Ideal-Typical Utility Infrastructure at Chemical Sites - Definition, Operation and Defossilization

The defossilization of the electricity and heat supply in the chemical industry poses a significant challenge. In particular,the intended feed-in of volatile renewable electricity into the chemical processes may conflict with the need for a constant,secure and affordable electricity and heat supply for chemical plants. Adapted concepts for the operation of the cogenera-tion plant, which is located at the chemical site, play a central role. The present work defines a so-called ideal-typical utilityinfrastructure (iUI). The iUI is a means to exemplarily investigate the operational behavior of utility infrastructures andfurthermore to identify defossilization options for process steam and electricity supply at chemical sites

How to improve prescription of inhaled salbutamol by providing standardised feedback on administration: a controlled intervention pilot study with follow-up

Background: The effectiveness of inhaled salbutamol in routine care depends particularly on prescribed dosage and applied inhalation technique. To achieve maximum effectiveness and to prevent drug-related problems, prescription and administration need to work in concert. Methods: We performed a controlled intervention pilot study with 4 consecutive groups in a general paediatric unit and assessed problems in salbutamol prescribing and administration. Control group [i]: Routine care without additional support. First intervention group [ii]: We carried out a teaching session for nurses aimed at preventing problems in inhalation technique. Independently from this, a pharmacist counselled physicians on problems in salbutamol prescribing. Second intervention group [iii]: Additionally to the first intervention, physicians received standardised feedback on the inhalation technique. Follow-up group [iv]: Subsequently, without any delay after the second intervention group had been completed, sustainability of the measures was assessed. We performed the chi-square test to calculate the level of significance with p ≤ 0.05 to indicate a statistically significant difference for the primary outcome. As we performed multiple testing, an adjusted p ≤ 0.01 according to Bonferroni correction was considered as significant. Results: We included a total of 225 patients. By counselling the physicians, we reduced the number of patients with problems from 55% to 43% (control [i] vs. first intervention [ii], n.s.). With additional feedback to physicians, this number was further reduced to 25% ([i] vs. [iii], p < 0.001). In the follow-up [iv], the number rose again to 48% (p < 0.01 compared to feedback group). Conclusions: Teaching nurses, counselling physicians, and providing feedback on the quality of inhalation technique effectively reduced problems in salbutamol treatment. However, for success to be sustained, continuous support needs to be provided. Trial registration: German Clinical Trials register: DRKS00006792

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)

Aktivitätsprofil von Calpain I und II im chronisch infarzierten Rattenmyokard : Einfluss des Calpaininhibitors CAL 9961

Als Folge eines akuten Myokardinfarktes kommt es zu einem Anstieg der intrazellulären Ca2+-Konzentration assoziiert mit einer Aktivierung der kardialen Cysteinproteasen Calpain I und II. Diese scheinen in der Pathogenese von Gewebeschäden und Nekrose nach Myokardinfarkt eine wesentliche Rolle zu spielen. Darüber hinaus gibt es Hinweise auf eine Beteiligung von Calpain I bei kardialen Umbauprozessen nach Infarkt. Calpaininhibitoren könnten daher in der Therapie des Myokardinfarkts erfolgreich eingesetzt werden. Unter den Bedingungen einer kardialen Ischämie konnte bei einigen dieser Substanzen eine kardioprotektive Wirkung demonstriert werden. Im Rahmen der vorliegenden Dissertation wurde ein Aktivitätsprofil der beiden Calpainformen im infarzierten und nicht-infarzierten Myokard erstellt und die Auswirkungen des Calpaininhibitors CAL 9961 in vitro und in vivo untersucht. Hierzu wurde an Ratten durch permanente Ligation der linken Koronararterie ein akuter Myokardinfarkt induziert. Ein, 3, 7 und 14 Tage nach Infarkt wurden Calpain I und II aus Gewebehomogenaten von interventrikulärem Septum (IS) und linker, freier Ventrikelwand (LVFW) mittels Chromatographie auf DEAE-Sepharose getrennt. Die Aktivität wurde in scheinoperierten und Infarkt-induzierten Tieren mit chronischer Placebo- oder CAL 9961-Therapie mithilfe eines Enzymassays mit synthetischem Substrat gemessen. Die Therapie wurde 3 Tage vor Infarktinduktion begonnen. Calpain I-Aktivität erreichte 14 Tage nach Infarkt höchste Werte im nicht-infarzierten Myokard (IS), während die maximale Calpain II-Aktivität 3 Tage nach Infarktereignis im infarzierten Herzgewebe (LVFW) gemessen wurde. In Experimenten in vitro hemmte CAL 9961 beide Calpainformen vollständig. In vivo verhinderte eine chronische Therapie mit CAL 9961 bei Tieren mit Myokardinfarkt teilweise den Anstieg der Calpain I-Aktivität im nicht-infarzierten Gewebe (IS) und reduzierte die Calpain II-Aktivität im infarzierten Myokard (LVFW) auf das Level scheinoperierter Tiere. Die in dieser Dissertation erbrachten Ergebnisse zeigen, dass die kardialen Calpaine I und II nach einem akuten Myokardinfarkt aktiviert werden, sich ihre Aktivierung jedoch innerhalb des Myokards zeitlich und regional unterscheidet. Die chronische Inhibition dieser Enzyme könnte die Calpain-vermittelten Gewebeschäden limitieren und zur Erhaltung der strukturellen Integrität des Myokards nach Infarkt beitragen.The calpains have been proposed to be activated following cardiac ischemia and to contribute to myocyte damage after myocardial infarction (MI). In this study, the activity of calpains I and II in the infarcted and non-infarcted rat myocardium and the action of the selective calpain inhibitor, CAL 9961, has been investigated. MI was induced by permanent ligation of the left coronary artery. One, 3, 7 and 14 days post MI, the enzymes calpain I and II were separated from homogenates of the interventricular septum (IS) and left ventricular free wall (LVFW) by chromatography on DEAE-Sepharose. The activity of the calpains was measured in sham-operated and MI animals chronically treated with placebo or CAL 9961 (15mg kg‾1 d‾1 s.c.) in a synthetic substrate assay. Treatment was started 3 days before MI induction. Calpain I activity reached highest values in IS 14 days post MI, whereas maximum activity of calpain II was measured in LVFW 3 days post MI. In experiments in vitro, CAL 9961 completely inhibited both calpains. In vivo, chronic treatment of MI animals with CAL 9961 partially prevented the increase in calpain I activity in IS and reduced calpain II activity in LVFW to sham levels. Our findings demonstrate that calpains I and II are activated after MI, however, both enzymes differ in their regional and temporal activation within the infarcted myocardium. Chronic inhibition of these enzymes with CAL 9961 might limit the calpain-induced myocardial damage and preserve cardiac structural integrity post MI

Atopic diseases in children and adolescents are associated with behavioural difficulties

Background!#!Atopic diseases and behavioural difficulties in children have both been on the rise in recent decades. This study seeks to assess associations between atopic diseases and behavioural difficulties, examining the differences considering child age and how behavioural difficulties were reported (via self-report or parent-report).!##!Methods!#!Data on behavioural difficulties, assessed through the Strengths and Difficulties Questionnaire (SDQ), and on atopic diseases, assessed through the participant's medical history, were available for 2701 study participants aged 3 to 18 years. Associations between atopic diseases and behavioural difficulties were evaluated using linear regression analyses. We split the study sample into two groups. I: 3-to 10-year-olds/parent-reported SDQ (n = 1764), II: 11- to 18-year-olds/parent-reported SDQ (n = 937) and self-reported SDQ (n = 915). All analyses were adjusted for age, gender, and socioeconomic status.!##!Results!#!In younger children, atopic dermatitis was strongly associated with higher total difficulties scores, more emotional problems and conduct problems, and more symptoms of hyperactivity/inattention. Parents reported higher total difficulties scores, more emotional problems, and more peer-relationship problems for adolescents with bronchial asthma and other allergies, whereas the adolescents themselves reported more peer relationship problems.!##!Conclusion!#!In younger children, atopic dermatitis is associated with internalizing and externalizing problems. In adolescents, bronchial asthma and other allergies are associated with a greater level of internalizing problems only. The findings further suggest that parents of adolescents are more likely to perceive associations between atopic diseases and behavioural difficulties than the adolescents themselves