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Successful products at least precisely meet the customers’ expectations and, in the best case, exceed them. To develop successful products, customer expectations must be translated into requirements. With the increasing functionalities of products in recent years, the customers’ expectations regarding product interaction and its behavior in different environmental conditions have also become more extensive. Current approaches of model-based systems engineering (MBSE) enable developing complex mechatronic products seamlessly from requirements to functions and solutions on a parameter level. However, there is a lack of approaches that systematically translate complex customer expectations into functional and design requirements as a starting point for further development.In this contribution we present a method and a corresponding meta-model that allows to systematically formalize the dependencies of different stakeholders and their expectations as well as different environmental conditions and constraints. From these dependencies, operating states are elicited that represent a set of simultaneously valid stakeholder expectations with their corresponding constraints. From these operating states, functional and design requirements are systematically derived as a basis for the model-based design of the system under development. Our meta-model is compatible to the established modeling language SysML, thus, existing approaches for the function-oriented model-based system development can benefit directly from these formally modeled requirements.Our publication signposts the potential for systematic and formal translation of customer expectations into operating states as well as requirements and thus enables a targeted, customer-centric and function-oriented development of mechatronic systems. We applied our method in an interdisciplinary, industrial project using the example of a thermal management system of a battery electric vehicle.

Background and objectives: Students with high levels of test anxiety frequently experience depersonalization during examinations. We investigated whether a brief cognitive behavioral group interven...

Zusammenfassung. Depersonalisations- / Derealisationssymptome sind während der Konfrontation mit angstbesetzten Reizen oder Situationen häufig. Zur Erfassung dieses situationsbezogenen Depersonalisationserlebens wurde die Cambridge Depersonalisation Scale adaptiert. Die psychometrischen Gütekriterien der CDS-Situational (CDS-S) wurden in 2 Studien untersucht. 53 Patientinnen und Patienten mit Sozialer Angststörung und 32 gesunde Kontrollprobandinnen und Kontrollprobanden führten zweimal im Abstand von 4 Monaten den Trier Social Stress Test durch und schätzten anschließend die Schwere der Depersonalisation / Derealisation (CDS-S) und der Angst während des Tests ein. Ferner bearbeiteten 26 Studierende mit Prüfungsangst und 43 Studierende ohne Prüfungsangst die CDS-S direkt nach einer mündlichen Prüfung sowie 7 Tage später. Je nach Studie waren Cronbachs α (α ≥ .88), Item-Trennschärfen, Split-Half-Reliabilität ( rtt ≥ .74) und Retest-Reliabilität ( rtt = .40 – .88) zufriedenstellend bis sehr gut. Die Überprüfung der Veränderungssensitivität, Konstruktvalidität und faktoriellen Validität ergab zufriedenstellende Ergebnisse. Die CDS-S erfasste in 2 Studien situationsbezogenes Depersonalisations- / Derealisationserleben hinreichend reliabel und valide und ist zur Messung von Depersonalisations- / Derealisationssymptomen im sozialen und Leistungskontext zu empfehlen.

W niniejszej pracy om��wiony zosta�� problem kwalifikacji podatkowej odsetek, nale��nych podatnikowi z tytu��u op����nienia w spe��nieniu ��wiadczenia, je��eli ��wiadczenie g����wne, od kt��rego odsetki s�� naliczane, korzysta ze zwolnienia podatkowego w podatku dochodowym od os��b fizycznych. W artykule podj��to pr��b�� udzielenia odpowiedzi na pytanie czy wprowadzenie zmian legislacyjnych, polegaj��cych na w����czeniu rzeczonych odsetek do katalogu zwolnie�� przedmiotowych z art. 21 ust. 1 u.p.d.o.f., by��o dzia��aniem koniecznym w celu jednoznacznego ustalenia ich podatkowej kwalifikacji. W pracy stawiana jest teza, i�� fakt przyj��cia niniejszych zmian, nie oznacza, ��e w stanie prawnym sprzed nowelizacji wskazane odsetki podlega��y opodatkowaniu. W kontek��cie omawianego problemu kluczowe jest bowiem zwr��cenie uwagi na spos��b dokonywania wyk��adni stosownych regulacji prawnych przez organy podatkowe, a zw��aszcza s��dy administracyjne. Autor przedstawia krytyczne uwagi dotycz��ce s��dowej metodologii interpretacji prawa, wskazuj��c, i�� jej rezultat obci����aj��cy podatkiem przedmiotowe nale��no��ci odsetkowe godzi w aksjologiczne podstawy systemu prawnego, w konsekwencji nie mo��e by�� akceptowany w demokratycznym pa��stwie prawnym, urzeczywistniaj��cym zasady sprawiedliwo��ci spo��ecznej.

In der Notfallmedizin sind die schnelle Verfugbarkeit und fruhestmogliche medizinische Therapie wesentliche Faktoren. Die fur den Rettungsdienst festgelegten Hilfsfristen von 10–15 min konnen nicht immer eingehalten werden. Um die Hilfsfrist zu verkurzen, etabliert sich parallel zum Regelrettungsdienst ein unabhangiges System von First respondern. Zu deren Prozess- oder Qualitatsdaten existieren nur wenige Informationen. Ziele der vorliegenden Analyse sind die Beschreibung und die Auswertung eines solchen First-responder-Systems. Die Analyse wertet retrospektiv die Einsatzprotokolle der Deutschen Lebens-Rettungs-Gesellschaft e.V.(DLRG)-Notfallhilfe Nordhardt aus dem Jahr 2017 aus. Der Fokus lag auf den Prozesszeiten und der Durchfuhrung der medizinischen Versorgung. Es wurden 363 anonyme Einsatzprotokolle (Aktennotiz der Notfalleinsatze) ausgewertet. Die Ankunft der First responder beim Patienten erfolgte im Median 4 min nach der Alarmierung. Durchschnittlich wurden die Patienten 5 min betreut, bis der Rettungsdienst eintraf. First responder haben 5 Patienten reanimiert, 23 Patienten mittels Sauerstoff oxygeniert und 4 Patienten beatmet. Weiter konnten 11 Patienten mit einer Hypoglykamie von einer zeitnahen Therapie profitieren. Bei 50 Verunfallten wurden insgesamt 5 Halswirbelsaulen-Stabilisationen und 38 Bodychecks durchgefuhrt. Zusammenfassend besteht ein taktischer Vorteil, First responder einzusetzen. Diese sind ortsnah und besitzen die notigen Fahigkeiten, Patienten bis zum Eintreffen des Rettungsdienstes medizinisch zu betreuen. Weitere Untersuchungen sind hierzu wunschenswert. Eine Standardisierung sowie Digitalisierung der Einsatzprotokolle konnten dazu hilfreiche Schritte sein.

Mining is an essential cornerstone of the Mongolian economy. 85% of all Mongolian exports are raw materials and natural resources. Mining and mining closure due have a significant impact on the Mongolian environment. The vision of Mongolia is “to become a developed nation that has created the conditions for maintaining and handing down to the future generation the environmental stability and ensuring the possibility of enjoying its long-term benefits by way of creating the economic growth that is based on Green development concept and ensures involvement of citizens”. A German-Mongolian advisory assistance project, agreed between the Mongolian Ministry for Environment and Tourism and the German Federal Ministry for Environment and implemented 2017 till 2019, provided support for the coal-mining sector to specify and to adopt overall rehabilitation standards and recommendations for the implementation of a geo-hydrological monitoring. A “Guideline on the Rehabilitation of Open-pit Coal-mines” (GROM) addresses mine rehabilitation, targeting managers at the operational level and environmental officers from the authorities, as well as public regulators. The technical guidline is framed around the operational sequence in mining operations, i.e. legal basis, planning, operations and mine closure. Particular emphasis is given to the rehabilitation of natural ecosystems and replacement and compensatory measures. Landscape design for rehabilitation requires a holistic view on mining operations as a whole. Environmental staff should be able to improve and assure the quality of executed rehabilitation work and to discover and settle deficits, right from the beginning on of mining projects. The EU Mining Waste Directive (2006/21/EC) were proposed as an approved international regulation with regard to easy applicable technical and pragmatic criteria to assess the impact and remedial requirements caused by hazardous substances impacts and geo-technical issues. For the implementation, the guidance document explains international standards and gives practical recommendations on the different fields of the rehabilitation work in open-pit coal mining. As an overall objective the guideline shall support the Sustainable Development Goals (especially SDG 15 “Protect, restore and promote sustainable use of terrestrial ecosystems, sustainably manage forests, combat desertification, and halt and reverse land degradation and halt biodiversity loss”). Rehabilitation measures support the concept of Land Degradation Neutrality (LDN) of the UN.

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed. © 2021

International Design Conference, DESIGN 2020, online, 26 Oct 2020 - 29 Oct 2020; Proceedings of the Design Society / DESIGN conference 1, 1105-1114 (2020). doi:10.1017/dsd.2020.303 special issue: "[International Design Conference, DESIGN 2020]", Published by Cambridge University Press, Cambridge

At-level and above-level hypersensitivity was assessed in patients with chronic complete thoracic spinal cord injury (SCI). Patients were classified using somatosensory mapping (brush, cold, pinprick) and assigned into 2 groups (ie, patients with at-level hypersensitivity [SCIHs, n = 8] and without at-level hypersensitivity [SCINHs, n = 7]). Gender and age-matched healthy subjects served as controls. Quantitative sensory testing (QST), electrically- and histamine-induced pain and itch, laser Doppler imaging, and laser-evoked potentials (LEP) were recorded at-level and above-level in SCI-patients. Six of 8 SCIHs, but 0 of 7 SCINHs patients suffered from neuropathic below-level pain. Clinical sensory mapping revealed spreading of hypersensitivity to more cranial areas (above-level) in 3 SCIHs. Cold pain threshold measures confirmed clinical hypersensitivity at-level in SCIHs. At-level and above-level hypersensitivity to electrical stimulation did not differ significantly between SCIHs and SCINHs. Mechanical allodynia, cold, and pin-prick hypersensitivity did not relate to impaired sensory function (QST), axon reflex flare, or LEPs. Clinically assessed at-level hypersensitivity was linked to below-level neuropathic pain, suggesting neuronal hyperexcitability contributes to the development of neuropathic pain. However, electrically evoked pain was not significantly different between SCI patients. Thus, SCI-induced enhanced excitability of nociceptive processing does not necessarily lead to neuropathic pain. QST and LEP revealed no crucial role of deafferentation for hypersensitivity development after SCI. Perspective At-level hypersensitivity after complete thoracic SCI is associated with neuropathic below-level pain if evoked by clinical sensory stimuli. QST, LEP, and electrically-induced axon reflex flare sizes did not indicate somatosensory deafferentation in SCIHs.

In emergency situations it is essential to get access to medical treatment as early as possible. In Germany, the time interval from alarm to arrival should be less than 10-15 min. The emergency medical service (EMS) cannot comply with this recommendation in approximately 10% of the emergencies in Baden-Württemberg. In addition to the traditional EMS system, a voluntary system of first responders has been developed over the last years to reduce this interval. They are incorporated into the alarm system of the traditional EMS and are alarmed as soon as an emergency call arrives. Data on process times (from alarm to begin of treatment or duration of treatment until arrival of EMS) and quality are rare. In Baden-Württemberg, the emergency aid "Deutsche Lebens-Rettungs-Gesellschaft e.V. (DLRG)" Nordhardt can only estimate times and quality of primary care. The objective of this analysis was to describe and evaluate such a first responder system.The presented study investigated the emergency responses of a first responder system in Nordhardt, close to Karlsruhe, Germany. A total of 367 emergency data sets from 2017 containing information on operating time, medical history, suspected diagnosis and medical treatment, were evaluated. Of these, 363 anonymized emergency records including the complete information (concerning process time and medical treatment) were analyzed. The focus was on different time intervals from alarm to treatment and until arrival of the EMS. Additionally, the quality of medical treatment and the measured vital data were examined.The median response time and time to access to the patient was 2 min in both. The patient was reached within approximately 4 min and treated for another 5 min until the EMS arrived. In two thirds of the patients, the vital parameters were measured, 5 patients were resuscitated, 23 received supplementary oxygen, 4 patients were ventilated and 11 patients suffering from hypoglycemia showed a clinical benefit from the early treatment. A total of 50 trauma patients were treated, 5 with cervical spine stabilization and 38 received a body check.The first responders from Nordhardt received an emergency call nearly every day. In two thirds of the calls they were faster than the EMS as they usually have local sites with a shorter distance to the emergency scene where they are able to deal with critical medical cases until the EMS arrives. Despite the small case numbers, it could be concluded that the early medical treatment with respect to resuscitation based on earlier arrival on site may help to increase the survival rate of patients. The first responders were also able to manage airway problems with additional oxygen or other airway devices. Other medical treatment performed by the first responders, such as administration of glucose in hypoglycemic patients positively affected the patient's condition. There is a tactical advantage to include first responders in traditional EMS services. Further studies are needed to examine these questions in larger samples also over a longer time period. Standardization and digitalization of the records could help to gain more data in this field.

Background:Anti-cyclic citrullinated peptide (CCP) antibodies are the most specific markers for rheumatoid arthritis (RA). Different generations of assays have been developed among which the anti-CCP2 and anti-CCP3 assays are most widely used.Objectives:Since some differences between these assays have been reported it was our aim to compare their diagnostic performance and evaluate their usefulness for diagnostics of early RA.Methods:The anti-CCP3.1 assay (Quanta Lite®CCP3.1 IgG/IgA, Inova Diagnostics) was compared to anti-CCP2 IgG and IgA assays (EliATMCCP, Thermo Fisher Scientific) employing sera of 184 early RA patients, 360 disease controls and 98 healthy subjects.Results:Anti-CCP2 IgG and IgA assays showed high specificity versus healthy subjects (98.9%; 98%) and disease controls (98.8%; 99.4%). Sensitivity was 52.2% for the IgG and 30.4% for the IgA assay, respectively, resulting in high positive likelihood ratios (LR+) of 47.5 (IgG) and 50.7 (IgA). However, IgA antibodies did not show an added diagnostic value since all positive patients were also IgG positive. The anti-CCP3.1 assay was slightly more sensitive than the anti-CCP2 IgG assay (55.4%) but specificity was markedly lower and amounted to 95.9% versus healthy subjects and 90.8% versus disease controls resulting in a LR+ of only 6.0. Out of 360 disease controls 33 (9.2%) were found to be positive for CCP3.1 but among these only four (1.1%) were positive for anti-CCP2 IgG (and 2 of these also for anti-CCP2 IgA). The most common diagnosis of CCP3.1 positive control patients was osteoarthritis (12 patients); six patients suffered from spondyloarthropathies, two patients had reactive arthritis, 10 patients were diagnosed with an autoimmune rheumatic disease (AI RMD) and two patients had osteoporosis. However, at a cut-off of 60 AU/ml only nine disease controls remained positive (3 OA, 1 SpA, 4 AI RMD, 1 ReA) and 3 of them were also positive in the anti-CCP2 assay (ReA, SpA, SLE). When applying 60 AU/ml (high positive) as cut-off value at the early RA cohort, sensitivity (52.7%) became comparable to the anti-CCP2 assay and both specificity (97.5%) and LR+ (21.08) increased substantially.Conclusion:When interpreting the results of anti-CCP assays disease specificity should be taken into account in order to reduce the risk of misclassification and a false positive diagnosis.Table 1.Specificity, sensitivity and positive likelihood ratio (LR+) of CCP2 (IgG, IgA) and CCP3.1 assays.CCP3.1CCP2 IgGCCP2 IgACut-off (U/ml)201010Patients positive (n)1029656Specificity % (healthy subjects)95.999.098.0Specificity % (disease controls)90.898.999.4Sensitivity %55.452.230.4LR+ (healthy)13.552.015.2LR+ (disease controls)6.047.550.7Disclosure of Interests:Daniela Sieghart Grant/research support from: Thermo Fisher Scientific, Speakers bureau: Thermo Fisher Scientific, Christian Konrad Employee of: Thermo Fisher Scientific, Sascha Swiniarski Employee of: Thermo Fisher Scientific, Helmuth Haslacher: None declared, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Günter Steiner Grant/research support from: Thermo Fisher Scientific, Speakers bureau: Thermo Fisher Scientific

Develop and validate a low-intensity sinusoidal electrical stimulation paradigm to preferentially activate C-fibers in human skin.Sinusoidal transcutaneous stimulation (4Hz) was assessed psychophysically in healthy volunteers (n = 14) and neuropathic pain patients (n = 9). Pursuing laser Doppler imaging and single nociceptor recordings in vivo in humans (microneurography) and pigs confirmed the activation of "silent" C-nociceptors. Synchronized C-fiber compound action potentials were evoked in isolated human nerve fascicles in vitro. Live cell imaging of L4 dorsal root ganglia in anesthetized mice verified the recruitment of small-diameter neurons during transcutaneous 4-Hz stimulation of the hindpaw (0.4mA).Transcutaneous sinusoidal current (0.05-0.4mA, 4Hz) activated "polymodal" C-fibers (50% at ∼0.03mA) and "silent" nociceptors (50% at ∼0.04mA), intensities substantially lower than that required with transcutaneous 1-ms rectangular pulses ("polymodal" ∼3mA, "silent" ∼50mA). The stimulation induced delayed burning (nonpulsating) pain and a pronounced axon-reflex erythema, both indicative of C-nociceptor activation. Pain ratings to repetitive stimulation (1 minute, 4Hz) adapted in healthy volunteers by Numeric Rating Scale (NRS) -3 and nonpainful skin sites of neuropathic pain patients by NRS -0.5, whereas pain even increased in painful neuropathic skin by approximately NRS +2.Sinusoidal electrical stimulation at 4Hz enables preferential activation of C-nociceptors in pig and human skin that accommodates during ongoing (1-minute) stimulation. Absence of such accommodation in neuropathic pain patients suggest axonal hyperexcitability that could be predictive of alterations in peripheral nociceptor encoding and offer a potential therapeutic entry point for topical analgesic treatment. Ann Neurol 2018;83:945-957.

Der plotzliche Herztod („sudden cardiac death“, SCD) bei jungen Sportlern unter korperlicher Belastung ist mit einer Inzidenz von 1–3 Fallen/100.000 Athleten pro Jahr eine insgesamt seltene Todesursache. Nach der hypertrophen Kardiomyopathie kommt eine Koronaranomalie als zweithaufigste Ursache infrage. Die vorliegende Kasuistik berichtet uber einen 35-jahrigen Mann, der an einem Volkslauf uber die Distanz eines Halbmarathons teilnahm und auf der Zielgeraden kollabierte. Trotz sofortiger Reanimation und initialem „return of spontaneous circulation“ (ROSC) kam es im Verlauf zu einer pulslosen elektrischen Aktivitat (PEA), und die Reanimation wurde 1 h nach Aufnahme in die internistische Schockraumeinheit abgebrochen. Die Autopsie ergab eine Koronaranomalie des interarteriellen Typs „anomalous left coronary artery“ (ALCA). Bei dieser anatomischen Variante kann es unter starker Belastung zu einer Ischamie des jeweiligen Endstromgebiets kommen.

Background Hydroxyethyl starch (HES) solutions compromise blood coagulation. Low molecular weight, low-substituted HES products, and electrolyte-balanced solutions might reduce this effect. We compared the effects of in vitro haemodilution on blood coagulation with a balanced 6% HES 130/0.42 solution (HESBAL), a saline-based 6% HES 130/0.4 solution (HESSAL), a balanced lactated Ringer’s solution (RL) and a saline-based 4% gelatin solution (GEL). Methods Blood was obtained from 10 healthy male volunteers and diluted with the test solutions by 33% and 66%. Quality of clot formation was measured using two viscoelastic coagulation tests: SONOCLOT™ and activated rotation thromboelastometry ROTEM™. Results Of 16 parameters measured by the viscoelastic devices, we found three statistically significant differences compared with baseline for RL, but 11 for GEL, 10 for HESSAL, and 11 for HESBAL in the 33% haemodilution group (P=0.01). Comparing the different solutions, we observed a significant difference between crystalloids and colloids but none between GEL and HES. In the 66% dilution group, effects on blood coagulation were increased when compared with the 33% dilution group. We found no differences in coagulation impairment between balanced and non-balanced HES products and no differences in the detection of impaired blood coagulation due to haemodilution between the two viscoelastic coagulation tests. Conclusions Both ROTEM™ and SONOCLOT™ are sensitive tests for the detection of impaired blood coagulation due to haemodilution. There are fewer effects on blood coagulation using crystalloids compared with colloids. The effects of GEL and HES are similar. There is no difference between balanced HES 130/0.42 and non-balanced HES 130/0.4.

Ventilator-associated pneumonia (VAP) is one of the most common and preventable infections in mechanically ventilated patients. It is associated with a high mortality rate. To prevent VAP, various strategies address this issue using "VAP-bundles", which are implemented in many intensive care units. The risk of acquiring VAP starts with the induction of anesthesia, strictly speaking at the time of intubation. This article considers measures to prevent VAP during general anesthesia in adult patients (18 years). Procedures beyond standard hygienic precautions for VAP prevention are reviewed.A literature search in different databases (PubMed, Cochrane, Ovid und CINAHL) over the last five years.Beyond standard hygienic precautions, microaspiration should be avoided to prevent VAP. During mechanical ventilation at least 5 cm H

In the German electric energy market, the share of regional and decentralized power generation based on renewables has become more and more signifi cant. The following study describes the initiative of the energy and utilities company ‘EnBW Energie Baden-Wurttemberg AG’ (EnBW) in Germany to investigate regional energy concepts based on agricultural biomass. The study focuses on two aspects: the development of more sustainable approaches for energy crops cultivation and the effi cient use of cogeneration heat produced by bioenergy-driven power plants in rural areas. For the development of concepts and tools, a study area including two counties in the South-West of Germany were chosen. This article focuses on the work done on the county of Ravensburg. Geographic information system (GIS) tools are used to collect data about current land use practices related to energy crops. Subsequently, the suitability of new and more sustainable energy crops for biogas production based on current production regimes is investigated by following a modeling approach. The approach followed includes the screening of new agricultural substrates as substitutes for maize, which is currently the dominant energy crop for biogas production in Germany, the modeling of new substrate mixtures, and the measurement of the methane potential of energy crop samples in a biogas laboratory. Bioenergy-driven power plants are usually implemented nearby high biomass potentials—in rural areas, where heat demand is scarce. Optimizing heat use in combined heat and power (CHP) generators is a major issue for the future of bioenergy. The effi cient utilization of residual heat is one of the targets of the upcoming update of the German Renewable Energy Sources Act in 2012. Therefore, the profi table operation of biogas plants increasingly depends on the level of heat use which can be reached. The possibilities for heat supply to potential consumers in rural areas have been investigated using a GIS methodology on an object-based level for residential and tertiary/industry sectors. Building age and type have been used as parameters to estimate the annual heat consumption. Scenarios illustrating a renovation rate of the investigated objects (buildings) have been calculated. For the purpose of verifi cation and calibration, measurements of the heat demand of more than 3,000 houses have been used. Furthermore, on the basis of existing biogas plants, a techno-economic comparison of heat networks with micro gas networks for the distribution of renewable energy to demand sites have been performed.

Fraud is as old as Mankind. There are an enormous number of historical documents which show the interaction between truth and untruth; therefore it is not really surprising that the prevalence of publication discrepancies is increasing. More surprising is that new cases especially in the medical field generate such a huge astonishment. In financial mathematics a statistical tool for detection of fraud is known which uses the knowledge of Newcomb and Benford regarding the distribution of natural numbers. This distribution is not equal and lower numbers are more likely to be detected compared to higher ones. In this investigation all numbers contained in the blinded abstracts of the 2009 annual meeting of the Swiss Society of Anesthesia and Resuscitation (SGAR) were recorded and analyzed regarding the distribution. A manipulated abstract was also included in the investigation. The χ(2)-test was used to determine statistical differences between expected and observed counts of numbers. There was also a faked abstract integrated in the investigation. A p

Background: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. Methods: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neuronal calcitonin gene-related peptide staining was quantified. Results: Perception of warm, cold and heat pain and nerve fibre density were reduced in the painful areas compared with the control sites and with healthy controls. Warm and cold detection thresholds correlated best with epidermal innervation density, whereas heat and cold pain thresholds and axon reflex flare correlated best with dermal innervation density. Clinical pain ratings correlated only with epidermal nerve fibre density (r = 0.38, p < 0.05)andbetterpreservedcolddetectionthresholds(r = 0.39,p < 0.05), but not with other assessed functional and structural parameters. Conclusions: Thermal thresholds, axon reflex measurements and assessment of skin innervation density are valuable tools to characterize and quantify peripheral neuropathy and link neuronal function to different layers of the skin. The severity of small fibre neuropathy, however, did not correspond to clinical pain intensity and a specific parameter or pattern that would predict pain intensity in peripheral neuropathy could not be identified.

The National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University (MSU), shown in Figure 1, is the largest campus-based nuclear science facility in the United States. NSCL is funded by the National Science Foundation (NSF) for operating its Coupled Cyclotron Facility (CCF) as a national user facility and for conducting research in nuclear physics, nuclear astrophysics, and accelerator physics.

Background and objectives The most abundant malignant brain tumor in human is glioblastoma and patients with this type of tumor have a poor prognosis with high mortality. Glioblastoma are characterized particularly by fast growth and a dependence on blood vessel formation for survival. Cannabinoids (CBs) inhibit tumor growth by inducing apoptosis of tumor cells and impairing tumor angiogenesis. The distribution of CB1 and CB2 receptors in glioblastoma and associated endothelial vessels is still unknown. Methods Tissue samples were collected consecutively after neurosurgery of 19 patients suspected glioblastoma and examined immunohistochemically for CB1 and CB2 receptor expression. Vessel endothelial cells of the sections were immunocytochemically identified by using a primary antibody against PECAM-1. Double labelling was performed for CB receptors and endothelial cells of the vessels by DAPI staining. Results In endothelia of control tissue, about 24% and 45% of the cells were positive for CB1 and CB2 receptors. In glioblastoma endothelial cells, CB1 and CB2 receptors were present in about 38% and 54% of the cells respectively. In comparison to CB1, an elevated CB2 receptor expression was identified in glioblastoma. Conclusions The abundant expression and distribution of CB2 receptors in glioblastoma and particularly endothelial cells of glioblastoma indicate that impaired tumor growth in presence of CB may be associated with CB2 activation. Selective CB2 agonists might become important targets attenuating vascular endothelial growth factor (VEGF) signalling and thereby diminishing neoangiogenesis and glioblastoma growth.

Michigan State University’s NSCL (National Superconducting Cyclotron Laboratory) is funded by the US National Science Foundation to operate the premier rare isotope user facility in the US. Beams of rare isotopes at NSCL are produced via projectile fragmentation or fission and separated in-flight. The current NSCL facility capabilities and main research directions will be outlined. The laboratory is currently expanding its capabilities by building an efficient gas-stopping and reacceleration capability initially up to 3.2 MeV per nucleon. For the longer term future, NSCL is proposing to replace the existing superconducting cyclotrons with a high-intensity, 200 MeV per nucleon superconducting heavy-ion linac.

Lokalanasthetika (LA), in klinischen Konzentrationen verabreicht, beinhalten ein gewebstoxisches Potenzial, dessen Auswirkungen in der Praxis jedoch selten beobachtet werden. Es wird uber den Fall einer 74-jahrigen Patientin (Body-Mass-Index 16,8 kg/m2) mit einem metastasierenden Bronchuskarzinom berichtet. Sie hatte wegen therapierefraktarer Schmerzen einen getunnelten thorakalen Periduralkatheter (PDK) erhalten. Unter einer kontinuierlichen periduralen Infusion von 0,49%igem Bupivacain, 0,0036%igem Morphium und 0,0001%igem Clonidin (3 ml/h) entwickelte sich nach 8 Wochen thorakal-paravertebral ein derbes Weichteilulkus mit kristallinem Fremdmaterial (KFM) im Ulkusgrund. Die thorakale Computertomographie (CT) bestatigte eine Dislokation des PDK in die Subkutis mit einer ausgedehnten Flussigkeitsansammlung bis zum M. erector spinae. Die histologische Untersuchung zeigte eine areaktive Nekrose mit Einschlussen von KFM; die chemische Analyse des KFM erbrachte den Nachweis von Bupivacain, Morphium und Natriumchlorid. Das Weichteilulkus war wahrscheinlich durch Ausfallungen des LA-Gemisches entstanden.

Background: The formation, prevalence, intensity, course, and predisposing factors of phantom limb pain were investigated to determine possible mechanisms of the origin of phantom limb pain in traumatic upper limb amputees. Methods: Ninety-six upper limb amputees participated in the study. A questionnaire assessed the following question: side, date, extension, and cause of amputation; preamputation pain; and presence or absence of phantom pain, phantom and stump sensations or stump pain or both. Results: The response rate was 84%. Sixty-five (81%) participants returned the questionnaire. In 64 (98.5%) participants a traumatic injury led to amputation; the amputation was necessary because of infection in one patient (1.5%). The median follow-up time (from amputation to evaluation) was 3.2 years (range, 0.9-3.8 years) The prevalence of phantom pain was 44.6%, phantom sensation 53.8%, stump pain 61.5%, and stump sensation 78.5%. After its first appearance, phantom pain had a decreasing course in 14 (48.2%) of 29 amputees, was stable in 11 (37.9%) amputees, and worsened in 2 (6.9%) of 29 amputees. Stump pain had a decreasing course in 19 (47.5%) of 40 amputees but was stable in 12 (30%) amputees. Phantom pain occurred immediately after amputation in 8 (28%) of 29 amputees between 1 month and 12 months in 3 (10%) amputees and after 12 or more months in 12 (41%) amputees. Conclusion: Stump pain and stump sensation predominate traumatic amputees' somatosensory experience immediately after amputation; phantom pain and phantom sensations are often long-term consequences of amputation. Amputees experience phantom sensations and phantom pain within 1 month after amputation, a second peak occurs 12 months after amputation. Revised diagnostic criteria for phantom pain are proposed on the basis of these data.

We investigated the dynamics of denitrification and nitrous oxide (N2O) accumulation in 4 nitrate (NO−3) contaminated denitrifying sand and gravel aquifers of northern Germany (Fuhrberg, Sulingen, Thülsfelde and Göttingen) to quantify their potential N2O emission and to evaluate existing concepts of N2O emission factors. Excess N2 – N2 produced by denitrification – was determined by using the argon (Ar) concentration in groundwater as a natural inert tracer, assuming that this noble gas functions as a stable component and does not change during denitrification. Furthermore, initial NO−3 concentrations (NO−3 that enters the groundwater) were derived from excess N2 and actual NO−3 concentrations in groundwater in order to determine potential indirect N2O emissions as a function of the N input. Median concentrations of N2O and excess N2 ranged from 3 to 89 μg N L−1 and from 3 to 10 mg N L−1, respectively. Reaction progress (RP) of denitrification was determined as the ratio between products (N2O-N + excess N2) and starting material (initial NO−3 concentration) of the process, characterizing the different stages of denitrification. N2O concentrations were lowest at RP close to 0 and RP close to 1 but relatively high at a RP between 0.2 and 0.6. For the first time, we report groundwater N2O emission factors consisting of the ratio between N2O-N and initial NO−3-N concentrations (EF1). In addition, we determined a groundwater emission factor (EF2) using a previous concept consisting of the ratio between N2O-N and actual NO−3-N concentrations. Depending on RP, EF(1) resulted in smaller values compared to EF(2), demonstrating (i) the relevance of NO−3 consumption and consequently (ii) the need to take initial NO−3-N concentrations into account. In general, both evaluated emission factors were highly variable within and among the aquifers. The site medians ranged between 0.00043–0.00438 for EF(1) and 0.00092–0.01801 for EF(2), respectively. For the aquifers of Fuhrberg and Sulingen, we found EF(1) median values which are close to the 2006 IPCC default value of 0.0025. In contrast, we determined significant lower EF values for the aquifers of Thülsfelde and Göttingen. Summing the results up, our study supports the substantial downward revision of the IPCC default EF5-g from 0.015 (1997) to 0.0025 (2006).

Summary Aims: Conventional approaches to the management of neuropathic pain (NeP) often yield unsatisfactory results. We aimed to investigate pregabalin, a gamma-aminobutyric acid (GABA)-analogue, in a wide range of pregabalin naive patients with treatment refractory NeP. Methods: Investigator-initiated, 4-week, open, prospective multicentre study in tertiary care. Pregabalin was prescribed at physicians’ discretion based on patients’ individual responses and tolerability, with or without concomitant analgesics. Consecutive patients were requested to fill in questionnaires at baseline and after 14 and 28 days with numerical pain rating scales (0, none; 10, worst possible), sleep rating scales, parts of the Brief Pain Inventory, Pain Experience Scale, Short Questionnaire on Current Burden and the SF-12 health-related quality of life scale. Results: In 55 patients, the mean pregabalin dose was 142 ± 26 mg at day 1 and 348 ± 161 mg at day 28. The mean pain score decreased from 6.5 ± 1.7 to 5.5 ± 1.9 at day 14 and to 4.9 ± 1.8 at day 28 (−24.6%, p

Background Hyperexcitability of N -methyl- d -aspartate acid (NMDA) receptors may play an important role in the development of phantom limb pain (PLP). Aim of the study To investigate whether early treatment with the NMDA antagonist memantine attenuates phantom pain memory formation in traumatic amputees. Methods In a randomized, double-blind, controlled trial 19 patients with acute traumatic amputation of the upper extremity were investigated. All patients received postoperative analgesia by continuous brachial plexus anesthesia (ropivacaine 0.375% 5 ml/h) for at least 7 days. In addition, the patients received either memantine (20–30 mg daily, n = 10) or placebo ( n = 9) for 4 weeks. Results Memantine treatment reduced the number of requested ropivacacine bolus injections during the first week and resulted in a significant decrease of PLP prevalence and intensity at 4 weeks and 6 months follow up, but not at 12 months follow up. Conclusions We conclude that memantine can reduce intensity of phantom limb pain and might also prevent the development of PLP. However, despite the very early begin of treatment; no long-term effect on established PLP was evident.

Cognitive deficits are common symptom presentations in neurology and psychiatry. Cognitive symptoms during major depressive episodes cause subjective distress as well as difficulties during therapy and psychosocial reintegration. Depression-associated cognitive symptoms are characterized by a mood-congruent information processing bias as well as by cognitive performance deficits. A diagnostically relevant profile of neuropsychological impairments specific to depression has not yet been identified. Nevertheless, deficits of executive and declarative memory functions have repeatedly been reported. The time course of cognitive deficits after remission of mood is not entirely clear. Depending on the point of time of the reinvestigation, patients may still exhibit pronounced cognitive deficits. This article presents the current knowledge about cognitive symptoms in major depression, including the pathophysiology and treatment options.

Bei einem 48-jahrigen Patienten mit einer seit 20 Jahren bestehenden sensorisch inkompletten, motorisch kompletten Tetraplegie C2 mit Spontanatmung mithilfe der Atemhilfsmuskulatur wurde zur Therapie einer schmerzhaften, therapierefraktaren abdominellen und beinbetonten Spastik mit gleichzeitig vorhandener hyperreflexiver Harnblase delta-9-Tetrahydrocannabinol in einer Dosierung von 2-mal 2,5 mg/Tag oral verabreicht. Zu Therapiebeginn war eine Besserung der Spastik der Beine und der Blase feststellbar. Im Verlauf klagte der Patient nach 3 Tagen jedoch uber Dyspnoe und Kurzatmigkeit bei objektiv noch ausreichender Oxygenierung. Delta-9-Tetrahydrocannabinol wurde am 6. Tag abgesetzt, dennoch musste anschliesend eine ansonsten nur nachts durchgefuhrte Heimbeatmung im Verlauf der nachsten 7 Tage auch tagsuber kontinuierlich erfolgen. Im Anschluss konnte der Patient wieder selbststandig atmen. Muskelrelaxierende, sedierende oder auch direkte, auf die Medulla oblongata wirkende Effekte sowie eine Begleitmedikation mit Baclofen sind denkbare Ursachen, weshalb delta-9-Tetrahydrocannabinol bei gefahrdeten Patienten zu einer respiratorischen Insuffizienz fuhren kann.

Die Daten einer bereits publizierten 12-wochigen randomisierten, doppelblinden, placebokontrollierten, multizentrischen Studie wurden in Bezug auf den Beginn der analgetischen Wirkung von Pregabalin bei neuropathischen Schmerzen analysiert. Nach einem Studiendesign gemas dem Vorgehen in der taglichen Praxis wurden 338 Patienten mit postherpetischer Neuralgie und schmerzhafter diabetischer Neuropathie mit Placebo (n=65) oder bis zu 600 mg Pregabalin/Tag in flexibler (n=141) oder fixer Dosierung (n=132) behandelt. Bezogen auf die jeweiligen Ausgangswerte (Tag 0), wurde unter fixer Dosierung (Startdosis 300 mg/Tag) eine Abnahme um einen Skalenwert auf der 11-stufigen numerischen Schmerzbewertungsskala bereits am 1. Tag erreicht, um 2 Skalenwerte am 13., und um 3 Skalenwerte am 23. Tag (unter flexibler Dosierung mit Startdosis 150 mg/Tag: am 6., 17. bzw. 30. Tag). Beide Dosierungsschemata verminderten die Schmerzen deutlich und statistisch signifikant (p=0,001 bzw. p=0,002 vs. Placebo). Bei Patienten mit chronischen neuropathischen Schmerzen zeigte Pregabalin in beiden Schemata neben einer hohen Wirksamkeit einen raschen Wirkungseintritt.

Fibromyalgia (FM) is a chronic pain syndrome characterized by a distinct mechanical hyperalgesia and chronic pain. Recently, cannabinoids have been demonstrated as providing anti-nociceptive and anti-hyperalgesic effects in animal and human studies. Here, we explored in nine FM patients the efficacy of orally administered delta-9-tetrahydrocannabinol (THC) on electrically induced pain, axon reflex flare, and psychometric variables.Patients received a daily dose of 2.5-15 mg of delta-9-THC, with a weekly increase of 2.5 mg, as long as no side effects were reported. Psychometric variables were assessed each week by means of the West Haven-Yale Multidimensional Pain Inventory (MPI), Pittsburgh Sleep Quality Index (PSQI), Medical outcome survey-short form (MOS SF-36), the Pain Disability Index (PDI), and the Fibromyalgia Impact Questionnaire (FIQ). In addition, patients recorded daily, in a diary, their overall pain intensity on a numeric scale. Each week, pain and axon reflex flare was evoked experimentally by administration of high intensity constant current pulses (1 Hz, pulse width 0.2 ms, current increase stepwise from 2.5-12.5 mA every 3 minutes) delivered via small surface electrodes, attached to the volar forearm skin.Daily pain recordings by the patient, experimentally induced pain, and axon reflex flare recorded by a laser Doppler scanner.Five of nine FM patients withdrew during the study due to adverse side effects. Delta-9-THC had no effect on the axon reflex flare, whereas electrically induced pain was significantly attenuated after doses of 10-15 mg delta-9-THC (p0.05). Daily-recorded pain of the FM patients was significantly reduced (p0.01).This pilot study demonstrated that a generalized statement that delta-9-THC is an analgetic drug cannot be made. However, a sub-population of FM patients reported significant benefit from the delta-9-THC monotherapy. The unaffected electrically induced axon reflex flare, but decreased pain perception, suggests a central mode of action of the cannabinoid.

Local anesthetics (LAs) possess a variety of effects that cannot be explained by the typical block of neuronal sodium channels. Antithrombotic effects of LAs are well known, but LAs also act as bactericides. Therefore, an investigation of the influence of LAs on the inflammatory response of the isolated rat lung (n = 78) to an N-formyl-l-leucin-methionyl-l-phenylalanine (FMLP) stimulus was performed.The experiments were performed on isolated and ventilated rat lungs perfused with cell-free and plasma-free buffer. LAs (lidocaine and mepivacaine) were injected in various concentrations before application and activation of human granulocytes by FMLP. Pulmonary arterial pressure (PAP) and lung weight gain were monitored continuously. LAs in final dosages from 10(-2) to 10(-7) mg/kg body weight (n = 6 each) were injected into the pulmonary artery before treatment with FMLP (10(-6) M) to induce pulmonary arterial hypertension. Perfusate samples were taken intermittently to determine thromboxane A(2) (TX A(2)) and endothelin-1 concentrations. Microscopic analyses were performed to assess the degree of lung injury.Pretreatment with LAs significantly reduced the FMLP-induced PAP increase (treatment group v sham group: 0.5 to 5 mm Hg v 8 mm Hg; P.05) and the release of endothelin-1 (2.4 v 5 fmol/mL). Histologic damage seen as acute granulocytic alveolitis was reduced by lidocaine and mepivacaine, even below clinically relevant concentrations.LA pretreatment reduces inflammatory reactions after FMLP stimulus.

Background and objective: An anti-inflammatory effect of α 2 -adrenoreceptor agonists has been suggested. Phospholipase A 2 is a key enzyme in the production of precursors of inflammatory lipid mediators. The aim of the present study was to investigate the effect of clonidine on phospholipase A 2 activity in an established in vitro model. Methods: Human being platelet membranes containing active phospholipase A 2 were exposed to buffer control or to three increasing concentrations of clonidine. Phospholipase A 2 was measured by a radioisotope technique. Results: A massive increase in phospholipase A 2 activity was measured after clonidine exposure leading to final values of 92.5 ′ 3.1 pmol mg protein - 1 min - 1 (4.5-fold higher than control values; P ≤ 0.01 vs. control). After clonidine exposure the maximal reaction velocity increased, while the Michaelis-Menten constant did not change. The Lineweaver-Burk representation suggested an interaction of clonidine with the phospholipase A 2 -substrate complex as well as the phospholipase A 2 molecule. Conclusion: We conclude that the putative anti-inflammatory effect of clonidine was not caused by inhibition of phospholipase A 2 .

Ansammlungen groser Menschenmengen bergen das Risiko des Auftretens medizinischer Notfalle, teilweise mit einer grosen Zahl Betroffener. Am Beispiel eines Pfadfinderlagers mit fast 3000 Teilnehmern wird aufgezeigt, in welcher Dichte medizinische Probleme bei einer nach etablierten Empfehlungen als problemlos oder unterschwellig einzustufenden Veranstaltung auftreten konnen. Wahrend der 11-tagigen Veranstaltung kam es zu 1229 medizinischen Versorgungen, 1,6% aller Teilnehmer bedurften einer stationaren oder ambulanten Abklarung. Besonders erwahnenswert sind das Auftreten einer Lebensmittelvergiftung bei 10 Teilnehmern und die epidemieartige Ausbreitung einer Impetigo contagiosa (Krustenflechte) mit 183 Betroffenen. Eine sorgfaltige Planung ist besonders bei Veranstaltungen angezeigt, die sich wie im dargestellten Fall in landlichen Regionen mit geringer Vorhaltung und in ungunstiger Verkehrslage abspielen.

Die Interaktion zwischen Neuronen, Gewebs- und Entzundungszellen in der Peripherie ist fur die Entstehung von chronischen Schmerzen von besonderer Bedeutung. Dabei wurde in letzter Zeit eine Vielzahl von aktivierenden und hemmenden Wechselwirkungen beschrieben. Neben den klassischen Rezeptoren fur Entzundungsmediatoren an den sensorischen Endigungen treten als therapeutische Ziele in zunehmendem Mase axonale Ionenkanale in den Vordergrund, die ursprunglich lediglich als bedeutsam fur die Weiterleitung von Aktionspotenzialen galten. Die Sensibilisierung der spinalen Verarbeitung von nozizeptiven Reizen ist wesentliches Element der Schmerzausbreitung uber die primare Verletzungsstelle hinaus und tragt auch zur Chronifizierung bei. Lernvorgange und die Loschung von negativen Gedachtnisinhalten sind fur die Entstehung, aber auch die Therapie von chronischen Schmerzzustanden von groser Bedeutung.

Laienersthelfer ergreifen bei Herz-Kreislauf-Stillstanden oft aus Angst vor methodischen Fehlern nicht oder zu spat die erforderlichen Masnahmen. Dies ist ein wesentlicher Grund fur das schlechte Outcome nach kardiopulmonaler Reanimation (CPR). Der Effektivitatsverlust bei Thoraxkompressionen ist oft bedingt durch die muskulare Erschopfung des Helfers. Daher wurde die CardioPump® als eine Thoraxkompressionshilfe untersucht, die eine Moglichkeit bietet, den Kompressionsdruck zu standardisieren und zu kontrollieren. In der prospektiven Cross-over-Untersuchung mit 10 Probanden wurde eine CPR als aktive Kompressions-Dekompression-CPR (ACD-CPR) bzw. nach ERC-Standardmethode (C-CPR) unter Anwendung der CardioPump® und der Resusci Anne® Skillguide durchgefuhrt. Mittels statistischer Prozesskontrolle wurde die Qualitat der Kompressionen analysiert. Die Prozessqualitat der durchgefuhrten Thoraxkompressionen unterschied sich zwischen beiden Verfahren. Bei Anwendung der CardioPump® bei der ACD-CPR fand sich ein stabiler Prozess mit einer signifikant hoheren Prozessqualitat verglichen mit der Standardmethode. Die CardioPump® kann auch von ungeubten Personen eingesetzt werden, um die Effektivitat der Thoraxkompressionen wahrend der CPR zu optimieren.

Assessment in anaesthesia traditionally takes the form of written papers and oral examinations. These are important for assessing trainee's knowledge and judgement, but do not test for competency in practical skills, which is essential for successful clinical practice. The presence of learning curves for practical skills in anaesthesia is now well recognized and they are useful tools to monitor a learning process. From these, estimates of the number of procedures that must be performed by trainees in order to reach an acceptable success rate can be produced. It is clear that these figures give some help for the rational design of training programs, however, numbers alone do not provide a sufficient basis to declare a trainee competent for a given procedure. Not only technical skills need to be taught, but also decision-making and even more important behavioral skills. In clinical practice there are often problems in providing all the necessary training on patients and by this reorganization of residency programs may be necessary. However, the role of medical simulation in the assessment of anesthetists in training is still unclear, and the introduction of simulator-based tests may be premature.

Sudden cardiac death (SCD) in young athletes during physical stress is a rare event with an incidence of 1-3 deaths per 100,000 athletes per year. A coronary anomaly is the second most common cause of death following hypertrophic cardiomyopathy. Symptomatic prodromes occur in 20% of cases prior to the SCD event. This case report describes a 35-year-old male who collapsed near the finishing line of a half marathon run. Despite immediate resuscitation attempts and initial return of spontaneous circulation (ROSC), a pulseless electrical activity (PEA) followed and the patient died 1 h after arrival in the resuscitation unit. The autopsy revealed an anomalous left coronary artery (ALCA), which can lead to ischemia of the respective heart muscles under severe stress.