Cardiac Relaxation Dynamics Investigated by Doppler Tissue Imaging (DTI)

Following an initial pilot study to explore the usefulness of Doppler tissue imaging (DTI) for the assessment of regional systolic dysfunction in the ischaemic heart, new techniques for the diagnosis of diastolic dysfunction have been developed In the refinement of the techniques further evidence to support the existence of the early diastolic mechanism was obtained prior to assessing its clinical utility. For this the relationship between peak early diastolic mitral ring tissue velocity (EA) as a surrogate for recoil, and the acceleration of early transmitral flow (ventricular filling) was investigated in patients with diastolic dysfunction and in normal subjects. This study supported the existence of recoil as the release mechanism for restoring forces (the early diastolic mechanism) in the normal and its delay or absence in patients with diastolic dysfunction To confirm the presence, absence or reversal of this early diastolic mechanism to echocardiographic waveforms need to be analysed on the same heart beat. The technique examines the diagnostic utility of the time to peak diastolic tissue velocity (EA) of the mitral ring measured by DTI compared with the time to peak mitral opening measured by M-mode, for the assessment of left ventricular relaxation in subjects with pathological and physiological athletic hypertrophy, and distinguishing these from normals. We postulate that a slack myocardial state occurs within a period between the peak myocardial tissue velocity measured at the mitral valve ring and the peak of the E-wave (M-mode velocity) through the mitral valve. This slack myocardial state constitutes the early diastolic mechanism and allows for proper filling. This mechanism is absent in stiffer hearts. As well as the early diastolic mechanism a further novel index of left ventricular performance based on the pressure volume relationship, (E/Ea)/LVIDd, was shown to be a promising index for distinguishing the three groups. Using two ultrasound systems and optimum operating conditions the characteristics of the technique were examined. Finally, further developments of the technique are discussed with possible future clinical applications, particularly to understanding and preventing sudden death in the young athlet

Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Objectives. Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods. ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results. Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion. Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies

What do I want? The effects of individual aspiration and relational capability on collaboration preferences

ESR

A new echocardiographic model for quantifying three-dimensional endocardial surface area

A new technique for quantitatively mapping the three-dimensional left ventricular endocardial surface was developed, using measurements from standard cross-sectional echocardiographic images. To validate the accuracy of this echocardiographic mapping technique in an animal model, the endocardial areas of 15 excised canine ventricles were calculated using measurements made from echocardiographic studies of the hearts and compared with areas determined with latex casts of the same ventricles. Close correlation (r = 0.87, p < 0.001) between these two measures of endocardial area provided preliminary confirmation of the accuracy of the maps.To further characterize the mapping algorithm, it was translated into computer format and used to map the surfaces of idealized hemiellipsoids. Areas measured with this mapping technique closely approximated the actual areas of idealized surfaces with a wide spectrum of shapes; maps were particularly accurate for ellipsoids with shapes similar to those of undistorted human ventricles. Also, the accuracies of area calculations were relatively insensitive to deviation from the assumed positions of the echocardiographic short-axis planes. Finally, although the accuracy of the mapping technique improved as data from more transverse planes were added, the procedure proved reliable for estimating surface areas when data from only three planes were used. These studies confirm the accuracy of the echocardiographic mapping technique, and they suggest that the resulting planar plots might be useful as templates for localizing and quantifying the overall extent of abnormal wall motion

Comparison of ultrasound-derived muscle thickness with computed tomography muscle cross-sectional area on admission to the intensive care unit : A pilot cross-sectional study

Introduction The development of bedside methods to assess muscularity is an essential critical care nutrition research priority. We aimed to compare ultrasound-derived muscle thickness at 5 landmarks with computed tomography (CT) muscle area at intensive care unit (ICU) admission. Secondary aims were to (1) combine muscle thicknesses and baseline covariates to evaluate correlation with CT muscle area and (2) assess the ability of the best-performing ultrasound model to identify patients with low CT muscle area. Methods Adult patients who underwent CT scanning at the third lumbar area <72 hours after ICU admission were prospectively recruited. Muscle thickness was measured at mid-upper arm, forearm, abdomen, and thighs. Low CT muscle area was determined using published cutoffs. Pearson correlation compared ultrasound-derived muscle thickness and CT muscle area. Linear regression was used to develop ultrasound prediction models. Bland-Altman analyses compared ultrasound-predicted and CT-measured muscle area. Results Fifty ICU patients were enrolled, aged 52 ± 20 years. Ultrasound-derived muscle thickness at each landmark correlated with CT muscle area (P < .001). The sum of muscle thickness at mid-upper arm and bilateral thighs, including age, sex, and the Charlson Comorbidity Index, improved the correlation with CT muscle area (r = 0.85; P < .001). Mean difference between ultrasound-predicted and CT-measured muscle area was −2 cm2 (95% limits of agreement, −40 cm2 to +36 cm2). The best-performing ultrasound model demonstrated good ability to identify 14 patients with low CT muscle area (area under curve = 0.79). Conclusion Ultrasound shows potential for assessing muscularity at ICU admission (Clinicaltrials.gov NCT03019913)

What happened to smokers' beliefs about light cigarettes when "light/mild" brand descriptors were banned in the UK? Findings from the International Tobacco Control (ITC) Four Country Survey

Aim: This paper reports findings of an evaluation that examined how beliefs of smokers in the United Kingdom (UK) were affected by the removal of light and mild brand descriptors which came into effect on September 30, 2003 for Member States of the European Union (EU). Participants: The data come from the first 4 waves (2002-2005) of the International Tobacco Control Policy Evaluation (ITC) 4 Country Survey, an annual cohort telephone survey of adult smokers in Canada, United States, United Kingdom, and Australia (15450 individual cases). Design: The UK ban on misleading descriptors occurred around the 2nd wave of data collection in the ITC survey, permitting us to compare beliefs about light cigarettes among adult smokers in the UK both before and after the ban, with beliefs in three other countries unaffected by the ban. Results: The findings reveal that high levels of misperceptions about light cigarettes existed among smokers in all four countries before and after the EU ban took effect. There was a substantial decline in reported beliefs about the benefits of Lights in the UK following the policy change and an associated public information campaign, but by 2006 (i.e., Wave 4), these beliefs rebounded slightly and the change in beliefs was no greater than in the United States, where there was no policy change. Conclusion: We cannot conclude that the policy which required removal of the misleading labels has been effective in changing beliefs about light cigarettes. What seems apparent is that efforts to correct decades of consumer misperceptions about light cigarettes will require more than simply removing brand descriptors

Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

Information, disturbance and Hamiltonian quantum feedback control

We consider separating the problem of designing Hamiltonian quantum feedback control algorithms into a measurement (estimation) strategy and a feedback (control) strategy, and consider optimizing desirable properties of each under the minimal constraint that the available strength of both is limited. This motivates concepts of information extraction and disturbance which are distinct from those usually considered in quantum information theory. Using these concepts we identify an information trade-off in quantum feedback control.Comment: 13 pages, multicol Revtex, 2 eps figure

The impact of dark matter cusps and cores on the satellite galaxy population around spiral galaxies

(Abridged) We use N-body simulations to study the effects that a divergent (i.e. "cuspy") dark matter (DM) profile introduces on the tidal evolution of dwarf spheroidal galaxies (dSphs). Our models assume cosmologically-motivated initial conditions where dSphs are DM-dominated systems on eccentric orbits about a host galaxy composed of a dark halo and a baryonic disc. We find that the resilience of dSphs to tidal stripping is extremely sensitive to the halo cuspiness; whereas dwarfs with a cored profile can be easily destroyed by the host disc, those with cusps always retain a bound remnant. For a given halo profile the evolution of the structural parameters as driven by tides is controlled solely by the total amount of mass lost. This information is used to construct a semi-analytic code that simulates the hierarchical build-up of spiral galaxies assuming different halo profiles and disc masses. We find that tidal encounters with discs tend to decrease the average mass of satellites at all galactocentric radii. Interestingly, satellites accreted before re-ionization (z>6), which may be singled out by anomalous metallicity patterns, survive only if haloes are cuspy. We show that the size-mass relation established from Milky Way (MW) dwarfs strongly supports the presence of cusps in the majority of these systems, as cored models systematically underestimate the masses of the known Ultra-Faint dSphs. Our models also indicate that a massive M31 disc may explain why many of its dSphs fall below the size-mass relationship derived from MW dSphs. We use our models to constrain the mass threshold below which star formation is suppressed in DM haloes, finding that luminous satellites must be accreted with masses above 10^8--10^9 M_sol in order to explain the size-mass relation observed in MW dwarfs.Comment: 17 pages, 14 figures, MNRAS accepted after minor revisio