Monitoring der mit Ruxolitinib behandelten Hochrisikopatienten (n= 20) ergab nach 5, 7 und 15 Tagen eine Inflammationssuppression um 42 % (15–70), 54 % (15–77) und 60 % (15–80). In dieser Gruppe lag die Mortalität bei 20 % (4/20). Die Gesamtmortalität adjustiert auf Patienten mit intendierter Maximaltherapie lag bei 8,7 % (17/196). Schlussfolgerung: Die COVID-19-Pneumonie mit hyperferritinämischer Inflammation ist verwandt mit der Makrophagen-Aktivierungssyndrom-ähnlichen Sepsis. Eine interdisziplinäre Fallkonferenz als Qualitätsinstrument der Intensivmedizin zur Erfassung seltener sepsisähnlicher Krankheitsbilder wird vorgestellt.

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th,2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

The coronavirus disease of 2019 (Covid-19) pandemic led to strict visitation restrictions in Intensive Care Units (ICUs), negatively impacting patients, families, and healthcare workers (HCWs). The ICU-open project is a phased approach to engage with ICU patients’ families and reintroduce family visits during the Covid-19 pandemic. The ICU-open project embodies the unwavering commitment to a family-centred approach of the Cà Foncello-Treviso Hospital's ICU staff. The present work reports the perception of the project amongst HCWs and provides a snapshot of the psychological well-being of the ICU staff after the project.

An 8-month-old girl presented with a 1-month history of developmental regression, irritability, and opisthotonic posturing. A brain MRI revealed abnormal T2 hyperintensities in the periventricular and deep cerebral white matter and peridentate cerebellar white matter. Reduced galactocerebrosidase activity in leukocytes confirmed the diagnosis of Krabbe disease.

Introduction: Guillain-Barre syndrome (GBS) is an acute inflammatory demyelinating disease involving peripheral nerves. It is usually postinfectious and common organisms associated with GBS are Campylobactor, Mycoplasma, HIV infection, CMV, EBV, [...]

The emergency landing is an important design criteria in airworthiness certification. It is associated to the cabin safety and consequently to the risk of serious injury for the occupant. The loads transmitted to the passengers during a hard landing can be fatal both in terms of intensity and duration time, and the energy absorbing systems play a fundamental role to dissipate the energies unleashed during the impacts. A barrel section was studied by the Finite Element Method to simulate the drop test consequences for the fuselage section of a wide body aircraft, and a medium velocity impact was applied to design devices and substructures able to dissipate the biggest amount of kinetic energy. A validation process was obtained following three different steps: firstly, investigating the materials, layups and material characteristics changing with load’s velocity, secondly different tests were performed on the demonstrators in order to verify the installation parameter of the devices devoted to absorb the energies, and finally the experimental results were extended on the lower lobe of the sub-cargo compartment tested at low velocity impact. These experimental results and the correlation with the numerical models allowed to extend the results on the barrel section and to evaluate the accelerations transmitted during the drop to the occupants. The satisfactory results estimated by the numerical solvers are able to aid the design and to reduce the experimental testing for the identification and the choice of different candidate solutions.

A numerical procedure to improve the performances of a Reynolds-Averaged Navier-Stokes code by including an accurate prediction of the location of the transition onset is presented. A transition prediction module is coupled with the Ansys Fluent flow solver. The transition location is predicted by coupling numerical methods based on the solution of the boundary layer equations in conical formulation, transition engineering criteria well assessed for boundary layer flows and the solution of RANS equations.

This paper presents an estimation of performances by tests on composite material structures. In order to evaluate the effects on the structural behavior, tests changing the percentage of orientation of the fiber at 0, 45 and 90 degrees and mixing the unidirectional plies with the fabric ones have been done. Fixed the lay-up configuration and so the stacking sequence, two typology of structures have been analyzed; the first one having only unidirectional plies while the second one having a fabric ply (plain weave 0/90) in place of the top and bottom unidirectional plies. The openhole compressive strength and the filled-hole tensile strength and moduli have been characterized by test. A total of 72 specimens have been used in the test campaign. In order to well compare the test results a Performance Weight Index (PWI) has been introduced by authors in order to normalize the strength of each laminate with respect to its weight/unit of surface. Results and different laminate behaviors have been evaluated and discussed.

The probabilities of the occurrence of extreme dry/wet years and seasons in Europe are estimated by using two ways of the Standardized Precipitation Index (SPI and SPI‐GEV) and the Standardized Nonstationary Precipitation Index (SnsPI). The latter is defined as the SPI by fitting precipitation data with a nonstationary Gamma distribution in order to model the precipitation time dependence under climate change. Bias‐corrected daily precipitation outputs from five different regional climate models (RCMs) provided by the ENSEMBLES project are used. The five RCMs are selected so as to represent the main statistical properties of the whole ENSEMBLES set and the most extreme deviation from the ensemble mean. All indicators are calculated for the ensemble of the five models over the period 1971–2098. Results show that under global warming, climate in Europe will significantly change from its current state with the probability of the occurrence of extreme dry and wet years and seasons increasing, respectively, over southern dry and northern wet regions. Comparing nonstationary and stationary indices, the SnsPI is found to be more robust than the common SPI in the prediction of precipitation changes with multimodel ensembles. Projection of occurrence of extreme wet and dry precipitation over EuropeDefinition of the Standardized non-stationary Precipitation IndexComparing projected precipitation estimated with SPI, SPI‐GEV, and SnsPI

Difficulties in endotracheal intubation increase morbidity and mortality in intensive care patients. We studied the problem in surgical intensive care patients with the aim of risk reduction. Patients intubated in the intensive care unit were evaluated. The intubations were performed or supervised by anaesthetists following the algorithm valid at the time of the study. Fifty percent of the 198 intubations were performed by specialist anaesthetists, 41.5% by anaesthesia trainees and 8.5% by surgical trainees. The initial attempt was by direct laryngoscopy (n=173), flexible fibrescope (n=8) or blind nasal technique (n=17). When direct laryngoscopy failed (n=7), intubation was accomplished with an intubating laryngeal mask airway (n=5), Frova stylet (n=1) or fibrescope (n=1). Thirty percent were rated as easy, 47% as moderately easy and 23% as difficult. Difficult intubations were associated with a higher incidence of anatomic anomalies, difficult bag-mask ventilation and severe oxygen desaturation. Every intubation in the ICU setting should be considered potentially difficult. The existing algorithm should be modified to incorporate the American Society of Anesthesiologists difficult airway algorithm adapted to the needs of the intensive care unit. A training program for alternative methods of airway management for difficult intubations should be established.

We have simulated the heating process of gold nanorods, elucidating a mechanism by which nanorods alter their aspect ratio at higher temperatures. We also studied the relative stabilities of nanorods by constructing nanorods with varying ratios of {110} to {100} exposed surfaces along the body of the nanorod. The least stable nanorod was found to be the nanorod with the largest {110} surfaces, followed by the nanorod with the largest {100} surfaces, while the nanorod with approximately equal surface areas of {100} and {110} surface was found to be the most stable. It was also found that the addition of surface disorder increased the stability of nanorods with large {110} surfaces, while paradoxically decreasing the stability of nanorods with large {100} surfaces. The reasons for this are elucidated and compared to experimental laser-induced gold nanorod transformation studies.

Recently, it has been reported that longer expansions of the polyalanine tract of the ARXgene could cause an early infantile encephalopathy with suppression burst pattern and that the length of this repeat region could be related to the severity of the electroclinical picture. We describe the history of two male individuals, born from monozygotic twin sisters, with Ohtahara syndrome (OS) that evolved into West syndrome phenotype and epileptic encephalopathy. In both children, we have found a previously unreported missense mutation in exon 5 of ARXgene (c.1604T>A) resulting in the substitution of a leucine with a glutamine in the aminoacid sequence. The two mothers and the maternal grandmother carry the same mutation which segregates with the disease phenotype in the family. This study confirms that ARXis involved in the pathogenesis of cryptogenic early onset epileptic encephalopathy, such as OS, and suggests that the severity of the electroclinical picture is likely to not exclusively correlate with the extent of expansions of the polyalanine tracts, but rather with the functional effect of different pathogenetic mutations. © 2010 Wiley‐Liss, Inc.

By replicating biological processes, it is hoped that many nanomaterials may be tailored for specific applications, but a detailed knowledge of the underlying mechanisms is imperative. A perfect example of this synergy is the similarity between the intracellular biomineralization of single nanocrystals of the nonmagnetic mineral iron pyrite in multicellular magnetotactic bacterium, and the solvo-thermal synthesis of iron sulfide nanoparticles in the laboratory. Although both processes occur in aqueous solutions, the relationship between the morphological stability of the individual nanocrystals and the chemistry of the nanoparticle−water interface is still largely unknown. In the present work, we use a theoretical model capable of describing the stability of nanocrystals as a function of size, shape, temperature, and chemical environment, and use it to examine the morphological stability of pyrite nanocrystals exposed to water, or formed during biomineralization.

The ambition of the CA3ViAR project is to design an open test case fan that experiences instability mechanisms, which are representative for ultra-high bypass ratio (UHBR) fans of civil aircrafts, and to perform a comprehensive experimental investigation to measure aerodynamic, aeroelastic and aeroacoustic performance in a wide range of operational conditions. Experimental tests will be performed in the Propulsion-Test-Facility (PTF) of the Institute of Jet Propulsion and Turbomachinery (IFAS) of Technische Universität Braunschweig, Germany. The final objective of the project is to provide an open test case for the entire research community, with geometries, numerical and experimental results to establish a new reference for composite UHBR fan design. This will support the development of new methods and tools for the development of safer, lighter and more efficient composite fans for greener UHBR engines. In this work the preliminary design of the low transonic fan (LTF) to be used as test article, whose main requirement is to be operated in a safe and controlled way in conditions of aerodynamic and/or aeroelastic instability during wind tunnel operations, is presented. More in particular, consolidated aerodynamic design, strategy adopted to drive the structural design, flutter analysis taking into account acoustic reflection at the intake, dynamic and stress analyses, as well as aeroacoustic measurement optimization are presented and discussed. The preliminary mechanical design of composite blades and the rotor hub, together with the rotor instrumentation and related studies to embed sensors in the composite blades, are also part of this article, and complemented by manufacturing trials and demonstration tests give the full picture of all the project activities up to the preliminary design review.

We present a numerical procedure to improve the performance of the classical Reynolds-Averaged Navier-Stokes approach for transitional flows by introducing a transition prediction tool in the RANS code. A black-box procedure able to estimate first the boundary layer quantities (starting from the pressure distribution) and then to compute the linear evolution of the fluctuations has been included in an existing RANS code. Thanks to the coupling to the eNmethod, the transition location is predicted and periodically imposed during the RANS computations. The approach proposed in this paper to predict the transition location and the laminar flow extension is based on a numerical framework based on the coupling between a high-fidelity, Reynolds–Averaged Navier–Stokes (RANS) tool and Linear Stability Equations. According to this method, boundary layer equations are written in conical formulation and the solution of RANS equations and transition onset is obtained through an eNmethod based on the PSE calculations. The validation of the present approach has been achieved by comparing the numerical results against the experimental data documented in the ETRIOLLA project.

In the frame of the CA3ViAR Clean Sky 2 (Composite fan Aerodynamic, Aeroelastic, and Aeroacoustic Validation Rig), the main objective is to design a low-speed (low-transonic) fan typical of a future large aircraft UHBR engine, in terms of aerodynamic shaping as well as structural design and analysis to make sure the test article experiences aerodynamic and aeroelastic instabilities in an expected way during wind tunnel (WT) operations. Eventually, open access to all the produced models will be provided, with the objective to establish an “open test-case” for the whole European scientific community, unique in the engine fans landscape. A preliminary fan stage design is presented in this paper, details about the aerodynamic design process and the results of the CFD analysis of the stage are shown. The present UHBR fan design fulfils the initial aerodynamic requirements and represents the starting point for the structural and aeroelastic analysis within the multidisciplinary design process employed to design the final CA3ViAR fan stage.

Over the past decades it has been widely established that many face-centered cubic metals exhibit various structural and morphological modifications at the nanoscale, such as icosahedral, decahedral, and truncated decahedral structures. One of the most widely studied among these is the nonconvex decahedral polyhedron introduced by Marks, but a survey of the literature reveals that a similar modification of the ideal icosahedron may be just as prevalent. In this paper we present a systematic study of a new truncated icosahedral structure, based on the results of Chui, and show that although it is less geometrically ideal than the Mackay icosahedron, it is more stable and thermodynamically realistic at large sizes.

The pyrite polymorph of iron disulfide (FeS2) has been attracting considerable attention, as it shows promise for solar energy conversion devices, solid-state batteries, and catalysis. As-prepared FeS2powders naturally displayed rod-like morphologies, but if tailor-made pyrite nanocrystals and nanorods are to be reliably exploited in future devices, it is desirable to be able to predict and precisely control the shape (and aspect ratio) of FeS2, and to understand the morphological stability under various conditions. Therefore, we have begun by investigating the relationship between size, shape, axial orientations, and aspect ratio of unpassivated FeS2nanostructures, using a thermodynamic model and energetic parameters calculated from first principles. The results show that the unusual morphologies such as the decahedral pyritohedron are less likely at the nanoscale than they are macroscopically, and that the preferred orientation of 1-D FeS2nanostructures is likely to be defined by kinetics, irrespective of aspect ratio.

The new CPR guidelines are based on a scientific consensus which was reached by 281 international experts. Chest compressions (100/min, 4–5 cm deep) should be performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s, FIO2if possible 1.0). After a single defibrillation attempt (initially biphasic 150–200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min. Endotracheal intubation is the gold standard; other airway devices may be employed as well depending on individual skills. Drug administration routes for adults and children: first choice IV, second choice intraosseous, third choice endobronchial [epinephrine dose 2–3× (adults) or 10× (pediatric patients) higher than IV]. Vasopressors: 1 mg epinephrine every 3–5 min IV. After the third unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg) possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous circulation only in myocardial infarction or massive pulmonary embolism; during CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in outcome by preventing cardiocirculatory collapse. Alternate chest thumps and chest compression (infants), or abdominal compressions (>1-year-old) in foreign body airway obstruction. Initially five breaths, followed by chest compressions (100/min; ~1/3 of chest diameter): ventilation ratio 15:2. Treatment of potentially reversible causes (4 “Hs”, “HITS”: hypoxia, hypovolemia, hypo- and hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism, tension pneumothorax). Epinephrine 10 µg/kg IV or intraosseously, or 100 µg (endobronchially) every 3–5 min. Defibrillation (4 J/kg; monophasic oder biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the lungs with bag-valve mask ventilation. If heart rate <60/min chest compressions:ventilation ratio 3:1 (120 chest compressions/min). Postresuscitation phase: initiate mild hypothermia [32–34°C for 12–24 h; slow rewarming (<0.5°C/h)]. Prediction of CPR outcome is not possible at the scene; determining neurological outcome within 72 h after cardiac arrest with evoked potentials, biochemical tests and physical examination. Even during low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG. In parallel to pain therapy, aspirin (160–325 mg PO or IV) and in addition clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion strategy depending on duration of symptoms until PCI (prevent delay >90 min until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A CT scan is the most important evaluation, MRT may replace a CT scan. After hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no aspirin, no heparin within the first 24 h). In severe hemorrhagic shock, definite control of bleeding is the most important goal. For successful CPR of trauma patients, a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation, and excessive ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad prognosis, CPR in trauma patients may be successful in select cases. Any CPR training is better than nothing; simplification of contents and processes remains important.The new CPR guidelines are based on a scientific consensus which was reached by 281 international experts. Chest compressions (100/min, 4–5 cm deep) should be performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s, FIO2if possible 1.0). After a single defibrillation attempt (initially biphasic 150–200 J, monophasic 360 J, subsequently with the respective highest energy), chest compressions are initiated again immediately for 2 min. Endotracheal intubation is the gold standard; other airway devices may be employed as well depending on individual skills. Drug administration routes for adults and children: first choice IV, second choice intraosseous, third choice endobronchial [epinephrine dose 2–3× (adults) or 10× (pediatric patients) higher than IV]. Vasopressors: 1 mg epinephrine every 3–5 min IV. After the third unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg) possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia, metabolic acidosis, or intoxication with tricyclic antidepressants. Consider atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous circulation only in myocardial infarction or massive pulmonary embolism; during CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in outcome by preventing cardiocirculatory collapse. Alternate chest thumps and chest compression (infants), or abdominal compressions (>1-year-old) in foreign body airway obstruction. Initially five breaths, followed by chest compressions (100/min; ~1/3 of chest diameter): ventilation ratio 15:2. Treatment of potentially reversible causes (4 “Hs”, “HITS”: hypoxia, hypovolemia, hypo- and hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism, tension pneumothorax). Epinephrine 10 µg/kg IV or intraosseously, or 100 µg (endobronchially) every 3–5 min. Defibrillation (4 J/kg; monophasic oder biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the lungs with bag-valve mask ventilation. If heart rate <60/min chest compressions:ventilation ratio 3:1 (120 chest compressions/min). Postresuscitation phase: initiate mild hypothermia [32–34°C for 12–24 h; slow rewarming (<0.5°C/h)]. Prediction of CPR outcome is not possible at the scene; determining neurological outcome within 72 h after cardiac arrest with evoked potentials, biochemical tests and physical examination. Even during low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG. In parallel to pain therapy, aspirin (160–325 mg PO or IV) and in addition clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion strategy depending on duration of symptoms until PCI (prevent delay >90 min until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A CT scan is the most important evaluation, MRT may replace a CT scan. After hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no aspirin, no heparin within the first 24 h). In severe hemorrhagic shock, definite control of bleeding is the most important goal. For successful CPR of trauma patients, a minimal intravascular volume status and management of hypoxia are essential. Aggressive fluid resuscitation, hyperventilation, and excessive ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad prognosis, CPR in trauma patients may be successful in select cases. Any CPR training is better than nothing; simplification of contents and processes remains important.

Die Intubations-LMA™ (ILMA) wurde konzipiert, um die endotracheale Intubation über eine Larynxmaske zu erleichtern und die Ventilation des Patienten zwischen den Intubationsversuchen zu ermöglichen. Da die Intubation ohne Sicht auf die laryngealen Strukturen jedoch die Gefahr einer ösophagealen Fehlintubation birgt, wird die tracheale Intubation häufig mithilfe eines flexiblen Endoskops durchgeführt. Dies führt zu erhöhtem materiellen und personellen Aufwand und zu verlängerten Intubationszeiten. Deshalb wurde die LMA CTrach™ Larynxmaske (CTrach) durch Integration fiberoptischer Bild- und Lichtleiter sowie einen aufsetzbaren Monitor entwickelt, sodass laryngeale Strukturen während der Intubation sichtbar gemacht werden können.Die Handhabung dieses neuen Instruments zur Atemwegssicherung wird bei 10 Patienten mit schwierigen Atemwegen dargestellt. Dabei wurde die Sicht auf die laryngealen Strukturen in einer für die CTrach spezifischen Einteilung in die Grade I (Aryknorpel, Glottis und Epiglottis eindeutig sichtbar) bis Grad IV (keine Sicht auf den Larynx möglich) unterteilt. Es werden definierte Maßnahmen vorgestellt, um die Sicht zu verbessern.Alle Patienten konnten erfolgreich über die LMA CTrach™ beatmet werden. Die Qualität der Beatmung war bei 9 Patienten suffizient, bei einem ausreichend möglich. Die Verteilung der initialen Sichtgrade I–IV betrug 1/2/1/6. Nach definierten Maßnahmen verbesserte sich die Verteilung der Sichtgrade auf 3/5/0/2. Die Intubation durch die CTrach gelang bei allen Patienten, bei 9 Patienten im ersten und bei einem Patienten im zweiten Versuch.Bei dieser kleinen untersuchten Patientengruppe mit schwierigen Atemwegsverhältnissen gewährleistete die CTrach eine hohe Erfolgsrate der Ventilation und Intubation. Die Durchführung definierter Maßnahmen verbesserte die Sicht auf die laryngealen Strukturen.The Intubating LMA™ was designed to facilitate blind intubation and to provide ventilation between two intubation attempts. However, blind intubation can be associated with a risk of oesophageal penetration, therefore, a flexible bronchoscope is frequently used to assist tracheal intubation. This leads to increased burdens on materials and personal resources and prolongs intubation times. Hence the LMA CTrach™ laryngeal mask airway (CTrach) was developed with an integrated fibreoptic system which can be connected to a monitor for visualisation of the larynx during intubation.We detail the initial experience gained with the practical handling of the CTrach and the application in 10 patients with difficult-to-manage airways. Laryngeal views were graduated in a CTrach-specific classification from grade I (clear view of the arytenoids, glottis and epiglottis) to grade IV (no part of the larynx can be identified). Adjusting manoeuvres were defined to improve the view of laryngeal structures.All patients could be successfully ventilated with the CTrach. Ventilation quality was rated adequate in nine and possible in one patient. The initial distribution of the laryngeal view between grades I–IV was 1/2/1/6 and after adjusting manoeuvres to improve the laryngeal view the grade distribution was 3/5/0/2. Intubation through the CTrach was successful in all patients, nine at first and one at the second attempt.In this small sample of patients with difficult-to-manage airways, the CTrach yielded high success rates for both ventilation and tracheal intubation. Adjusting manoeuvres can improve the laryngeal view further.

Die anästhesiologische und notfallmedizinische Versorgung von Säuglingen und Kleinkindern ist mit hohen klinischen Anforderungen verbunden. Dabei erfolgt ein Großteil der Maßnahmen durch pädiatrisch nichtspezialisierte Anästhesisten und Notärzte, die häufig wenig Routine im Umgang mit kinderanästhesiologischen Zwischenfällen und pädiatrischen Notfällen besitzen. Die Korrelation zwischen höherem Spezialisierungsgrad einerseits und verminderter perioperativer Morbidität und Mortalität andererseits ist durch umfangreiche Untersuchungen gut belegt. Die Etablierung verbesserter Ausbildungskonzepte scheitert jedoch häufig an den klinischen Strukturen und an den relativ geringen pädiatrischen Fallzahlen der meisten Einrichtungen. Seit kurzem nun stehen leistungsfähige Säuglingssimulatoren zur Verfügung, die ein sehr realitätsnahes Training eines großen Spektrums aus Kinderanästhesie und Kindernotfallmedizin ermöglichen. Ein multimodales Ausbildungskonzept, unter Einbeziehung simulatorunterstützter Techniken, könnte die weit verbreiteten Erfahrungsdefizite lindern und damit Behandlungsqualität und Patientensicherheit nachhaltig verbessern.

Im Bereich der Notfallmedizin ist die akzidentelle Hypothermie bei nicht traumatisierten Patienten ein seltenes Ereignis. Um auf die Bedeutung einer präzisen präklinischen Temperaturmessung hinzuweisen, werden zwei Fälle von akzidenteller Hypothermie (28,2°C und 29,3°C Körperkerntemperatur) vorgestellt, die unter Bedingungen aufgetreten sind, die eine starke Auskühlung zunächst nicht vermuten ließen. In dem einen Fall führten die schnelle Diagnose und die Therapie innerhalb weniger Stunden zur Restitutio ad integrum, im anderen verstarb der Patient im Multiorganversagen. Initiale Verdachtsdiagnosen, Diagnosefindung und Therapie sowie primäre Versorgung werden darüber hinaus dargestellt und diskutiert.

Purpose To investigate whether topical nonsteroidal anti inflammatory drugs (NSAIDs) are useful, in the absence of concomitant corticosteroid therapy, in limiting postoperative inflammation after uncomplicated cataract surgery.Methods A total of 328 patients were enrolled in a prospective, randomized, double-masked, parallel-group, active-controlled study. Anterior chamber inflammation (ACI) was evaluated as the primary efficacy parameter. Only patients with moderate inflammation (ACI score of ≤4) the day after surgery were randomized and treated with NSAIDs. A novel topical formulation containing 0.2% sodium naproxen was compared with 0.1% diclofenac. Both were administered three times a day for 14 consecutive days. Ocular inflammation was measured after 7 and 14 days by using slit-lamp biomicroscopy. Safety parameters were also evaluated at the same time.Results Both treatments were equally effective in controlling postsurgical inflammation. No statistically significant differences between treatment groups were observed for the safety variables. No serious adverse events (AEs) occurred during the course of the study. The most frequent AE reported with naproxen was eye redness.Conclusions NSAIDs can effectively be used without concurrent administration of corticosteroids to control postoperative inflammation after uncomplicated cataract surgery. In addition, naproxen ophthalmic solution may be considered a suitable alternative to the currently available NSAIDs.

Zusammenfassung Die Inzidenz respiratorisch bedingter Morbidität und Mortalität als Folge von Intubationsschwierigkeiten und unerkannter ösophagealer Intubation bleibt hoch, obwohl zahlreiche neue Atemwegstechniken und Strategien zur Bewältigung des schwierigen Atemwegs entwickelt wurden. Die Problematik liegt offenbar im Transfer dieser Techniken in die klinische Praxis. Vorträge und Übungen am Phantom und am Tierkadaver sind bislang die üblichen Methoden der Anleitung. Patientensimulatoren geben die Möglichkeit, unter sehr realistischen Bedingungen Fertigkeiten und Lösungen spezieller Situationen zu trainieren, erleichtern die Umsetzung von kognitiven, psychomotorischen und affektiven Fähigkeiten im klinischen Alltag und helfen, das Verhalten in kritischen Situationen zu verbessern. Dieser Artikel erläutert die Möglichkeiten von neuen Trainingskonzepten zur Sicherung der Atemwege, die mithilfe spezieller Simulationen und Simulatoren durchgeführt werden können. Es werden die technischen Voraussetzungen beschrieben und Hinweise zur praktischen Durchführung von schwierigen Atemwegsszenarien gegeben.

Abstract: The effect of titanium and titanium diboride inoculation on the spatial variation of local solidification time for direct chill (DC) cast ingots of aluminum alloy 5182 (AA5182) was studied. The results have been compared to those of an ingot cast without grain refining. To accomplish this, the effect of grain refining on a number of ingot characteristics such as grain size, macrosegregation, spatial variation of dendrite arm spacing, and thermal conductivity was investigated. Furthermore, the effect of grain refining on the well-known relationship between dendrite arm spacing and local solidification time had to be established for AA5182. The results indicated that the spatial variation of dendrite arm spacing in the industrial ingots was independent of grain refining, although the nonrefined ingot produced significantly finer dendrite arm spacings in its center. This was attributed to the influence of showering crystals in the nonrefined ingot. The relationship between dendrite arm spacing and local solidification time was also found to be independent of grain refining.

Hyperbranched (HB) aromatic polyamides (aramids), synthesized from A2 + B3 reagents (A = p-phenylenediamine; B = trimesic acid), have been used as polymeric supports for palladium(0) nanoparticles. The chemical−physical properties of these aramids, denoted as pPDT, have been compared to those of the polymer pABZAIA obtained from the AB2 monomer 5-(4-aminobenzamido)isophthalic acid. The two HB polymers show structural differences in the shape of the macromolecule as well as the nature of the end groups. The pPDT materials exhibit a less regular structure with both amino and carboxy terminal groups, while the pABZAIA polymer contains a single amine focal unit per molecule and carboxy end groups. HB aramid-supported Pd⁰ nanoparticles were obtained by reduction of polymer-supported PdCl2 with an aqueous solution of NaBH4. Some model compounds, mimicking the polymeric hyperbranched structure, were investigated to gain insight into the nature of the interactions occurring between PdCl2 and the support. The nature of the interactions between the polymeric matrix and PdCl2 was investigated by means of FT IR and XPS techniques. XPS spectroscopy, performed on both polymers and model molecules, indicated that the interaction between the support and the metallic precursor involves the terminal amino groups. The particle dimensions and the metallic dispersion were determined by TEM analysis. This study showed that the dimensions and dispersion of the metal clusters on pABZAIA are smaller than those on pPDT. A preliminary study of the catalytic performance of a specific Pd⁰/pPDT catalyst in the hydrogenation of relevant unsaturated substrates (benzene, benzylideneacetone, phenylacetylene, diphenylacetylene, and quinoline) has been carried out in either nonpolar or polar solvents. In most cases, the catalyst proved to be efficient, selective, and recyclable, yet the nature of the solvent affected remarkably the catalysis outcome in terms of both activity and selectivity.

The first synthesis of a polyurethane by frontal polymerization has been successfully carried out. Namely, the two reactants (1,6-hexamethylene diisocyanate and ethylene glycol) and the catalyst (dibutyltin dilaurate) were mixed together at room temperature in the presence of an additive (pyrocatechol, necessary for extending pot life), dimethyl sulfoxide (as the solvent), and a filler (fumed silica, added for stabilizing the propagating front). The reactions were thermally ignited at one end of the tubular reactor, and the resultant hot fronts were allowed to self-propagate throughout the reaction vessel. The effects of relative amounts of the above components on the most relevant parameters relating to frontal polymerization (temperature profile, front velocity, and temperature) were thoroughly investigated.

Purpose To describe the clinical manifestations in a patient with Sjögren reticular dystrophy of the retinal pigment epithelium, and the evolution of the disease over a 20-year follow-up period.Case Report A 45-year-old woman with Sjögren reticular dystrophy of the retinal pigment epithelium was seen for the first time in 1983; the patient underwent 20 years of annual check-ups.Results Over the follow-up period, fundus photographs, computerized perimetry, electroretinogram, and electro-oculogram findings had either normal or slightly subnormal outcome.Conclusions The results confirm that this disease involves only the retinal pigment epithelium and should not be considered a central tapeto-retinal degeneration or late onset retinopathy.

Matrix polymerization can be viewed as an intriguing procedure for the preparation of homogeneous blends that are otherwise difficult or practically impossible to prepare. Poly(p-phenyleneterephthalamide) has been synthesized by direct polycondensation in the presence of poly(N-vinylpyrrolidone) or poly(4-vinylpyridine) as polymer matrices. The molecular weight effect of the latter polymers on the intrinsic viscosity of the aramid has been investigated. Poly(p-phenyleneterephthalamide), characterized by intrinsic viscosity as high as 14.2 dL/g, is obtained when high molecular weight poly(N-vinylpyrrolidone) is used. The intimate composites formed in situ have been characterized by solid-state NMR. The parent and daughter polymers in the composite present the same proton T1 relaxation times in the rotating frame, and this value differs from that of the neat polymers; this result demonstrates the intimacy of the blend at the level of a few nanometers.

Wilcox et al. (THEOCHEM 2000, 528, 95; THEOCHEM 2001, 538, 67) have developed a fast running ab initio model based on the B3LYP/6-31G(d,p) model supplemented with parametric corrections for C,H,N atoms; the model proved to be sufficiently accurate to be useful in unraveling complicated kinetic schemes. This model is reexamined, and by fitting a subset of the singlet C,H,N molecules in the G2/97 database, three variants have been developed that provide more accurate and/or faster running protocols. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 770–774, 2001

Abstract:: We examine the critical behavior of a magnetic superlattice which made up of two magnetic materials, A and B. Using the effective field theory with a probability distribution technique that accounts for the single-site spin correlation, we derive the analytical equation for the Curie temperature of the superlattice which alternates as ABAB...AB. The dependence of the Curie temperature on the interface coupling strength Jab and the layer number of the finite superlattice was calculated. The effects of the surface modification are also studied.

The structure of hyperbranched aromatic polyamides synthesized from different ratios of p-phenylenediamine and trimesic acid (A2 + B3 reagent pair) has been investigated by means of ¹H and ¹³C NMR spectroscopy. On the basis of a detailed NMR signal assignment six 1,3,5-trisubstituted benzene moieties with different substitution patterns can be distinguished. The different monomer ratios influence the polymer architecture with respect to the content of these substructures, the degree of branching and the predominant functionalities (COOH or NH2). An excess of B3 results in a larger number of branches and a predominant COOH functionalization. ¹H NMR proves site-specific interactions between lithium cations and the polymer substructures. The observed chemical shift effects simplify the quantification of the spectra. Finally, acetylation of amino groups by acetic acid, an impurity in commercial trimesic acid, could be proven.

Calcium ions and various amounts of proteoglycans were removed from porcine articular cartilage explants using ethylenediaminetetraacetic acid or guanidinium chloride solutions. The water proton magnetic parameters such as T1 and T2 relaxation times, diffusion (D), and magnetization transfer (MS/M0) were then measured by 1D MR microscopy on native specimens, after incubation in the extracting solutions and after final reconditioning in a physiological saline. While the replacement of the interstitial fluid by the treating solutions strongly affected the various MR parameters, calcium depletion did not show any influence on the MRI appearance of the chondral tissue. Interestingly, only the longitudinal relaxation time T1 and the diffusion coefficient D were seen to be sensitive to an extensive proteoglycan depletion of the tissue. Our results indicate that a modest proteoglycan depletion, as it occurs in the early stage of a pathological cartilage degradation, has little relevance to the above MR parameters. Further MRI studies on the macromolecular components of cartilage are, therefore, necessary for a better understanding of the interaction mechanisms between water and extracellular matrix that might lead to the early diagnosis of the cartilage damage.

Recognition of conspecifics is an essential precursor of sexual reproduction. Most mammals and birds learn salient features of their parents or siblings early in ontogeny and later recognize individuals whose phenotypes match the mental image (template) of relatives closely enough as conspecifics. However, the young of brood parasites are reared among heterospecifics, so social learning will yield inappropriate species recognition templates. Initially, it was inferred that conspecific recognition in brood parasites depended on genetically determined templates. More recently it was demonstrated that learning plays a critical role in the development of parasites' social preferences. Here we propose a mechanism that accommodates the interaction of learned and genetic components of recognition. We suggest that conspecific recognition is initiated when a young parasite encounters some unique species–specific signal or 'password' (e.g. a vocalization, behaviour or other characteristic) that triggers learning of additional aspects of the password–giver's phenotype. We examined the possibility that nestlings of the obligately brood–parasitic brown–headed cowbird (Molothrus ater) could use a species–specific vocalization, the 'chatter', as a password. We found that six–day–old nestlings responded (begged) significantly more frequently to playbacks of chatters than to other avian sounds and that two–month–old fledglings approached playbacks of chatters more quickly than vocalizations of heterospecifics. Free–living cowbird fledglings and adults also approached playbacks of chatters more often than control sounds. Passwords may be involved in the ontogeny of species recognition in brood parasites generally.

The latest generation of shock wave lithotripters, with therapy heads mounted on articulated arms, have found widespread application in the treatment of orthopedic diseases. Currently, integration of an ultrasound probe in the therapy head is the dominant modality for positioning the shock wave focus on the treatment area. For orthopedic applications, however, X-ray imaging is often preferred. This article describes a new method to locate the therapy head of a lithotripter. In the first step, the surgeon positions the tissue to be treated at the isocenter of a C-arc. This is achieved using AP and 30-degree lateral projections, with corresponding horizontal and vertical movements of the patient under fluoroscopic guidance. These movements register the anatomic location in the coordinate system of the C-arc. In the second step, the therapy head is navigated to align the shock wave focus with the isocenter. Position data are reported from an optical tracker mounted on the X-ray system, which tracks an array of infrared LEDs on the therapy head. The accuracy of the tracking system was determined on a test bench, and was calculated to be 1.55 mm (RMS) for an angular movement of ±15 degrees around a calibrated position. Free-hand navigation and precise alignment are performed with a single virtual reality display. The display is calculated by a computer system in real time, and uses graphical symbols to represent the shock wave path and isocenter. In an interactive process, the physician observes the display while navigating the therapy head towards the isocenter. Precise alignment is achieved by displaying an enlarged view of the intersecting graphical symbols. Results from the first tests on 100 patients demonstrate the feasibility of this approach in a clinical environment. Comp Aid Surg 6:22–31 (2001). © 2001 Wiley-Liss, Inc.

Surfactant protein C (SP-C) is a lung-specific secreted protein, which is synthesized as a 21-kDa propeptide (SP-C(21)) and then proteolytically processed as a bitopic transmembrane protein in subcellular compartments distal to the medial Golgi to produce a 3.7 kDa mature form. We have shown that initial processing of SP-C(21) involves two endoproteolytic cleavages of the C terminus and that truncation of nine amino acids from the C-flanking peptide resulted in retention of mutant protein in proximal compartments. Because these truncations involved removal of a conserved cysteine residue (Cys(186)), we hypothesized that intralumenal disulfide-mediated folding of the C terminus of SP-C(21) is required for intracellular trafficking. To test this, cDNA constructs encoding heterologous fusion proteins consisting of enhanced green fluorescent protein (EGFP) attached to the N terminus of wild-type rat proSP-C (EGFP/SP-C(1-194)), C-terminally deleted proSP-C (EGFP/SP-C(1-185); EGFP/SP-C(1-191)) or point mutations of conserved cysteine residues (EGFP/SP-C(C122G); EGFP/SP-C(C186G); or EGFP/SP-C(C122/186G)) were transfected into A549 cells. Fluorescence microscopy revealed that transfected EGFP/SP-C(1-194) and EGFP/SP-C(1-191 )were expressed in a punctate pattern within CD-63 positive, EEA-1 negative cytoplasmic vesicles. In contrast, EGFP/SP-C(1-185), EGFP/SP-C(C122G), EGFP/SP-C(C186G) and EGFP/SP-C(C122/186G) were expressed but retained in a juxtanuclear compartment that stained for ubiquitin and that contained (&ggr;)-tubulin and vimentin, consistent with expression in aggresomes. Treatment of cells transfected with mutant proSP-C with the proteasome inhibitor lactacysteine enhanced aggresome formation, which could be blocked by coincubation with nocodazole. Western blots using a GFP antibody detected a single form in lysates of cells transfected with EGFP/SP-C cysteine mutants, without evidence of smaller degradation fragments. We conclude that residues Cys(122) and Cys(186) of proSP-C are required for proper post-translational trafficking. Mutation or deletion of one or both of these residues results in misfolding with mistargeting of unprocessed mutant protein, leading to formation of stable aggregates within aggresomes.