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Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

Key Points Question Is the implementation of the Swiss diagnosis-related group reimbursement system associated with a reduction in length of hospital stay without negatively affecting in-hospital mortality and readmission rates in adult patients? Findings In this cohort study of data from 2 426 722 adult patients, the gradual decrease in length of hospital stay observed from 2009 to 2015 was not substantially greater after the implementation of the Swiss diagnosis-related group system in 2012. An increase in 30-day readmission rates and a decrease in in-hospital mortality were observed after the introduction of the Swiss diagnosis-related group system. Meaning Swiss diagnosis-related group implementation appeared to be associated with higher readmission rates and lower in-hospital mortality but not with a substantial decrease in length of hospital stays., Importance In 2012, hospital reimbursement in Switzerland changed from a fee-for-service per diem system to a diagnosis-related group (SwissDRG) system. Whether this change in reimbursement is associated with harmful implications for quality of care and patient outcomes remains unclear. Objective To examine the association of the SwissDRG implementation with length of hospital stay (LOS), in-hospital mortality, and 30-day readmission rates in the overall adult inpatient population and stratified by 5 individual diagnoses. Design, Setting, and Participants This cohort study used administrative data from the Swiss Federal Statistical Office to investigate medical hospitalizations in Switzerland from January 1, 2009, through December 31, 2015. All hospitalizations for adult medical inpatients were included in the main analysis. Patients who presented with 1 of the 5 common medical diagnoses were included in the subanalyses: community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, acute myocardial infarction, acute heart failure, and pulmonary embolism. An interrupted time series model was used to determine changes in time trends for risk-adjusted LOS, in-hospital mortality, and 30-day readmission after the implementation of SwissDRG in 2012. Analyses were performed from March 1, 2018, to June 30, 2018, and from November 1, 2018, to December 18, 2018. Main Outcomes and Measures Monthly patient-level data for LOS, in-hospital mortality, and 30-day readmission rates. Results The sample included a total of 2 426 722 hospitalized adult patients. Of this total, 1 018 404 patients (41.9%; 531 226 [52.2%] male, median [interquartile range (IQR)] age of 69 [55-80] years) composed the before-SwissDRG period; 1 408 318 patients (58.0%; 730 228 [51.9%] male, median [IQR] age of 70 [56-81] years) composed the after-SwissDRG period. The overall LOS gradually decreased from unadjusted mean (SD) 8.0 (12.7) days in 2009 to 7.2 (17.3) days in 2015. This reduction in LOS, however, was not substantially greater with the implementation of SwissDRG in 2012 (risk-adjusted slope, –0.0166 days; 95% CI, –0.0223 to –0.0110 days), with an adjusted difference in slopes of 0.0000 days (95% CI, –0.0072 to 0.0072 days). Risk-adjusted all-cause in-hospital mortality declined from 4.9% in 2009 to 4.6% in 2015, with a substantially greater decline after implementation of SwissDRG (difference between monthly slopes before and after implementation, –0.0115%; 95% CI, –0.0190% to –0.0039%). In the same period, risk-adjusted 30-day readmission rates increased from 14.4% in 2009 to 15.0% in 2015, with a greater increase after SwissDRG implementation (change in monthly slope, 0.0339%; 95% CI, 0.0254%-0.0423%). Patients with acute myocardial infarction were found to have a substantially greater increase after SwissDRG implementation in 30-day readmission rates (adjusted difference in slopes, 0.1144%; 95% CI, 0.0617%-0.1671%). Conclusions and Relevance Among medical hospitalizations in Switzerland, SwissDRG implementation appeared to be associated with an increase in readmission rates and a decrease in in-hospital mortality but not with the gradual decrease in LOS observed in the historical control period., This cohort study examines hospitalization and patient outcomes data of hospitalized adult patients before and after the implementation of the diagnosis-related group reimbursement system in Switzerland.

EuroQol Group 5-Dimension Self-Report Questionnaire. (PDF 149â kb)

After the successful start of the hard X-ray FEL at SwissFEL in 2016, the soft X-ray FEL ATHOS at SwissFEL is expected to deliver the first beam by end of 2019. This contribution describes the beamlines attached to the FEL and reports on the status and plans for this soft X-ray facility. The ATHOS facility will operate three end stations. Two stations are already defined and are currently in the design and construction phase whereas the third station will be defined in the future. The first station (AMO) is dedicated to Atomic and Molecular physics as well as nonlinear spectroscopy. It is expected to get light in mid 2020. The second station (Furka) is for condensed matter physics. The beamline consists of a grating monochromator and distributes the beam downstream of the grating chamber by means of horizontal deflecting mirrors. Pink and monochromatic beam operation is foreseen at all branches. The monochromator uses variable line-spacing gratings on spherical substrates with a variable included angle and operates without an entrance slit. Its mechanics is based on the SX-700 design, but with the grating facing up and the mirror facing down. The installation of the beamline will start in August 2019., Proceedings of the 39th Free Electron Laser Conference, FEL2019, Hamburg, Germany

Yield of screening and number needed to screen. Yield of screening for active TB per 1000 screened individuals and number needed to screen to detect 1 case of TB with 95% credible intervals, stratified by age group, sex, year of screening, and asylum seekersâ country of origin. (PDF 77 kb)

Structured questionnaire to perform phone interviews with all included patients 30â days after hospital admission to assess their outcome data and satisfaction. (PDF 265â kb)

The SwissFEL Aramis beamline provides hard X-ray FEL radiation down to 1 Angström with 5.8 GeV and short period, 15 mm, in-vacuum undulators (U15). To reach the maximum designed K-value of 1.8 the U15s have to be operated with vacuum gaps down to 3.0 mm. The thirteen-undulator modules are 4 m long and each of them is equipped with a pair of permanent magnet quadrupoles at the two ends, aligned magnetically to the undulator axis. Optical systems and dedicated photon diagnostics are used to check the alignment and improve the K-value calibration. In this talk the main steps of the undulator commissioning will be recalled and a systematic comparison between the magnetic results and the electron and photon based measurements will be reported to highlight achievements and open issues., Proceedings of the 39th Free Electron Laser Conference, FEL2019, Hamburg, Germany

Die Wirkungskanäle von Lobbyismus sind vielfältig und – zumindest in der Theorie – weitgehend bekannt. Jedoch gibt es nur wenig empirische Evidenz hinsichtlich der Wahrnehmung von Lobbyismus in der Bevölkerung. Vor diesem Hintergrund hat das ZEW – Leibniz-Zentrum für Europäische Wirtschaftsforschung gemeinsam mit der Universität Mannheim eine repräsentative Umfrage in Deutschland durchgeführt. Das Haupter-gebnis: Die große Mehrheit der Bevölkerung sieht nicht nur einen enormen Einfluss von Lobbygruppen auf die nationale und die in Brüssel gemachte Politik (EU-Politik), sondern steht diesem Einfluss auch sehr ablehnend gegenüber.

The Athos line will cover the photon energy range from 250 to 1900 eV and will operate in parallel to the hard X-ray line Aramis of SwissFEL. The paper will describe the current layout of the Athos FEL line starting from the fast kicker magnet followed by the dogleg transfer line, the small linac and the 16 APPLE undulators. From there the photon beam passes through the photonics front end and the beamline optics before reaching the experimental stations AMO and FURKA. The focus of this contribution will be on the two bunch operation commissioning (two bunches in the same RF macropulse), which started in 2018, and the characterization of the major components like the APPLE X undulator UE38, the CHIC chicane and the dechirper. The Athos installation inside the tunnel is alternating with Aramis FEL user operation and the first lasing is planned for winter 2019 / 2020., Proceedings of the 39th Free Electron Laser Conference, FEL2019, Hamburg, Germany

The number of supermarkets offering grocery delivery has increased in recent years. Many studies conclude that CO2 emission savings result from this concept. Since the delivery of groceries also consumes energy and produces emissions, break-even points can be calculated, where the delivery is environmentally beneficial compared to customer pickup. In this paper, influences of differing vehicle use on break-even points for savings of energy and CO2 emissions are analyzed for the case of Haidhausen S&uuml, d, a district in Munich, Germany. Internal combustion engine and electric vehicles are investigated to depict current as well as future trends. After an introduction to the methodology used, the potential to save energy and CO2 emissions related to the delivery of groceries in the chosen district of Munich are evaluated. Subsequently, influences on the break-even points are presented and discussed. As the results show, a delivery of groceries leads to energy and carbon dioxide savings in a wide range of private vehicle use for grocery shopping trips. Nevertheless, if the complete customer vehicle fleet is electrified, the use of delivery vehicles with an internal combustion engine could cause an additional environmental impact at the current modal split for shopping trips in Germany.

Die Wirkungskanäle von Lobbyismus sind vielfältig und – zumindest in der Theorie – weitgehend bekannt. Jedoch gibt es nur wenig empirische Evidenz hinsichtlich der Wahrnehmung von Lobbyismus in der Bevölkerung. Vor diesem Hintergrund hat das ZEW – Leibniz-Zentrum für Europäische Wirtschaftsforschung gemeinsam mit der Universität Mannheim eine repräsentative Umfrage in Deutschland durchgeführt. Das Haupter-gebnis: Die große Mehrheit der Bevölkerung sieht nicht nur einen enormen Einfluss von Lobbygruppen auf die nationale und die in Brüssel gemachte Politik (EU-Politik), sondern steht diesem Einfluss auch sehr ablehnend gegenüber.

Technical appendix. Technical appendix containing additional details related to methods, data sources, and analysis. (PDF 542 kb)

Eine Facette des klinischen Erscheinungsbildes der „chronic obstructive pulmonary disease“ (COPD) ist die chronische Bronchitis mit einem überwiegend inflammatorischen Korrelat. Der Pathogenese der chronischen Bronchitis liegen komplexe pathophysiologische Vorgänge zugrunde, welche bislang nur unvollstädig bekannt und im Einzelnen nicht vollständig geklärt sind. Die Definition der „global initiative on obstructive lung disease“ (GOLD) erwähnt eine abnormale inflammatorische Reaktion der Lunge auf schädliche Partikel und Gase und rückt somit die Entzündung ins Zentrum der Pathogenese. Zigarettenrauch und wichtige Umweltnoxen wie Stickstoffdioxid (NO2) führen über die hervorgerufene Entzündung bei Menschen und anderen Spezies zu Veränderungen des Atemwegsepithels und zur Stimulation der Produktion von proinflammatorischen Zytokinen wie dem Granulozyten-Makrophagen-Kolonie-stimulierenden Faktor (GM-CSF). Die strukturellen Veränderungen schließen auch die Muzin-produzierenden epithelialen Komponenten ein. Ein relevantes klinisches Symptom der chronischen Bronchitis stellt die Hypersekretion dar. Die Regulation der Muzinsynthese und -sekretion unterliegt komplexen neuralen, neuroendokrinen und parakrinen Mechanismen. Mit dem Ziel, zugrunde liegende Regulationsmechanismen der Mukussekretion bei der chronisch inflammatorischen Erkrankung COPD näher zu charakterisieren, liegt der Schwerpunkt dieser Arbeit in der Bedeutung des proinflammatorischen Zytokins GM-CSF. Folgenden Fragen, welchen eine Bedeutung bei der Regulation der Mukussekretion zukommt, wird in der vorliegenden Arbeit nachgegangen: Welchen Einfluss hat die Lang- und Kurzzeitexposition von NO2 auf die tracheobronchiale Muzinsekretion? Welchen Einfluss zeigt die peptiderge Substanz Substanz P (SP) auf die Muzinsekretion exponierter Tiere auch im Speziesvergleich? Wirkt das proinflammatorische Zytokin GM-CSF sekretagog? Gibt es interaktive Prozesse zwischen dem Zytokin GM-CSF und dem Tachykinin SP im Hinblick auf die Sekretomodulation? Zur experimentellen Klärung dieser Fragestellungen wurde ein etabliertes Tiermodell gewählt. Für das Studium der Reaktionsweise entzündlich alterierter Atemwege erfolgte die inhalative Exposition gegenüber NO2 im Rattenmodell. Die Muzinsekretion wurde an Trachealexplantaten von Fischerratten (F344-Ratten) und Sprague-Dawley-Ratten (SD-Ratten) durch die Anwendung der etablierten Ussing-Kammer-Methode untersucht. Zur Quantifizierung der Sekretion trachealer submuköser Drüsen erfolgte die radioaktive Markierung der Muzine mit 35S. Zum Studium der trachealen Muzinsekretion erfolgte die inhalative Exposition mit Induktion einer Schädigung und Herbeiführung einer akuten und subakuten bis chronischen Tracheobronchitis. Mit standardisierter Methodik wurden bei männlichen Ratten der jeweiligen Spezies Expositionszeiten von 1, 3 und 20 Tagen sowie darüber hinaus teilweise von 2 und 28 Tagen gegenüber NO2 bei einer Konzentration von 10 ppm gewählt. Kontrolltiere wurden einer Atmosphäre ohne NO2 ausgesetzt. Neben der Basalsekretion wurde zunächst an den Trachealexplantaten die maximal stimulierte Sekretion durch Acetylcholin (ACh) in Stadien der artifiziellen Entzündung und im Nativzustand erfasst. Mit diesen Grundlagen kann ein sekretomodulatorischer Effekt des Peptides SP und eine Dosis-Wirkungs-Beziehung des proinflammatorischen Zytokins GM-CSF im zeitlichen Verlauf unter NO2-Exposition untersucht werden. Zudem wurde hinsichtlich des Sekretionsergebnisses die Frage nach einem additiven Effekt von GM-CSF und SP an langzeit-exponierten Tracheen untersucht. Die Sekretionsanalyse ergab, dass eine NO2-Exposition von 10 ppm die Muzinsekretion der Rattentrachea beider Spezies zeitabhängig nicht signifikant beeinflusst. Es zeigten sich allerdings gleichgerichtete Tendenzen ohne Signifikanz im Sekretionsverlauf. Im Speziesvergleich zeigten dabei SD-Ratten eine größere sekretorische Potenz im Vergleich zu F344-Ratten im Sinne eines nahezu parallel verschobenen Sekretionsniveaus auf. Darüber hinaus wurde die Sekretionsrate nativ und bis zu einer Expositionsdauer von 20 Tagen bei beiden Spezies durch Acetylcholin im Vergleich zur Basalsekretion signifikant gesteigert. Hierbei fanden sich im direkten Vergleich zu den nativen Fischerratten wiederum signifikante Differenzen nach 3 sowie 20 Tagen. Signifikante sekretagoge Effekte von Substanz P ließen sich bei Fischerratten und SD-Ratten sowohl bei den Kontrolltieren als auch bei nahezu allen untersuchten Expositionsgruppen aufzeigen. GM-CSF zeigte in unserem Rattenmodell der COPD dosis- und expositionszeitabhängig eine Stimulation der trachealen Muzinsekretion. Eine signifikante Sekretionsantwort in der 3-Tages-Expositionsgruppe konnte für 0,1 ng/ml GM-CSF und für 0,4 ng/ml GM-CSF demonstriert werden. Zudem fand sich eine Signifikanz in der 20-Tages-Expositionsgruppe für 0,1 und 0,15 sowie 0,2 ng/ml GM-CSF. Für die Dosis von 0,2 ng/ml GM-CSF ergab sich ein hochsignifikantes Ergebnis. Die gleichzeitige Gabe von GM-CSF und SP zeigte in der Langzeitexposition keinen messbaren additiven sekretagogen Effekt und ergab das Sekretionsniveau von SP. Dies wurde nach 20 Tagen Expositionsdauer untersucht, da für diese Gruppe für beide Einzelsubstanzen jeweils eine signifikante Sekretionsantwort gesehen wurde. Die mutmaßlich unterschiedlichen sekretagogen Mechanismen von SP und GM-CSF sind vereinbar mit der Beobachtung, dass SP auch unabhängig vom Vorhandensein einer Atemwegsinflammation wirksam ist. Diese Ergebnisse liefern einen Beitrag zum Verständnis der Komplexität der bei der Regulation der Muzinsekretion beteiligten Pathomechanismen des Tracheobronchialepithels in der chronischen Bronchitis. Der sekretagoge Effekt von GM-CSF in der chronischen Inflammation wurde demonstriert. Mit dem Ziel einer Beeinflussung der Hypersekretion bei der COPD ist hier ein zielgerichteter therapeutischer Ansatz denkbar. Der Einsatz von neutralisierenden Antikörpern gegen GM-CSF oder dessen Rezeptor ist als spezifisches Therapiekonzept vorstellbar. Dieses ist in Ergänzung zu den etablierten antiinflammatorischen therapeutischen Möglichkeiten bei der COPD zu sehen und ermöglicht im Gegensatz dazu ein zielgerichtetes Eingreifen in die inflammatorische Kaskade. Es bedarf weiterer Untersuchungen, um die Rolle einer solchen Herangehensweise zu konkretisieren., One facet of the clinical manifestation of chronic obstructive pulmonary disease (COPD) is chronic bronchitis, with inflammation being the predominant correlating factor. The pathogenesis of chronic bronchitis is based on complex pathophysiological processes, which are currently not fully known and have not yet been fully clarified, in detail. The definition from the "global initiative on obstructive lung disease" (GOLD) mentions an abnormal inflammatory reaction of the lung to harmful particles and gases, thus putting inflammation at the centre of the pathogenesis. Cigarette smoke and important environmental noxae such as nitrogen dioxide (NO2) cause changes in the respiratory epithelium of humans and other species through eliciting inflammation and stimulate the production of pro-inflammatory cytokines, such as granulocyte-macrophage colony stimulating factor (GM-CSF). These structural changes also involve the mucin-producing epithelial components. One relevant clinical symptom of chronic bronchitis is hypersecretion. The regulation of mucin synthesis and secretion is subject to complex neural, neuro-endocrine and paracrine mechanisms. With the aim of characterising the underlying regulatory mechanisms of mucus secretion in the chronic inflammatory disease COPD, the focus of this work is on the significance of the pro-inflammatory cytokine GM-CSF. The following questions that are of importance for the regulation of mucus secretion will be investigated in this paper: What influence do long- and short-term exposure of NO2 have on tracheobronchial mucin secretion? What influence does the peptidergic substance substance P (SP) have on the mucin secretion of exposed animals, and how does this compare by species? Does the pro-inflammatory cytokine GM-CSF act as a secretagogue? Are there interactive processes between the cytokine GM-CSF and the tachykinin SP with regard to secretion modulation? An established animal model was chosen for the experimental clarification of these questions. To study the mode of response of respiratory tracts altered through inflammation, inhalative exposure to NO2 was implemented in rats. Mucin secretion was investigated in tracheal explants of Fischer rats (F344 rats) and Sprague-Dawley rats (SD rats) using the established Ussing chamber method. In order to quantify the secretion of tracheal submucosal glands, the mucin underwent radioactive labelling with 35S. In order to study tracheal mucin secretion, inhalative exposure was implemented, with damage induced and acute and subacute to chronic tracheobronchitis brought about. Using standardised methods, exposure times of 1, 3 and 20 days were selected for male rats of the species in question, as well as of 2 and 28 days, in some cases, to NO2 at a concentration of 10 ppm. Control animals were subject to an atmosphere without NO2. In addition to basal secretion, initially, the maximum stimulated secretion due to acetylcholine (ACh) was recorded on the tracheal implants in stages of artificial inflammation and in the natural state. With an understanding of these foundations, the secreto-modulatory effect of the peptide SP and the dose–response relationship of the pro-inflammatory cytokine GM-CSF can then be investigated over time under exposure to NO2. In addition, the question of any additive effect of GM-CSF and SP in terms of secretion result was investigated in tracheas exposed long-term. The secretion analysis showed that NO2 exposure of 10 ppm does not significantly influence tracheal mucin secretion in rats of either species in a time-dependent manner. However, similar trends were demonstrated that were of no significance over the course of secretion. In the species comparison, SD rats exhibited a greater secretory potential compared to F344 rats, in line with an almost parallel shift in secretion level. What is more, in both species, the natural secretion rate and that up until an exposure duration of 20 days was significantly increased by acetylcholine compared to basal secretion. Here, again, in a direct comparison with the native Fischer rats, significant differences were noted after 3 and 20 days. Significant secretagogic effects were able to be demonstrated for substance P in Fischer rats and SD rats, both in the control animals and in almost all the exposure groups investigated. GM-CSF was shown to stimulate tracheal mucin secretion in our COPD rat model in a manner that was both dose- and exposure-time-dependent. A significant secretory response was able to be demonstrated in the 3-day exposure group for 0.1 ng/ml GM-CSF and for 0.4 ng/ml GM-CSF. In addition, significance was noted in the 20-day exposure group for 0.1 and 0.15 as well as 0.2 ng/ml GM-CSF. A highly significant result was obtained for the dose of 0.2 ng/ml GM-CSF. Simultaneous administration of GM-CSF and SP did not indicate any measurable additive secretagogic effect over long-term exposure and resulted in the secretion level of SP. This was investigated after 20 days of exposure, since for this group, a significant secretory response was seen for both individual substances. The supposedly different secretagogic mechanisms of SP and GM-CSF are compatible with the observation that SP is in any case effective regardless of the presence of any respiratory inflammation. These results contribute to the understanding of the complexity of the tracheobronchial epithelium pathomechanisms involved in the regulation of mucin secretion in chronic bronchitis. The secretagogic effect of GM-CSF in the presence of chronic inflammation was demonstrated. Here, a targeted therapeutic approach is conceivable, with the aim of influencing hypersecretion in cases of COPD. The use of neutralising antibodies against GM-CSF or its receptor is plausible as a specific therapy concept. This should be viewed in addition to the established anti-inflammatory therapeutic options for COPD and, by contrast, enables targeted intervention in the inflammatory cascade. Further research is needed to substantiate the role of such an approach.

Period averaged incidence of tuberculosis (per 100,000) and 95% confidence intervals reported by WHO, 1990–2014. Overview of period averaged incidence of tuberculosis (per 100,000) and 95% confidence intervals reported by WHO (1990–2014) based on own calculations for countries used in this study. (PDF 113 kb)

TThe number of supermarkets offering a grocery delivery has been increasing during the last years. Many studies deduce CO2 emission savings using this concept. Since the delivery of groceries also consumes energy and produces emissions, break-even points can be calculated, from where the delivery has environmental advantages compared to the customer pickup. In this paper, influences of differing vehicle use on break-even points for savings of energy and CO2 emissions are analyzed for the case of Haidhausen Süd, a city district of Munich in Germany. Internal combustion engine and electric vehicles are investigated to depict current as well as future trends. After an introduction to the used methodology, the potential to save energy and CO2 emissions related to the delivery of groceries in the chosen district of Munich is evaluated. Afterwards, influences on the break even points are presented and discussed. As the results show, a delivery of groceries leads to energy and carbon dioxide savings in a wide range of private vehicle use for grocery shopping trips. Nevertheless, if the complete customer vehicle fleet is electrified, the use of delivery vehicles with an internal combustion engine can cause an additional environmental impact at the current modal split for shopping trips in Germany.