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Biomedical subjects

R J Stanley

Publications and source records attributed to R J Stanley.

At least 19 recordsLinked to original sources

Microarray image spot segmentation using the method of projections.

Microarray technology is increasingly used as a means of high throughput analysis of human, non-human and plant genomes. Manual methods of array production using this technology lead to many inherent problems in the microarray image produced. The density of the spots in the images produced is very high, such that neighboring spots can overlap. The image background is often not uniform, containing noise that is often difficult to distinguish from actual spots. In this research, a projections-based approach is investigated for spot segmentation in paired radio probe microarray images. An important aspect of spot segmentation is the capability to perform corresponding spot-to-spot comparisons between the paired images. Experimental results are presented for spot segmentation in isolated and paired microarray images.

Algorithms↗

Evidence of powerful substrate electric fields in DNA photolyase: implications for thymidine dimer repair.

DNA photolyase is a flavoprotein that repairs cyclobutylpyrimidine dimers by ultrafast photoinduced electron transfer. One unusual feature of this enzyme is the configuration of the FAD cofactor, where the isoalloxazine and adenine rings are nearly in vdW contact. We have measured the steady-state and transient absorption spectra and excited-state decay kinetics of oxidized (FAD-containing, folate-depleted) Escherichia coli DNA photolyase with and without dinucleotide and polynucleotide single-stranded thymidine dimer substrates. The steady-state absorption spectrum for the enzyme-polynucleotide substrate complex showed a blue shift, as seen previously by Jorns et al. (1). No shift was observed for the dinucleotide substrate, suggesting that there are significant differences in the binding geometry of dinucleotide versus polynucleotide dimer lesions. Evidence was obtained from transient absorption experiments for a long-lived charge-transfer complex involving the isoalloxazine of the FAD cofactor. No evidence of excited-state quenching was measurable upon binding either substrate. To explain these data, we hypothesize the existence of a large substrate electric field in the cavity containing the FAD cofactor. A calculation of the magnitude and direction of this dipolar electric field is consistent with electrochromic band shifts for both S(0) --> S(1) and S(0) --> S(2) transitions. These observations suggest that the substrate dipolar electric field may be a critical component in its electron-transfer-mediated repair by photolyase and that the unique relative orientation of the isoalloxazine and adenine rings may have resulted from the consequences of the dipolar substrate field.

DNA Damage↗

Advances in flavin and flavoprotein optical spectroscopy.

Flavins and flavoproteins are versatile redox cofactors that can perform both one- and two-electron transfer. Because they are highly colored in all three oxidation states, optical spectroscopy has been exploited for decades to study these redox changes. This review summarizes the application of optical spectroscopies to flavins and flavoproteins since 1990. Special emphasis is placed on new techniques, such as Stark spectroscopy, as well as significant refinements in more well known techniques, such as resonance Raman spectroscopy and ultrafast spectroscopy.

DNA Repair↗

A radius of curvature-based approach to cervical spine vertebra image analysis.

Radiologists interpret the normality of vertebras within cervical spine x-rays for determining the presence of osteoporosis. Features relating to vertebra fracture such as contrasting anterior and posterior heights are used in the vertebra normality assessment. Vertebra distortion along the anterior boundary can be used as an indicator of vertebra normality. As the vertebra becomes less normal in appearance, the vertebra boundary increasingly deviates from the general rectangular shape. This research introduces a radius of curvature-based approach to quantify the distortion in vertebra boundary shape for anterior osteophytes classification of vertebras within cervical spine x-ray images. An adaptive histogram analysis technique is used to enhance the vertebras within cervical spine x-ray images to facilitate vertebra feature extraction. A least squares technique is used for calculating the radii of curvature along the vertebra boundary. Radius of curvature and gray-level based features are computed using the anterior boundary point position with the minimum radius of curvature as the reference. A total of 118 cervical spine vertebras are used for training and testing various classifiers including a standard back propagation neural network, K-Means algorithm, quadratic discriminant classifier and LVQ3. The results from those classifiers are reported for recognizing vertebras as normal or abnormal.

Artificial Intelligence↗

Data-driven homologue matching for chromosome identification.

Karyotyping involves the visualization and classification of chromosomes into standard classes. In "normal" human metaphase spreads, chromosomes occur in homologous pairs for the autosomal classes 1-22, and X chromosome for females. Many existing approaches for performing automated human chromosome image analysis presuppose cell normalcy, containing 46 chromosomes within a metaphase spread with two chromosomes per class. This is an acceptable assumption for routine automated chromosome image analysis. However, many genetic abnormalities are directly linked to structural or numerical aberrations of chromosomes within the metaphase spread. Thus, two chromosomes per class cannot be assumed for anomaly analysis. This paper presents the development of image analysis techniques which are extendible to detecting numerical aberrations evolving from structural abnormalities. Specifically, an approach to identifying "normal" chromosomes from selected class(es) within a metaphase spread is presented. Chromosome assignment to a specific class is initially based on neural networks, followed by banding pattern and centromeric index criteria checking, and concluding with homologue matching. Experimental results are presented comparing neural networks as the sole classifier to our homologue matcher for identifying class 17 within normal and abnormal metaphase spreads.

Chromosome Banding↗

Two-photon excitation of 4'-hydroxymethyl-4,5',8-trimethylpsoralen.

Psoralens are a class of pharmaceutical agents commonly used to treat several cutaneous disorders. When irradiated with a mode-locked titanium: sapphire (Ti:sapphire) laser tuned to 730 nm, an aqueous solution of 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) emits blue light. The emission spectrum is centered at 452 nm and is identical to that obtained by one-photon excitation with UVA excitation, and its magnitude depends quadratically on the intensity of laser excitation. These results suggest that two-photon excitation occurs to a potentially photochemically active state. To estimate the two-photon absorption cross section, it was first necessary to measure the emission quantum yield of HMT using 365 nm excitation at room temperature that resulted in a value of 0.045 +/- 0.007. The two-photon absorption cross section of HMT at 730 nm is therefore estimated to be 20 x 10(-50) cm4 s (20 Göppert-Mayer). The excited-state photophysics and photochemistry of psoralens suggest potential applications to cutaneous phototherapy in diseases such as psoriasis and dystrophic epidermolysis bullosa.

Aluminum Oxide↗

Homologue matching using the Choquet integral.

Automated Giemsa-banded chromosome image research has been largely restricted to classification schemes associated with isolated chromosomes within metaphase spreads. In normal human metaphase spreads, there are 46 chromosomes occurring in homologous pairs for the autosomal classes, 1-22, and X chromosome for females. For optimizing automated human chromosome image analysis, many existing techniques assume cell normalcy. With many genetic abnormalities directly linked to structural and numerical aberrations of chromosomes within the metaphase spread, the two chromosome per class assumption may not be appropriate for anomaly analysis. At the University of Missouri, a data-driven homologue matching approach has been developed to identify all normal chromosomes within a metaphase spread from a selected class. Chromosome assignment to a specific class is initially based on neural networks, followed by banding pattern and centromeric index criteria checking, and concluding with homologue matching utilizing a density profile-based classifier, a shape profile-based classifier, and a binary band profile-based classifier. Based on preliminary results for the profile-based classifiers assigning chromosome 17, the Choquet integral is presented as an extension to the homologue matching approach. Experimental results are presented comparing the extended homologue matching approach to the transportation algorithm for identifying chromosome 21 within normal metaphase spreads.

Chromosome Aberrations↗

The effects of image manipulation on automated karyotyping.

Karyotyping is one of the standard tools for human genetic investigations. Karyotyping involves the classification and interpretation of chromosomes found in a metaphase spread. As part of the automated karyotyping process, image manipulation is required for appropriately positioning metaphase spread chromosomes in their corresponding karyotype. Image manipulation, specifically image rotation, reorganizes the grey-level information within chromosomes to facilitate analysis. Statistical tests are performed to compare features related to banding pattern and length between unmanipulated chromosomes and corresponding rotated chromosomes. Based on experimental results, reorganizing the grey-level information yields statistically different chromosome features. Depending on the purpose of chromosome image analysis, the interpretation process of karyotyping could be impaired with chromosome feature distortion due to image rotation.

Humans↗

Endoscopic therapy for organized pancreatic necrosis.

BACKGROUND & AIMS: The treatment of patients with extensive pancreatic necrosis remains controversial; a subpopulation of patients with extensive acute pancreatic necrosis develop complex, organized collections. This study examined the feasibility of endoscopic drainage in patients with extensive organized pancreatic necrosis. METHODS: Eleven patients with organized pancreatic necrosis (8 sterile and 3 infected) after severe acute necrotizing pancreatitis underwent attempted endoscopic drainage. Dynamic contrast-enhanced computerized tomography showed > or = 50% pancreatic necrosis in 10 of 11 patients in whom endoscopic drainage was performed. In 8 patients, an intrapancreatic nasobiliary lavage catheter was placed into the collection concurrently with 10F stents. RESULTS: Complete resolution was achieved nonoperatively in 9 patients. At a mean follow-up of 12 months, 1 patient developed a pseudocyst, which was successfully drained endoscopically. Complications occurred in 5, including bleeding that precluded entry into one collection. CONCLUSIONS: Endoscopic therapy may be a viable management option for a subset of patients who remain symptomatic after an episode of acute pancreatic necrosis after the necrosis has become organized and partially liquefied. Intrapancreatic lavage catheter placement is essential to the success of this procedure. Further evaluation of this technique is needed before this method can be adopted into clinical practice.

Adolescent↗

Centromere attribute integration based chromosome polarity assignment.

Automated karyotyping involves evaluating quantified chromosome attributes for proper classification. Chromosome attributes derived from the banding pattern require the correct chromosome polarity for correct banding sequence interpretation. Chromosome polarity is defined in terms of determining the short and long arms of the chromosome using the centromere as the reference point for measuring the chromosome length on both sides of the centromere. In addition to banding sequence interpretation, polarity is used in the chromosome orientation for chromosome repositioning from the metaphase spread to the karyotype. Automated polarity determination is often not performed for classifying chromosomes in the metaphase spread image. Polarity may be determined user interactively, by the system, or not at all. In order to reduce the computational complexity of evaluating banding sequence features using both chromosome ends as reference points, there is a need to improve chromosome polarity determination in automated karyotyping. A centromere attribute integration approach has been developed at the University of Missouri-Columbia which performs correct chromosome polarity assessment at a rate comparable to other studies of 96.1% on a diversified data set.

Algorithms↗

Tonsil cancer. Patterns of failure after surgery alone and surgery combined with postoperative radiation therapy.

BACKGROUND: The authors determined the patterns of treatment failure in patients treated with surgery alone or surgery combined with postoperative radiation therapy for squamous cell carcinoma of the tonsil. METHODS: Seventy-two patients underwent surgery alone (56) or surgery and postoperative adjuvant radiation therapy (16). All patients were followed up until death (40 patients) or for a minimum of 3.5 years. For patients treated with surgery alone, clinic notes, operative notes, and pathology reports and slides were reviewed to identify clinical or pathologic predictors of recurrence above the clavicles, cause-specific survival, and overall survival. For patients undergoing postoperative adjuvant radiation therapy, demographic, treatment, and pathologic variables were analyzed to identify factors associated with control of disease above the clavicles, disease-free survival, and overall survival. RESULTS: The main pattern of treatment failure was above the clavicles. It occurred in 39% of patients treated with surgery alone and was significantly related (P = 0.002) to the overall clinical TNM stage. Disease recurrence above the clavicles occurred in 31% of patients undergoing surgery and postoperative adjuvant radiation therapy, despite their more advanced neck disease. Five-year overall survival for patients with clinical Stage III and IV disease who were treated with surgery and post-operative adjuvant radiation therapy was 100% and 78%, respectively. Five-year overall survival for patients treated with surgery alone who had clinical Stage III, IVA, or IVB disease was 56%, 43%, and 50%, respectively. CONCLUSION: We recommend postoperative adjuvant radiation therapy for patients with clinical Stage III or IV squamous cell carcinoma of the tonsil who have undergone complete surgical resection because this appears to improve control of disease above the clavicles and overall survival.

Adult↗

Primary head and neck cancer. Histopathologic predictors of recurrence after neck dissection in patients with lymph node involvement.

OBJECTIVE: Retrospectively analyze several histopathologic variables that may predict neck recurrence after neck dissection. DESIGN: From 1970 through 1980, 284 patients with pathologically confirmed metastatic squamous cell carcinoma underwent neck dissection and received no adjuvant therapy. Kaplan-Meier evaluation estimated a 74% 2-year neck recurrence-free rate. After adjusting for the standard covariates of age, gender, neck stage, and tumor grade, we also controlled for the time-dependent covariates of primary recurrence, occurrence in the side of the neck not operated on, or development of new head and neck primary disease. SETTING: A large referral-based practice. RESULTS: The number of lymph nodes involved, invasion of vascular/lymphatic space, invasion of soft tissue, and desmoplastic lymph node pattern adversely affect neck recurrence. A desmoplastic stromal pattern was associated with almost a sevenfold increased risk of neck recurrence. To our knowledge, this finding has not been reported previously. CONCLUSION: Histopathologic evaluation of metastatically involved cervical nodes can identify patients with head and neck cancer who are at high risk for recurrence.

Adult↗

Colliding forces in radiology: technologic imperative, resource limitations, and accountability demands.

Advances in radiology over the past 20 years are the product of a technologic imperative that has produced new approaches to the acquisition of medical images and modifications to conventional approaches. The imperative has placed radiology at the leading edge of the computer-technology era of modern medicine and has also produced several big-ticket technologies that have been identified as major contributors to rising health care costs. Consequently, the demands for quantitative data on the impact and cost-effectiveness of the use of these technologies in the clinical arena are increasing. Meeting the growing demand for accountability in radiology requires that the discipline adopt innovative approaches for assessing its technologies and acquire new types of data, including documentation of cost savings accrued by selective use of radiologic technologies and demonstration of the efficiency and cost-effectiveness of triage schemes that lead to more effective decision making. The requirement of quantitative accountability represents a new way of doing business for radiology and a new approach to management for those responsible for business.

Cost-Benefit Analysis↗