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The electroweak interaction in the Standard Model (SM) is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this work, we present the most precise measurement of tensor currents in the low-energy regime by examining the $\beta$-$\bar{\nu}$ correlation of trapped $^{8}$Li ions with the Beta-decay Paul Trap. We find $a_{\beta\nu} = -0.3325 \pm 0.0013_{stat} \pm 0.0019_{syst}$ at $1\sigma$ for the case of coupling to right-handed neutrinos $(C_T=-C_T')$, which is consistent with the SM prediction., Comment: 6 pages, 3 figures, 1 table

The electroweak interaction in the Standard Model (SM) is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this work, we present the most precise measurement of tensor currents in the low-energy regime by examining the $β$-$\barν$ correlation of trapped $^{8}$Li ions with the Beta-decay Paul Trap. We find $a_{βν} = -0.3325 \pm 0.0013_{stat} \pm 0.0019_{syst}$ at $1σ$ for the case of coupling to right-handed neutrinos $(C_T=-C_T')$, which is consistent with the SM prediction., 6 pages, 3 figures, 1 table

Background The prevalence of end-stage renal disease of unknown etiology in adult patients is globally high and accounts for almost 20% of all dialysis patients. Recent studies have suggested that the percentage of adult patients with a causal genetic variant has been underestimated so far. Despite severe prognostic and therapeutic implications, awareness about prevalence and manifestations of genetic kidney diseases in adult renal patients is still limited. Methods We recruited 58 individuals from 39 families at our transplantation center, fulfilling at least one of the following criteria: (i) unclear etiology of kidney disease, (ii) clinically suspected genetic kidney disease and (iii) positive family history for nephropathies. The cohort consisted of patients waitlisted for kidney transplantation and patients in the follow-up after transplantation. Detailed documentation of family history and phenotype was obtained before initiating gene panel sequencing of 479 nephropathy-associated genes. Results With this study design, a molecular genetic diagnosis was established in one-third of all patients. Mutations in the collagen COL4A genes, and mutations in MUC1 and UMOD were the most frequent among all detected causal variants. Overall, rare genetic variants were detected in more than half of all cases. Conclusion The combination of detailed phenotyping prior to next-generation sequencing diagnostics was highly efficient. Elucidating the underlying genetic causes in a cohort of adult renal patients has considerable clinical impact on medical management.

Cardiac autonomic modulation of heart rate, assessed by heart rate variability (HRV), is commonly used to monitor training status. HRV is usually measured in athletes after awakening in the morning in the supine position. Whether recording during standing reveals additional information compared to supine remains unclear. We aimed to evaluate the association between short-duration HRV, assessed both in the supine and standing position, and a low-intensity long-duration performance (walking ultramarathon), as well as training experience. Twenty-five competitors in a 100 km walking ultramarathon underwent pre-race supine (12 min) and standing (6 min) HR recordings, whereas performance and subjective training experience were assessed post-race. There were no significant differences in both supine and standing HRV between finishers (n = 14) and non-finishers (n = 11, mean distance 67 km). In finishers, a slower race velocity was significantly correlated with a higher decrease in parasympathetic drive during position change [larger decrease in High Frequency power normalized units (HFnu: r = −0.7, p = 0.01) and higher increase in the detrended fluctuation analysis alpha 1 index (DFA1: r = 0.6, p = 0.04)]. Highly trained athletes accounted for higher HFnu during standing compared to poorly trained competitors (+11.5, p = 0.01). Similarly, greater training volume (total km/week) would predict higher HFnu during standing (r = 0.5, p = 0.01). HRV assessment in both supine and standing position may provide additional information on the dynamic adaptability of cardiac autonomic modulation to physiologic challenges and therefore be more valuable for performance prediction than a simple assessment of supine HRV. Self-reported training experience may reliably associate with parasympathetic drive, therefore indirectly predicting long-term aerobic performance in ultramarathon walking races.

Cardiac autonomic modulation of heart rate, assessed by heart rate variability (HRV), is commonly used to monitor training status. HRV is usually measured in athletes after awakening in the morning in the supine position. Whether recording during standing reveals additional information compared to supine remains unclear. We aimed to evaluate the association between short-duration HRV, assessed both in the supine and standing position, and a low-intensity long-duration performance (walking ultramarathon), as well as training experience. Twenty-five competitors in a 100 km walking ultramarathon underwent pre-race supine (12 min) and standing (6 min) HR recordings, whereas performance and subjective training experience were assessed post-race. There were no significant differences in both supine and standing HRV between finishers (n = 14) and non-finishers (n = 11, mean distance 67 km). In finishers, a slower race velocity was significantly correlated with a higher decrease in parasympathetic drive during position change [larger decrease in High Frequency power normalized units (HF nu : r = -0.7, p = 0.01) and higher increase in the detrended fluctuation analysis alpha 1 index (DFA1: r = 0.6, p = 0.04)]. Highly trained athletes accounted for higher HF nu during standing compared to poorly trained competitors (+11.5, p = 0.01). Similarly, greater training volume (total km/week) would predict higher HF nu during standing (r = 0.5, p = 0.01). HRV assessment in both supine and standing position may provide additional information on the dynamic adaptability of cardiac autonomic modulation to physiologic challenges and therefore be more valuable for performance prediction than a simple assessment of supine HRV. Self-reported training experience may reliably associate with parasympathetic drive, therefore indirectly predicting long-term aerobic performance in ultramarathon walking races.

Nowadays, varistors are widely used because of their energy absorption capability (EAC) with concomitant economy and efficiency. Surges and overvoltage transients unnoticeably degrade Metal Oxide Varistors (MOV) over time. A newly developed condition monitoring system is based on a time-resolved measurement of the discharge current. In order to be able to compare and interpret acquired data sets from the monitoring system with relevant aging models, extensive investigations of the measurable influences are required. Therefore, an experimental setup has been developed for determining different aging characteristics and process influences. A precise continuous curve recording over nine current decades from the ohmic leakage current area to the limiting resistance region up to several thousand Amperes allows studying aging characteristics of differently stressed MOVs. This method combines common spot-measurements from the curves like mA-Point, leakage current and the nonlinearity exponent alpha. In this paper, a fully automated test bench is presented. The performance of the system and its advantages are compared to manually operated tests and different test equipment. First experimental results show that single point measurements, depending on the type of stress, are insufficient to detect degradation characteristics. Especially in the transition area from the ohmic linear range to the non-linear range, irregularities terms of degradation are ascertained. These studies are the basis for building up relevant aging models depending on the process measurement variables. This results in more accurate predictions for the state of health of varistor ceramics by using recorded data sets as the time-resolved measurement of the discharge current. Finally, it helps to understand the change of characterization by different impacts. In addition, the system is scalable for the study of layered surge arresters and thus applicable to all network levels.

The increasing number of sensitive electrical equipment demands Surge Protective Devices (SPDs) with major challenges and a high degree of reliability. The enquiry for early-warning systems for unwanted and unexpected equipment failure is strongly rising over the last years. The integration of early warning systems as a condition monitoring in Industrial Internet of Things (1IoT) is in contrast to most of the common devices an unsolved subject in electric power distribution. This paper presents an advanced measuring method for lightning disturbance with cloud-based monitoring of SPDs. Due to an advanced bandwidth, this device is capable of the simultaneous measurement of low-energy Electromagnetic Interferences (EMI), high-energy lightning surge currents and finally long duration currents with amplitudes of about 300 A over several milliseconds. Therefore a new type of a retrofittable coreless current transformer has been developed. The induced signal is converted with a wide dynamic range and a linear frequency response. Results show that the signal is digitized with a high accuracy for the monitoring of SPDs to permit condition-oriented and predictive maintenance. The data transmission and storage is realized by a cloud solution and offers storage and Big Data processing options. The analysis allows an adaptation of iteratively improved aging models by increasing records of overvoltage events.

A smart monitoring system with internet connectivity opens up the possibility to bring surge protective devices (SPDs) into the internet of things (IoT). Each voltage or current impulse at the SPD is measured and the measurement data is transferred into a cloud based storage. The cloud frontend opens many options to analyze the measured data and to derive the actual status of the SPD. By assessment of the impact of all stress events the pre-damages of the arrester can be determined to evaluate its actual “State of Health” (SoH). Even an estimation of the residual lifetime becomes feasible. With all this collected information maintenance requirements become predictable and maintenance work can be planned much more efficiently.

Antibiotic combination therapies are an approach used to counter the evolution of resistance; their purported benefit is they can stop the successive emergence of independent resistance mutations in the same genome. Here, we show that bacterial populations with ‘mutators’, organisms with defects in DNA repair, readily evolve resistance to combination antibiotic treatment when there is a delay in reaching inhibitory concentrations of antibiotic—under conditions where purely wild-type populations cannot. In populations subjected to combination treatment, we detected a remarkable amount of genomic diversity in resistance-determining mutations, multi-drug efflux pumps, and mutation-rate altering genes. However, using eco-evolutionary simulations, we demonstrate that only the initial mutator allele is required to explain multi-resistance evolution. Unexpectedly, mutators not only allowed multi-resistance to evolve under combination treatment where it was favoured, but also under single-drug treatments. Under both conditions, the mutator allele swept to fixation through hitch-hiking with single-drug resistance, enabling subsequent resistance mutations to emerge. Ultimately, our results suggest that mutators may hinder the utility of combination therapy when mutators are present. Additionally, by raising the rates of population mutation, selection for multi-resistance may have the unwanted side-effect of increasing the potential to evolve resistance to future antibiotic treatments.Significance statementThe global rise in antimicrobial resistance means that we urgently need new approaches to halt its spread. Antibiotic combination therapy, treatment involving more than one antibiotic, is a strategy proposed to do just that. Evolving resistance to combinations is thought to be exceedingly rare, as it would require two independent mutations to occur in the same genetic background before microbial growth is inhibited. We find that wild-type populations cannot achieve this, even when antibiotic concentrations increase gradually. However, populations with ‘mutators’, organisms with elevated mutation rates through DNA repair defects, can readily evolve multi-drug resistance under both single-drug and combination treatments. Further, hitch-hiking of mutator alleles alongside resistance increases the evolutionary potential for acquiring further resistance mutations. As mutators are commonly found in natural populations, including infection, our results suggest that combination therapy may not be as resilient a strategy against resistance evolution as was once thought.

Today’s passenger car diesel engines are distinguished by low exhaust emissions and low fuel consumption. In the lower load and engine speed range, however, dominant combustion noises are produced by the higher combustion delay, particularly when the engine is started and warming up. Although multiple pilot injections are used nowadays to reduce irritating combustion noise of this type, they clash with higherpriority exhaust emissions.

Background COPD influences cardiac function and morphology. Changes of the electrical heart axes have been largely attributed to a supposed increased right heart load in the past, whereas a potential involvement of the left heart has not been sufficiently addressed. It is not known to which extent these alterations are due to changes in lung function parameters. We therefore quantified the relationship between airway obstruction, lung hyperinflation, several echo- and electrocardiographic parameters on the orientation of the electrocardiographic (ECG) P, QRS and T wave axis in COPD. Methods Data from the COPD cohort COSYCONET were analyzed, using forced expiratory volume in 1 s (FEV1), functional residual capacity (FRC), left ventricular (LV) mass, and ECG data. Results One thousand, one hundred and ninety-five patients fulfilled the inclusion criteria (mean ± SD age: 63.9 ± 8.4 years; GOLD 0–4: 175/107/468/363/82). Left ventricular (LV) mass decreased from GOLD grades 1–4 (p = 0.002), whereas no differences in right ventricular wall thickness were observed. All three ECG axes were significantly associated with FEV1 and FRC. The QRS axes according to GOLD grades 0–4 were (mean ± SD): 26.2° ± 37.5°, 27.0° ± 37.7°, 31.7° ± 42.5°, 46.6° ± 42.2°, 47.4° ± 49.4°. Effects of lung function resulted in a clockwise rotation of the axes by 25°-30° in COPD with severe airway disease. There were additional associations with BMI, diastolic blood pressure, RR interval, QT duration and LV mass. Conclusion Significant clockwise rotations of the electrical axes as a function of airway obstruction and lung hyperinflation were shown. The changes are likely to result from both a change of the anatomical orientation of the heart within the thoracic cavity and a reduced LV mass in COPD. The influences on the electrical axes reach an extent that could bias the ECG interpretation. The magnitude of lung function impairment should be taken into account to uncover other cardiac disease and to prevent misdiagnosis. Electronic supplementary material The online version of this article (10.1186/s12931-019-1025-y) contains supplementary material, which is available to authorized users.

[nicht vorhanden / not available], Bonner Jahrbücher, Bd. 82 (1886): Jahrbücher des Vereins von Altertumsfreunden im Rheinlande

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference.Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, post-bronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores.Main outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points.Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points.Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. (C) 2017 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

This paper presents the results of a test campaign meant to determine coupling paths into a laboratory test setup of typical power grid substation SCADA (Supervisory Control and Data Acquisition) electronics. The devices were tested against conducted threats in a bulk current injection (BCI) setup and radiated threats inside a transverse electromagnetic (TEM) waveguide as well as with a near-field TEM horn antenna. The various excitation methods and different test setups offer the possibility to trace back the observed effects to coupling paths into the tested system. For frequencies below 300 MHz the dominating coupling path to the system under test (SUT) was determined to be the Ethernet cable connected to the telecontrol device. Above 800 MHz direct radiated coupling into the test devices was identified to be dominating. The conducted coupling via a predefined wiring harness with supply cabling was less relevant for both selected substation devices.

Background Mild hypothermia treatment (32–34°C) in survivors after cardiac arrest (CA) is clearly recommended by the current guidelines. The effects of cooling procedure towards QT interval have not been evaluated so far outside of case series. In a prospective study 34 consecutive survivors after cardiac arrest were continuously monitored with Holter ECG over the first 48h. Patients and methods A total of 34 patients were analysed and received mild therapeutic hypothermia treatment (MTH) according to the current guidelines and irrespective of the initial rhythm. At admission to hospital and in the field in case of OHCA, a 12-lead ECG was performed in all patients. Results During cooling the incidence of ventricular tachycardia was low (8.8%) and in none of the patients Torsade de pointes occurred. The QTc interval was within normal range at first patient contact with EMS in the field (440.00ms; IQR 424.25–476.75; n =17) but during hypothermia treatment the QTc interval was significantly prolonged at 33°C after 24h of cooling (564.47ms; IQR 512.41–590.00; p =0.0001; n =34) and decreased after end of hypothermia to baseline levels (476.74ms; 448.71–494.97; p =0.15). Conclusion The QTc interval was found to be significantly prolonged during MTH treatment, and some severe prolongations >670ms were observed, without a higher incidence of life-threatening arrhythmias, especially no Torsade des pointes were detected. However, routine and frequent ECG recording with respect to the QTc interval should become part of any hypothermia standard operation protocol and should be recommended by official guidelines.

Der Trend zum Leichtbau fuhrt zu einem vermehrten Einsatz von Kunststoffbauteilen im Automobilbau. Hiervon sind auch stark schallabstrahlende Motoranbauteile wie Ventildeckel und Olwannen betroffen. Im Rahmen eines am Lehrstuhl fur Verbrennungskraftmaschinen (VKA) der RWTH Aachen und am Institut fur Kunststoffverarbeitung (IKV) an der RWTH Aachen durchgefuhrten ZuTech-Forschungsvorhabens wurde eine Methodik zur Vorausberechnung des akustischen Verhaltens von Kunststoffbauteilen entwickelt und validiert. Die Aufgabe wurde von der Forschungsvereinigung Verbrennungskraftmaschinen e. V. (FVV, Frankfurt/Main) unter der Nr. 899 und der Vereinigung zur Forderung des IKV gestellt. Die Integration des Verfahrens in den Entwicklungsprozess ermoglicht bereits fruhzeitig die Detektion und akustische Optimierung lokaler Schwachstellen der Bauteilstruktur.

As a consequence of the trend towards lightweight construction, plastic components are increasingly being used in automobile manufacturing. This includes engine components which emit a considerable degree of noise, such as valve covers and oil pans. Within the context of a ZuTech research project carried out at the Institute for Internal Combustion Engines (VKA) at RWTH Aachen University and the Institute of Plastics Processing (IKV) at RWTH Aachen University, a method of predicting the acoustic behavior of plastic components has been developed and validated. The assignment was given by the Forschungsvereinigung Verbrennungskraftmaschinen e. V. (FVV, Frankfurt / Main, Germany) under No. 899 and the Vereinigung zur Forderung des IKV. Integrating the method into the development process enables local weaknesses of the structure to be detected and the acoustics to be optimized at a very early stage.

Background The aim of the study was to report the impact of our hypothermia protocol on survival and neurological outcome. Furthermore, we were interested in the risk of bleeding complications in patients with acute myocardial infarction (AMI) being treated with percutaneous coronary revascularisation (PCI) and therapeutic hypothermia. Methods and results In a prospective observational study we identified 31 comatose patients (25 male, age 65±13 years) admitted to our intensive care unit with out-of-hospital cardiac arrest due to AMI who were treated with hypothermia. They were compared to 31 historical age- and gender-matched controls (25 male, age 65±12 years) admitted after out-of-hospital cardiac arrest due to AMI in the era prior to hypothermia treatment. Peak creatinine kinase-MB was 118 U/L (94–248) in the hypothermia group and 131 U/L (98–257) in controls ( p =0.51). In the hypothermia group, 19 patients were discharged with a favourable neurological outcome, whereas in controls, such outcome was observed in only six patients ( p =0.002). In both groups, haemoglobin values and platelet counts declined during the first 48 h (all p p =1.0), transfusion requirements ( p =1.0), and the number of transfusions ( p =0.9) were observed between the groups. Conclusions A major improvement in neurological outcome was observed in patients treated with hypothermia. Our results indicate that the combination of reperfusion strategies and the application of hypothermia do not carry an excessive risk of bleeding complications. Patients with AMI and out-of-hospital cardiac arrest should receive the optimal therapy for both conditions, that is, either thrombolysis or PCI and therapeutic hypothermia.

The solventless asymmetric alkylation of a nickel complex in a ball mill gives amino acid precursors with stereochemical control.

In diesem Beitrag werden die Einflusse und Wechselwirkungen verschiedener Motorkomponenten auf das Klopfsensorsignal dargestellt. Diese Einflusse erschweren zunehmend die Applikation einer Klopferkennung. Durch Bauteilvariationen gelang es, gezielt Storungen in das Klopfsensorsignal einzubringen und anschliesend mittels DoE-Modellen (DoE: Design of Experiments) sowie mit Zeit-Frequenzanalysen die qualitativen und quantitativen Zusammenhange zu ermitteln. Der vorliegende Bericht stellt eine Zusammenfassung des FVV-Forschungsvorhabens „Storgerausche in Klopfregelsystemen“ dar.

This paper examines the influences and reciprocal effects of many different engine components (e.g. pistons, valve train) on the knock sensor signal. These influences are making it increasingly difficult to calibrate a knock detection system. By varying components it was possible to introduce specific disturbances into the knock sensor signal and then determine the qualitative and quantitative relationships using DoE models (DoE: Design of Experiments) as well as time-frequency analyses. The following report summarizes the research project carried out by FVV (Forschungsvereinigung Verbrennungskraftmaschinen) in relation to disturbing noises in knock control systems.

Dominierende Gerauschquellen von modernen Verbrennungsmotoren sind oft die uber Dichtungen angekoppelten Bauteile wie Olwanne oder Ventildeckel [1,2,3]. Die akustische Optimierung solcher fuspunkterregten Komponenten wird in der Regel an Einzelstrukturen vorgenommen. Dabei bleiben mogliche akustische Wechselwirkungen durch den strukturdynamischen Einfluss der Dichtung weitgehend unberucksichtigt. Aus diesem Grund ist am Lehrstuhl fur Verbrennungskraftmaschinen der RWTH Aachen (VKA) ein Verfahren entwickelt worden, das es ermoglicht, das Strukturubertragungsverhalten von Elastomerdichtungen zu berechnen und zu optimieren.

A new chiral Ni(II)—complex (I) is synthesized from proline-derived amide, glycine, and Ni(NO3)2.

Besides amyloidosis and light chain deposition disease, the most common histological type of renal lesion is cast nephropathy in 30% of patients with multiple myeloma [2]. In contrast to amyloidosis, cast nephropathy is believed to be potentially reversible when circulating light chains are rapidly reduced. We report on three patients with multiple myeloma and cast nephropathy treated with a bortezomib-based chemotherapy in addition to a newly developed high-cutoff polyflux® haemofilter. Reduction in serum free light chain levels was achieved within 10-12 days, with all three patients improving their renal function.

Covers of combustion engines are often dominant noise sources. The NVH optimization of such structures is usually carried out on single components. These structures may exhibit unwanted noise emissions when combined into the entire powertrain structure. Possible acoustical interactions due to the dynamic transfer behavior of the gasket systems are neglected. The Institute for Combustion Engines of Aachen Technical University under the direction of Prof. S. Pischinger developed a method which allows to simulate and optimize the structure borne noise transfer of elastomeric gaskets.

Global youth unemployment stands at record levels and significantly outstrips that of joblessness rates for other age groups. Everywhere you look, the numbers are deeply troubling. The latest statistics from the International Labour Organization put the global youth unemployment rate at more than 81 million workers – 40 percent of the total unemployed. The developing world, with generally younger populations, is disproportionately affected. According to the ILO, the highest regional youth unemployment rates exist in the Middle East and North Africa, where close to one out of every four young people are out of work.

The use of chiral thioureas as catalysts for the solvent-free anti-selective Michael reaction of 2-nitrocyclohexan-1-one and nitrovinyl compounds under ball milling is described.

Clotting of the extracorporal system is the main complication of heparin free hemodialysis performed in patients with an increased risk of bleeding. The authors compared thromboxane B2, platelet factor 4, beta-thromboglobulin, and thromboelastography in systemic blood as markers of thrombogenicity during hemodialysis in eight patients with an increased risk of bleeding. Measurements were performed during hemodialysis with and without heparin. Thromboxane B2 levels in centrifuged blood were evaluated by an 125I assay system using a special extraction with mini-columns and magnetic separation (normal 32-64 pg/ml). At the onset of hemodialysis, thromboxane B2 concentrations in the inflow arterial blood line were lower than normal (30 +/- 23 pg/ml). Thromboxane B2 increased (97 +/- 105 versus 40 +/- 26 pg/ml) and was significantly higher during heparin free hemodialysis than during hemodialysis with heparin (p = 0.01, Wilcoxon matched pairs signed rank test). The highest values were observed in 5 cases with signs of clotting (152 +/- 122 pg/ml). Among the investigated parameters, thromboxane B2 proved to be the most significant serum parameter correlated with platelet activation and the consequently increased risk of incipient clotting during heparin free hemodialysis.

A series of new thiourea catalysts of type THU (19 examples) is prepared from natural amino acids and applied in the reaction with nitroalkene (IId).

Summary Intestinal transplantation (ITX) can be a successful treatment for patients with irreversible intestinal failure and associated severe complications. Because of long waiting periods and organ shortages, the precise identification of eligible patients and their early referral to centers that perform ITX is important. We retrospectively analyzed all patients who were referred to our center between 2000 and 2011 concerning their referral criteria, waitlist characteristics, and outcome. A total of 87 patients (47 male patients, 40 female patients; median age 39.8 ± 13.4 years) were referred to our center. All patients presented with intestinal failure caused by short bowel syndrome or motility disorders. About 80.5% of patients were evaluated for isolated ITX, modified multivisceral (mMVTX), or multivisceral transplantation (MVTX). About 56.3% were listed at EUROTRANSPLANT, 33.3% suffered from severe secondary organ failure requiring MVTX, and 34.5% were transplanted. 14.3% (all MVTX-candidates) died on the waitlist as a result of infectious complications. The high proportion of MVTX candidates underlines the need for early referral to specialized centers. MVTX-candidates have a high waitlist mortality for different reasons. However, the current allocation policy for MVTX does not mirror the severity of disease and may therefore contribute to high waitlist mortality.

A convenient synthesis of enantiopure (S)-2-(diphenylmethylsilyl)pyrrolidine is described and its organocatalytic activity in asymmetric Michael reactions is demonstrated.

In intensive care medicine, correctly identifying the underlying cause of illness in patients presenting to critical care units is often the key to applying a successful therapeutic regimen. We report on a patient in whom, despite anamnestic hints, the correct diagnosis was obscured by misleading laboratory results. A previously healthy male physician aged 36 years presented to the emergency room because of balance disturbances and gait problems. These symptoms began a few hours after ingestion of remarkably bitter tasting mineral water in the office of the research laboratory. Soon after admission, the patient became progressively confused and reported visual hallucinations; his neurological symptoms rapidly worsened. The findings of initial diagnostic tests, including blood tests, microbiological and toxicological screening, cranial computed tomography scanning and magnetic resonance imaging, were unremarkable. Nevertheless, the patient soon had to be sedated and intubated to prevent aspiration. Within the next 24 hours the patient developed multiple organ failure with renal, liver, respiratory and circulatory failure, and signs of disseminated intravascular coagulation and rhabdo-myolysis. Severe sepsis of unknown cause was presumed, and empirical treatment with antibiotics and a course of activated protein C was initiated; clinical management required high amounts of fluids and catecholamines. Extensive microbiological tests, including repeated blood and sputum cultures, serology for leptospira and borrelia, and polymerase chain reaction for herpes simplex virus DNA, were unfruitful. On day 3 after admission repeated toxicological examination of blood samples and the mineral water revealed contamination with acrylamide at high concentrations. Treatment with antibiotics and activated protein C was immediately terminated, and therapy with high doses of N-acetylcysteine was initiated to replenish hepatic glutathione stores. Between days 4 and 8 cardiac function gradually returned to normal, and platelet count, coagulation parameters and renal function also improved. On day 6 the patient was extubated; he exhibited signs of severe peripheral polyneuropathy with initial tetraplegia, bilateral affection of the vagal nerve and resulting laryngoplegia. When he was transferred for further neurological rehabilitation after 21 days of intensive care, the patient was still suffering from occasional confusion and hallucinations and was unable to walk. Acute acrylamide intoxication in humans is a rare event that has been reported only once in the literature [1]. The diagnosis should be considered in individuals with access to acrylamide (for instance, those working in molecular laboratories) who develop symptoms of central nervous system disturbances followed by cardiovascular, respiratory and other organ manifestations [2]. Gas chromatographic tandem mass spectrometry has been proven to be a sensitive method for the detection of acrylamide [3]. The clinical picture of acrylamide intoxication might suggest severe sepsis with acute onset, but this diagnosis should be challenged as long as it remains a working hypothesis.

Therapeutic hypothermia after cardiac arrest is a treatment with a high level of evidence. In 2003 the International Liaison Committee on Resuscitation (ILCOR) recommended such treatment for all comatose survivors of out-of-hospital cardiac arrest when the initial rhythm was ventricular fibrillation [1]. However, recent studies have shown that only a minority of resuscitated patients are treated with therapeutic hypothermia in both American and European intensive care units [2-4]. A letter recently published in Critical Care reported the use of therapeutic hypothermia in Germany in only 38% of departments treating patients after cardiac arrest [5]. To improve adherence to the ILCOR guidelines we developed a written standard operating procedure (SOP) for patients after cardiac arrest admitted to our 38-bed medical intensive care unit. Starting in December 2005 the SOP was to be applied to all comatose patients after cardiac arrest, irrespective of the initial rhythm. Since then the SOP has been applied in 28 out of 34 eligible patients. For four patients the physician in charge did not consider therapeutic hypothermia despite clear indication. In two other patients hypothermia was considered to be contraindicated because of extensive coronary vasospasm or massive pulmonary bleeding of a bronchial carcinoma, respectively. In all the remaining 28 patients surface cooling with technical devices (CritiCool from MTRE, Yavne Israel, and ArcticSun from Medivance, Louisville, KY, USA) was used to induce and maintain hypothermia for 24 hours. The target temperature of 33°C was reached in 6.0 ± 3.2 hours (mean ± SD). In none of the patients were serious adverse events potentially related to therapeutic hypothermia, such as clinically relevant bleeding episodes or arrhythmias, observed. In 12 out of 28 patients (42.9%) treated with therapeutic hypothermia a favourable neurologic outcome was reached (Cerebral Performance Category 1 or 2). Although our limited experience does not yet permit a valid statistical evaluation of the impact of therapeutic hypothermia on the neurological outcome of the patients, initial results are encouraging. We are currently trying to shorten the time to target temperature, which we feel was still too long in some patients. However, the simple availability of a written SOP has already led to the application of therapeutic hypothermia in the vast majority of our patients after cardiac arrest. All physicians caring for such patients should be encouraged to establish their own protocol for therapeutic hypothermia at their institutions, to facilitate the widespread application of this evidence-based treatment.

Background— Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms. Methods and Results— We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by 33%. Western blotting made it apparent that VSMC infection resulted in increased cell membrane-associated RhoA and Rac1, implying increased prenylation of these proteins. This effect was blocked by statin but circumvented by mevalonate. Cytochrome C assays showed that infected VSMCs produced increased reactive oxygen species that was blocked by statin. Infection increased nuclear transcription factor-κB expression in VSMCs that was dose-dependently suppressed by statin. Infected VSMCs produced and released RANTES and MCP-1. Statin dose-dependently blocked this production both at the mRNA and protein levels. Mevalonate and M geranylgeranylpyrophosphate circumvented these effects. Conclusions— C pneumoniae can be transmitted from macrophages to VSMCs. VSMCs showed an activation profile typical of atherosclerosis, namely Rac1 and RhoA prenylation, nuclear transcription factor-κB activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae -induced signaling and transmission.

Seasonal Affective Disorder (SAD) has received formal research attention only within the last eight years. Diagnostic criteria for SAD include many characteristics typical of depression: sadness, low self-esteem, lack of energy, social withdrawal, and suicide ideation, and features of atypical depression: carbohydrate craving, overeating, weight gain, and hypersomnia. Differential diagnosis of the disorder depends on an onset in fall/winter and remission in spring/summer. It was hypothesized that spinal cord injury (SCI) patients would have a higher incidence of the disorder in the northern latitudes because of decreased outdoor activities in winter and because of such light-depriving winter survival tactics as installing opaque plastic for storm windows. SCI patient responded to a postal survey which included Rosenthal's Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI). Results showed a substantially higher rate of SAD among SCI patients than in the normative sample.

Motility of Euglena gracilis shows free running circadian rhythms. The circadian system is sensitive to light and temperature signals, but it is always masked by direct responses of motility to light (photokinesis) and temperature (thermokinesis). By means of a compartimental model which defines the interrelations between the pathways of thermokinesis, photokinesis and the circadian system a unifying view of effects of temperature and light input signals is outlined. According to the model, and using double sine input signals the dynamics of thermokinesis is described by a differential amplifier with constant gain. Although thermokinesis heavily masks circadian responses to temperature signals, the limited range of circadian entrainment is indirectly demonstrated by a limited reappearance of free running circadian oscillations after stopping the temperature program. Free running circadian oscillations do reappear only after pretreatment with temperature periods near the circadian eigenperiod. A white mutant lacking photosynthesis is used to investigate the role of photosynthesis in the signal processing. Although light synchronizes the circadian rhythms of the white mutant if applied as single input, it does not affect the motility if applied together with temperature inputs near the circadian eigenperiod. These results indicate frequency dependent mutual interactions between the model compartments.

The well-known glycolytic oscillator has been investigated with respect to temperature responses. The examination of the NADH oscillations driven by sinusoidal temperature cycles should give new aspects for a more general system description and improve existing models.

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