Instantons and the Path to Intermittency in Turbulent Flows.

Processes leading to anomalous fluctuations in turbulent flows, referred to as intermittency, are still challenging. We consider cascade trajectories through scales as realizations of a stochastic Langevin process for which multiplicative noise is an intrinsic feature of the turbulent state. The trajectories are conditioned on their entropy exchange. Such selected trajectories concentrate around an optimal path, called instanton, which is the minimum of an effective action. The action is derived from the Langevin equation, estimated from measured data. In particular instantons with negative entropy pinpoint the trajectories responsible for the emergence of non-Gaussian statistics at small scales.

[General treatment principles, coordination of care and patient education in fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Allgemeine Behandlungsgrundsätze, Versorgungskoordination und Patientenschulung beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews on randomized, controlled trials on patient education and shared decision-making from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was achieved by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences, clinical and practical applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: The diagnosis of fibromyalgia syndrome should be explicitly communicated to the affected individual. Shared decision-making with the patient on the therapeutic options based on individual preferences of the patient, comorbidities and the success of previous treatment is recommended. A step-wise treatment approach depending on the severity of fibromyalgia syndrome and the response to therapeutic measures is recommended.

CT-guided irreversible electroporation in an acute porcine liver model: effect of previous transarterial iodized oil tissue marking on technical parameters, 3D computed tomographic rendering of the electroporation zone, and histopathology.

PURPOSE: To evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance. METHODS: After Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann-Whitney test. Histopathological differences were assessed. RESULTS: Mean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm(3), and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm(3), and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone. CONCLUSION: There is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

[Fibromyalgia syndrome. General principles and coordination of clinical care and patient education]. / Das Fibromyalgiesyndrom. Allgemeine Behandlungsgrundsätze, Versorgungskoordination und Patientenschulung.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: A diagnosis of FMS should be explicitly communicated with the afflicted individual. A step-wise treatment, depending on the severity of FMS and the responses to therapeutic measures, is recommended. Therapy should only be continued if the positive effects outweigh the side effects. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Complete nutrient recovery from source-separated urine by nitrification and distillation.

In this study we present a method to recover all nutrients from source-separated urine in a dry solid by combining biological nitrification with distillation. In a first process step, a membrane-aerated biofilm reactor was operated stably for more than 12 months, producing a nutrient solution with a pH between 6.2 and 7.0 (depending on the pH set-point), and an ammonium to nitrate ratio between 0.87 and 1.15 gN gN(-1). The maximum nitrification rate was 1.8 ± 0.3 gN m(-2) d(-1). Process stability was achieved by controlling the pH via the influent. In the second process step, real nitrified urine and synthetic solutions were concentrated in lab-scale distillation reactors. All nutrients were recovered in a dry powder except for some ammonia (less than 3% of total nitrogen). We estimate that the primary energy demand for a simple nitrification/distillation process is four to five times higher than removing nitrogen and phosphorus in a conventional wastewater treatment plant and producing the equivalent amount of phosphorus and nitrogen fertilizers. However, the primary energy demand can be reduced to values very close to conventional treatment, if 80% of the water is removed with reverse osmosis and distillation is operated with vapor compression. The ammonium nitrate content of the solid residue is below the limit at which stringent EU safety regulations for fertilizers come into effect; nevertheless, we propose some additional process steps that will increase the thermal stability of the solid product.

Principal axes for stochastic dynamics.

We introduce a general procedure for directly ascertaining how many independent stochastic sources exist in a complex system modeled through a set of coupled Langevin equations of arbitrary dimension. The procedure is based on the computation of the eigenvalues and the corresponding eigenvectors of local diffusion matrices. We demonstrate our algorithm by applying it to two examples of systems showing Hopf bifurcation. We argue that computing the eigenvectors associated to the eigenvalues of the diffusion matrix at local mesh points in the phase space enables one to define vector fields of stochastic eigendirections. In particular, the eigenvector associated to the lowest eigenvalue defines the path of minimum stochastic forcing in phase space, and a transform to a new coordinate system aligned with the eigenvectors can increase the predictability of the system.

Prevalence and predictors of depressive symptoms and wellbeing during and up to nine years after outpatient cardiac rehabilitation.

BACKGROUND AND AIM: Depression is an important independent prognostic variable in cardiac patients. The prevalence and predictors of depressive symptoms up to nine years after cardiac rehabilitation were studied. METHODS: Follow-up questionnaires were sent to 2199 patients who had completed a 12-week exercise-based outpatient cardiac rehabilitation (OCR) programme between June 1999 and March 2006. Medical outcome, general wellbeing, and depressive symptoms were assessed, the latter by using two screening questions according to Arrol. Patients with incomplete data due to language problems, lack of compliance and non-response were excluded. RESULTS: Complete data for analysis was available for 710 patients. The median follow up period was 46 months (Interquartile range (IQR) 22-71, min. 6 months). At follow-up, 132 patients (19%) indicated low wellbeing, whereas 81 (11%) were having depressive symptoms. Multivariate analyses revealed impaired quality of life (p <0.001), diabetes (p = 0.013) and low exercise capacity after OCR (p = 0.003) to be independent predictors of low wellbeing at follow-up. Persistent smoking (p = 0.045) as well as negative mood (p = 0.022) at the end of OCR were independent predictors of depressive symptoms at follow-up. CONCLUSIONS: In a selected patient population a mean of four years after OCR, persistent smoking, diabetes, low exercise capacity and impaired quality of life at the end of OCR were independent long term predictors of low wellbeing and depressive symptoms, rather than specific cardiac variables. This highlights the need for close cooperation between cardiovascular and psychological specialists in cardiac rehabilitation.

The role of routine echocardiography in unselected patients with cerebrovascular ischaemic events.

BACKGROUND: Cardiac embolism is an important etiology of cerebrovascular ischaemic events (CIE). Echocardiography is routinely performed in patients with CIE despite guidelines recommending restriction of echocardiography to patients with clinically suspected cardioembolism. OBJECTIVE: The aim of this study was to examine the therapeutic impact and prognostic role of echocardiographic findings in an unselected population suffering from CIE. METHODS: Between November 2006 and November 2007, 319 patients with CIE underwent evaluation by transthoracic echocardiography (TTE) and in addition by transesophageal echocardiography (TEE) if deemed mandatory (n = 49). The combined clinical end-point included death or recurrent CIE, occurring during a follow-up period of 3 and 12 months, respectively. RESULTS: After 3 months of follow-up, the combined end-point was noted in 30 (9%) and after 12 months in 43 (13%) patients. In multivariate analysis, atrial fibrillation (AF) (HR 2.12, 95% CI 1.38-3.25; P < 0.001) and coronary artery disease (CAD: HR 1.85, 95% CI 1.21-2.81; P = 0.004) were predictors of events occurring during short-term follow-up. After 1 year of follow-up, AF (HR 1.67, 95% CI 1.19-2.32; P = 0.003) and CAD (HR 1.5, 95% CI 1.09-2.06; P = 0.01) were associated with the combined end-point. Echocardiographic parameters assessed at study entry were not independently related to an adverse outcome. CONCLUSION: Whereas AF and CAD appear to increase the risk of events after suffering from CIE, echocardiographic findings were not independently associated with the combined end-point of recurrent CIE or death.

[Principles of treatment, coordination of medical care and patient education in fibromyalgia syndrome and chronic widespread pain]. / Allgemeine Behandlungsgrundsätze, Versorgungskoordination und Patientenschulung beim Fibromyalgiesyndrom und chronischen Schmerzen in mehreren Körperregionen.

BACKGROUND: A guideline for the treatment and diagnostic procedures for fibromyalgia syndrome (FMS) was developed in cooperation with 10 German medical and psychological associations and 2 patient self-help groups. METHODS: A systematic literature search including all controlled studies evaluating physiotherapy, exercise and strength training as well as physical therapies was performed in the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-12/2006), PsychInfo (1966-12/2006) and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. RESULTS: Patient's information at first diagnosis of FMS is strongly recommended (grade A). Patient-centered communication is recommended (grade B). A stepwise treatment approach depending on the adapatation to restrictions in daily life and response to treatment options can be considered (grade C). CONCLUSIONS: The long-term treatment should be based on principles of basic psychosomatic care and shared decision making on treatment options.

Safety improvement issues for mission aborts of future space transportation systems.

Two-stage winged space access vehicles consisting of a carrier stage with airbreathing turbo/ram jet engines and a rocket propelled orbital stage which may significantly reduce space transport costs and have additional advantages offer a great potential for mission safety improvements. Formulating the nominal mission and abort scenarios caused by engine malfunctions as an optimal control problem allows full exploitation of safety capabilities. The shaping of the nominal mission has a significant impact on the prospective safety. For this purpose, most relevant mission aborts are considered together with the nominal mission, treating them as an optimization problem of branched trajectories where the branching point is not fixed. The applied procedure yields a safety improved nominal trajectory, showing the feasibility of the included mission aborts with minimum payload penalty. The other mission aborts can be separately treated, with the initial condition given by the state of the nominal trajectory at the time when a failure occurs. A mission abort plan is set up, covering all emergency scenarios.

Lactobacillus acidifarinae sp. nov. and Lactobacillus zymae sp. nov., from wheat sourdoughs.

Three heterofermentative lactic acid bacteria, obtained from Greek and Belgian artisanal wheat sourdoughs, were preliminarily identified as Lactobacillus brevis-like after screening using whole-cell protein fingerprinting and 16S rRNA gene sequence analysis. The three sourdough isolates showed nearly identical sequences (>99.7 % sequence similarity), and highest similarities of 98.2 and 97.6 % were obtained to the species Lactobacillus spicheri and Lactobacillus brevis, respectively. Growth characteristics, biochemical features, amplified fragment length polymorphism fingerprinting, DNA-DNA hybridizations and DNA G+C contents demonstrated that the isolates represent two novel Lactobacillus species. The names Lactobacillus acidifarinae sp. nov. and Lactobacillus zymae sp. nov. are proposed and the type strains are LMG 22200(T) (=R-19065(T)=CCM 7240(T)) and LMG 22198(T) (=R-18615(T)=CCM 7241(T)), respectively.

Frequency-dependent characterization of THz Sommerfeld wave propagation on single-wires.

In this work, measurements and numerical field simulations highlighting the characteristic propagation behavior of THz surface-wave pulses along bare and dielectrically coated metal wires are presented. An optoelectronic time-domain measurement setup with a freely-positionable probe-tip is used for detection of electrical field transients after different propagation lengths along the wires. Frequency-dependent attenuation and dispersion parameters are determined in the range of 0.02 THz to 0.4 THz. Our results are in good agreement with numerical field simulations considering the propagation of an axial Sommerfeld surface-wave with metallic and dielectric losses. We discuss the influence of wire radius on wave propagation behavior and the application of THz single-wires for sensing.

Aquaspirillum dispar Hylemon et al. 1973 and Microvirgula aerodenitrificans Patureau et al. 1998 are subjective synonyms.

The 16S rDNA sequences of [Aquaspirillum] dispar LMG 4329(T) and Microvirgula aerodenitrificans SGLY2(T) (=LMG 18919(T)) were found to be very similar (>99 %). DNA-DNA hybridizations between the two strains revealed a high level of DNA-DNA binding (84 %), showing that they represent a single species. M. aerodenitrificans and [A.] dispar were also phenotypically very similar. It is concluded that [A.] dispar and M. aerodenitrificans are subjective synonyms. As [A.] dispar was wrongly assigned to the genus Aquaspirillum, we propose that strains of [A.] dispar must be reclassified in the genus MICROVIRGULA: The name Microvirgula aerodenitrificans must be retained for the unified taxon since it is the type of the genus MICROVIRGULA:

Design, synthesis, and biological activity of diiminoisoindolines as complement component 3a antagonists.

The failure to fully regulate the inflammation response has been linked to diseases such as rheumatoid arthritis, septic shock syndrome, and asthma. The human complement system initiates and regulates the inflammation response through a cascade of regulatory factors. Complement Component 3a (C3a) is an essential regulatory factor and inhibiting its binding to a C3a receptor will diminish the inflammation response by disrupting the cascade. We report the design, synthesis, in vitro and in vivo activity of diiminoisoindolines as C3a antagonists.

C/EBPepsilon -/- mice: increased rate of myeloid proliferation and apoptosis.

CCAAT/enhancer binding protein epsilon (C/EBPepsilon) is essential for terminal granulocytic differentiation. Its expression begins at the transition between the proliferative and non-proliferative compartments of myelopoiesis. We studied the effect of targeted disruption of the C/EBPepsilon gene on murine myeloid proliferation and apoptosis. Bone marrow cellularity of C/EBPepsilon -/- and wild-type mice was 95% and 65%, respectively. The C/EBPepsilon -/- mice had an expansion in the number of their CFU-GM/femur. The number of myeloid committed progenitor cells in the peripheral blood and the spleen of these mice was also increased. Bromodeoxyuridine (BrDU) pulse labeling studies demonstrated that the fraction of actively proliferating cells was two-fold higher in the bone marrow of C/EBPepsilon -/- mice. However, the number of myeloid colonies arising from purified Sca-1+/lin- early hematopoietic progenitor cells and from bone marrow mononuclear cells grown in different cytokine combinations was not significantly different between wild-type and knock-out mice. Also, long-term marrow growth, and CFU were not different between the wild-type and C/EBPepsilon -/- mice. The sensitivity to induction of apoptosis in the committed progenitor cell compartment after either withdrawal of growth factor or brief exposure to etoposide was normal. However, Gr-1 antigen-positive C/EBPepsilon -/- granulocytic cells showed an increased rate of apoptosis in comparison to their wild-type counterparts. In summary, the myeloid compartment appears to be expanded in mice lacking C/EBPepsilon. However, this is not the consequence of an intrinsic myeloproliferation but due to an indirect, possibly cytokine-mediated stimulation of myelopoiesis in vivo. C/EBPepsilon may have a role in the inhibition of apoptosis in maturing granulocytic cells.

[Psychosocial stress and utilization of medical services after coronary bypass operation]. / Psychosoziale Belastung und Inanspruchnahme medizinischer Leistungen nach koronarer Bypassoperation.

This study examines the relationship between psychosocial stress and social support before coronary surgery and the amount of health care utilization in a sample of 136 patients during postoperative hospitalization. The aim of the study is to test the hypothesis that there is a correlation between a high psychosocial stress profile and the utilization of medical care (so called high utilizers). The sample consists of 80.7% men and 19.3% women aged between 31 and 78 years (mean 64; sd 9.1). In this first data analysis psychosocial impact is assessed by anxiety, depression and social support (HADS-D, F-SOZU). Detailed somatic factors concerning severity of the illness, inpatient course and the utilization of health care (medication, technical examinations, consultations) are assessed by means of a documentation system. With regard to anxiety, depression and social support the sample is located within the normal range. In contrast to our expectations the results show that high scores of anxiety and depression as well as a low level of emotional support do not correlate significantly with an increased use of medication, the number of consultations and technical examinations. Furthermore no correlation has been found between the length of hospitalization and preoperative comorbidity as compared to the mentioned psychosocial stress variables. On the other hand the data analysis showed that about 30% of the patients during the postoperative period utilize about half of the total amount of the different medical treatments. In the postoperative period these high utilizers cannot be distinguished from the other patients, neither by sociodemographic variables nor by means of an increased psychosocial stress or severity of illness.

1,3-Diarylcycloalkanopyrazoles and diphenyl hydrazides as selective inhibitors of cyclooxygenase-2.

Novel 1,3-diarylcycloalkanopyrazoles 1, and diphenyl hydrazides 2 were identified as selective inhibitors of cyclooxygenase-2. The 1,3-diaryl substitution pattern of the pyrazole ring in 1 differentiates these compounds from most of the known selective COX-2 inhibitors that contain two aryl rings at the adjacent positions on a heterocyclic or a phenyl ring. Similarly, the two phenyl rings in 2 are also separated by three atoms. SAR of both phenyl rings in 1 and 2, and the aliphatic ring in 1 will be discussed.

RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by activated monocytes/macrophages and T lymphocytes, has been implicated in several disease states, including rheumatoid arthritis, inflammatory bowel disease, septic shock, and osteoporosis. Monocyte/macrophage production of TNF-alpha is dependent on the mitogen-activated protein kinase p38. RWJ 67657 (4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H-imidazol -2-yl]-3-butyn-1-ol) inhibited the release of TNF-alpha by lipopolysaccharide (a monocyte stimulus)-treated human peripheral blood mononuclear cells with an IC(50) of 3 nM, as well as the release of TNF-alpha from peripheral blood mononuclear cells treated with the superantigen staphylococcal enterotoxin B (a T cell stimulus), with an IC(50) value of 13 nM. This compound was approximately 10-fold more potent than the literature standard p38 kinase inhibitor SB 203580 in all p38 dependent in vitro systems tested. RWJ 67657 inhibited the enzymatic activity of recombinant p38alpha and beta, but not gamma or delta, in vitro and had no significant activity against a variety of other enzymes. In contrast, SB 203580 significantly inhibited the tyrosine kinases p56 lck and c-src (IC(50) = 5 microM). RWJ 67657 did not inhibit T cell production of interleukin-2 or interferon-gamma and did not inhibit T cell proliferation in response to mitogens. RWJ 67657 inhibited TNF-alpha production in lipopolysaccharide-injected mice (87% inhibition at 50 mg/kg) and in rats (91% inhibition at 25 mg/kg) after oral administration. Based on these favorable biological properties, RWJ 67657 may have use as a treatment for inflammatory diseases.

N-hydroxyurea and hydroxamic acid inhibitors of cyclooxygenase and 5-lipoxygenase.

Two series of compounds (1 and 2) having structural features of the dual COX/5-LO inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared. Many of these hybrid compounds are potent COX and 5-LO inhibitors; two compounds (1a and 2t) inhibit eicosanoid biosynthesis in an ex vivo assay.

How useful is Leuven personalism in the world of bioethics? The test case of artificial insemination.

Personalism in ethics denotes any system based upon the value of the person. Several versions of personalist morals have been developed over the past 50 years. Some have had particular interest in the field of medical ethics. Here the question is being studied about one such system, the so-called Leuven personalist morals and its usefulness in today's world of bioethics. In order to test the usefulness of this system the case of artificial insemination is examined both in the early 1970s in the context of the Leuven clinics and, subsequently, in the 1990s in a US policy document. The investigation reveals strengths and weaknesses of this personalism. Regarding AID it reveals unresolved oppositions. The conclusion seems to be that this personalism had, no doubt, a profound impact upon medical ethics within its own circle but, as regards the universal usefulness of the system, serious doubts remain.