Synergy of stereo cloud top height and ORAC optimal estimation cloud retrieval: evaluation and application to AATSR

In this paper we evaluate the retrievals of cloud top height when stereo derived heights are combined with the radiometric cloud top heights retrieved from the ORAC (Optimal Retrieval of Aerosol and Cloud) algorithm. This is performed in a mathematically rigorous way using the ORAC optimal estimation retrieval framework, which includes the facility to use independent a priori information. Key to the use of a priori information is a characterisation of their associated uncertainty. This paper demonstrates the improvements that are possible using this approach and also considers their impact on the microphysical cloud parameters retrieved. The AATSR instrument has two views and three thermal channels so is well placed to demonstrate the synergy of the two techniques. The stereo retrieval is able to improve the accuracy of the retrieved cloud top height when compared to collocated Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), particularly in the presence of boundary layer inversions and high clouds. The impact on the microphysical properties of the cloud such as optical depth and effective radius was evaluated and found to be very small with the biggest differences occurring over bright land surfaces and for high clouds. Overall the cost of the retrievals increased indicating a poorer radiative fit of radiances to the cloud model, which currently uses a single layer cloud model. Best results and improved fit to the radiances may be obtained in the future if a multi-layer model is used

Incidence of Diabetes in the Working Population in Spain: Results from the ICARIA Cohort

INTRODUCTION: Our objective was to evaluate the incidence of type 2 diabetes mellitus (T2DM) in a working population in Spain and to assess associations between its development and several risk factors. METHODS: The ICARIA (Ibermutuamur CArdiovascular RIsk Assessment) cohort (n = 627,523) includes ~3% of Spanish workers. This analysis was undertaken in individuals whose glycaemic status during the index period (May 2004-December 2007) was determined to be normal or indicative of prediabetes [fasting plasma glucose (FPG) 100-125 mg/dl] and who had at least one FPG measurement taken 9 months after a first measurement during follow-up (May 2004-June 2014) (n = 380,366). T2DM patients were defined as those with an FPG ? 126 mg/day and those who had already been diagnosed with T2DM or were taking antihyperglycaemic medications. RESULTS: The incidence rate of T2DM was 5.0 [95% confidence interval (CI) 4.9-5.1] cases per 1000 person-years. Under multivariate logistic regression analysis, the factor showing the strongest association with the occurrence of T2DM was the baseline FPG level, with the likelihood of T2DM almost doubling for every 5 mg/dl increase in baseline FPG between 100 and < 126 mg/dl. The presence of other cardiometabolic risk factors and being a blue-collar worker were also significantly associated with the occurrence of T2DM. CONCLUSIONS: The incidence of T2DM in the working population was within the range encountered in the general population and prediabetes was found to be the strongest risk factor for the development of diabetes. The workplace is an appropriate and feasible setting for the assessment of easily measurable risk factors, such as the presence of prediabetes and other cardiometabolic factors, to facilitate the early detection of individuals at higher risk of diabetes and the implementation of diabetes prevention programmes

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

Influence of oxygen tension on myocardial performance. Evaluation by tissue Doppler imaging

BACKGROUND: Low O(2 )tension dilates coronary arteries and high O(2 )tension is a coronary vasoconstrictor but reports on O(2)-dependent effects on ventricular performance diverge. Yet oxygen supplementation remains first line treatment in cardiovascular disease. We hypothesized that hypoxia improves and hyperoxia worsens myocardial performance. METHODS: Seven male volunteers (mean age 38 ± 3 years) were examined with echocardiography at respiratory equilibrium during: 1) normoxia (≈21% O(2), 79% N(2)), 2) while inhaling a hypoxic gas mixture (≈11% O(2), 89% N(2)), and 3) while inhaling 100% O(2). Tissue Doppler recordings were acquired in the apical 4-chamber, 2-chamber, and long-axis views. Strain rate and tissue tracking displacement analyses were carried out in each segment of the 16-segment left ventricular model and in the basal, middle and apical portions of the right ventricle. RESULTS: Heart rate increased with hypoxia (68 ± 4 bpm at normoxia vs. 79 ± 5 bpm, P < 0.001) and decreased with hyperoxia (59 ± 5 bpm, P < 0.001 vs. normoxia). Hypoxia increased strain rate in four left ventricular segments and global systolic contraction amplitude was increased (normoxia: 9.76 ± 0.41 vs hypoxia: 10.87 ± 0.42, P < 0.001). Tissue tracking displacement was reduced in the right ventricular segments and tricuspid regurgitation increased with hypoxia (7.5 ± 1.9 mmHg vs. 33.5 ± 1.8 mmHg, P < 0.001). The TEI index and E/E' did not change with hypoxia. Hyperoxia reduced strain rate in 10 left ventricular segments, global systolic contraction amplitude was decreased (8.83 ± 0.38, P < 0.001 vs. normoxia) while right ventricular function was unchanged. The spectral and tissue Doppler TEI indexes were significantly increased but E/E' did not change with hyperoxia. CONCLUSION: Hypoxia improves and hyperoxia worsens systolic myocardial performance in healthy male volunteers. Tissue Doppler measures of diastolic function are unaffected by hypoxia/hyperoxia which support that the changes in myocardial performance are secondary to changes in vascular tone. It remains to be settled whether oxygen therapy to patients with heart disease is a consistent rational treatment

An antibody-based biomarker discovery method by mass spectrometry sequencing of complementarity determining regions

Autoantibodies are increasingly used as biomarkers in the detection of autoimmune disorders and cancer. Disease specific antibodies are generally detected by their binding to specific antigens. As an alternative approach, we propose to identify specific complementarity determining regions (CDR) of IgG that relate to an autoimmune disorder or cancer instead of the specific antigen(s). In this manuscript, we tested the technical feasibility to detect and identify CDRs of specific antibodies by mass spectrometry. We used a commercial pooled IgG preparation as well as purified serum IgG fractions that were spiked with different amounts of a fully human monoclonal antibody (adalimumab). These samples were enzymatically digested and analyzed by nanoLC Orbitrap mass spectrometry. In these samples, we were able to identify peptides derived from the CDRs of adalimumab. These peptides could be detected at an amount of 110 attomole, 5 orders of magnitude lower than the total IgG concentration in these samples. Using higher energy collision induced dissociation (HCD) fragmentation and subsequent de novo sequencing, we could successfully identify 50% of the detectable CDR peptides of adalimumab. In addition, we demonstrated that an affinity purification with anti-dinitrophenol (DNP) monoclonal antibody enhanced anti-DNP derived CDR detection in a serum IgG background. In conclusion, specific CDR peptides could be detected and sequenced at relatively low levels (attomole-femtomole range) which should allow the detection of clinically relevant CDR peptides in patient samples

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

We investigated toxicity of 2-3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis

Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review

The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL

Time-Dependent Subcellular Distribution and Effects of Carbon Nanotubes in Lungs of Mice

BACKGROUND AND METHODS:Pulmonary deposited carbon nanotubes (CNTs) are cleared very slowly from the lung, but there is limited information on how CNTs interact with the lung tissue over time. To address this, three different multiwalled CNTs were intratracheally instilled into female C57BL/6 mice: one short (850 nm) and tangled, and two longer (4 μm and 5.7 μm) and thicker. We assessed the cellular interaction with these CNTs using transmission electron microscopy (TEM) 1, 3 and 28 days after instillation. RESULTS:TEM analysis revealed that the three CNTs followed the same overall progression pattern over time. Initially, CNTs were taken up either by a diffusion mechanism or via endocytosis. Then CNTs were agglomerated in vesicles in macrophages. Lastly, at 28 days post-exposure, evidence suggesting CNT escape from vesicle enclosures were found. The longer and thicker CNTs more often perturbed and escaped vesicular enclosures in macrophages compared to the smaller CNTs. Bronchoalveolar lavage (BAL) showed that the CNT exposure induced both an eosinophil influx and also eosinophilic crystalline pneumonia. CONCLUSION:Two very different types of multiwalled CNTs had very similar pattern of cellular interactions in lung tissue, with the longer and thicker CNTs resulting in more severe effects in terms of eosinophil influx and incidence of eosinophilic crystalline pneumonia (ECP)

Experiences with surgical treatment of ventricle septal defect as a post infarction complication

<p>Abstract</p> <p>Background</p> <p>Complications of acute myocardial infarction (AMI) with mechanical defects are associated with poor prognosis. Surgical intervention is indicated for a majority of these patients. The goal of surgical intervention is to improve the systolic cardiac function and to achieve a hemodynamic stability. In this present study we reviewed the outcome of patients with post infarction ventricular septal defect (PVSD) who underwent cardiac surgery.</p> <p>Methods</p> <p>We analysed retrospectively the hospital records of 41 patients, whose ages range from 48 to 81, and underwent a surgical treatment between 1990 and 2005 because of PVSD.</p> <p>Results</p> <p>In 22 patients concomitant coronary artery bypass grafting (CAGB) was performed. In 15 patients a residual shunt was found, this required re-op in seven of them. The time interval from infarct to rupture was 8.7 days and from rupture to surgery was 23.1 days. Hospital mortality in PVSD group was 32%. The mortality of urgent repair within 3 days of intractable cardiogenic shock was 100%. The mortality of patients with an anterior VSD and a posterior VSD was 29.6% vs 42.8%, respectively. All patients who underwent the surgical repair later than day 36 survived.</p> <p>Conclusion</p> <p>Surgical intervention is indicated for a majority of patients with mechanical complications. Cardiogenic shock remains the most important factor that affects the early results. The surgical repair of PVSD should be performed 4–5 weeks after AMI. To improve surgical outcome and hemodynamics the choice of surgical technique and surgical timing as well as preoperative management should be tailored for each patient individually.</p