Marked global reduction in mGluR5 receptor binding in smokers and ex-smokers determined by [11C]ABP688 positron emission tomography

Nicotine addiction is a major public health problem, resulting in primary glutamatergic dysfunction. We measured the glutamate receptor binding in the human brain and provided direct evidence for the abnormal glutamate system in smokers. Because antagonism of the metabotropic glutamate receptor 5 (mGluR5) reduced nicotine self-administration in rats and mice, mGluR5 is suggested to be involved in nicotine addiction. mGluR5 receptor binding specifically to an allosteric site was observed by using positron emission tomography with [(11)C]ABP688. We found a marked global reduction (20.6%; P < 0.0001) in the mGluR5 distribution volume ratio (DVR) in the gray matter of 14 smokers. The most prominent reductions were found in the bilateral medial orbitofrontal cortex. Compared with 14 nonsmokers, 14 ex-smokers had global reductions in the average gray matter mGluR5 DVR (11.5%; P < 0.005), and there was a significant difference in average gray matter mGluR5 DVR between smokers and ex-smokers (9.2%; P < 0.01). Clinical variables reflecting current nicotine consumption, dependence and abstinence were not correlated with mGluR5 DVR. This decrease in mGluR5 receptor binding may be an adaptation to chronic increases in glutamate induced by chronic nicotine administration, and the decreased down-regulation seen in the ex-smokers could be due to incomplete recovery of the receptors, especially because the ex-smokers were abstinent for only 25 wk on average. These results encourage the development and testing of drugs against addiction that directly target the glutamatergic system.

Control of ventricular unloading using an electrocardiogram-synchronized Thoratec paracorporeal ventricular assist device

OBJECTIVE: Current pulsatile ventricular assist devices operate asynchronous with the left ventricle in fixed-rate or fill-to-empty modes because electrocardiogram-triggered modes have been abandoned. We hypothesize that varying the ejection delay in the synchronized mode yields more precise control of hemodynamics and left ventricular loading. This allows for a refined management that may be clinically beneficial. METHODS: Eight sheep received a Thoratec paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, Calif) via ventriculo-aortic cannulation. Left ventricular pressure and volume, aortic pressure, pulmonary flow, pump chamber pressure, and pump inflow and outflow were recorded. The pump was driven by a clinical pneumatic drive unit (Medos Medizintechnik AG, Stolberg, Germany) synchronously with the native R-wave. The start of pump ejection was delayed between 0% and 100% of the cardiac period in 10% increments. For each of these delays, hemodynamic variables were compared with baseline data using paired t tests. RESULTS: The location of the minimum of stroke work was observed at a delay of 10% (soon after aortic valve opening), resulting in a median of 43% reduction in stroke work compared with baseline. Maximum stroke work occurred at a median delay of 70% with a median stroke work increase of 11% above baseline. Left ventricular volume unloading expressed by end-diastolic volume was most pronounced for copulsation (delay 0%). CONCLUSIONS: The timing of pump ejection in synchronized mode yields control over left ventricular energetics and can be a method to achieve gradual reloading of a recoverable left ventricle. The traditionally suggested counterpulsation is not optimal in ventriculo-aortic cannulation when maximum unloading is desired.

Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry

OBJECTIVES: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. METHODS: The REACH Registry recruited >68000 outpatients aged >/=45 years with established atherothrombotic disease or >/=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. RESULTS: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. CONCLUSIONS: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Structural response and dynamics of fluid-structure-control interaction in wind turbine blades

Reducing the uncertainties related to blade dynamics by the improvement of the quality of numerical simulations of the fluid structure interaction process is a key for a breakthrough in wind-turbine technology. A fundamental step in that direction is the implementation of aeroelastic models capable of capturing the complex features of innovative prototype blades, so they can be tested at realistic full-scale conditions with a reasonable computational cost. We make use of a code based on a combination of two advanced numerical models implemented in a parallel HPC supercomputer platform: First, a model of the structural response of heterogeneous composite blades, based on a variation of the dimensional reduction technique proposed by Hodges and Yu. This technique has the capacity of reducing the geometrical complexity of the blade section into a stiffness matrix for an equivalent beam. The reduced 1-D strain energy is equivalent to the actual 3-D strain energy in an asymptotic sense, allowing accurate modeling of the blade structure as a 1-D finite-element problem. This substantially reduces the computational effort required to model the structural dynamics at each time step. Second, a novel aerodynamic model based on an advanced implementation of the BEM(Blade ElementMomentum) Theory; where all velocities and forces are re-projected through orthogonal matrices into the instantaneous deformed configuration to fully include the effects of large displacements and rotation of the airfoil sections into the computation of aerodynamic forces. This allows the aerodynamic model to take into account the effects of the complex flexo-torsional deformation that can be captured by the more sophisticated structural model mentioned above. In this thesis we have successfully developed a powerful computational tool for the aeroelastic analysis of wind-turbine blades. Due to the particular features mentioned above in terms of a full representation of the combined modes of deformation of the blade as a complex structural part and their effects on the aerodynamic loads, it constitutes a substantial advancement ahead the state-of-the-art aeroelastic models currently available, like the FAST-Aerodyn suite. In this thesis, we also include the results of several experiments on the NREL-5MW blade, which is widely accepted today as a benchmark blade, together with some modifications intended to explore the capacities of the new code in terms of capturing features on blade-dynamic behavior, which are normally overlooked by the existing aeroelastic models.

EVALUATION OF INTELLIGENT COMPACTION CONTROL IN THE M-189 RECONSTRUCTION PROJECT AT IRON RIVER, MICHIGAN

This research evaluated an Intelligent Compaction (IC) unit on the M-189 highway reconstruction project at Iron River, Michigan. The results from the IC unit were compared to several traditional compaction measurement devices including Nuclear Density Gauge (NDG), Geogauge, Light Weight Deflectometer (LWD), Dynamic Cone Penetrometer (DCP), and Modified Clegg Hammer (MCH). The research collected point measurements data on a test section in which 30 test locations on the final Class II sand base layer and the 22A gravel layer. These point measurements were compared with the IC measurements (ICMVs) on a point-to-point basis through a linear regression analysis. Poor correlations were obtained among different measurements points using simple regression analysis. When comparing the ICMV to the compaction measurements points. Factors attributing to the weak correlation include soil heterogeneity, variation in IC roller operation parameters, in-place moisture content, the narrow range of the compaction devices measurement ranges and support conditions of the support layers. After incorporating some of the affecting factors into a multiple regression analysis, the strength of correlation significantly improved, especially on the stiffer gravel layer. Measurements were also studied from an overall distribution perspective in terms of average, measurement range, standard deviation, and coefficient of variance. Based on data analysis, on-site project observation and literature review, conclusions were made on how IC performed in regards to compaction control on the M-189 reconstruction project.

Lung volume reduction surgery for severe emphysema

BACKGROUND: We report mid-term results after 25 consecutive lung volume reduction operations (LVRS) for the treatment of severe dyspnea due to advanced emphysema. METHODS: Study design: patients were studied prospectively up to 12 months after surgery. Setting: preoperative evaluation, surgery and postoperative care took place in our university hospital. Patients: patient selection was based on severe dyspnea and airway obstruction despite optimal medical treatment, lung overinflation and completed rehabilitation programme. Patients with severe hypercarbia (PCO2>50 mmHg) were excluded. Nineteen rehabilitated patients who fulfilled our inclusion criteria but postponed or denied LVRS were followed up clinically. Interventions: LVRS was performed bilaterally in 22 patients (median sternotomy) and unilaterally in 3 patients (limited thoracotomy). Measures: Outcome was measured by dyspnea evaluation, 6-minute-walking distance and pulmonary function tests. RESULTS: Twelve months postoperatively dyspnea and mobility improved significantly (MRC score from 3.3+/-0.7 to 2.12+/-0.8, 6-min-walk from 251+/-190 to 477+/-189 m). These results were superior compared to the results of the conservatively treated patients. Significant improvement could also be documented in airway obstruction (FEV1 from 960+/-369 to 1438+/-610 ml) and overinflation (TLC from 133+/-14 to 118+/-21% predicted and RV from 280+/-56 to 186+/-59% predicted). CONCLUSIONS: LVRS is an effective and promising treatment option for selected patients with end-stage emphysema and could be offered as an alternative and / or bridge to lung transplantation.

[Bilateral surgical lung volume reduction in severe emphysema]

OBJECTIVE: To report preliminary results with a new surgical method of treating terminal emphysema by bilateral reduction of lung volume. PATIENTS AND METHODS: In a prospective study, the results obtained with the first 20 consecutive patients (mean FEV1: 590 +/- 180 ml) who underwent operative reduction of lung volume were recorded. 19 of the 20 patients had required continuous oxygen supply. RESULTS: The patients were extubated 8.5 +/- 6 h postoperatively; thoracic drainage was removed after 9 +/- 6 days. The degree of dyspnoea was decreased in all patients (3.5 +/- 0.5 vs 0.5 +/- 0.1). Significant reduction of overinflation occurred soon after the operation (residual volume 273 +/- 125 to 201 +/- 107% of normal; total capacity from 142 +/- 18 to 109 +/- 22% of normal), as well as reduction in the degree of obstruction (FEV1 from 18 +/- 6 to 24 +/- 7% of normal; for each, P < 0.05). One patient died 3 weeks post-operatively of Candida infection. CONCLUSION: The method looks promising for the treatment of selected patients and may thus provide an alternative to lung transplantation.

[Lung volume reduction in severe emphysema]

BACKGROUND: Lung volume reduction (LVR) surgery is an effective and organ-preserving treatment option for patients suffering from severe dyspnea due to endstage emphysema. METHOD: Resection of functionally inactive lung parenchyma reduces over-inflation and restores the elastic recoil of the lungs. Thus it results in improvement of dyspnea, mobility and pulmonary function. Patient selection is crucial. Of simliar importance is pulmonary rehabilitation, as well as sufficient expertise in the treatment of endstage chronic respiratory failure. RESULTS AND CONCLUSION: The in-hospital morbidity and mortality after LVR are acceptable (0 to 5%) and the good results seem to last at least 18 to 24 months. LVR can be offered to selected patients either as an alternative or as bridge to lung transplantation.

Combined cardiac and lung volume reduction surgery

Coronary artery disease is prevalent in patients who have severe emphysema and who are being considered for lung volume reduction surgery (LVRS). Significant valvular heart diseases may also coexist in these patients. Few thoracic surgeons have performed LVRS in patients who have severe cardiac diseases. Conversely, few cardiac surgeons have been willing to undertake major cardiac surgery in patients who have severe emphysema. This report reviews the evidence regarding combined cardiac surgery and LVRS to determine the optimal management strategy for patients who have severe emphysema and who are suitable for LVRS, but who also have coexisting significant cardiac diseases that are operable.

Small quantity but large effect — How minor phases control strain localization in upper mantle shear zones

Low viscosity domains such as localized shear zones exert an important control on the geodynamics of the uppermost mantle. Grain size reduction and subsequent strain localization related to a switch from dislocation to diffusion creep is one mechanism to form low viscosity domains. To sustain strain localization, the grain size of mantle minerals needs to be kept small over geological timescales. One way to keep olivine grain sizes small is by pinning of mobile grain boundaries during grain growth by other minerals (second phases). Detailed microstructural studies based on natural samples from three shear zones formed at different geodynamic settings, allowed the derivation of the olivine grain-size dependence on the second-phase content. The polymineralic olivine grain-size evolution with increasing strain is similar in the three shear zones. If the second phases are to pin the mobile olivine grain boundary the phases need to be well mixed before grain growth. We suggest that melt-rock and metamorphic reactions are crucial for the initial phase mixing in mantle rocks. With ongoing deformation and increasing strain, grain boundary sliding combined with mass transfer processes and nucleation of grains promotes phase mixing resulting in fine-grained polymineralic mixtures that deform by diffusion creep. Strain localization due to the presence of volumetrically minor minerals in polymineralic mantle rocks is only important at high strain deformation (ultramylonites) at low temperatures (<~800°C). At smaller strain and stress conditions and/or higher temperatures other parameters like overall energy available to deform a given rock volume, the inheritance of mechanical anisotropies or the presence of water or melts needs to be considered to explain strain localization in the upper mantle.

Radiation dose reduction in postoperative computed position control of cochlear implant electrodes in lambs - An experimental study

OBJECTIVE Cochlear implants (CI) are standard treatment for prelingually deafened children and postlingually deafened adults. Computed tomography (CT) is the standard method for postoperative imaging of the electrode position. CT scans accurately reflect electrode depth and position, which is essential prior to use. However, routine CT examinations expose patients to radiation, which is especially problematic in children. We examined whether new CT protocols could reduce radiation doses while preserving diagnostic accuracy. METHODS To investigate whether electrode position can be assessed by low-dose CT protocols, a cadaveric lamb model was used because the inner ear morphology is similar to humans. The scans were performed at various volumetric CT dose-indexes CTDIvol)/kV combinations. For each constant CTDIvol the tube voltage was varied (i.e., 80, 100, 120 and 140kV). This procedure was repeated at different CTDIvol values (21mGy, 11mGy, 5.5mGy, 2.8mGy and 1.8mGy). To keep the CTDIvol constant at different tube voltages, the tube current values were adjusted. Independent evaluations of the images were performed by two experienced and blinded neuroradiologists. The criteria diagnostic usefulness, image quality and artifacts (scaled 1-4) were assessed in 14 cochlear-implanted cadaveric lamb heads with variable tube voltages. RESULTS Results showed that the standard CT dose could be substantially reduced without sacrificing diagnostic accuracy of electrode position. The assessment of the CI electrode position was feasible in almost all cases up to a CTDIvol of 2-3mGy. The number of artifacts did not increase for images within this dose range as compared to higher dosages. The extent of the artifacts caused by the implanted metal-containing CI electrode does not depend on the radiation dose and is not perceptibly influenced by changes in the tube voltage. Summarizing the evaluation of the CI electrode position is possible even at a very low radiation dose. CONCLUSIONS CT imaging of the temporal bone for postoperative electrode position control of the CI is possible with a very low and significantly radiation dose. The tube current-time product and voltage can be reduced by 50% without increasing artifacts. Low-dose postoperative CT scans are sufficient for localizing the CI electrode.

Lung Volume Reduction in Pulmonary Emphysema from the Radiologist's Perspective

Pulmonary emphysema causes decrease in lung function due to irreversible dilatation of intrapulmonary air spaces, which is linked to high morbidity and mortality. Lung volume reduction (LVR) is an invasive therapeutical option for pulmonary emphysema in order to improve ventilation mechanics. LVR can be carried out by lung resection surgery or different minimally invasive endoscopical procedures. All LVR-options require mandatory preinterventional evaluation to detect hyperinflated dysfunctional lung areas as target structures for treatment. Quantitative computed tomography can determine the volume percentage of emphysematous lung and its topographical distribution based on the lung's radiodensity. Modern techniques allow for lobebased quantification that facilitates treatment planning. Clinical tests still play the most important role in post-interventional therapy monitoring, but CT is crucial in the detection of postoperative complications and foreshadows the method's high potential in sophisticated experimental studies. Within the last ten years, LVR with endobronchial valves has become an extensively researched minimally-invasive treatment option. However, this therapy is considerably complicated by the frequent occurrence of functional interlobar shunts. The presence of "collateral ventilation" has to be ruled out prior to valve implantations, as the presence of these extraanatomical connections between different lobes may jeopardize the success of therapy. Recent experimental studies evaluated the automatic detection of incomplete lobar fissures from CT scans, because they are considered to be a predictor for the existence of shunts. To date, these methods are yet to show acceptable results. KEY POINTS Today, surgical and various minimal invasive methods of lung volume reduction are in use. Radiological and nuclear medical examinations are helpful in the evaluation of an appropriate lung area. Imaging can detect periinterventional complications. Reduction of lung volume has not yet been conclusively proven to be effective and is a therapeutical option with little scientific evidence.

Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

OBJECTIVE To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan. METHODS 30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans. RESULTS Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively. CONCLUSION An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients. ADVANCES IN KNOWLEDGE Further dose reductions are possible owing to a change in the individual patient's imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure.

Implementation of active surveillance cultures and associated infection control practices for the reduction of methicillin resistant Staphylococcus aureus in the healthcare setting: An interrupted time series analysis

OBJECTIVE. To determine the effectiveness of active surveillance cultures and associated infection control practices on the incidence of methicillin resistant Staphylococcus aureus (MRSA) in the acute care setting. DESIGN. A historical analysis of existing clinical data utilizing an interrupted time series design. ^ SETTING AND PARTICIPANTS. Patients admitted to a 260-bed tertiary care facility in Houston, TX between January 2005 through December 2010. ^ INTERVENTION. Infection control practices, including enhanced barrier precautions, compulsive hand hygiene, disinfection and environmental cleaning, and executive ownership and education, were simultaneously introduced during a 5-month intervention implementation period culminating with the implementation of active surveillance screening. Beginning June 2007, all high risk patients were cultured for MRSA nasal carriage within 48 hours of admission. Segmented Poisson regression was used to test the significance of the difference in incidence of healthcare-associated MRSA during the 29-month pre-intervention period compared to the 43-month post-intervention period. ^ RESULTS. A total of 9,957 of 11,095 high-risk patients (89.7%) were screened for MRSA carriage during the intervention period. Active surveillance cultures identified 1,330 MRSA-positive patients (13.4%) contributing to an admission prevalence of 17.5% in high-risk patients. The mean rate of healthcare-associated MRSA infection and colonization decreased from 1.1 per 1,000 patient-days in the pre-intervention period to 0.36 per 1,000 patient-days in the post-intervention period (P<0.001). The effect of the intervention in association with the percentage of S. aureus isolates susceptible to oxicillin were shown to be statistically significantly associated with the incidence of MRSA infection and colonization (IRR = 0.50, 95% CI = 0.31-0.80 and IRR = 0.004, 95% CI = 0.00003-0.40, respectively). ^ CONCLUSIONS. It can be concluded that aggressively targeting patients at high risk for colonization of MRSA with active surveillance cultures and associated infection control practices as part of a multifaceted, hospital-wide intervention is effective in reducing the incidence of healthcare-associated MRSA.^