Demonstration of Machine Learning-Based Model-Independent Stabilization of Source Properties in Synchrotron Light Sources.

Synchrotron light sources, arguably among the most powerful tools of modern scientific discovery, are presently undergoing a major transformation to provide orders of magnitude higher brightness and transverse coherence enabling the most demanding experiments. In these experiments, overall source stability will soon be limited by achievable levels of electron beam size stability, presently on the order of several microns, which is still 1-2 orders of magnitude larger than already demonstrated stability of source position and current. Until now source size stabilization has been achieved through corrections based on a combination of static predetermined physics models and lengthy calibration measurements, periodically repeated to counteract drift in the accelerator and instrumentation. We now demonstrate for the first time how the application of machine learning allows for a physics- and model-independent stabilization of source size relying only on previously existing instrumentation. Such feed-forward correction based on a neural network that can be continuously online retrained achieves source size stability as low as 0.2 µm (0.4%) rms, which results in overall source stability approaching the subpercent noise floor of the most sensitive experiments.

Hartmann characterization of the PEEM-3 aberration-corrected X-ray photoemission electron microscope.

Aberration correction by an electron mirror dramatically improves the spatial resolution and transmission of photoemission electron microscopes. We will review the performance of the recently installed aberration corrector of the X-ray Photoemission Electron Microscope PEEM-3 and show a large improvement in the efficiency of the electron optics. Hartmann testing is introduced as a quantitative method to measure the geometrical aberrations of a cathode lens electron microscope. We find that aberration correction leads to an order of magnitude reduction of the spherical aberrations, suggesting that a spatial resolution of below 100 nm is possible at 100% transmission of the optics when using x-rays. We demonstrate this improved performance by imaging test patterns employing element and magnetic contrast.

Accuracy, Precision, and Trending Ability of Electrical Cardiometry Cardiac Index versus Continuous Pulmonary Artery Thermodilution Method: A Prospective, Observational Study.

INTRODUCTION: Evaluation of accuracy, precision, and trending ability of cardiac index (CI) measurements using the Aesculon™ bioimpedance electrical cardiometry (Aesc) compared to the continuous pulmonary artery thermodilution catheter (PAC) technique before, during, and after cardiac surgery. METHODS: A prospective observational study with fifty patients with ASA 3-4. At six time points (T), measurements of CI simultaneously by continuous cardiac output pulmonary thermodilution and thoracic bioimpedance and standard hemodynamics were performed. Analysis was performed using Bland-Altman, four-quadrant plot, and polar plot methodology. RESULTS: CI obtained with pulmonary artery thermodilution and thoracic bioimpedance ranged from 1.00 to 6.75 L min-1 and 0.93 to 7.25 L min-1, respectively. Bland-Altman analysis showed a bias between CIBIO and CIPAC of 0.52 liters min-1 m-2, with LOA of [-2.2; 1.1] liters min-1 m-2. Percentage error between the two techniques was above 30% at every time point. Polar plot methodology and 4-quadrant analysis showed poor trending ability. Skin incision had no effect on the results. CONCLUSION: CI obtained by continuous PAC and CI obtained by Aesculon bioimpedance are not interchangeable in cardiac surgical patients. No effects of skin incision were found. International clinical trial registration number is ISRCTN26732484.

Correlation-Driven Insulator-Metal Transition in Near-Ideal Vanadium Dioxide Films.

We use polarization- and temperature-dependent x-ray absorption spectroscopy, in combination with photoelectron microscopy, x-ray diffraction, and electronic transport measurements, to study the driving force behind the insulator-metal transition in VO_{2}. We show that both the collapse of the insulating gap and the concomitant change in crystal symmetry in homogeneously strained single-crystalline VO_{2} films are preceded by the purely electronic softening of Coulomb correlations within V-V singlet dimers. This process starts 7 K (±0.3 K) below the transition temperature, as conventionally defined by electronic transport and x-ray diffraction measurements, and sets the energy scale for driving the near-room-temperature insulator-metal transition in this technologically promising material.

Routine labour epidural analgesia versus labour analgesia on request: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect on mode of delivery of the routine use of labour epidural analgesia (EA) compared with analgesia on request. DESIGN: Randomised non-inferiority trial. SETTING: One university and one non-university teaching hospital in The Netherlands. POPULATION: Women with a singleton pregnancy in cephalic presentation beyond 36 + 0 weeks' gestation. METHODS: Participants were randomly allocated to receive either routine EA or analgesia on request. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed, with confidence intervals (CI) calculated for the differences in percentages or means. MAIN OUTCOME MEASURES: Rate of operative delivery (instrumental vaginal or caesarean), labour characteristics, and adverse labour and neonatal outcomes. RESULTS: A total of 488 women were randomly allocated to the routine EA (n = 233) or analgesia on request group (n = 255). In the routine EA group, 89.3% (208/233) received EA. According to ITT analysis, 34.8% (81/233) women in the routine EA group had an operative delivery, compared with 26.7% (68/255) in the analgesia on request group (difference 8.1%, 95% CI -0.1 to 16.3). The difference in rate of operative deliveries according to the PP analysis was statistically significant (difference 8.9%, 95% CI 0.4 to 17.4). Inferiority of EA could not be rejected, as in both analyses the upper bound of the confidence interval exceeded the pre-specified inferiority criterion of +10%. Women in the routine EA group had more adverse effects, including hypotension (difference 9.5%, 95% CI 4.2 to 14.9), and motor blockade (difference 6.8%, 95% CI 1.1 to 12.5). CONCLUSION: Non-inferiority of routine EA could not be demonstrated in this trial. Routine EA use is likely to lead to more operative deliveries and more maternal adverse effects. The results of our study do not justify routine use of EA.

Tailoring the topology of an artificial magnetic skyrmion.

Despite theoretical predictions, it remains an experimental challenge to realize an artificial magnetic skyrmion whose topology can be well controlled and tailored so that its topological effect can be revealed explicitly in a deformation of the spin textures. Here we report epitaxial magnetic thin films in which an artificial skyrmion is created by embedding a magnetic vortex into an out-of-plane aligned spin environment. By changing the relative orientation between the central vortex core polarity and the surrounding out-of-plane spins, we are able to control and tailor the system between two skyrmion topological states. An in-plane magnetic field is used to annihilate the skyrmion core by converting the central vortex state into a single domain state. Our result shows distinct annihilation behaviour of the skyrmion core for the two different skyrmion states, suggesting a topological effect of the magnetic skyrmions in the core annihilation process.

Neonatal sepsis is mediated by maternal fever in labour epidural analgesia.

Women delivering with EA (EA group) were matched on parity with 453 women with deliveries without EA (non-EA group). Significantly more neonates born in the EA-group had fever ≥ 38.0°C (11.6% vs 1.8%, p < 0.001) at birth. The overall incidence of neonatal sepsis, based on clinical symptoms and defined as proven (by a positive blood culture) or suspected (no positive blood culture), was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA turned out to be an independent risk factor for neonatal sepsis (adjusted OR 2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non-EA group, the incidence of neonatal sepsis was significantly higher in mothers with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we conclude, that the positive association between neonatal sepsis and labour EA is possibly mediated by maternal intrapartum fever.

Additive roles of platelets and fibrinogen in whole-blood fibrin clot formation upon dilution as assessed by thromboelastometry.

Blood dilution after transfusion fluids leads to diminished coagulant activity monitored by rotational thromboelastometry, assessing elastic fibrin clot formation, or by thrombin generation testing. We aimed to determine the contributions of blood cells (platelets, red blood cells) and plasma factors (fibrinogen, prothrombin complex concentrate) to fibrin clot formation under conditions of haemodilution in vitro or in vivo.Whole blood or plasma diluted in vitro was supplemented with platelets, red cells, fibrinogen or prothrombin complex concentrate (PCC). Thromboelastometry was measured in whole blood as well as plasma; thrombin generation was determined in parallel. Similar tests were performed with blood from 48 patients, obtained before and after massive fluid infusion during cardiothoracic surgery.Addition of platelets or fibrinogen, in additive and independent ways, reversed the impaired fibrin clot formation (thromboelastometry) in diluted whole blood. In contrast, supplementation of red blood cells or prothrombin complex concentrate was ineffective. Platelets and fibrinogen independently restored clot formation in diluted plasma, resulting in thromboelastometry curves approaching those in whole blood. In whole blood from patients undergoing dilution during surgery, elastic clot formation was determined by both the platelet count and the fibrinogen level. Thrombin generation in diluted (patient) plasma was not changed by fibrinogen, but improved markedly by prothrombin complex concentrate. In conclusion, in dilutional coagulopathy, platelets and fibrinogen, but not red blood cells or vitamin K-dependent coagulation factors, independently determine thromboelastometry parameters measured in whole blood and plasma. Clinical decisions for transfusion based on thromboelastometry should take into account the platelet concentration.

Perioperative dilutional coagulopathy treated with fresh frozen plasma and fibrinogen concentrate: a prospective randomized intervention trial.

BACKGROUND AND OBJECTIVES: Treatment of dilutional coagulopathy by transfusing fresh frozen plasma (FFP) remains sub-optimal. We hypothesized that partial replacement of transfused FFP by fibrinogen concentrate results in improved coagulant activity and haemostasis. This was tested in a controlled clinical intervention trial with patients experiencing massive bleeding during major surgery. METHODS: Patients undergoing major elective surgery were treated according to current protocols. When transfusion with FFP was required, patients were randomized as follows: group A received 4 units FFP and group B received 2 units FFP plus 2 g fibrinogen concentrate. Blood samples were taken before and after the intervention. Analysts were blinded to the treatment type. RESULTS: Group A (B) consisted of 21 (22) patients, in 16 (17) of whom bleeding stopped after intervention. Plasma fibrinogen increased significantly more in group B (0·57 g/l) than in group A (0·05 g/l). However, levels of prothrombin and factors VIII, IX and X increased more in group A than in group B. Rotational thromboelastometry (ROTEM) of whole blood and plasma revealed improved fibrin clot formation in group B but not in group A. Thrombin generation [calibrated automated thrombogram (CAT)] in plasma increased more in group A. Principal parameters determining whole-blood thromboelastometry were the fibrinogen level and platelet count. In vitro addition of fibrinogen and prothrombin complex concentrate to pre-intervention samples restored both ROTEM and CAT parameters. CONCLUSIONS: Partial replacement of transfused FFP by fibrinogen increases fibrin clot formation at the expense of less improved thrombin generation. Coagulation factors other than fibrinogen alone are required for full restoration of haemostasis.

Platelet concentrate transport in pneumatic tube systems--does it work?

Blood sample transport via pneumatic tube systems (PTS) reduces the turnaround time of laboratories, but it might influence analysis results. Its effect on platelet concentrates (PCs) is not known. Platelet function was investigated after single and multiple PTS transport in comparison with storage and irradiation. Optical and impedance aggregation, CD-62, and microparticles changed as a result of storage, but not due to transport. Irradiation lowered platelet function independently. Multiple transport impaired thrombin receptor-activating peptide-induced aggregation. This investigation demonstrates the feasibility of PTS transport. As platelet function depends on storage, it may be more important to transfuse fresh PCs.

Endotracheal intubation using videolaryngoscopy causes less cardiovascular response compared to classic direct laryngoscopy, in cardiac patients according a standard hospital protocol.

INTRODUCTION: Previous studies comparing Glidescope and classic direct laryngoscopy did not show an attenuation of CV responses to endotracheal intubation. In the present study, we hypothesize that indirect videolaryngoscopy can attenuate cardiovascular responses to endotracheal intubation. METHODS: In a randomized cross-over study, eighty adults (ASA PS II-III) were included. Both direct and indirect videolaryngoscopies were used in a random order, in the same patient. Cardiovascular responses to intubation were recorded as a relative change in rate pressure product (RPP = systolic blood pressure times heart rate) from baseline values. A linear mixed model was used to study the association between the outcome variable RPP and the type of laryngoscope used. RESULTS: The relative increase of the RPP at intubation was significantly smaller (i.e. 27%, P < 0.001) using videolaryngoscopy compared to the classic direct laryngoscopy. Cardiovascular responses were blunted by an additional 10.2% (P = 0.029), when the patient was on beta blockade. CONCLUSIONS: Our study shows less hemodynamic responses during endotracheal intubation using indirect videolaryngoscopy compared to classic direct laryngoscopy.

Early versus late epidural analgesia and risk of instrumental delivery in nulliparous women: a systematic review.

OBJECTIVE: Review of the literature regarding the relation between the timing of epidural analgesia and the rate of caesarean or instrumental vaginal deliveries. SEARCH STRATEGY: Pubmed, Embase and the Cochrane Library were searched for articles published until 31 July 2010. SELECTION CRITERIA: Studies were selected in which the effects of early latent phase (defined as a cervical dilatation of 3 cm or less) epidural analgesia (including combined-spinal epidural) and late active phase epidural analgesia on the mode of delivery in nulliparous women at 36 weeks of gestation or more were evaluated. DATA COLLECTION AND ANALYSIS: Data extraction was completed by using a data-extraction form. Risk ratio and its 95% confidence intervals were calculated for caesarean delivery and instrumental vaginal delivery. Pooled data were calculated. MAIN RESULTS: The search retrieved 20 relevant articles, of which six fulfilled the selection criteria of inclusion. These six studies reported on 15,399 nulliparous women in spontaneous or induced labour with a request for analgesia. Risk of caesarean delivery (pooled risk ratio 1.02, 95% CI 0.96-1.08) or instrumental vaginal delivery (pooled risk ratio 0.96, 95% CI 0.89-1.05) was not significantly different between groups. AUTHORS' CONCLUSIONS: This systematic review showed no increased risk of caesarean delivery or instrumental vaginal delivery for women receiving early epidural analgesia at cervical dilatation of 3 m or less in comparison with late epidural analgesia.

Transplacental transfer of remifentanil in the pregnant ewe.

BACKGROUND AND PURPOSE: While remifentanil can be used either during labour or fetal surgery, more should be known about the transplacental transfer of this opioid. The aim of this study was to investigate the placental transfer and haemodynamic effects of remifentanil after i.v. administration to pregnant ewes. EXPERIMENTAL APPROACH: Seven pregnant ewes received a continuous infusion of remifentanil (0.33 µg·kg⁻¹·min⁻¹) for 1 h, and maternal and fetal arterial blood samples were drawn at regular intervals during and up to 1 h after the discontinuation of the infusion. Haemodynamic parameters were monitored continuously. Blood gas samples were drawn at baseline and once during the infusion. KEY RESULTS: Peak maternal remifentanil plasma levels of 4.0 ± 0.9 ng·mL⁻¹ (mean ± SD) and peak fetal plasma levels of 0.4 ± 0.3 ng·mL⁻¹ were obtained. Remifentanil plasma levels dropped rapidly after the discontinuation of the infusion. The continuous infusion of remifentanil did not result in significant maternal or fetal haemodynamic changes. CONCLUSIONS AND IMPLICATIONS: Remifentanil rapidly passes through the placenta of pregnant ewes and although remifentanil concentrations stay significantly lower in the fetus compared with those in the mother, remifentanil can be detected in significant amounts in the fetus.

Predictors of physical and emotional recovery 6 and 12 months after surgery.

BACKGROUND: A proportion of patients do not recover fully from surgery or they develop chronic postsurgical pain. The aim of this study was to examine the incidence and predictors of unfavourable long-term outcome after surgery using a prospective cohort design. METHODS: Some 401 patients undergoing various elective surgical procedures filled in the RAND 36-item Health Survey 1.0 health-related quality-of-life questionnaire before operation and at 6 and 12 months of follow-up to assess changes in pain, physical functioning, mental health and vitality. Preoperative psychological assessment was obtained. RESULTS: Most patients showed improvement in the various aspects of health-related quality of life after surgery, but a considerable proportion (14-24 per cent) still showed deterioration at 6 and 12 months. Multivariable linear regression analysis identified acute postoperative pain, duration of the operation and preoperative physical condition as the most important predictors of long-term pain and physical functioning. Preoperative surgical fear also had a small but significant contribution. The main predictors of mental health and vitality were physical condition before surgery, surgical fear and optimism. CONCLUSION: Up to a quarter of patients experienced suboptimal recovery after surgery. Both somatic and psychological factors were associated with the long-term outcome. Optimal recovery could be promoted by effective interventions on malleable factors.

Systemic but not local administration of retinoic acid reduces early transcript levels of pro-inflammatory cytokines after experimental spinal cord injury.

Early rises of pro-inflammatory cytokines play a key role in tissue damage and has detrimental consequences for functional outcome after spinal cord injury (SCI). All-trans retinoic acid (RA) has been shown to be a therapeutic agent reducing cytokine expression in vitro, but its use may be limited due to adverse side effects associated with systemic delivery. Local delivery of RA may circumvent adverse side effects, but may simultaneously reduce the therapeutic benefits of the therapy. Here, we investigated whether local or systemic RA treatment differentially affected pro-inflammatory cytokine expression early after rat SCI. Pro-inflammatory cytokines IL-1ß, IL-6 and TNFα were investigated at 6h after moderate contusion injury of the thoracic (T9) spinal cord, when mRNA levels are known to peak. Rats were either treated with intrathecal RA (0, 2.5, 10, or 100ng) or received an intraperitoneal injection of RA (15mg/kg bodyweight). Surprisingly intrathecal RA up to amounts of 100ng did not attenuate SCI-induced increases in gene-expression of pro-inflammatory cytokines. In contrast, intraperitoneal RA rendered a 60%, 35% and 58% reduction of IL-1ß, IL-6 and TNFα mRNA levels, respectively. Although local doses higher than 100ng RA may reduce pro-inflammatory cytokine gene-expression, such doses precipitate and possibly increase risks of adverse side effects. We conclude that in contrast to systemic delivery, intrathecal administration of RA up to doses of 100ng is ineffective in reducing early pro-inflammatory cytokine gene-expression. Future studies are required to investigate the effects of single intraperitoneal RA treatment on long-term SCI outcome.

[Old and new anticoagulants. Antidotes and measures for acute hemorrhaging and urgent interventions]. / Alte und neue Gerinnungshemmer. Antidota und Massnahmen bei akuter Blutung sowie dringenden Eingriffen.

Anticoagulation medications are frequently used for primary and secondary treatment of several thrombo-embolic disorders. An important side effect of all anticoagulants is hemorrhagic diathesis which necessitates acute treatment, ideally using medicinal therapy with an antidote. Much experience has been gained in treating bleeding while on traditional anticoagulants, such as heparins and vitamin K antagonists by the use of antagonists. A multitude of factor-specific anticoagulants have recently been introduced or will soon receive approval. With this new generation of anticoagulants no valid laboratory parameters or effective antagonists are presently available. Due to a lack of adequate studies regarding acute treatment this can at present only be carried out on a symptomatic basis.

Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery.

Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

Spinal anesthesia for a parturient with the triad of Currarino.

The triad of Currarino, also known as Currarino syndrome or complex, is a rare hereditary syndrome involving a bony sacral defect, an anorectal malformation and a presacral mass. Thus far, only 250 cases have been reported, but milder cases may not be recognized, and many cases may not be published. In addition to disorders of the gastrointestinal and urogenital tracts, sensory and motor deficits may be present. Currently, there are no reports of women with the triad of Currarino undergoing cesarean delivery with the use of neuraxial anesthesia. Neuraxial anesthesia in patients with congenital malformations of the spine may be complicated or contraindicated, depending on the level and severity of the anatomic abnormality. We present the case of a pregnant woman at 36 weeks of gestation who underwent uncomplicated neuraxial anesthesia for cesarean delivery. When neuraxial anesthesia is contemplated in such patients, they should first receive careful neurologic and radiologic evaluation.

Maternal cardiac arrest in early pregnancy.

A primigravid woman suffered a prolonged cardiac arrest at 18 weeks of gestation. Dilated ischemic cardiomyopathy was diagnosed. After recovery, the patient received an implantable cardioverter-defibrillator. At 38 weeks of gestation she had an elective caesarean delivery. Both mother and child had a favourable outcome. The effect of pregnancy on underlying cardiac disease and the management of maternal cardiac arrest with a pre-viable fetus are discussed. The importance of a multidisciplinary approach is emphasized. Continued neurodevelopmental assessment of the newborn is necessary to detect the long-term effects of fetal hypoxia in early pregnancy.