Strain diversity of mycobacteria isolated from pulmonary tuberculosis patients at Debre Birhan Hospital, Ethiopia.

BACKGROUND: Ethiopia ranks seventh in the list of 22 high tuberculosis (TB) burden countries, with an incidence rate of 379 cases per 100 000 population for TB all forms. However, information on the genomic diversity of Mycobacterium tuberculosis in Ethiopia is limited. OBJECTIVE: To investigate the molecular characteristics of M. tuberculosis strains implicated in pulmonary TB in the study area. METHODS AND RESULTS: A cross-sectional study was conducted using socio-demographic, clinical and culture data combined with molecular typing analysis. The proportion of TB and M. tuberculosis isolates was not associated with risk factors (P > 0.05). Of 99 sputum samples, 80.8% were culture-positive. Speciation of isolates showed that 88.8% were M. tuberculosis. Further characterisation led to the identification of 27 different spoligotype patterns of M. tuberculosis; the most dominant shared types were SIT149, SIT53 and SIT54. Of the 27 strains, three strains were new and were reported to the SITVIT database. More than two thirds of the strains belonged to the Euro-American lineage. CONCLUSION: This study shows the presence of several clusters and new strains of M. tuberculosis circulating in pulmonary TB patients in the study area, suggesting recent transmission. Nationwide studies are recommended to map the population structure of M. tuberculosis and set control measures.

Variability of radioiodine measurements in the thyroid.

Monte Carlo simulations were carried out to study the response of a thyroid monitor for measuring intake activities of (125)I and (131)I. The aim of the study was 3-fold: to cross-validate the Monte Carlo simulation programs, to study the response of the detector using different phantoms and to study the effects of anatomical variations. Simulations were performed using the Swiss reference phantom and several voxelised phantoms. Determining the position of the thyroid is crucial for an accurate determination of radiological risks. The detector response using the Swiss reference phantom was in fairly good agreement with the response obtained using adult voxelised phantoms for (131)I, but should be revised for a better calibration for (125)I and for any measurements taken on paediatric patients.

TECTONICS OF THE HELVETIC NAPPE SYSTEM (W SWITZERLAND): CONTROL OF STRAIN LOCALIZATION AND BASEMENT-COVER DEFORMATION. Insights from models based on continuum mechanics

The Helvetic nappe system in Western Switzerland is a stack of fold nappes and thrust sheets em-placed at low grade metamorphism. Fold nappes and thrust sheets are also some of the most common features in orogens. Fold nappes are kilometer scaled recumbent folds which feature a weakly deformed normal limb and an intensely deformed overturned limb. Thrust sheets on the other hand are characterized by the absence of overturned limb and can be defined as almost rigid blocks of crust that are displaced sub-horizontally over up to several tens of kilometers. The Morcles and Doldenhom nappe are classic examples of fold nappes and constitute the so-called infra-Helvetic complex in Western and Central Switzerland, respectively. This complex is overridden by thrust sheets such as the Diablerets and Wildhörn nappes in Western Switzerland. One of the most famous example of thrust sheets worldwide is the Glariis thrust sheet in Central Switzerland which features over 35 kilometers of thrusting which are accommodated by a ~1 m thick shear zone. Since the works of the early Alpine geologist such as Heim and Lugeon, the knowledge of these nappes has been steadily refined and today the geometry and kinematics of the Helvetic nappe system is generally agreed upon. However, despite the extensive knowledge we have today of the kinematics of fold nappes and thrust sheets, the mechanical process leading to the emplacement of these nappe is still poorly understood. For a long time geologist were facing the so-called 'mechanical paradox' which arises from the fact that a block of rock several kilometers high and tens of kilometers long (i.e. nappe) would break internally rather than start moving on a low angle plane. Several solutions were proposed to solve this apparent paradox. Certainly the most successful is the theory of critical wedges (e.g. Chappie 1978; Dahlen, 1984). In this theory the orogen is considered as a whole and this change of scale allows thrust sheet like structures to form while being consistent with mechanics. However this theoiy is intricately linked to brittle rheology and fold nappes, which are inherently ductile structures, cannot be created in these models. When considering the problem of nappe emplacement from the perspective of ductile rheology the problem of strain localization arises. The aim of this thesis was to develop and apply models based on continuum mechanics and integrating heat transfer to understand the emplacement of nappes. Models were solved either analytically or numerically. In the first two papers of this thesis we derived a simple model which describes channel flow in a homogeneous material with temperature dependent viscosity. We applied this model to the Morcles fold nappe and to several kilometer-scale shear zones worldwide. In the last paper we zoomed out and studied the tectonics of (i) ductile and (ii) visco-elasto-plastic and temperature dependent wedges. In this last paper we focused on the relationship between basement and cover deformation. We demonstrated that during the compression of a ductile passive margin both fold nappes and thrust sheets can develop and that these apparently different structures constitute two end-members of a single structure (i.e. nappe). The transition from fold nappe to thrust sheet is to first order controlled by the deformation of the basement. -- Le système des nappes helvétiques en Suisse occidentale est un empilement de nappes de plis et de nappes de charriage qui se sont mis en place à faible grade métamorphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement défor-mé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Mordes et la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glariis en Suisse centrale se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. Aujourd'hui la géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général. Malgré cela, les processus mécaniques par lesquels ces nappes se sont mises en place restent mal compris. Pendant toute la première moitié du vingtième siècle les géologues les géologues ont été confrontés au «paradoxe mécanique». Celui-ci survient du fait qu'un bloc de roche haut de plusieurs kilomètres et long de plusieurs dizaines de kilomètres (i.e., une nappe) se fracturera de l'intérieur plutôt que de se déplacer sur une surface frictionnelle. Plusieurs solutions ont été proposées pour contourner cet apparent paradoxe. La solution la plus populaire est la théorie des prismes d'accrétion critiques (par exemple Chappie, 1978 ; Dahlen, 1984). Dans le cadre de cette théorie l'orogène est considéré dans son ensemble et ce simple changement d'échelle solutionne le paradoxe mécanique (la fracturation interne de l'orogène correspond aux nappes). Cette théorie est étroitement lié à la rhéologie cassante et par conséquent des nappes de plis ne peuvent pas créer au sein d'un prisme critique. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la méca-nique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous avons dérivé un modèle d'écoulement dans un chenal d'un matériel homogène dont la viscosité dépend de la température. Nous avons appliqué ce modèle à la nappe de Mordes et à plusieurs zone de cisaillement d'échelle kilométrique provenant de différents orogènes a travers le monde. Dans le dernier article nous avons considéré le problème à l'échelle de l'orogène et avons étudié la tectonique de prismes (i) ductiles, et (ii) visco-élasto-plastiques en considérant les transferts de chaleur. Nous avons démontré que durant la compression d'une marge passive ductile, a la fois des nappes de plis et des nappes de charriages peuvent se développer. Nous avons aussi démontré que nappes de plis et de charriages sont deux cas extrêmes d'une même structure (i.e. nappe) La transition entre le développement d'une nappe de pli ou d'une nappe de charriage est contrôlé au premier ordre par la déformation du socle. -- Le système des nappes helvétiques en Suisse occidentale est un emblement de nappes de plis et de nappes de chaînage qui se sont mis en place à faible grade métamoiphique. Les nappes de plis et les nappes de charriage sont parmi les objets géologiques les plus communs dans les orogènes. Les nappes de plis sont des plis couchés d'échelle kilométrique caractérisés par un flanc normal faiblement déformé, au contraire de leur flanc inverse, intensément déformé. Les nappes de charriage, à l'inverse se caractérisent par l'absence d'un flanc inverse bien défini. Elles peuvent être définies comme des blocs de croûte terrestre qui se déplacent de manière presque rigide qui sont déplacés sub-horizontalement jusqu'à plusieurs dizaines de kilomètres. La nappe de Morcles and la nappe du Doldenhorn sont des exemples classiques de nappes de plis et constitue le complexe infra-helvétique en Suisse occidentale et centrale, respectivement. Ce complexe repose sous des nappes de charriages telles les nappes des Diablerets et du Widlhörn en Suisse occidentale. La nappe du Glarüs en Suisse centrale est certainement l'exemple de nappe de charriage le plus célèbre au monde. Elle se distingue par un déplacement de plus de 35 kilomètres qui s'est effectué à la faveur d'une zone de cisaillement basale épaisse de seulement 1 mètre. La géométrie et la cinématique des nappes alpines fait l'objet d'un consensus général parmi les géologues. Au contraire les processus physiques par lesquels ces nappes sont mises en place reste mal compris. Les sédiments qui forment les nappes alpines se sont déposés à l'ère secondaire et à l'ère tertiaire sur le socle de la marge européenne qui a été étiré durant l'ouverture de l'océan Téthys. Lors de la fermeture de la Téthys, qui donnera naissance aux Alpes, le socle et les sédiments de la marge européenne ont été déformés pour former les nappes alpines. Le but de cette thèse était de développer et d'appliquer des modèles basés sur la théorie de la mécanique des milieux continus et sur les transferts de chaleur pour comprendre l'emplacement des nappes. Ces modèles ont été solutionnés de manière analytique ou numérique. Dans les deux premiers articles présentés dans ce mémoire nous nous sommes intéressés à la localisation de la déformation à l'échelle d'une nappe. Nous avons appliqué le modèle développé à la nappe de Morcles et à plusieurs zones de cisaillement provenant de différents orogènes à travers le monde. Dans le dernier article nous avons étudié la relation entre la déformation du socle et la défonnation des sédiments. Nous avons démontré que nappe de plis et nappes de charriages constituent les cas extrêmes d'un continuum. La transition entre nappe de pli et nappe de charriage est intrinsèquement lié à la déformation du socle sur lequel les sédiments reposent.

Measurements of three-dimensional glenoid erosion when planning the prosthetic replacement of osteoarthritic shoulders.

The three-dimensional (3D) correction of glenoid erosion is critical to the long-term success of total shoulder replacement (TSR). In order to characterise the 3D morphology of eroded glenoid surfaces, we looked for a set of morphological parameters useful for TSR planning. We defined a scapular coordinates system based on non-eroded bony landmarks. The maximum glenoid version was measured and specified in 3D by its orientation angle. Medialisation was considered relative to the spino-glenoid notch. We analysed regular CT scans of 19 normal (N) and 86 osteoarthritic (OA) scapulae. When the maximum version of OA shoulders was higher than 10°, the orientation was not only posterior, but extended in postero-superior (35%), postero-inferior (6%) and anterior sectors (4%). The medialisation of the glenoid was higher in OA than normal shoulders. The orientation angle of maximum version appeared as a critical parameter to specify the glenoid shape in 3D. It will be very useful in planning the best position for the glenoid in TSR.

Biotic Factors Affecting Expression of the 2,4-Diacetylphloroglucinol Biosynthesis Gene phlA in Pseudomonas fluorescens Biocontrol Strain CHA0 in the Rhizosphere.

ABSTRACT Production of the polyketide antimicrobial metabolite 2,4-diacetyl-phloroglucinol (DAPG) is a key factor in the biocontrol activity of Pseudomonas fluorescens CHA0. Strain CHA0 carrying a translational phlA'-'lacZ fusion was used to monitor expression of the phl biosynthetic genes in vitro and in the rhizosphere. Expression of the reporter gene accurately reflected actual production of DAPG in vitro and in planta as determined by direct extraction of the antimicrobial compound. In a gnotobiotic system containing a clay and sand-based artificial soil, reporter gene expression was significantly greater in the rhizospheres of two monocots (maize and wheat) compared with gene expression in the rhizospheres of two dicots (bean and cucumber). We observed this host genotype effect on bacterial gene expression also at the level of cultivars. Significant differences were found among six additional maize cultivars tested under gnotobiotic conditions. There was no difference between transgenic maize expressing the Bacillus thuringiensis insecticidal gene cry1Ab and the near-isogenic parent line. Plant age had a significant impact on gene expression. Using maize as a model, expression of the phlA'-'lacZ reporter gene peaked at 24 h after planting of pregerminated seedlings, and dropped to a fourth of that value within 48 h, remaining at that level throughout 22 days of plant growth. Root infection by Pythium ultimum stimulated bacterial gene expression on both cucumber and maize, and this was independent of differences in rhizosphere colonization on these host plants. To our knowledge, this is the first comprehensive evaluation of how biotic factors that commonly confront bacterial inoculants in agricultural systems (host genotype, host age, and pathogen infection) modulate the expression of key biocontrol genes for disease suppression.

Primary activity measurements with a 4πβ-4πγ coincidence counting system.

The radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba solutions have been standardised using a 4πβ-4πγ coincidence counting system we have recently set up. The detection in the beta channel is performed using various geometries of a UPS-89 plastic scintillator optically coupled to a selected low-noise 1in. diameter photomultiplier tube. The light-tight thin capsule that encloses this beta detector is housed within the well of a 5in.×5in. NaI(Tl) monocrystal detector. The beta detection efficiency can be varied either by optical filtering or electronic discrimination when the electrons loose all their energy in the plastic scintillator. This 4πβ-4πγ coincidence system improves on our 4πβ(PC)-γ system in that its sample preparation is less labour intensive, it yields larger beta- and gamma-counting efficiencies thus enabling the standardisation of low activity sources with good statistics in reasonable time, and it makes standardising short-lived radionuclides easier. The resulting radioactive concentrations of (166m)Ho, (134)Cs and (133)Ba are found to agree with those measured with other primary measurement methods thus validating our 4πβ-4πγ coincidence counting system.

A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements.

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.

Biomechanical characterization and in vitro mechanical injury of elderly human femoral head cartilage: comparison to adult bovine humeral head cartilage.

OBJECTIVES: In vitro mechanical injury of articular cartilage is useful to identify events associated with development of post-traumatic osteoarthritis (OA). To date, many in vitro injury models have used animal cartilage despite the greater clinical relevance of human cartilage. We aimed to characterize a new in vitro injury model using elderly human femoral head cartilage and compare its behavior to that of an existing model with adult bovine humeral head cartilage. DESIGN: Mechanical properties of human and bovine cartilage disks were characterized by elastic modulus and hydraulic permeability in radially confined axial compression, and by Young's modulus, Poisson's ratio, and direction-dependent radial strain in unconfined compression. Biochemical composition was assessed in terms of tissue water, solid, and glycosaminoglycan (GAG) contents. Responses to mechanical injury were assessed by observation of macroscopic superficial tissue cracks and histological measurements of cell viability following single injurious ramp loads at 7 or 70%/s strain rate to 3 or 14 MPa peak stress. RESULTS: Confined compression moduli and Young's moduli were greater in elderly human femoral cartilage vs adult bovine humeral cartilage whereas hydraulic permeability was less. Radial deformations of axially compressed explant disks were more anisotropic (direction-dependent) for the human cartilage. In both cartilage sources, tissue cracking and associated cell death during injurious loading was common for 14 MPa peak stress at both strain rates. CONCLUSION: Despite differences in mechanical properties, acute damage induced by injurious loading was similar in both elderly human femoral cartilage and adult bovine humeral cartilage, supporting the clinical relevance of animal-based cartilage injury models. However, inherent structural differences such as cell density may influence subsequent cell-mediated responses to injurious loading and affect the development of OA.

Impact of biocontrol strain Pseudomonas fluorescens CHA0 on rhizosphere bacteria isolated from barley (Hordeum vulgare L.) with special reference to Cytophaga-like bacteria.

AIMS: To assess the impact of the biocontrol strain Pseudomonas fluorescens CHA0 on a collection of barley rhizosphere bacteria using an agar plate inhibition assay and a plant microcosm, focusing on a CHA0-sensitive member of the Cytophaga-like bacteria (CLB). METHODS AND RESULTS: The effect of strain CHA0 on a collection of barley rhizosphere bacteria, in particular CLB and fluorescent pseudomonads sampled during a growth season, was assessed by a growth inhibition assay. On average, 85% of the bacteria were sensitive in the May sample, while the effect was reduced to around 68% in the July and August samples. In the May sample, around 95% of the CLB and around 45% of the fluorescent pseudomonads were sensitive to strain CHA0. The proportion of CHA0-sensitive CLB and fluorescent pseudomonad isolates decreased during the plant growth season, i.e. in the July and August samples. A particularly sensitive CLB isolate, CLB23, was selected, exposed to strain CHA0 (wild type) and its genetically modified derivatives in the rhizosphere of barley grown in gnotobiotic soil microcosms. Two dry-stress periods were imposed during the experiment. Derivatives of strain CHA0 included antibiotic or exopolysaccharide (EPS) overproducing strains and a dry-stress-sensitive mutant. Despite their inhibitory activity against CLB23 in vitro, neither wild-type strain CHA0, nor any of its derivatives, had a major effect on culturable and total cell numbers of CLB23 during the 23-day microcosm experiment. Populations of all inoculants declined during the two dry-stress periods, with soil water contents below 5% and plants reaching the wilting point, but they recovered after re-wetting the soil. Survival of the dry-stress-sensitive mutant of CHA0 was most affected by the dry periods; however, this did not result in an increased population density of CLB23. CONCLUSIONS: CLB comprise a large fraction of barley rhizosphere bacteria that are sensitive to the biocontrol pseudomonad CHA0 in vitro. However, in plant microcosm experiments with varying soil humidity conditions, CHA0 or its derivatives had no major impact on the survival of the highly sensitive CLB strain, CLB23, during two dry-stress periods and a re-wetting period; all co-existed well in the rhizosphere of barley plants. SIGNIFICANCE AND IMPACT OF THE STUDY: Results indicate a lack of interaction between the biocontrol pseudomonad CHA0 and a sensitive CLB when the complexity increases from agar plate assays to plant microcosm experiments. This suggests the occurrence of low levels of antibiotic production and/or that the two bacterial genera occupy different niches in the rhizosphere.

Characterization of a new clinical yeast species, Candida tunisiensis sp. nov., isolated from a strain collection from Tunisian hospitals.

From a collection of yeast isolates isolated from patients in Tunisian hospitals between September 2006 and July 2010, the yeast strain JEY63 (CBS 12513), isolated from a 50-year-old male that suffered from oral thrush, could not be identified to the species level using conventional methods used in clinical laboratories. These methods include matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), germ tube formation, and the use of CHROMagar Candida and metabolic galleries. Sequence analysis of the nuclear rRNA (18S rRNA, 5.8S rRNA, and 26S rRNA) and internal transcribed spacer regions (ITS1 and ITS2) indicated that the ribosomal DNA sequences of this species were not yet reported. Multiple gene phylogenic analyses suggested that this isolate clustered at the base of the Dipodascaceae (Saccharomycetales, Saccharomycetes, and Ascomycota). JEY63 was named Candida tunisiensis sp. nov. according to several phenotypic criteria and its geographical origin. C. tunisiensis was able to grow at 42°C and does not form chlamydospores and hyphae but could grow as yeast and pseudohyphal forms. C. tunisiensis exhibited most probably a haploid genome with an estimated size of 10 Mb on at least three chromosomes. Using European Committee for Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) Candida albicans susceptibility breakpoints as a reference, C. tunisiensis was resistant to fluconazole (MIC = 8 μg/ml), voriconazole (MIC = 0.5 μg/ml), itraconazole (MIC = 16 μg/ml), and amphotericin B (MIC = 4 μg/ml) but still susceptible to posaconazole (MIC = 0.008 μg/ml) and caspofungin (MIC = 0.5 μg/ml). In conclusion, MALDI-TOF MS permitted the early selection of an unusual isolate, which was still unreported in molecular databases but could not be unambiguously classified based on phylogenetic approaches.

Comparison of the polynomial model against explicit measurements of noise components for different mammography systems.

Given the adverse impact of image noise on the perception of important clinical details in digital mammography, routine quality control measurements should include an evaluation of noise. The European Guidelines, for example, employ a second-order polynomial fit of pixel variance as a function of detector air kerma (DAK) to decompose noise into quantum, electronic and fixed pattern (FP) components and assess the DAK range where quantum noise dominates. This work examines the robustness of the polynomial method against an explicit noise decomposition method. The two methods were applied to variance and noise power spectrum (NPS) data from six digital mammography units. Twenty homogeneously exposed images were acquired with PMMA blocks for target DAKs ranging from 6.25 to 1600 µGy. Both methods were explored for the effects of data weighting and squared fit coefficients during the curve fitting, the influence of the additional filter material (2 mm Al versus 40 mm PMMA) and noise de-trending. Finally, spatial stationarity of noise was assessed.Data weighting improved noise model fitting over large DAK ranges, especially at low detector exposures. The polynomial and explicit decompositions generally agreed for quantum and electronic noise but FP noise fraction was consistently underestimated by the polynomial method. Noise decomposition as a function of position in the image showed limited noise stationarity, especially for FP noise; thus the position of the region of interest (ROI) used for noise decomposition may influence fractional noise composition. The ROI area and position used in the Guidelines offer an acceptable estimation of noise components. While there are limitations to the polynomial model, when used with care and with appropriate data weighting, the method offers a simple and robust means of examining the detector noise components as a function of detector exposure.