Design and experimental testing of air slab caps which convert commercial electron diodes into dual purpose, correction-free diodes for small field dosimetry

Purpose Two diodes which do not require correction factors for small field relative output measurements are designed and validated using experimental methodology. This was achieved by adding an air layer above the active volume of the diode detectors, which canceled out the increase in response of the diodes in small fields relative to standard field sizes. Methods Due to the increased density of silicon and other components within a diode, additional electrons are created. In very small fields, a very small air gap acts as an effective filter of electrons with a high angle of incidence. The aim was to design a diode that balanced these perturbations to give a response similar to a water-only geometry. Three thicknesses of air were placed at the proximal end of a PTW 60017 electron diode (PTWe) using an adjustable “air cap”. A set of output ratios (ORfclin Det ) for square field sizes of side length down to 5 mm was measured using each air thickness and compared to ORfclin Det measured using an IBA stereotactic field diode (SFD). k fclin, f msr Qclin,Qmsr was transferred from the SFD to the PTWe diode and plotted as a function of air gap thickness for each field size. This enabled the optimal air gap thickness to be obtained by observing which thickness of air was required such that k fclin, f msr Qclin,Qmsr was equal to 1.00 at all field sizes. A similar procedure was used to find the optimal air thickness required to make a modified Sun Nuclear EDGE detector (EDGEe) which s “correction-free” in small field relative dosimetry. In addition, the feasibility of experimentally transferring k fclin, f msr Qclin,Qmsr values from the SFD to unknown diodes was tested by comparing the experimentally transferred k fclin, f msr Qclin,Qmsr values for unmodified PTWe and EDGEe diodes to Monte Carlo simulated values. Results 1.0 mm of air was required to make the PTWe diode correction-free. This modified diode (PTWeair) produced output factors equivalent to those in water at all field sizes (5–50 mm). The optimal air thickness required for the EDGEe diode was found to be 0.6 mm. The modified diode (EDGEeair) produced output factors equivalent to those in water, except at field sizes of 8 and 10 mm where it measured approximately 2% greater than the relative dose to water. The experimentally calculated k fclin, f msr Qclin,Qmsr for both the PTWe and the EDGEe diodes (without air) matched Monte Carlo simulated results, thus proving that it is feasible to transfer k fclin, f msr Qclin,Qmsr from one commercially available detector to another using experimental methods and the recommended experimental setup. Conclusions It is possible to create a diode which does not require corrections for small field output factor measurements. This has been performed and verified experimentally. The ability of a detector to be “correction-free” depends strongly on its design and composition. A nonwater-equivalent detector can only be “correction-free” if competing perturbations of the beam cancel out at all field sizes. This should not be confused with true water equivalency of a detector.

Growing rod analysis for the fusionless correction of early onset scoliosis (EOS)

Managing spinal deformities in young children is challenging, particularly early onset scoliosis (EOS). Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option for EOS is fusionless scoliosis surgery. Similar to bracing, this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods are one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semi-constrained growing rods (Medtronic Sofamor Danek Memphis, TN, USA) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard rigid rods and hence potentially provide a more physiological mechanical environment for the growing spine. This study found that semi-constrained growing rods would be expected to allow growth via the telescopic rod components while maintaining the axial flexibility of the spine and the improved capacity for final correction.

A biomechanical investigation of dual growing rods used for fusionless scoliosis correction

Background The use of dual growing rods is a fusionless surgical approach to the treatment of early onset scoliosis (EOS), which aims of harness potential growth in order to correct spinal deformity. The purpose of this study was to compare the in-vitro biomechanical response of two different dual rod designs under axial rotation loading. Methods Six porcine spines were dissected into seven level thoracolumbar multi-segmental units. Each specimen was mounted and tested in a biaxial Instron machine, undergoing nondestructive left/right axial rotation to peak moments of 4Nm at a constant rotation rate of 8deg.s-1. A motion tracking system (Optotrak) measured 3D displacements of individual vertebrae. Each spine was tested in an un-instrumented state first and then with appropriately sized semi-constrained growing rods and ‘rigid’ rods in alternating sequence. Range of motion, neutral zone size and stiffness were calculated from the moment-rotation curves and intervertebral ranges of motion were calculated from Optotrak data. Findings Irrespective of test sequence, rigid rods showed significantly reduction of total rotation across all instrumented levels (with increased stiffness) whilst semi-constrained rods exhibited similar rotation behavior to the un-instrumented (P<0.05). An 11% and 8% increase in stiffness for left and right axial rotation respectively and 15% reduction in total range of motion was recorded with dual rigid rods compared with semi-constrained rods. Interpretation Based on these findings, the semi-constrained growing rods do not increase axial rotation stiffness compared with un-instrumented spines. This is thought to provide a more physiological environment for the growing spine compared to dual rigid rod constructs.

Fast and accurate business process drift detection

Business processes are prone to continuous and unexpected changes. Process workers may start executing a process differently in order to adjust to changes in workload, season, guidelines or regulations for example. Early detection of business process changes based on their event logs – also known as business process drift detection – enables analysts to identify and act upon changes that may otherwise affect process performance. Previous methods for business process drift detection are based on an exploration of a potentially large feature space and in some cases they require users to manually identify the specific features that characterize the drift. Depending on the explored feature set, these methods may miss certain types of changes. This paper proposes a fully automated and statistically grounded method for detecting process drift. The core idea is to perform statistical tests over the distributions of runs observed in two consecutive time windows. By adaptively sizing the window, the method strikes a trade-off between classification accuracy and drift detection delay. A validation on synthetic and real-life logs shows that the method accurately detects typical change patterns and scales up to the extent it is applicable for online drift detection.

Large-scale interlaboratory study to develop, analytically validate and apply highly multiplexed, quantitative peptide assays to measure cancer-relevant proteins in plasma

There is an increasing need in biology and clinical medicine to robustly and reliably measure tens-to-hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma, and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and 7 control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to sub-nanogram/mL sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and inter-laboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy isotope labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an inter-laboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality c`ontrol measures, enables sensitive, specific, reproducible and quantitative measurements of proteins and peptides in complex biological matrices such as plasma.

Cone location and correction of keratoconus with rigid gas-permeable contact lenses

Purpose To evaluate the influence of cone location and corneal cylinder on RGP corrected visual acuities and residual astigmatism in patients with keratoconus. Methods In this prospective study, 156 eyes from 134 patients were enrolled. Complete ophthalmologic examination including manifest refraction, Best spectacle visual acuity (BSCVA), slit-lamp biomicroscopy was performed and corneal topography analysis was done. According to the cone location on the topographic map, the patients were divided into central and paracentral cone groups. Trial RGP lenses were selected based on the flat Sim K readings and a ‘three-point touch’ fitting approach was used. Over contact lens refraction was performed, residual astigmatism (RA) was measured and best-corrected RGP visual acuities (RGPVA) were recorded. Results The mean age (±SD) was 22.1 ± 5.3 years. 76 eyes (48.6%) had central and 80 eyes (51.4%) had paracentral cone. Prior to RGP lenses fitting mean (±SD) subjective refraction spherical equivalent (SRSE), subjective refraction astigmatism (SRAST) and BSCVA (logMAR) were −5.04 ± 2.27 D, −3.51 ± 1.68 D and 0.34 ± 0.14, respectively. There were statistically significant differences between central and paracentral cone groups in mean values of SRSE, SRAST, flat meridian (Sim K1), steep meridian (Sim K2), mean K and corneal cylinder (p-values < 0.05). Comparison of BSCVA to RGPVA shows that vision has improved 0.3 logMAR by RGP lenses (p < 0.0001). Mean (±SD) RA was −0.72 ± 0.39 D. There were no statistically significant differences between RGPVAs and RAs of central and paracentral cone groups (p = 0.22) and (p = 0.42), respectively. Pearson's correlation analysis shows that there is a statistically significant relationship between corneal cylinder and BSCVA and RGPVA, However, the relationship between corneal cylinder and residual astigmatism was not significant. Conclusions Cone location has no effect on the RGP corrected visual acuities and residual astigmatism in patients with keratoconus. Corneal cylinder and Sim K values influence RGP-corrected visual acuities but do not influence residual astigmatism.

Correction: Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA

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Stability of a Random Diffusion with Linear Drift

We consider a Linear system with Markovian switching which is perturbed by Gaussian type noise, If the linear system is mean square stable then we show that under certain conditions the perturbed system is also stable, We also shaw that under certain conditions the linear system with Markovian switching can be stabilized by such noisy perturbation.

Robust estimating functions and bias correction for longitudinal data analysis

Robust methods are useful in making reliable statistical inferences when there are small deviations from the model assumptions. The widely used method of the generalized estimating equations can be "robustified" by replacing the standardized residuals with the M-residuals. If the Pearson residuals are assumed to be unbiased from zero, parameter estimators from the robust approach are asymptotically biased when error distributions are not symmetric. We propose a distribution-free method for correcting this bias. Our extensive numerical studies show that the proposed method can reduce the bias substantially. Examples are given for illustration.

Influence of environmental and instrumental variables on the non-invasive prediction of Brix in pineapple using near infrared spectroscopy

The Brix content of pineapple fruit can be non-invasively predicted from the second derivative of near infrared reflectance spectra. Correlations obtained using a NIRSystems 6500 spectrophotometer through multiple linear regression and modified partial least squares analyses using a post-dispersive configuration were comparable with that from a pre-dispersive configuration in terms of accuracy (e.g. coefficient of determination, R2, 0.73; standard error of cross validation, SECV, 1.01°Brix). The effective depth of sample assessed was slightly greater using the post-dispersive technique (about 20 mm for pineapple fruit), as expected in relation to the higher incident light intensity, relative to the pre-dispersive configuration. The effect of such environmental variables as temperature, humidity and external light, and instrumental variables such as the number of scans averaged to form a spectrum, were considered with respect to the accuracy and precision of the measurement of absorbance at 876 nm, as a key term in the calibration for Brix, and predicted Brix. The application of post-dispersive near infrared technology to in-line assessment of intact fruit in a packing shed environment is discussed.