Search

in press Background Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. Methods This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. Conclusions In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

Neck pain is one of the most common musculoskeletal disorders encountered by healthcare providers. A precise assessment of functional deficits, including sensorimotor control impairment, is regarded necessary for tailored exercise programmes. Sensorimotor control can be measured by kinematic characteristics, such as velocity, acceleration, smoothness, and temporal measures, or by assessing movement accuracy. This systematic review aims to identify movement tasks and distinct outcome variables used to measure kinematics and movement accuracy in patients with neck pain and present their results in comparison to asymptomatic controls.Electronic searches were conducted in MEDLINE, PEDro, Cochrane Library and CINAHL databases from inception to August 2020. Risk of bias of included studies was assessed. Movement tasks and specific outcome parameters used were collated. The level of evidence for potential group differences in each outcome variable between patients with neck pain and controls was evaluated.Twenty-seven studies examining head kinematics and movement accuracy during head-aiming, functional and unconstrained movement tasks of the head were included. Average Risk of Bias of included studies was moderate. In total, 23 different outcome variables were assessed. A strong level of evidence for an increased movement time and for an increased number of errors during head aiming tasks was found. Moderate evidence was found in traumatic neck pain for a decreased mean velocity, peak acceleration, and reaction time, and for point deviation and time on target during head aiming tasks. Moderate evidence was found for decreased acceleration during unconstrained movements, too. Results on the remaining movement task and outcome variables showed only limited, very limited or even conflicting level of evidence for patients with neck pain to differ from controls.Sensorimotor control in NP in the way of kinematic and movement accuracy characteristics of head motion was examined in head aiming, functional or unconstrained movement tasks. The results from this review indicate that for some characteristics that describe sensorimotor control, patients with NP differ from healthy controls.PROSPERO registration number: CRD42020139083.

ZusammenfassungZiel des Verbundprojekts AKTIV-kommunal war die Entwicklung, pilothafte Umsetzung und Evaluierung einer integrierten Toolbox für die digitale Transformation kommunaler Energieversorger. In drei integriert bearbeiteten Teilprojekten standen die Digitalisierung von Arbeitsprozessen, digitale Arbeitsmodelle sowie Digital Leadership im Mittelpunkt der Projektaktivitäten. Dabei bildeten jeweils ein Forschungspartner und ein Anwendungsunternehmen ein Tandem, um zu wissenschaftlich fundierten und praxistauglichen Ergebnissen zu gelangen. Der Projektbeirat, dem namhafte Vertreter/-innen aus Unternehmen, von Verbänden, der Sozialpartner und weitere Wissenschaftler angehörten, gab zusätzliche Impulse für die Projektarbeit. Im vorliegenden Beitrag werden die zentralen Ergebnisse von AKTIV-kommunal vorgestellt. Darüber hinaus werden Hinweise zu den im Projektverlauf erstellten Transfermaterialien gegeben und erfolgt ein Ausblick auf zukünftige Forschungsaktivitäten.

The coordinated Denial of Service attacks in Estonia 2007, the successful hacker attacks against the German Bundestag 2015 and the increasing number of cyber-crimes challenge the European Union (EU). In order to overcome these challenges the EU initiated a cyber security strategy in 2013. This paper follows up the question, whether the measures of this strategy are adequate in order to tackle the challenges of the cyberspace in modern times and which improvements can be done. The focus will rely on the analysis of the EU’s cyber security strategy 2013 as well as its advancement of 2017. The three issues ‘cyber resilience‘, ‘reducing cybercrime’ and ‘cyber defence policy and capabilities’ shall be analyzed. The unlimited sphere of the cyberspace, the invisible and barely identifiable opponents and the focus on national regulations seem to be an unsolved dilemma in the EU. After analyzing the current state, the paper shall formulate future recommendations for action to postulate an improved ‘pooling and sharing’ as well as the coordination and involvement of existing member states’ cyber capabilities. The devolution of responsibilities regarding cyber security to the EU stage is desirable in order to increase the European potency, because a divided EU will have great difficulties enforcing its interests over attacking opponents.

Der vorliegende Beitrag zeigt methodische Moglichkeiten mithilfe empirischer Daten den Forschungsstand zu Dienstleistungsnetzwerken zu bereichern. Dabei fokussiert der Beitrag auf die Verbindung von Kooperation und Wettbewerb (Coopetition) als neuer Blickwinkel auf Unternehmensnetzwerke. Dieser wird fur das Dienstleistungsmanagement als Service Coopetition konkretisiert. Neben einer kompakten Einfuhrung in die Netzwerkanalyse werden ausgewahlte Netzwerkkennzahlen vorgestellt. Abschliesend wird eine quantitative Literaturrecherche vorgenommen, um den aktuellen Forschungsstand zu Coopetition in Zusammenhang mit Dienstleistungsnetzwerken zu beleuchten.

Die Hotellerie bleibt in Bewegung. Zunehmender Wettbewerbsdruck durch die digitale Transformation und neue Geschäftsmodelle, aber auch erforderliche Investitionen oder der Fachkräftemangel zwingen verantwortliche Entscheidungsträger heute mehr denn je zu Kreativität und Durchsetzungskraft. Erfahrene Akteure aus Hotellerie und Forschung gehen in diesem Band den vielseitigen branchenspezifischen Herausforderungen auf den Grund – und liefern dabei so überraschende wie praktikable Lösungsansätze. Ein erstklassiger Querschnitt zu aktuellen Themen und Tendenzen in der Hotellerie.

Background: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist. Methods: A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II–IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths. Findings: An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (−18.8% from baseline) vs. placebo (+6.9%). Interpretation: Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.

Objectives The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45 degrees s-1 reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation. Methods In a randomized, double-blind fashion, 35 patients with mild to moderate essential hypertension received placebo run-in medication for 2 weeks, followed by 4 weeks' moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG. Results On day 1 there was a significant, but not clinically relevant, reduction in the time-corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38 degrees s-1; 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9 degrees s-1; 95% CI -17, 35) and 4 weeks (6.9 degrees s-1; 95% CI -16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG alpha- and beta-power and an increase in delta-power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks' moxonidine treatment. Conclusions Four weeks' treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure-lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment.

Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, antiischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d. and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest [day 1:-13.6 versus −15.4 bpm; day 6: −14.8 versus −22.2 bpm, resp.; p > 0.05] and exercise [day 1; −9.1 versus −18.3 bpm; p = 0.001; day 6; −12.0 versus −24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: −1.01 versus −1.19 l/min; p > 0.05; day 6: −0.86 versus −1.10 l/min, resp.; p > 0.05] and exercise [day 1: −0.82 versus −1.28 l/min; p > 0.05; day 6: −0.65 versus −2.68 l/min, resp.; p = 0.03], while stroke volume remained unchanged. Right atrial pressure changed during exercise only: it decreased with tedisamil (−1.7 mmHg) and increased with atenolol (+3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (−0.5 mmHg) and exercise (−6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: +1.7; exercise: +3.7 mmHg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (−93 pg/ml) but elevated by atenolol (+172 pg/ml) (p = 0.001). As compared to atenolol, tedisamil produced a prolongation of QTc interval [+31 versus 8 ms] at initial values of 0.408 ± 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and antiischemic effects. The antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.

Klinische Limitationen bei der Behandlung der stabilen Angina pectoris mittels Betablocker fuhrten zur Entwicklung von alternativen frequenzsenkenden Substanzen wie beispielsweise dem K+-Kanalblocker Tedisamil, der neben antiischamischen auch antiarrhythmische Eigenschaften aufweist. In der vorliegenden Untersuchung (doppelblinder, randomisierter Gruppenvergleich) wurden die hamodynamischen, antiischamischen, metabolischen und neurohumoralen Auswirkungen von 2× 100 mg Tedisamil und 2× 50 mg Atenolol als Monotherapie bei 48 Patienten mit stabiler Angina pectoris uber einen Zeitraum von 6 Tagen verglichen. Tedisamil und Atenolol fuhrten zu einer Senkung der Herzfrequenz sowohl in Ruhe (Tag 1: –14 vs –15 min-1; p > 0,05; Tag 6: –15 vs –22 min-1; p > 0,05) als auch unter Belastung (Tag 1: –9 vs –18 min-1; p = 0,001; Tag 6: –12 vs –25 min-1; p = 0,001) bei gleichzeitiger Erhohung der Angina-pectoris-Schwelle. Das Herzzeitvolumen wurde unter beiden Substanzen sowohl in Ruhe (Tag 1: –1,01 vs –1,19 l/min; p > 0,05; Tag 6: –0,86 vs –1,01 l/min; p > 0,05) als auch unter Belastung (Tag 1: –0,82 vs –1,28 l/min; p > 0,05); Tag 6: –0,65 vs –2,68 l/min; p = 0,03) gesenkt, wobei das Schlagvolumen unverandert blieb. Der rechtsatriale Druck anderte sich nur unter Belastung mit einem Abfall unter Tedisamil (–1,7 mm Hg) und einem Anstieg unter Atenolol (+3,7 mm Hg) (p = 0,001). In der Tedisamil-Gruppe fiel der mittlere pulmonalkapillare Verschlusdruck am 6. Behandlungstag sowohl in Ruhe (–0,5 mm Hg) als auch unter Belastung (–6,9 mm Hg), zeigte jedoch unter Atenolol eine Tendenz zum Anstieg (Ruhe: +1,7 mm Hg; Belastung: +3,7 mm Hg) (p = 0,03). Eine Senkung des arteriellen Druckes zeigte sich nur unter Behandlung mit Atenolol. Wahrend die belastungsinduzierten Noradrenalin-Plasmaspiegel nach Tedisamil-Gabe gesenkt wurden (–93 pg/ml), zeigte sich unter Atenolol eine Erhohung (+172 pg/ml) (p = 0,001). Nach Tedisamil fand sich eine im Vergleich zu Atenolol signifikante Verlangerung des QTc-Intervalls (+31 vs –8 ms) 8p = 0,002) bei einem Ausgangswert von 0,408 ± 0,018 und unveranderten PQ- und QRS-Zeiten. In der vorliegenden Studie zeigte Tedisamil gunstige hamodynamische, metabolische und neurohumorale Effekte bei Patienten mit stabiler Angina pectoris. Die antiischamische Wirkung von Tedisamil, gemessen an der ST-Strecken-Senkung und der Angina-pectoris-Schwelle, ist mit der von Atenolol vergleichbar.

During the oxidative degradation of 2,4-dimethylaniline (2,4-xylidine) by means of the H2O2/UV method, a series of hydroxylated aromatic amines are formed, this result confirming the role of the hydroxyl radical as an initiator of the oxidative chain reaction. Thermal or photochemically enhanced Fenton reactions in the presence of 2,4-dimethylaniline (2,4-xylidine) yield primarily 2,4-dimethylphenol as an intermediate product, the genesis of which may only be explained by an electron transfer mechanism. Experimental evidence for such a mechanism is presented, and values for the quantum yields of the photochemically enhanced reduction of iron(III) to iron(II) in aqueous solutions of 2,4-xylidine are given.

Background Possible immunization to blood group or other antigens and subsequent inhibition of remodeling or incorporation after use of untreated human bone allograft was described previously. This study presents the immunological, clinical and radiological results of 30 patients with acetabular revisions using fresh frozen non-irradiated bone allograft. Methods AB0-incompatible (donor-recipient) bone transplantation was performed in 22 cases, Rh(D) incompatible transplantation in 6 cases. The mean follow up of 23 months included measuring Harris hip score and radiological examination with evaluation of remodeling of the bone graft, implant migration and heterotopic ossification. In addition, all patients were screened for alloimmunization to Rh blood group antigens. Results Compared to the whole study group, there were no differences in clinical or radiological measurements for the groups with AB0- or Rh(D)-incompatible bone transplantation. The mean Harris Hip Score was 80.6. X-rays confirmed total remodeling of all allografts with no acetabular loosening. At follow up, blood tests revealed no alloimmunization to Rh blood group donor antigens. Conclusions The use of fresh frozen non-irradiated bone allograft in acetabular revision is a reliable supplement to reconstruction. The risk of alloimmunization to donor-blood group antigens after AB0- or Rh-incompatible allograft transplantation with a negative long-term influence on bone-remodeling or the clinical outcome is negligible.

Background — In chronic heart failure, sympathetic activation is increased. Moxonidine acts on central nervous system receptors to decrease sympathetic activation. We investigated the dose-response relationship of a new sustained-release (SR) preparation of moxonidine and the plasma concentration of norepinephrine in patients with chronic heart failure. Methods and Results — A total of 268 patients with chronic heart failure in NYHA functional class II to IV on optimal standard therapy were randomized to placebo or 1 of 5 doses of moxonidine SR: 0.3, 0.6, 0.9, 1.2, or 1.5 mg BID. After a dose-titration phase (7 weeks), patients were followed up for another 12 weeks at their maximally tolerated dose. Blood samples for plasma norepinephrine were collected at baseline and weekly during the initial 7 weeks, at week 19, and at the end of the study. At baseline and 7 and 19 weeks, sampling was also done 4 hours after the dose. After the active phases of the study, plasma norepinephrine was evaluated for an additional 3 days. A marked, statistically significant dose-related decrease in plasma norepinephrine was observed for predose levels as well as 4 hours after the dose at week 19. At the highest dose (1.5 mg BID), the trough reduction in norepinephrine was 52%. These reductions were accompanied by a modest decrease in heart rate, a modest increase in left ventricular ejection fraction, and a dose-related increase in adverse events. Conclusions — Plasma norepinephrine was markedly reduced in a dose-related manner by moxonidine SR. This reduction was accompanied by evidence of reverse remodeling, but also by an increase in adverse events.