Regional variations in ex-vivo diffusion tensor anisotropy are associated with cardiomyocyte remodeling in rats after left ventricular pressure overload

Background Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. Methods We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. Results We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections (p < 0.001, R2 = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. Conclusions These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a non-invasive, comprehensive method to detect regional structural myocyte LV remodeling during disease

On fractionality of the path packing problem

In this paper, we study fractional multiflows in undirected graphs. A fractional multiflow in a graph G with a node subset T, called terminals, is a collection of weighted paths with ends in T such that the total weights of paths traversing each edge does not exceed 1. Well-known fractional path packing problem consists of maximizing the total weight of paths with ends in a subset S of TxT over all fractional multiflows. Together, G,T and S form a network. A network is an Eulerian network if all nodes in N\T have even degrees. A term "fractionality" was defined for the fractional path packing problem by A. Karzanov as the smallest natural number D so that there exists a solution to the problem that becomes integer-valued when multiplied by D. A. Karzanov has defined the class of Eulerian networks in terms of T and S, outside which D is infinite and proved that whithin this class D can be 1,2 or 4. He conjectured that D should be 1 or 2 for this class of networks. In this paper we prove this conjecture.Comment: 18 pages, 5 figures in .eps format, 2 latex files, main file is kc13.tex Resubmission due to incorrectly specified CS type of the article; no changes to the context have been mad

Endoscopic ultrasound reduces surgical mediastinal staging in lung cancer: A randomized trial

A

Birth and early evolution of a planetary nebula

The final expulsion of gas by a star as it forms a planetary nebula --- the ionized shell of gas often observed surrounding a young white dwarf --- is one of the most poorly understood stages of stellar evolution. Such nebulae form extremely rapidly (about 100 years for the ionization) and so the formation process is inherently difficult to observe. Particularly puzzling is how a spherical star can produce a highly asymmetric nebula with collimated outflows. Here we report optical observations of the Stingray Nebula which has become an ionized planetary nebula within the past few decades. We find that the collimated outflows are already evident, and we have identified the nebular structure that focuses the outflows. We have also found a companion star, reinforcing previous suspicions that binary companions play an important role in shaping planetary nebulae and changing the direction of successive outflows.Comment: 9 pages + 3 figures. To appear in Nature, 2 April 199

Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation

Background: In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face-to-face, psychotherapeutic assessment service for doctors in London and South-East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved. Methods: A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002–2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE-Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory. Results: The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick. Conclusion: Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK

Effect of a multidisciplinary stress treatment programme on the return to work rate for persons with work-related stress. A non-randomized controlled study from a stress clinic

<p>Abstract</p> <p>Background</p> <p>In recent years an increasing number of patients have been referred to the medical sector with stress symptoms. Moreover, these conditions imply increased sickness absence. This indicates a need for treatment programmes in general medical practice. The aim of this study was to test the effect of a multidisciplinary stress treatment programme on the return to work (RTW) rate in persons with work-related stress and establish predictive factors for this outcome.</p> <p>Methods</p> <p>During a two-year period 63 out of 73 referrals to the Stress Clinic (a section of a Clinic of Occupational Medicine) completed a stress treatment programme consisted of the following:</p> <p>1) Identification of relevant stressors. 2. Changing the coping strategies of the participants. 3. Evaluating/changes in participant workload and tasks. 4. Relaxation techniques. 5. Physical exercise. 6. Psychiatric evaluation when indicated by depression test score.</p> <p>On average each patient attended six one-hour sessions over the course of four months.</p> <p>A group of 34 employees referred to the Clinic of Occupational Medicine by their general practitioners served as a control group. Each participant had a one-hour consultation at baseline and after four months. A specialist in occupational medicine carried out all sessions.</p> <p>Return To Work (RTW), defined as having a job and not being on sick leave at the census, was used as outcome measure four months after baseline, and after one and two years.</p> <p>Results</p> <p>The level of sick leave in the stress treatment group dropped from 52% to 16% during the first four months of follow-up and remained stable. In the control group, the reduction in sick leave was significantly smaller, ranging from 48% at baseline to 27% after four months and 24% after one year. No statistically significant difference between the two groups was observed after one and two years. Age below 50 years and being a manager increased the odds ratio for RTW after one and two years, while gender and depression had no predictive value.</p> <p>Conclusions</p> <p>The stress treatment programme showed a significant effect on the return to work rate. The stress treatment programme seems feasible for general practitioners.</p> <p>Trial Registration</p> <p>ISRCTN04354658</p

The impact of image dynamic range on texture classification of brain white matter

<p>Abstract</p> <p>Background</p> <p>The Greylevel Cooccurrence Matrix method (COM) is one of the most promising methods used in Texture Analysis of Magnetic Resonance Images. This method provides statistical information about the spatial distribution of greylevels in the image which can be used for classification of different tissue regions. Optimizing the size and complexity of the COM has the potential to enhance the reliability of Texture Analysis results. In this paper we investigate the effect of matrix size and calculation approach on the ability of COM to discriminate between peritumoral white matter and other white matter regions.</p> <p>Method</p> <p>MR images were obtained from patients with histologically confirmed brain glioblastoma using MRI at 3-T giving isotropic resolution of 1 mm³. Three Regions of Interest (ROI) were outlined in visually normal white matter on three image slices based on relative distance from the tumor: one peritumoral white matter region and two distant white matter regions on both hemispheres. Volumes of Interest (VOI) were composed from the three slices. Two different calculation approaches for COM were used: i) Classical approach (CCOM) on each individual ROI, and ii) Three Dimensional approach (3DCOM) calculated on VOIs. For, each calculation approach five dynamic ranges (number of greylevels N) were investigated (N = 16, 32, 64, 128, and 256).</p> <p>Results</p> <p>Classification showed that peritumoral white matter always represents a homogenous class, separate from other white matter, regardless of the value of N or the calculation approach used. The best test measures (sensitivity and specificity) for average CCOM were obtained for N = 128. These measures were also optimal for 3DCOM with N = 128, which additionally showed a balanced tradeoff between the measures.</p> <p>Conclusion</p> <p>We conclude that the dynamic range used for COM calculation significantly influences the classification results for identical samples. In order to obtain more reliable classification results with COM, the dynamic range must be optimized to avoid too small or sparse matrices. Larger dynamic ranges for COM calculations do not necessarily give better texture results; they might increase the computation costs and limit the method performance.</p

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

North Flinders Reef (Coral Sea, Australia) Porites sp. corals as a candidate Global Boundary Stratotype Section and Point for the Anthropocene Series

Corals are unique in the suite of proposed Anthropocene Global Boundary Stratotype Section and Point (GSSP) archives, as living organisms that produce aragonite exoskeletons preserved in the geological record that contain highly accurate and precise (<±1 year) internal chronologies. The GSSP candidate site North Flinders Reef in the Coral Sea (Australia) is an offshore oceanic reef, and therefore less vulnerable to local human influences than those closer to the coast. Here, we present geochemical records from two Porites sp. corals sampled at an annual to pluri-annual (i.e. 3–5 years) resolution that shows clear global and regional human impacts. Atmospheric nuclear bomb testing by-products (14C,239+240Pu) show a clear increase in the Flinders Reef corals coincident with well-dated nuclear testing operations. By contrast, the radionuclides 241Am and 137Cs are present at low or undetectable levels, as are spheroidal carbonaceous fly-ash particles. Coral δ13C shows centennial variability likely influenced by growth effects in the 18th century and with a progression to lower values starting in 1880 and accelerating post-1970. The latter may be related to the Suess Effect resulting from 13C-depleted fossil fuel burning. Coral δ15N decreased between 1710 and 1954 with a reversal post-1954. Coral temperature proxies indicate prominent centennial variability with equally warm conditions in the 18th and end of 20th century. However, the exact mechanisms responsible for the mid-20th century changes in these parameters need to be scrutinised in further detail. Plain Language summary: This work proposes a candidate natural archive for the official marker of the Anthropocene that geologists will use to mark this important interval in time. Our candidate is a live coral from North Flinders Reef in the Coral Sea (Australia), located 150 km east of the Great Barrier Reef, a location that is remote from direct local human influences. Corals are a unique archive of tropical ocean change because they incorporate the geochemical signature from seawater into their limestone skeleton during their long life-spans. Here we investigated a number of geochemical markers in yearly growth layers of the corals to define several markers for the Anthropocene based on changes in temperature, water chemistry, chemicals from pollution and fertilisers, radioactive products from nuclear bomb testing, and by-products from burning fossil fuels. We have detected clear human influences in several of these markers