Comparing ultrastable lasers at 7 × 10-17 fractional frequency instability through a 2220 km optical fibre network.

Ultrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10-17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.

Antibiotic prophylaxis of infective endocarditis in oral and maxillofacial surgery: incomplete implementation of guidelines in everyday clinical practice.

Infective endocarditis (IE) is a devastating disease with high mortality. Most guidelines recommend routine use of antibiotic prophylaxis during oral surgery to prevent IE in patients with specific predisposing cardiac conditions, but this is not the case in the UK. The conflicting opinions and guidance are confusing and may affect IE prophylaxis implementation. We investigated how IE prophylaxis standards are defined in hospitals and outpatient clinics of oral and maxillofacial surgery. A survey was sent to 80 surgeons heading departments of oral and maxillofacial surgery in Germany. We observed significant heterogeneity in IE prophylaxis implementation among the clinics. This diversity was in relation to the definition of predisposing cardiac conditions, the type of dental and surgical procedures performed that require IE prophylaxis, the spectrum of compounds used, and the timing of antibiotic prophylaxis. We observed under-prescription of IE prophylaxis in high-risk patients, the overuse of antibiotic prophylaxis in patients not at high risk of IE, and the use of inappropriate drugs. These findings suggest that educational strategies and guideline implementation advice are needed to improve standards of IE prophylaxis in oral and maxillofacial surgery clinics.

Management and design of biogas digesters: A non-calibrated heat transfer model.

A thermal balance modeling framework is developed, based on heat transfer-resistance networks. The heat transfer model accounts for effects of digester- design, location and operation, including effects of solar irradiance, external heating and ambient climate. We demonstrate extendibility of the framework by using the model in dynamic simulations of substrate temperature for digesters comprising two very different designs. Digester designs modeled include fixed-dome, buried, uninsulated and unheated household digesters in Hanoi, Vietnam, and an industrial-scale anaerobic digester located at a wastewater treatment plant in Esbjerg, Denmark. The modeled temperature profiles were evaluated against measured substrate temperatures over long periods, from 7 months and up. For the two Hanoi digesters, root-mean-square-error were 1.43 °C and 0.92 °C, with Nash-Sutcliffe model efficiency coefficients (NS-C) of 0.87 and 0.93 respectively. For the industrial digester in Esbjerg root-mean-square-error was 0.48 °C with an NS-C of 0.94. The model was not calibrated prior simulation, suggesting good predictive performance.

Discovery and characterization of a positive allosteric modulator of transient receptor potential canonical 6 (TRPC6) channels.

The non-selective second messenger-gated cation channel TRPC6 (transient receptor potential canonical 6) is activated by diacylglycerols (DAG) in a PKC-independent manner and plays important roles in a variety of physiological processes and diseases. In order to facilitate novel therapies, the development of potent inhibitors as well as channel-activating agents is of great interest. The screening of a chemical library, comprising about 17,000 small molecule compounds, revealed an agent, which induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in a concentration-dependent manner (EC50 = 2.37 ± 0.25 µM) in stably TRPC6-expressing HEK293 cells. This new compound (C20) selectively acts on TRPC6, unlike OAG (1-oleoyl-1-acetyl-sn-glycerol), which also activates PKC and does not discriminate between TRPC6 and the closely related channels TRPC3 and TRPC7. Further evaluation by Ca2+ assays and electrophysiological studies revealed that C20 rather operated as an enhancer of channel activation than as an activator by itself and led to the assumption that the compound C20 is an allosteric modulator of TRPC6, enabling low basal concentrations of DAG to induce activation of the ion channel. Furthermore, C20 was tested in human platelets that express TRPC6. A combined activation of TRPC6 with C20 and OAG elicited a robust increase in [Ca2+]i in human platelets. This potentiated channel activation was sensitive to TRPC6 channel blockers. To achieve sufficient amounts of C20 for biological studies, we applied a one-pot synthesis strategy. With regard to studies in native systems, the sensitizing ability of C20 can be a valuable pharmacological tool to selectively exaggerate TRPC6-dependent signals.

Cells respond to deletion of CAV1 by increasing synthesis of extracellular matrix.

A range of cellular functions have been attributed to caveolae, flask-like invaginations of the plasma membrane. Here, we have used RNA-seq to achieve quantitative transcriptional profiling of primary embryonic fibroblasts from caveolin 1 knockout mice (CAV1-/- MEFs), and thereby to gain hypothesis-free insight into how these cells respond to the absence of caveolae. Components of the extracellular matrix were decisively over-represented within the set of genes displaying altered expression in CAV1-/- MEFs when compared to congenic wild-type controls. This was confirmed biochemically and by imaging for selected examples. Up-regulation of components of the extracellular matrix was also observed in a second cell line, NIH-3T3 cells genome edited to delete CAV1. Up-regulation of components of the extracellular matrix was detected in vivo by assessing collagen deposition and compliance of CAV1-/- lungs. We discuss the implications of these findings in terms of the cellular function of caveolae.

Comparison of the bactericidal effect of cold atmospheric pressure plasma (CAPP), antimicrobial photodynamic therapy (aPDT), and polihexanide (PHX) in a novel wet surface model to mimic oral cavity application.

PURPOSE: Cold atmospheric pressure plasma (CAPP) is increasingly used for medical applications. The first devices are available from commercial manufactures, promising to improve wound healing and disinfection. The underlying antimicrobial mechanisms of CAPP are discussed, while the first results on its bactericidal efficiency against common bacterial species have already been published, with promising results. Most of the plasma sources used in these studies were built by the investigators themselves, and are not commercially available or licensed for clinical use. To evaluate the postulated bactericidal effects in clinical practice, we studied a commercially available, ready-to-use CAPP-device, which is also designed to be used in the field of dental, oral, and maxillofacial treatment. MATERIALS AND METHODS: Standardized bacterial cultures of two different pathogens (Acinetobacter baumannii and Staphylococcus aureus) were produced with defined colony-forming unit concentrations. Dilutions of these cultures were treated with a commercially available CAPP product according to the manufacturer's instructions in order to evaluate the antimicrobial activity of the technique. This in vitro study compared the CAPP treatment with established clinical therapies like polihexanide (PHX) and antimicrobial photodynamic therapy (aPDT). RESULTS: The bactericidal effect was evaluated in terms of reduction in colony-forming units after treatment of the bacterial samples with a defined dose of plasma, aPDT, or PHX. For CAPP, the bactericidal effect was found to be stronger in the Gram-negative isolate (A. baumannii) than in the Gram-positive S. aureus. A strong depth dependency was observed, especially with the Gram-negative isolate. Good bactericidal effects, with a reduction in bacterial load of more than 2 × log10, could only be observed in conditions of 0.3 mm of water-film thickness or less. Such a significant reduction in bactericidal effect depending on depth was not observed using aPDT or PHX in the studied depth range of 0.3-1.8 mm. CONCLUSION: CAPP treatment performed by the device (Plasma ONE) and configuration we used in this study seems to be ill suited for sufficiently killing Acinetobacter baumannii or Staphylococcus aureus in a moist infection site, as would be expected in the oral cavity. Established local antimicrobial therapies using PHX or aPDT showed better disinfectant properties. The clinical effect of improved wound healing, described by the manufacturer and some scientists, could not be investigated using this model. Given the results, however, it seems unlikely to be a direct consequence of bactericidal effects of CAPP in a wet environment. Further development of CAPP devices, or a different configuration (e.g. with a higher output, resulting in reactive nitrogen species-dominated, gas-phase chemistry), may enhance antibacterial effects in future, while tissue compatibility of such techniques remains to be elucidated further.

1.5 µm Lasers with Sub-10 mHz Linewidth.

We report on two ultrastable lasers each stabilized to independent silicon Fabry-Pérot cavities operated at 124 K. The fractional frequency instability of each laser is completely determined by the fundamental thermal Brownian noise of the mirror coatings with a flicker noise floor of 4×10^{-17} for integration times between 0.8 s and a few tens of seconds. We rigorously treat the notorious divergences encountered with the associated flicker frequency noise and derive methods to relate this noise to observable and practically relevant linewidths and coherence times. The individual laser linewidth obtained from the phase noise spectrum or the direct beat note between the two lasers can be as small as 5 mHz at 194 THz. From the measured phase evolution between the two laser fields we derive usable phase coherence times for different applications of 11 to 55 s.

Transportable Optical Lattice Clock with 7×10

We present a transportable optical clock (TOC) with ^{87}Sr. Its complete characterization against a stationary lattice clock resulted in a systematic uncertainty of 7.4×10^{-17}, which is currently limited by the statistics of the determination of the residual lattice light shift, and an instability of 1.3×10^{-15}/sqrt[τ] with an averaging time τ in seconds. Measurements confirm that the systematic uncertainty can be reduced to below the design goal of 1×10^{-17}. To our knowledge, these are the best uncertainties and instabilities reported for any transportable clock to date. For autonomous operation, the TOC has been installed in an air-conditioned car trailer. It is suitable for chronometric leveling with submeter resolution as well as for intercontinental cross-linking of optical clocks, which is essential for a redefinition of the International System of Units (SI) second. In addition, the TOC will be used for high precision experiments for fundamental science that are commonly tied to precise frequency measurements and its development is an important step to space-borne optical clocks.

[Coercive measures in German hospitals for psychiatry and psychotherapy : A pilot study by the DGPPN to evaluate a uniform assessment instrument]. / Zwangsmaßnahmen in deutschen Kliniken für Psychiatrie und Psychotherapie : Eine Pilotstudie der DGPPN zur Erprobung eines einheitlichen Erfassungsinstrumentes.

STUDY OBJECTIVE: A simple instrument to record case-related coercive measures was tested as part of a pilot project of the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN). METHODS: To assess coercive measures data were collected for 3 months in 8 German hospitals for psychiatry and psychotherapy. The type of measures used, the main diagnosis and the legal basis for the coercive measures were documented. RESULTS: In the sample studied, coercive measures were applied in 8% of cases. Coercive measures were most commonly used in patients with a schizophrenic disorder. The principle of justifiable necessity according to § 34 of the German Penal Code was used particularly often as the legal basis for justifying the coercive measures. CONCLUSION: Suitable measurement instruments and reliable data that enable the learning of best practices represent the basis for a reduction of coercive measures.

A clock network for geodesy and fundamental science.

Leveraging the unrivalled performance of optical clocks as key tools for geo-science, for astronomy and for fundamental physics beyond the standard model requires comparing the frequency of distant optical clocks faithfully. Here, we report on the comparison and agreement of two strontium optical clocks at an uncertainty of 5 × 10(-17) via a newly established phase-coherent frequency link connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote comparison is limited only by the instability and uncertainty of the strontium lattice clocks themselves, with negligible contributions from the optical frequency transfer. A fractional precision of 3 × 10(-17) is reached after only 1,000 s averaging time, which is already 10 times better and more than four orders of magnitude faster than any previous long-distance clock comparison. The capability of performing high resolution international clock comparisons paves the way for a redefinition of the unit of time and an all-optical dissemination of the SI-second.

[Admission and discharge decisions in psychiatric hospitals : The 7-day cycle: analysis based on the VIPP database]. / Aufnahme- und Entlassentscheidungen in der Psychiatrie : Der 7-Tage-Zyklus: Analyse auf Grundlage der VIPP-Datenbank.

BACKGROUND: The legislation requires all scientific societies in the field of inpatient psychiatric and psychosomatic healthcare to survey and assess the effects and financial incentives of the new flat rate day-based remuneration system in psychiatric and psychosomatic facilities (PEPP system). As day-based remuneration systems may be an incentive to extend treatment, it is necessary to measure and analyze the future development of the number of cases and the duration of treatment. OBJECTIVES: This article surveys admission and discharge decisions of psychiatric and psychosomatic facilities. The distribution of admissions and discharges throughout the days of the week were analyzed to search for evidence of a systematic extension of treatment over the weekend. MATERIAL AND METHODS: The analysis is based on data from the Versorgungsrelevante Indikatoren in der Psychiatrie und Psychosomatik (VIPP, treatment-relevant indicators in psychiatry and psychosomatics) project database, which contains routine data from psychiatric and psychosomatic facilities. On this basis the distributions of admissions and discharges throughout the days of the week were analyzed on aggregate and diagnosis-specific levels. RESULTS: Patients were mostly admitted to hospitals within the first 3 weekdays. The discharge mostly took place on Fridays and not as a financial incentive on Mondays. Regarding the patient length of stay a 7-day cycle can be observed, which may indicate the importance of medical and organizational factors in discharge decisions. CONCLUSION: The results do not show evidence for a systematic extension of treatment over the weekend. Over the next years it will be important to observe the development of the duration of treatment and the number of cases to assess the influence of the economic incentives of the PEPP system on the utilization of psychiatric and psychosomatic healthcare.

Prevalence of nosocomial pathogens in German ambulances: the SEKURE study.

OBJECTIVE: The increasing prevalence of multidrug resistant bacteria is a problem in the inpatient care setting, and in the emergency care system. The aim of this observational, cross-sectional study was to evaluate the prevalence of pathogens on well-defined surfaces in German ambulances that have been designated as 'ready for service'. METHODS: After informed consent was obtained, ambulance surfaces were sampled with agar plates for microbiological examination during an unannounced visit. A standardised questionnaire was used to obtain information regarding the disinfection protocols used at each rescue station. RESULTS: Methicillin resistant staphylococcus aureus contamination was present in 18 sampling surfaces from 11 out of 150 ambulance vehicles (7%) that were designated as ready for service. Contact surfaces directly surrounding patients or staff were most frequently contaminated with pathogens. However, bacterial contamination was not related to annual missions, methods or frequency of disinfection. CONCLUSIONS: In accordance with previous studies, disinfection and cleaning of areas with direct contact to patients or staff seem to be the most challenging. This should also be reflected in disinfection guidelines and the related continuing education.

[Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager]. / Kardiale und metabolische Risikofaktoren bei schweren psychischen Erkrankungen. Aufgaben eines Präventionsmanagers.

People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

Injectable microcarriers as human mesenchymal stem cell support and their application for cartilage and degenerated intervertebral disc repair.

Degeneration of the intervertebral disc (IVD) is a progressive and chronic process, and the high incidence of discogenic disorders calls for new therapeutic approaches, such as cell-based therapies using three dimensional cultures and mesenchymal stem cells (MSC), which can differentiate to chondrogenic- and IVD-lineages. Here, we investigated the growth and differentiation of human MSC culture on biodegradable collagen scaffolds in order to obtain an injectable suspension. Commercially available wound dressings were downsized to dimensions between 100 and 1500 µm and seeded with freshly isolated or early passages MSC. Proliferation rate and chondrogenic differentiation potential was tested at oxygenation levels of 2%, 5%, 10% and 21% in static and dynamic cultures. Evaluation methods included cell viability test, disc marker genes expression (aggrecan, collagen type I and type II), histological detection of proteoglycans and immunohistochemical analysis. On microcarriers, freshly isolated MSC had lower proliferation rate and chondrogenic differentiation potential compared with early passages MSC. Proliferation of MSC was significantly increased 1.7-fold at 5% oxygen level and in combination with dynamic culture was further increased to 2.3-fold, with respect to normoxia. Chondrogenesis was positively affected by 2% and 5% hypoxia, as shown by increased transcription levels and protein expression of collagen type II and proteoglycan accumulation in static cultures, while it was inhibited in dynamic cultures. Collagen type I and aggrecan expression were not affected by hypoxia. In conclusion, collagen based microcarriers are a suitable support for in vitro MSC growth and chondrogenesis especially when cultured at 5% oxygen level.

Observation of Efimov resonances in a mixture with extreme mass imbalance.

We observe two consecutive heteronuclear Efimov resonances in an ultracold Li-Cs mixture by measuring three-body loss coefficients as a function of magnetic field near a Feshbach resonance. The first resonance is detected at a scattering length of a_((0))=-320(10)a_((0)), corresponding to ∼7(∼3) times the Li-Cs (Cs-Cs) van der Waals range. The second resonance appears at 5.8(1.0)a_((0)), close to the unitarity-limited regime at the sample temperature of 450 nK. Indication of a third resonance is found in the atom loss spectra. The scaling of the resonance positions is close to the predicted universal scaling value of 4.9 for zero temperature. Deviations from universality might be caused by finite-range and temperature effects, as well as magnetic field-dependent Cs-Cs interactions.

[Friedrich Schiller and Psychosomatics from the Perspective of Recent Research]. / Friedrich Schiller und die Psychosomatik aus der Perspektive der rezenten Forschung.

RESEARCH QUESTION: The aim of this study is to show that Friedrich Schiller (1759 - 1805) was very early in life inclined towards psychosomatic interactions. MATERIAL AND METHODS: An analysis of the secondary literature since the death of Friedrich Schiller for the subjects "Friedrich Schiller" and "psychosomatics" was undertaken. RESULTS: Already during his medical studies at the "Hohe Karlsschule" in Stuttgart (Germany) Schiller studied very intensively psychosomatic issues on account of the disease of another student, Joseph Frédéric Grammont, and included the topic in his three theses. Not inclined to practical work as a physician, there are many psychosomatic thoughts and medical concepts in his writings, especially in the play "Die Räuber" (1781) and in "Don Carlos, Infant von Spanien" (1787). Towards the then upcoming topic mesmerism he remained very sceptic. In coping with his own illness there are many psychosomatic aspects, too. Despite his own severe somatic illness he could cope with pain and emphasised in his writings the importance of the freedom of anxiety before death.

How much does it hurt to be lonely? Mental and physical differences between older men and women in the KORA-Age Study.

OBJECTIVE: Loneliness has a deep impact on quality of life in older people. Findings on sex-specific differences on the experience of loneliness remain sparse. This study compared the intensity of and factors associated with loneliness between men and women. METHODS: Analyses are based on the 2008/2009 data of the KORA-Age Study, comprising 4127 participants in the age range of 64-94 years. An age-stratified random subsample of 1079 subjects participated in a face-to-face interview. Loneliness was measured by using a short German version of the UCLA-Loneliness-Scale (12 items, Likert scaled, ranging from 0 to 36 points). Multiple logistic regression analysis was conducted to analyze the associations of socio-demographic, physical, and psychological factors with loneliness. RESULTS: The mean level of loneliness did not significantly differ between men (17.0 ± 4.5) and women (17.5 ± 5.1). However, among the oldest old (≥85 years), loneliness was higher in women (p value = 0.047). Depression, low satisfaction with life, and low resilience were associated significantly with loneliness, which was more pronounced in men. Living alone was not associated with loneliness, whereas lower social network was associated with a three time higher risk for feeling lonely in both men and women. CONCLUSIONS: The extent of loneliness was equally distributed between men and women, although women were more disadvantaged regarding living arrangements as well as physical and mental health. However, loneliness was stronger associated with adverse mental health conditions in men. These findings should be considered when developing intervention strategies to reduce loneliness.

Hypertension and depressed symptomatology: a cluster related to the activation of the renin-angiotensin-aldosterone system (RAAS). Findings from population based KORA F4 study.

CONTEXT: Preliminary evidence points to aldosterone being not only prominently involved in the systemic regulation of the blood pressure but also to play a role in the pathophysiology of depression. OBJECTIVE: We evaluated whether the combination of hypertension and depressed symptomatology is useful to screen for individuals suffering an activation of the renin-angiotensin-aldosterone system (RAAS). DESIGN: We conducted a cross-sectional analysis in participants from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. A total of 1805 participants of the F4 study were included in the study. METHODS: The association between aldosterone and renin levels and the different combinations of hypertension and depressed symptomatology was examined in four different models of multiple linear regression adjusted for age, sex, creatinine levels, potassium levels, body mass index (BMI) and behavioural risk factors. RESULTS: Individuals suffering both, depressed symptomatology and hypertension exhibited highly significantly increased aldosterone levels (p<0.001) and slightly, not significantly increased renin levels (p=0.08) compared to individuals with no depressed symptomatology and no hypertension. No significant activation of the RAAS was seen in only depressed or only hypertensive individuals. CONCLUSIONS: The finding of highly significantly increased aldosterone levels and increased renin levels in individuals suffering both, depressed symptomatology and hypertension provides further evidence for the involvement of the RAAS in the pathogenesis of depressed symptomatology. These findings have important implications for future research concerning the pathophysiological pathways that link depression and cardiovascular disease.

Green algal peritonitis in 2 cows.

Peritonitis due to infections with green algae was diagnosed at slaughter (in Texas and South Dakota) in 2 cows. One cow also had a generalized lymphadenitis. The intralesional green algae were histologically similar to those previously associated with bovine lymphadenitis. Amplified and sequenced algal ITS2 genes had higher homology with the genus Scenedesmus than with Chlorella.