A LC-tandem MS assay for the simultaneous measurement of new antiretroviral agents: Raltegravir, maraviroc, darunavir, and etravirine.

Raltegravir (RAL), maraviroc (MVC), darunavir (DRV), and etravirine (ETV) are new antiretroviral agents with significant potential for drug interactions. This work describes a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of plasma drug levels. Single-step extraction of RAL, MVC, DRV, ETV and RTV from plasma (100 microl) is performed by protein precipitation using 600 microl of acetonitrile, after the addition of 100 microl darunavir-d(9) (DRV-d(9)) at 1000 ng/ml in MeOH/H(2)O 50/50 as internal standard (I.S.). The mixture is vortexed, sonicated for 10 min, vortex-mixed again and centrifuged. An aliquot of supernatant (150 microl) is diluted 1:1 with a mixture of 20 mM ammonium acetate/MeOH 40/60 and 10 microl is injected onto a 2.1 x 50 mm Waters Atlantis-dC18 3 microm analytical column. Chromatographic separations are performed using a gradient program with 2 mM ammonium acetate containing 0.1% formic acid and acetonitrile with 0.1% formic acid. Analytes quantification is performed by electrospray ionisation-triple quadrupole mass spectrometry using the selected reaction monitoring detection in the positive mode. The method has been validated over the clinically relevant concentrations ranging from 12.5 to 5000 ng/ml, 2.5 to 1000 ng/ml, 25 to 10,000 ng/ml, 10 to 4000 ng/ml, and 5 to 2000 ng/ml for RAL, MRV, DRV, ETV and RTV, respectively. The extraction recovery for all antiretroviral drugs is always above 91%. The method is precise, with mean inter-day CV% within 5.1-9.8%, and accurate (range of inter-day deviation from nominal values -3.3 to +5.1%). In addition our method enables the simultaneous assessment of raltegravir-glucuronide. This is the first analytical method allowing the simultaneous assay of antiretroviral agents targeted to four different steps of HIV replication. The proposed method is suitable for the Therapeutic Drug Monitoring Service of these new regimen combinations administered as salvage therapy to patients having experienced treatment failure, and for whom exposure, tolerance and adherence assessments are critical.

Looking for Validity or Testing It? The Perils of Stepwise Regression, Extreme-Scores Analysis, Heteroscedasticity, and Measurement Error

When researchers introduce a new test they have to demonstrate that it is valid, using unbiased designs and suitable statistical procedures. In this article we use Monte Carlo analyses to highlight how incorrect statistical procedures (i.e., stepwise regression, extreme scores analyses) or ignoring regression assumptions (e.g., heteroscedasticity) contribute to wrong validity estimates. Beyond these demonstrations, and as an example, we re-examined the results reported by Warwick, Nettelbeck, and Ward (2010) concerning the validity of the Ability Emotional Intelligence Measure (AEIM). Warwick et al. used the wrong statistical procedures to conclude that the AEIM was incrementally valid beyond intelligence and personality traits in predicting various outcomes. In our re-analysis, we found that the reliability-corrected multiple correlation of their measures with personality and intelligence was up to .69. Using robust statistical procedures and appropriate controls, we also found that the AEIM did not predict incremental variance in GPA, stress, loneliness, or well-being, demonstrating the importance for testing validity instead of looking for it.

The career indecision profile : measurement equivalence in two international samples

This study tested for the measurement equivalence of a four-factor measure of career indecision (Career Indecision Profile-65 [CIP-65]) between a U.S. sample and two international samples; one composed of French-speaking young adults from France and Switzerland and the other of Italian ado- lescents. Previous research had supported the four-factor structure of the CIP-65 in both the United States and Iceland but also showed that items on two of the four scales may be interpreted differently by young adults growing up in these two countries. This study extends previous research by testing whether the four CIP-65 factors are measured equivalently in two additional international samples. Results largely supported the configural and metric invariance of the CIP-65 in the United States and international samples, but several scales showed a lack of scalar invariance. Some explanations are offered for these findings along with suggestions for future research and implications for practice.

Radiographic total disc replacement angle measurement accuracy using the Oxford Cobbometer: precision and bias.

Total disc replacement (TDR) clinical success has been reported to be related to the residual motion of the operated level. Thus, accurate measurement of TDR range of motion (ROM) is of utmost importance. One commonly used tool in measuring ROM is the Oxford Cobbometer. Little is known however on its accuracy (precision and bias) in measuring TDR angles. The aim of this study was to assess the ability of the Cobbometer to accurately measure radiographic TDR angles. An anatomically accurate synthetic L4-L5 motion segment was instrumented with a CHARITE artificial disc. The TDR angle and anatomical position between L4 and L5 was fixed to prohibit motion while the motion segment was radiographically imaged in various degrees of rotation and elevation, representing a sample of possible patient placement positions. An experienced observer made ten readings of the TDR angle using the Cobbometer at each different position. The Cobbometer readings were analyzed to determine measurement accuracy at each position. Furthermore, analysis of variance was used to study rotation and elevation of the motion segment as treatment factors. Cobbometer TDR angle measurements were most accurate (highest precision and lowest bias) at the centered position (95.5%), which placed the TDR directly inline with the x-ray beam source without any rotation. In contrast, the lowest accuracy (75.2%) was observed in the most rotated and off-centered view. A difference as high as 4 degrees between readings at any individual position, and as high as 6 degrees between all the positions was observed. Furthermore, the Cobbometer was unable to detect the expected trend in TDR angle projection with changing position. Although the Cobbometer has been reported to be reliable in different clinical applications, it lacks the needed accuracy to measure TDR angles and ROM. More accurate ROM measurement methods need to be developed to help surgeons and researchers assess radiological success of TDRs.

Effect of Grooved Concrete on Curing Efficiency, MLR-83-4, 1983

The textured concrete surface on all PCC primary paving projects (and when specified on secondary projects) is required to be grooved in a specified manner. The laboratory test for determining the efficiency index of concrete curing compounds is made on slabs that are not grooved. This short investigation was undertaken to determine any changes in the curing efficiency index when using various rates of application of curing compound on grooved concrete. Currently a 95 percent curing efficiency index is specified at an application rate of 15 square yards per gallon. Can this efficiency be achieved, and if so at what application rate, on grooved concrete? Grooving the concrete greatly increases the surface area and also causes the liquid curing compound to run off the high spots and collect in the grooves.

Cervical radiculopathy: Efficiency of CT-guided cervical facet joint corticosteroid injection : 47

Purpose: Cervical foraminal injection performed with a direct approach of the foramen may induce serious neurologic complications. Cervical facet joint (CFJ) injections are easier to perform and safe, and may diffuse in the epidural and foraminal spaces. We analyzed the efficiency and tolerance of CT-guided CFJ slow-acting corticosteroid injection in patients with radiculopathy related to disc herniation. Methods and materials: Pilot study included 17 patients presenting typical cervical radiculopathy related to disc herniation without relief of pain after medical treatment (one month duration). CFJ puncture was performed under CT guidance with a lateral approach. CT control of the CFJ opacification was performed after injections of contrast agent (1 ml), followed by slow-acting corticosteroid (25 mg). Main criteria for judgment was pain relief one month later (delta visual analogical scale VAS for 0 to 100 mm). Diffusion of iodinated contrast agent in the foramen was assessed by two radiologists in consensus. Results: Pain relief was significant at one month (delta VAS 22 ± 23 mm, p = 0.001) and 41% (7/17) of patients had pain relief more than 50%. In cases with foraminal diffusion, pain relief more than 50% occured in 5 patients (50%) and only in 2 patients (29%) in cases without foraminal diffusion. No complication occurred. Conclusion: CT-guided CFJ slow-acting corticosteroid injection is safe and provided good results at one month follow-up. It may be considered as an interesting percutaneous treatment in patients suffering from cervical radicular pain related to disc herniation.

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted b diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

MHC class II hierarchy of superantigen presentation predicts efficiency of infection with mouse mammary tumor virus.

Superantigens (SAgs) encoded by infectious mouse mammary tumor viruses (MMTVs) play a crucial role in the viral life cycle. Their expression by infected B cells induces a proliferative immune response by SAg-reactive T cells which amplifies MMTV infection. This response most likely ensures stable MMTV infection and transmission to the mammary gland. Since T cell reactivity to SAgs from endogenous Mtv loci depends on MHC class II molecules expressed by B cells, we have determined the ability of MMTV to infect various MHC congenic mice. We show that MHC class II I-E+ compared with I-E- mouse strains show higher levels of MMTV infection, most likely due to their ability to induce a vigorous SAg-dependent immune response following MMTV encounter. Inefficient infection is observed in MHC class II I-E- mice, which have been shown to present endogenous SAgs poorly. Therefore, during MMTV infection the differential ability of MHC class II molecules to form a functional complex with SAg determines the magnitude of the proliferative response of SAg-reactive T cells. This in turn influences the degree of T cell help provided to infected B cells and therefore the efficiency of amplification of MMTV infection.

Efficiency of split nitrogen fertilization with adjusted irrigation on potato

Selostus: Jaetun typpilannoituksen käyttömahdollisuudet perunalle

Measurement of the specific heat and determination of the thermodynamic functions of relaxed amorphous silicon

The specific heat, cp, of two amorphous silicon (a-Si) samples has been measured by differential scanning calorimetry in the 100–900K temperature range. When the hydrogen content is reduced by thermal annealing, cp approaches the value of crystalline Si (c-Si). Within experimental accuracy, we conclude that cp of relaxed pure a-Si coincides with that of c-Si. This result is used to determine the enthalpy, entropy, and Gibbs free energy of defect-free relaxed a-Si. Finally, the contribution of structural defects on these quantities is calculated and the melting point of several states of a-Si is predicted

Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations.

Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.2 deletion syndrome (22q11.2DS). Cerebral MRIs were acquired for 46 patients and 48 age and gender matched controls (aged 6-26, respectively mean age = 15.20 ± 4.53 and 15.28 ± 4.35 years old). Using the Connectome mapper pipeline (connectomics.org) that combines structural and diffusion MRI, we created a whole brain network for each individual. Graph theory was used to quantify the global and local properties of the brain network organization for each participant. A global degree loss of 6% was found in patients' networks along with an increased Characteristic Path Length. After identifying and comparing hubs, a significant loss of degree in patients' hubs was found in 58% of the hubs. Based on Allen's brain network model for hallucinations, we explored the association between local efficiency and symptom severity. Negative correlations were found in the Broca's area (p < 0.004), the Wernicke area (p < 0.023) and a positive correlation was found in the dorsolateral prefrontal cortex (DLPFC) (p < 0.014). In line with the dysconnection findings in schizophrenia, our results provide preliminary evidence for a targeted alteration in the brain network hubs' organization in individuals with a genetic risk for schizophrenia. The study of specific disorganization in language, speech and thought regulation networks sharing similar network properties may help to understand their role in the hallucination mechanism.

Road Use Tax Fund Efficiency Report Savings Status, December 31, 2014

Senate File 2355, 85th General Assembly, states the Iowa Department of Transportation shall submit annual reports regarding the implementation of efficiency measures identified in the “Road Use Tax Fund Efficiency Report,” January 2012. This report shall provide details of activities undertaken in the previous year relating to one-time and long-term program efficiencies and partnership efficiencies. Issues to be covered in the reports shall include but are not limited to savings realized from the implementation of particular efficiency measures; updates concerning measures that have not been implemented; efforts involving cities, counties, other jurisdictions, or stakeholder interest groups; any new efficiency measures identified or undertaken; and identification of any legislative action that may be required to achieve efficiencies.

Effects of plant population and nitrogen fertilizer on yield and efficiency of maize-bean intercropping

Nitrogen supply and plant population are basic parameters for cereal-legume intercropping. In order to study plant population and nitrogen fertilizer effects on yield and yield efficiency of maize-bean intercropping, a field experiment was established. Three bean plant populations and three nitrogen levels were used. Maize dry matter accumulation decreased with increases in bean plant population. Competitive effect of intercrop beans on maize yields was high at higher plant populations, being decreased by nitrogen fertilizer; application of 50 kg ha-1 N was very efficient in increasing maize cob yield. Intercropping significantly decreased harvest index of beans in all plant population and nitrogen fertilizer situations. The efficiency of intercropping, compared to sole cropping, was evidenced by the values obtained for Land Equivalent Ratio (LER) for biomass, cob and pod yields that increased with increases in bean plant populations and nitrogen fertilizer levels.

A comparative study on inter and intralaboratory reproducibility of renin measurement with a conventional enzymatic method and a new chemiluminescent assay of immunoreactive renin.

BACKGROUND: The activity of the renin-angiotensin system is usually evaluated as plasma renin activity (PRA, ngAI/ml per h) but the reproducibility of this enzymatic assay is notoriously scarce. We compared the inter and intralaboratory reproducibilities of PRA with those of a new automated chemiluminescent assay, which allows the direct quantification of immunoreactive renin [chemiluminescent immunoreactive renin (CLIR), microU/ml]. METHODS: Aliquots from six pool plasmas of patients with very low to very high PRA levels were measured in 12 centres with both the enzymatic and the direct assays. The same methods were applied to three control plasma preparations with known renin content. RESULTS: In pool plasmas, mean PRA values ranged from 0.14 +/- 0.08 to 18.9 +/- 4.1 ngAI/ml per h, whereas those of CLIR ranged from 4.2 +/- 1.7 to 436 +/- 47 microU/ml. In control plasmas, mean values of PRA and of CLIR were always within the expected range. Overall, there was a significant correlation between the two methods (r = 0.73, P < 0.01). Similar correlations were found in plasmas subdivided in those with low, intermediate and high PRA. However, the coefficients of variation among laboratories found for PRA were always higher than those of CLIR, ranging from 59.4 to 17.1% for PRA, and from 41.0 to 10.7% for CLIR (P < 0.01). Also, the mean intralaboratory variability was higher for PRA than for CLIR, being respectively, 8.5 and 4.5% (P < 0.01). CONCLUSION: The measurement of renin with the chemiluminescent method is a reliable alternative to PRA, having the advantage of a superior inter and intralaboratory reproducibility.

Sample size for measurement of root traits on common bean by image analysis

Evaluation of root traits may be facilitated if they are assessed on samples of the root system. The objective of this work was to determine the sample size of the root system in order to estimate root traits of common bean (Phaseolus vulgaris L.) cultivars by digital image analysis. One plant was grown per pot and harvested at pod setting, with 64 and 16 pots corresponding to two and four cultivars in the first and second experiments, respectively. Root samples were scanned up to the completeness of the root system and the root area and length were estimated. Scanning a root sample demanded 21 minutes, and scanning the entire root system demanded 4 hours and 53 minutes. In the first experiment, root area and length estimated with two samples showed, respectively, a correlation of 0.977 and 0.860, with these traits measured in the entire root. In the second experiment, the correlation was 0.889 and 0.915. The increase in the correlation with more than two samples was negligible. The two samples corresponded to 13.4% and 16.9% of total root mass (excluding taproot and nodules) in the first and second experiments. Taproot stands for a high proportion of root mass and must be deducted on root trait estimations. Samples with nearly 15% of total root mass produce reliable root trait estimates.