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Biomedical subjects

Angela Davies

Publications and source records attributed to Angela Davies.

13 recordsLinked to original sources

Self-calibration for transmitted wavefront measurements.

Micro-optic components and subsystems are becoming increasingly important in optical sensors, communications, data storage, and many other diverse applications. To adequately predict the performance of the final system, it is important to understand the element's effect on the wavefront as it propagates through the system. The wavefront can be measured using interferometric means, however, random and systematic errors contribute to the measurement. Self-calibration techniques exploit symmetries of the measurement or averaging techniques to separate the systematic errors of the instrument from the errors in the test lens. If the transmitted wavefront of a ball lens is measured in a number of random orientations and the measurements are averaged, the only remaining deviations from a perfect wavefront will be spherical aberration from the ball lens and the systematic errors of the interferometer. If the radius, aperture, and focal length of the ball lens are known, the spherical aberration can be calculated and subtracted, leaving only the systematic errors of the interferometer. We develop the theory behind the technique and illustrate the approach with a description of the calibration of a microinterferometer used to measure the transmitted wavefront error of micro-optics.

Journal Article↗

Modeling the interferometric radius measurement using Gaussian beam propagation.

We model the interferometric radius measurement using Gaussian beam propagation to identify biases in the measurement due to using a simple geometric ray-trace model instead of the more complex Gaussian model. The radius measurement is based on using an interferometer to identify the test part's position when it is at two null locations, and the distance between the positions is an estimate of the part's radius. The null condition is observed when there is no difference in curvature between the reflected reference and the test wavefronts, and a Gaussian model will provide a first-order estimate of curvature changes due to wave propagation and therefore changes to the radius measurement. We show that the geometric ray assumption leads to radius biases (errors) that are a strong function of the test part radius and increase as the radius of the part decreases. We tested for a bias for both microscaled (<1 mm) and macroscaled parts. The bias is of the order of parts in 10(5) for micro-optics with radii a small fraction of a millimeter and much smaller for macroscaled optics. The amount of bias depends on the interferometer configuration (numerical aperture, etc.), the nominal radius of the test part, and the distances in the interferometer.

Journal Article↗

Effective wavelength calibration for moiré fringe projection.

The fringe patterns seen when using moiré instruments are similar to the patterns seen in traditional interferometry but differ in the spacing between consecutive fringes. In traditional interferometry, the spacing is constant and related to the wavelength of the source. In moiré fringe projection, the spacing (the effective wavelength) may not be constant over the field of view and the spacing depends on the system geometry. In these cases, using a constant effective wavelength over the field of view causes inaccurate surface height measurements. We examine the calibration process of the moiré fringe projection measurement, which takes this varying wavelength into account to produce a pixel-by-pixel wavelength map. The wavelength calibration procedure is to move the object in the out-of-plane direction a known distance until every pixel intensity value goes through at least one cycle. A sinusoidal function is then fit to the data to extract the effective wavelength pixel by pixel, yielding an effective wavelength map. A calibrated step height was used to validate the effective wavelength map with results within 1% of the nominal value of the step height. The error sources that contributed to the uncertainty in determining the height of the artifact are also investigated.

Journal Article↗

Correcting for stage error motions in radius measurements.

Traceable radius of curvature measurements are critical for precision optics manufacturing. An optical bench measurement is repeatable and is the preferred method for low-uncertainty applications. With an optical bench, the displacement of the optic is measured as it is moved between the cat's eye and the confocal positions, each identified using a figure measuring interferometer. The translated distance is nominally the radius of curvature; however, errors in the motion of the stage add a bias to the measurement, even if the error motions are zero on average. Estimating the bias and resulting measurement uncertainty is challenging. We have developed a new mathematical definition of the radius measurand that intrinsically corrects for error motion biases and also provides a means of representing other terms such as figure error-correction, wave-front aberration biases, displacement gauge calibration and their uncertainties. With this formalism, it is no long necessary to design a high-quality radius bench to carry out a precision measurement; rather a lower quality is adequate, provided that error motions are repeatable and characterized and error motion measurement uncertainties are estimated.

Journal Article↗

Integration of novel therapeutics into combined modality therapy of locally advanced non-small cell lung cancer.

Novel therapeutic agents (NTA) directed against a wide array of newly described molecular targets are now entering clinical investigation, many in the treatment of non-small cell lung cancer (NSCLC). The great majority of these clinical trials have been directed toward patients with advanced stage (metastatic) disease. More recently, study of NTAs has turned toward earlier-stage disease. Locally advanced, or stage III, NSCLC represents a large and heterogeneous group of patients and several clinically distinct substages. During the last 15 years, randomized clinical trials have shown improved survival with sequential chemoradiation compared with radiation alone and, more recently, the superiority of concurrent versus sequential chemoradiation. As NTAs have increasingly shown clinical activity against NSCLC, questions of how to incorporate them into clinical trials in stage III disease, whether they should be given together with radiotherapy, substituting for chemotherapy, or whether they should be added to current chemoradiation strategies, all remain as issues. Here, we describe conceptual issues, preclinical rationale, and ongoing or planned clinical trials incorporating NTAs into current treatment paradigms for unresectable stage III NSCLC.

Antineoplastic Agents↗

Optimisation and evaluation of a high-throughput mammalian protein expression system.

Transient transfection of mammalian cells with episomal vectors is a very useful method for producing high levels of recombinant proteins. Transient systems remove the need for the laborious and time-consuming process of creating stable cell lines. Here, we describe the optimisation and evaluation of a high-throughput transient expression system in HEK293-EBNA cells. The process was developed for the expression of 10 constructs simultaneously in deep-well plates and subsequent purification using 96-well plate affinity chromatography. This enabled multiple combinations of different constructs, vectors, and expression conditions to be studied in parallel.

Animals↗

Deletion of the distal long arm of chromosome 10; is there a characteristic phenotype? A report of 15 de novo and familial cases.

It has been suggested previously that patients with terminal deletions of chromosome 10q have a recognizable phenotype including a characteristic facial appearance combined with other abnormalities including mental retardation, cardiac and anogenital anomalies. We report the largest published series of new cases of terminal 10q deletion, including eight familial and four de novo cases and three cases with interstitial deletions involving chromosome bands 10q25.2-26.3. The deleted regions were defined by FISH using YAC probes, as well as standard karyotyping. The most consistent clinical features in our cases are cranial anomalies including facial asymmetry, prominent nose and nasal bridge, prominent ears, thin upper lip, along with growth retardation, developmental delay, and digital abnormalities. Visceral abnormalities were only identified in a small number of the patients, with renal involvement in three cases and structural cardiac malformations in two others. Learning difficulties of varying severity were found in 11 cases and behavioral problems described in four. Candidate genes for behavioral and learning difficulties within the deleted region include Calcyon. Other genes in the region that might have a role in causing the phenotype include the genes coding for fibroblast growth factor receptor type 2 (FGFR2) and C-terminal binding protein 2 (CTBP2).

Abnormalities, Multiple↗

Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region.

Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.

Anophthalmos↗

Current and future therapeutic approaches in locally advanced (stage III) non-small cell lung cancer.

In the treatment of locally advanced (stage III) non-small cell lung cancer, randomized clinical trials have shown that sequential administration of platinum-based chemotherapy followed by radiotherapy improves outcome compared with radiotherapy alone. More recently, concurrent chemoradiotherapy has been shown to be superior to sequential therapy. Incorporating full-dose chemotherapy into induction or consolidation phases is aimed at the eradication of distant micrometastases. These approaches are currently being examined in clinical trials. The role of neoadjuvant and adjuvant therapy in resectable stage IIIA patients remains controversial. Integration of newer cytotoxic agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) and molecularly targeted agents into the treatment of stage-III patients may result in improved long-term outcomes and is currently under study.

Antineoplastic Combined Chemotherapy Protocols↗

Concurrent chemoradiation strategies in the management of unresectable stage III non-small-cell lung cancer.

Locally advanced or unresectable stage III non-small-cell lung cancer (NSCLC) patients treated with combined-modality therapy with chemotherapy plus thoracic radiation have improved survival compared to those treated with radiotherapy alone. Furthermore, recent studies in good performance status, stage III patients have shown that concurrent chemoradiotherapy improves survival compared to sequential chemoradiotherapy. However, the optimal chemoradiation approach continues to evolve and is the subject of this review. Since the majority of patients completing chemoradiotherapy will succumb to distant metastatic disease, active systemic agents targeting this tumor compartment are required. Recent data suggest that full-dose chemotherapy designed to eradicate distant micrometastases given either as induction or consolidation has the potential to yield improved patient outcomes. Many of these chemotherapeutic agents are also potent radiosensitizers, hence providing enhanced local control. The integration of these chemotherapeutic agents into chemoradiotherapy programs in stage III NSCLC is the focus of current trials. Ongoing research with novel therapeutic agents with activity against distant micrometastases, refined radiation techniques, and enhanced imaging methodologies to aid in accurate staging are being pursued and should lead to improved survival and toxicity outcomes in this disease.

Journal Article↗

Invasiveness in chickens, stress resistance and RpoS status of wild-type Salmonella enterica subsp. enterica serovar typhimurium definitive type 104 and serovar enteritidis phage type 4 strains.

The heat and acid resistance and the ability to survive airdrying on commonly used kitchen surfaces were assessed for clinical and environmental strains of Salmonella enterica subsp. enterica serovar Typhimurium, definitive type (DT) 104. Three out of thirty-eight strains of DT 104 were found to be more sensitive in stationary phase to the stresses examined than the other strains. This compares to a previous study by the authors which showed that seven out of forty serovar Enteritidis phage type (PT) 4 strains were more sensitive. RpoS activity was examined indirectly in selected strains of DT 104 and PT 4. In those with normal stress resistance a 100-fold induction of an RpoS-dependent spvR/A:'::luxCDABE fusion was observed upon entry into stationary phase. The sensitive strains examined showed either no induction or a reduced level of spvR/A:'::luxCDABE expression. The rpoS gene was sequenced from these strains and three were found to harbour mutations including one deletion, one base-pair substitution resulting in a nonsense codon, and one insertion causing a frameshift resulting in an early stop codon. Strains with negligible or reduced spvR/A:'::luxCDABE expression had low stress resistance. All strains of DT 104 could be recovered from liver and spleen tissues of infected hens 14 d post-infection, but one with no induction of spvR/A:'::luxCDABE expression was significantly less likely to be recovered from chicken reproductive tissues, liver or spleen than the majority of other strains, including one with reduced spvR/A:'::luxCDABE expression. This work has demonstrated that clinical and environmental strains of DT 104 and PT 4 not infrequently harbour mutations in the rpoS allele. It is possible that the rpoS mutations may have occurred during the initial isolation of the strains. The ability of a strain to cause infection, however, also depends on factors such as host susceptibility and dose.

Animals↗

An evaluation of barriers to accrual in the era of legislation requiring insurance coverage of cancer clinical trial costs in California.

PURPOSE: Clinical trials are essential to improve cancer therapy, but only 3% of newly diagnosed adult cancer patients enroll annually. We previously conducted a prospective analysis of factors affecting trial accrual at the UC Davis Cancer Center between 1997 and 2000. It was found that the accrual rate was 14% and that patients with private insurance were significantly less likely than patients with government insurance to enroll, suggesting that fear of insurance denial was a barrier. In 2002, a new California law (SB37) required insurers to reimburse routine costs of care for cancer trials. METHODS: To assess the impact of SB37 on accrual, we repeated our study using the same sur vey instrument. Oncologists seeing new patients at the UC Davis Cancer Center from August to November 2002 completed questionnaires that inquired about patient characteristics and eligibility, protocol availability, and patient willingness to participate. RESULTS: Physicians considered clinical trials for 55% (118/216) of patients, but trials were available for only 53% (62/118). Eligibility criteria were met by 82% (51/62). Of these, 69% (35/51) agreed to participate (vs 51% previously). No patient declined to participate because of insurance limitations (vs 8% previously). Furthermore, insurance type was no longer a significant factor in determining whether patients would enroll. This suggests that although the overall rate of accrual is only slightly increased after passage of SB37, patients may be more willing to enroll. Efforts to increase participation must include enhancing physician and patient awareness of SB37.

Adolescent↗

Nursing a patient with frostbite.

Frostbite is a condition that is associated with people living in countries with an extremely cold climate. However, it can affect people in the UK who are involved in winter sports, and is also associated with the homeless, people with a psychiatric illness, and those who misuse drugs and alcohol. Angela Davies describes the assessment and management of a patient with frostbite and identifies the challenges of managing these complex tissue injuries

Adult↗