TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BackgroundComparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.ObjectivesTo reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.MethodsProposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey.ResultsA total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.ConclusionsThis core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers)

Kinetic power of quasars and statistical excess of MOJAVE superluminal motions

The MOJAVE survey contains 101 quasars with a total of 354 observed radio components that are different from the radio cores, among which 95% move with apparent projected superluminal velocities with respect to the core, and 45% have projected velocities larger than 10c (with a maximum velocity 60c). Doppler boosting effects are analyzed to determine the statistics of the superluminal motions. We integrate over all possible values of the Lorentz factor the values of the kinetic energy corresponding to each component. The calculation of the mass in the ejection is carried out by assuming the minimum energy state. This kinetic energy is multiplied by the frequency at which the portions of the jet fluid identified as "blobs" are produced. Hence, we estimate the average total power released by the quasars in the form of kinetic energy in the long term on pc-scales. RESULTS. A selection effect in which both the core and the blobs of the quasar are affected by huge Doppler-boosting enhancement increases the probability of finding a jet ejected within 10 degrees of the line of sight >~40 times above what one would expect for a random distribution of ejection, which explains the ratios of the very high projected velocities given above. The average total kinetic power of each MOJAVE quasar should be very high to obtain this distribution: ~7E47 erg/s. This amount is much higher than previous estimates of kinetic power on kpc-scales based on the analysis of cavities in X-ray gas or radio lobes in samples of objects of much lower radio luminosity but similar black hole masses. The kinetic power is a significant portion of the Eddington luminosity, on the order of the bolometric luminosity, and proportional on average to square root of the radio luminosity, although this correlation might be induced by Malmquist-like bias.Comment: Published in A&A; v2: minor changes to fit the published versio

Opacity in compact extragalactic radio sources and its effect on astrophysical and astrometric studies

The apparent position of the "core" in a parsec-scale radio jet (a compact, bright emitting region at the narrow end of the jet) depends on the observing frequency, owing to synchrotron self-absorption and external absorption. While providing a tool probing physical conditions in the vicinity of the core, this dependency poses problems for astrometric studies using compact radio sources. We investigated the frequency-dependent shift in the positions of the cores (core shift) observed with very long baseline interferometry (VLBI) in parsec-scale jets. We discuss related physics, as well as its effect on radio astrometry and the connection between radio and optical positions of astrometric reference objects. We searched for the core shift in a sample of 277 radio sources imaged at 2.3 GHz (13 cm) and 8.6 GHz (4 cm) frequency bands using VLBI observations made in 2002 and 2003. The core shift was measured by referencing the core position to optically thin jet features whose positions are not expected to change with frequency. We present here results for 29 selected active galactic nuclei (AGN) with bright distinct VLBI jet features that can be used in differential measurements and that allow robust measurements of the shift to be made. In these AGN, the magnitude of the measured core shift between 2.3 and 8.6 GHz reaches 1.4 mas, with a median value for the sample of 0.44 mas. Nuclear flares result in temporal variability of the shift. An average shift between the radio (4 cm) and optical (6000 Angstrom) bands is estimated to be approximately 0.1 mas, and it should be taken into account in order to provide the required accuracy of the radio-optical reference frame connection. This can be accomplished with multi-frequency VLBI measurements... (abridged)Comment: 11 pages, 8 figures, 2 tables, accepted for publication in the Astronomy and Astrophysics; minor corrections to the manuscript are mad

Avoiding or Reversing Hartmann’s Procedure Provides Improved Quality of Life After Perforated Diverticulitis

# 2010 The Author(s). This article is published with open access at Springerlink.com Introduction The existing literature regarding acute perforated diverticulitis only reports about short-term outcome; longterm following outcomes have not been assessed before. The aim of this study was to assess long-term quality of life (QOL) after emergency surgery for perforated diverticulitis. Patients and Methods Validated QOL questionnaires (EQ-VAS, EQ-5D index, QLQ-C30, and QLQ-CR38) were sent to all eligible patients who had undergone emergency surgery for perforated diverticulitis in five teaching hospitals between 199

Reversal of Hartmann's procedure through the stomal side: A new even more minimal invasive technique

Background: Several minimal invasive, mainly laparoscopic-assisted, techniques for reversal of Hartmann's procedure (HP) have been published. The purpose of this pilot study was to assess a minimal invasive procedure through the stomal site that may compare favorably with open or laparoscopic-assisted procedures in terms of operative time, hospital stay and postoperative complications. Methods: HP reversal through the stomal side was attempted in 13 consecutive patients. Lysis of intra-abdominal adhesions was done manually through an incision at the formal stoma side, without direct vision between thumb and index finger. The rectal stump was identified intra-abdominally using a transanal rigid club. A manually controlled stapled end-to-end colorectal anastomosis was created. Results: Mean duration of operation was 81 min (range 58-109 min); mean hospital stay was 4.2 days (range 2-7 days). In two patients the procedure was converted because of strong adhesions in the lower pelvic cavity around the rectal stump that could not be lysed manually safely. No complications occurred in the patients in whom reversal was completely done through the stomal site. Conclusions: In our opinion, restoration of intestinal continuity through the stomal side after HP is a feasible operation, without need for additional incisions. In the hands of a specialist gastrointestinal surgeon this technique can be attempted in all patients, as conversion to a laparoscopic-assisted or an open procedure can be performed when necessary

Experimental loophole-free violation of a Bell inequality using entangled electron spins separated by 1.3 km

For more than 80 years, the counterintuitive predictions of quantum theory have stimulated debate about the nature of reality. In his seminal work, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory. Bell showed that in any local realist theory the correlations between distant measurements satisfy an inequality and, moreover, that this inequality can be violated according to quantum theory. This provided a recipe for experimental tests of the fundamental principles underlying the laws of nature. In the past decades, numerous ingenious Bell inequality tests have been reported. However, because of experimental limitations, all experiments to date required additional assumptions to obtain a contradiction with local realism, resulting in loopholes. Here we report on a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell's inequality. We employ an event-ready scheme that enables the generation of high-fidelity entanglement between distant electron spins. Efficient spin readout avoids the fair sampling assumption (detection loophole), while the use of fast random basis selection and readout combined with a spatial separation of 1.3 km ensure the required locality conditions. We perform 245 trials testing the CHSH-Bell inequality $S \leq 2$ and find $S = 2.42 \pm 0.20$. A null hypothesis test yields a probability of $p = 0.039$ that a local-realist model for space-like separated sites produces data with a violation at least as large as observed, even when allowing for memory in the devices. This result rules out large classes of local realist theories, and paves the way for implementing device-independent quantum-secure communication and randomness certification.Comment: Raw data will be made available after publicatio

Positive and negative well-being and objectively measured sedentary behaviour in older adults: evidence from three cohorts

Background: Sedentary behaviour is related to poorer health independently of time spent in moderate to vigorous physical activity. The aim of this study was to investigate whether wellbeing or symptoms of anxiety or depression predict sedentary behaviour in older adults. Method: Participants were drawn from the Lothian Birth Cohort 1936 (LBC1936) (n = 271), and the West of Scotland Twenty-07 1950s (n = 309) and 1930s (n = 118) cohorts. Sedentary outcomes, sedentary time, and number of sit-to-stand transitions, were measured with a three-dimensional accelerometer (activPAL activity monitor) worn for 7 days. In the Twenty-07 cohorts, symptoms of anxiety and depression were assessed in 2008 and sedentary outcomes were assessed ~ 8 years later in 2015 and 2016. In the LBC1936 cohort, wellbeing and symptoms of anxiety and depression were assessed concurrently with sedentary behaviour in 2015 and 2016. We tested for an association between wellbeing, anxiety or depression and the sedentary outcomes using multivariate regression analysis. Results: We observed no association between wellbeing or symptoms of anxiety and the sedentary outcomes. Symptoms of depression were positively associated with sedentary time in the LBC1936 and Twenty-07 1950s cohort, and negatively associated with number of sit-to-stand transitions in the LBC1936. Meta-analytic estimates of the association between depressive symptoms and sedentary time or number of sit-to-stand transitions, adjusted for age, sex, BMI, long-standing illness, and education, were β = 0.11 (95% CI = 0.03, 0.18) and β = − 0.11 (95% CI = − 0.19, −0.03) respectively. Conclusion: Our findings indicate that depressive symptoms are positively associated with sedentary behavior. Future studies should investigate the causal direction of this association

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

Liposarcoma cells with aldefluor and CD133 activity have a cancer stem cell potential

Aldehyde dehydrogenase (ALDH) has recently been shown to be a marker of cancer stem-like cells (CSCs) across tumour types. The primary goals of this study were to investigate whether ALDH is expressed in liposarcomas, and whether CSCs can be identified in the ALDHhigh subpopulation. We have demonstrated that ALDH is indeed expressed in 10 out of 10 liposarcoma patient samples. Using a liposarcoma xenograft model, we have identified a small population of cells with an inducible stem cell potential, expressing both ALDH and CD133 following culturing in stem cell medium. This potential CSC population, which makes up for 0, 1-1, 7% of the cells, displayed increased self-renewing abilities and increased tumourigenicity, giving tumours in vivo from as few as 100 injected cells