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.

[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").

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.

Discordant maturation as the primary biological defect in chronic myelogenous leukemia.

Comparative studies of the in vitro growth characteristics of normal and chronic myelogenous leukemic (CML) progenitor cells have provided further evidence that discordant maturation is the primary biological defect in CML. The in vitro growth of total normal and CML granulocyte/macrophage colony forming unit (CFU-GM) populations were compared with early and intermediate (HLA-DR positive) CFU-GM derived from the same marrows. The absolute number of total CML CFU-GM exceeded the number generated by normal marrow through 7 days of culture due entirely to an excess of CML CFU-GM with limited proliferative capacity. Unlike normal colonies, relatively few of the leukemic colonies grew to a large size; the early and intermediate (HLA-DR positive) CML progenitors also exhibited limited proliferative capacity compared to normal. Highly enriched progenitor populations were prepared, and it was observed that the primitive (small) CML CFU-GM also had greatly reduced proliferative potential compared to primitive normal progenitors, but rather behaved similarly to normal mature (large) CFU-GM. Similarly, CML erythroid burst forming units were at a more advanced stage of maturation than normal erythroid burst forming units as evidenced by their reduced proliferative capacity, the observation that a reduced proportion required burst promoting activity to enable them to respond to erythropoietin and the observation that a larger fraction than normal could sustain a limited period of erythropoietin deprivation in the absence of burst promoting activity. Based on these findings and supporting evidence from our previous studies and those reported by other investigators, it is concluded that the dominance of the leukemic population is not due to unregulated proliferation but rather to discordant maturation resulting in expansion in the later maturational compartments which are not under strict regulatory control.

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.

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.

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.

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.

Synthesis and antifertility activity of zoapatanol analogues.

The synthesis of and guinea pig contragestational screening data for several oxepane and 3,8-dioxabicyclo[3.2.1]octane analogues of zoapatanol (1) are described and their structure-activity relationships discussed. Conversion of the 5-keto group on the nonenyl side chain of 1 into a hydroxyl function enhanced the potency. Further significant enhancement in the potency was realized with the transformation of several oxepanes into the 3,8-dioxabicyclo-[3.2.1]octane-1-acetic acid derivatives. Detailed, comparative contragestational evaluation of the three most potent compounds 9, 33, and 37 is presented, which led to the selection of 33 (ORF 13811) for further biological evaluation.

Mutations affecting hemolysin production in Listeria monocytogenes located outside the listeriolysin gene.

We have investigated the molecular basis of spontaneous mutations leading to non-hemolytic and avirulent variants of the Listeria monocytogenes serotype 1/2a strain NCTC 7973 using Southern hybridization to DNA fragments that harbor the listeriolysin gene (hlyA) and adjacent regions cloned from a L. monocytogenes serotype 1/2a strain. The analysis of such non-hemolytic variants revealed the presence of a deletion of 300 base pairs, located 1.6 kb upstream of an otherwise intact listeriolysin gene. The importance of regions upstream of the hlyA gene in controlling the expression of the listeriolysin gene was further emphasized by the detection of a transposon-derived nonhemolytic mutant in which the transposon had inserted approximately 200 bp upstream of the listeriolysin gene. We conclude that at least two elements, contained within a region encompassing 1.6 kb of sequences upstream of the hlyA gene, may be required for expression of the listeriolysin gene.

Lumi-mestranol and epi-lumi-mestranol.

Treatment of lumi-estrone 3-methyl ether (I) with acetylene gave the C-17-epimeric compounds lumi-mestranol (3-methoxy-17 alpha-ethynyl-13 alpha-estra-1,3,5(10)-trien-17 beta-ol, III ) and epi-lumi-mestranol (3-methoxy-17 beta-ethynyl-13 alpha-estra-1,3,5(10)-trien-17 alpha-ol, IV). The structures of the two isomers were assigned on the basis of their molecular rotations and shift-reagent experiments in the NMR. The irradiation of estrone 3-methyl ether (II) to provide compound I was investigated in two solvent systems. Minor products of these reactions were the seco-steroids VII, VIII and X.

Contribution to the contamination problem in transmission electron microscopy.

The contamination of different supporting films is measured by irradiating a circular area of a few micron diameter and by using an electron probe of a few ten nm diameter. Contamination rings are generated by this method. They can be explained by diffusion of the hydrocarbon molecules on the specimen surface and by adsorption from the vacuum. The influence of specimen heating and charging are discussed. Some specimen cleaning methods have been examined. The best results were obtained by immersion of the specimen and the cartridge in methanol.

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.

The European convention on bioethics.

Nearly fifteen years after the Council of Europe first called for a pan-European convention on issues in bioethics to harmonize disparate national regulations, in November 1996 the council's Committee of Ministers approved the Convention on Human Rights and Biomedicine for formal adoption. The draft convention, released in July 1994, provoked strong public, professional, and governmental debate among European nations, particularly regarding provisions for biomedical research with subjects unable to give informed consent. If ratified, the "bioethics convention" will become the first such document to have binding force internationally.

Is death and dying merely an ethical issue?

Some people worry about the current tendency to ignore the distinction of religious and ethical issues in the area of death and dying. This article attempts to identify sources and consequences of such blending. One of the countries offering a microcosm of religious and ethical trends with regard to death and dying is the Netherlands. Issues identified in Dutch society are, therefore, being compared with similar listings in North American and European literature on death and dying. In an even more paradigmatic way the unfinished debate on the distinction between active and passive euthanasia remains representatives of a religious approach to death and dying.

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.

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.

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.