Biomedical subjects

R A Price

Publications and source records attributed to R A Price.

At least 19 recordsLinked to original sources

PubMed2006

Pitfalls and modelling inconsistencies in computational radiation dosimetry: lessons learnt from the QUADOS intercomparison. Part I: Neutrons and uncertainties.

The QUADOS EU cost shared action conducted an intercomparison on the usage of numerical methods in radiation protection and dosimetry. The eight problems proposed were intended to test the usage of Monte Carlo and deterministic methods by assessing the accuracy with which the codes are applied and also the methods used to evaluate uncertainty in the answer gained through these methods. The overall objective was to spread good practice through the community and give users information on how to assess the uncertainties associated with their calculated results.

Bayes Theorem↗

PubMed2006

Pitfalls and modelling inconsistencies in computational radiation dosimetry: lessons learnt from the QUADOS intercomparison. Part II: Photons, electrons and protons.

'QUADOS', a concerted action of the European Commission, has promoted an intercomparison aimed at evaluating the use of computational codes for dosimetry in radiation protection and medical physics. This intercomparison was open to all users of radiation transport codes. Eight problems were selected for their relevance to the radiation dosimetry community, five of which involved photon and proton transport. This paper focuses on a discussion of lessons learned from the participation in solving the photon and charged particle problems. The lessons learned from the participation in solving the neutron problems are presented in a companion paper (in this issue).

Angioplasty↗

PubMed2006

Extreme obesity is associated with attempted suicides: results from a family study.

This study was conducted to explore the association between attempted suicides and body mass index (BMI, kg/m2) in a family sample of 2547 individuals. As a comparison, a national NESARC (the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions) sample of 41 589 individuals was included to validate the observed association. Compared to average weight, extreme obesity showed significantly increased odds for attempted suicides both in family sample (odds ratio (OR) = 3.37 and 95% confidence interval (CI) = 1.59-7.13 for BMI = 40- < 50 kg/m2; OR = 3.85 and 95% CI = 1.71-8.66 for BMI > or = 50 kg/m2) and in NESARC sample (OR = 2.11 and 95% CI = 1.59-2.81 for BMI = 40- < 50 kg/m2; OR = 2.56 and 95% CI = 1.34-4.92 for BMI> or = 50 kg/m2) after adjustment for sociodemographic factors. Compared to general population, the risk for attempted suicide was 87 and 122% higher for those with BMI=40- < 50 and > or = 50 kg/m2, respectively. The pattern of results in the family and population studies indicates that extreme obesity is strongly associated with attempted suicide.

Black or African American↗

PubMed2005

Elongated beamlets: a simple technique for segment and MU reduction for sMLC IMRT delivery on accelerators utilizing 5 mm leaf widths.

The focus of this work is to demonstrate the effects of using an elongated beamlet to achieve similar dose conformity as achieved with a square beamlet while reducing the number of segments and subsequent MU required. A series of 10 patients were planned for IMRT delivery to the prostate using minimum beamlet sizes of 5x5 mm2 (default scheme), 10x5 mm2 with the short axis parallel to the prostate-rectum interface (scheme 1), and 10x5 mm2 with the short axis perpendicular to the prostate-rectum interface (scheme 2). All other parameters between plans were left unchanged. Plans were appropriately normalized and evaluated for R65, R40, conformity index, total number of segments and MU. All plans were generated using the Corvus inverse planning system. The average number of segments in this study decreased by approximately 49% for both schemes 1 and 2. The subsequent number of MU required decreased by approximately 34.6%. The resultant modified modulation scaling factor (MSFmod) decreased by approximately 34.3%. Additionally, we found that each isodose distribution using scheme 2 would still meet our clinical acceptance criteria with no visible degradation in the dose distribution as compared with the default scheme. In conclusion, we have demonstrated that it is possible to achieve similar results as those obtained using a 5x5 mm2 beamlet with respect to target coverage and critical structure sparing by using strategically oriented elongated beamlets. This technique directly translates to a decreased MSF(mod) allowing for decreased leakage dose to the patient, a decreased risk of exceeding secondary shielding limits in pre-existing vaults, and shorter treatment times.

Algorithms↗

PubMed2005

QUADOS intercomparison: a summary of photon and charged particle problems.

QUADOS, a Concerted Action of the European Commission, has promoted an intercomparison aimed at evaluating the use of computational codes for dosimetry in radiation protection and medical physics. This intercomparison was open to all users of radiation transport codes. Eight problems were selected for their relevance to the radiation dosimetry community, five of which involved photon and proton transport. This paper focuses on the analysis of the photon and charged particle problems. The neutron problems were presented in a paper at the NEUDOS9 conference.

Algorithms↗

PubMed2004

Dosimetric evaluation of MRI-based treatment planning for prostate cancer.

The purpose of this study is to evaluate the dosimetric accuracy of MRI-based treatment planning for prostate cancer using a commercial radiotherapy treatment planning system. Three-dimensional conformal plans for 15 prostate patients were generated using the AcQPlan system. For each patient, dose distributions were calculated using patient CT data with and without heterogeneity correction, and using patient MRI data without heterogeneity correction. MR images were post-processed using the gradient distortion correction (GDC) software. The distortion corrected MR images were fused to the corresponding CT for each patient for target and structure delineation. The femoral heads were delineated based on CT. Other anatomic structures relevant to the treatment (i.e., prostate, seminal vesicles, lymph notes, rectum and bladder) were delineated based on MRI. The external contours were drawn separately on CT and MRI. The same internal contours were used in the dose calculation using CT- and MRI-based geometries by directly transferring them between MRI and CT as needed. Treatment plans were evaluated based on maximum dose, isodose distributions and dose-volume histograms. The results confirm previous investigations that there is no clinically significant dose difference between CT-based prostate plans with and without heterogeneity correction. The difference in the target dose between CT- and MRI-based plans using homogeneous geometry was within 2.5%. Our results suggest that MRI-based treatment planning is suitable for radiotherapy of prostate cancer.

Humans↗

PubMed2004

Optimization of combined electron and photon beams for breast cancer.

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

Breast↗

PubMed2004

Monitor unit calculation for Monte Carlo treatment planning.

In this work, we investigate a formalism for monitor unit (MU) calculation in Monte Carlo based treatment planning. By relating MU to dose measured under reference calibration conditions (central axis, depth of dose maximum in water, 10 cm x 10 cm field defined at 100 cm source-to-surface distance) our formalism determines the MU required for a treatment plan based on the prescription dose and Monte Carlo calculated dose distribution. Detailed descriptions and formulae are given for various clinical situations including conventional treatments and advanced techniques such as intensity-modulated radiotherapy (IMRT) and modulated electron radiotherapy (MERT). Analysis is made of the effects of source modelling, beam modifier simulation and patient dose calculation accuracy, all of which are important factors for absolute dose calculations using Monte Carlo simulations. We have tested the formalism through phantom measurements and the predicted MU values were consistent with measured values to within 2%. The formalism has been used for MU calculation and plan comparison for advanced treatment techniques such as MERT, extracranial stereotactic IMRT, MRI-based treatment planning and intensity-modulated laser-proton therapy studies. It is also used for absolute dose calculations using Monte Carlo simulations for treatment verification, which has become part of our comprehensive IMRT quality assurance programme.

Dose-Response Relationship, Radiation↗

PubMed2004

Relationship of obesity to depression: a family-based study.

OBJECTIVE: To examine the relationship between obesity and depression in a sample of extremely obese individuals and their siblings and parents. SUBJECTS: A total of 1730 European Americans (558 men, 1172 women, aged 49.29+/-15.42 y, body mass index (BMI) of 35.57+/-11.53 kg/m(2)) and 373 African Americans (103 men, 270 women, aged 44.85+/-15.08 years, BMI of 36.83+/-11.31 kg/m(2)) in a sample of 482 nuclear families segregating extreme obesity and normal weight. MEASUREMENTS: Individual BMI, history of depression treatment and covariates (age, sex, race, education, marital status, socioeconomic status, chronic medical conditions and exercise program). RESULTS: Greater odds for depression were found for the obese, European American, women, the unmarried, the more educated, those with chronic physical disorder(s) and the offspring of depressed parents. A trend test found that the odds ratios for depression increased with BMI and number of chronic medical conditions (P<0.0001). Multivariate logistic regression analyses indicated that BMI, race, marital status, chronic medical conditions and family history were the predicators of depression for both the genders. Hierarchical analyses revealed that BMI significantly increased the risk above that predicated by the combined effects of all other variables. CONCLUSIONS: Extreme obesity was associated with the increased risk for depression across gender and racial groups, even after controlling for chronic physical disease, familial depression and demographic risk factors. More detailed research is needed to determine the underlying mechanisms.

Adolescent↗

PubMed2004

Intercomparison on the usage of computational codes in radiation dosimetry.

'QUADOS', a Concerted Action of the European Commission, has run an intercomparison aimed at evaluating the use of computational codes for dosimetry in radiation protection and medical physics. This intercomparison was open to all users of Monte Carlo, analytic and semi-analytic codes or deterministic methods. Its main aim was to provide a snapshot of the methods and codes currently in use. It also intended to furnish information on the methods used to assess the reliability of computational results and disseminate 'good practice' throughout the radiation dosimetry community. Eight problems were selected for their relevance to the radiation dosimetry community, three of which involve neutron transport. This paper focuses on the analysis of the neutron problems.

Algorithms↗

PubMed2003

Central neuro-inflammatory gene response following soman exposure in the rat.

Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.

Animals↗

PubMed2003

The sodium channel blocker RS100642 reverses down-regulation of the sodium channel alpha-subunit Na(v) 1.1 expression caused by transient ischemic brain injury in rats.

In this study we evaluated the expression of five sodium channel (NaCh) Alpha-subunit genes after transient middle cerebral artery occlusion (MCAo) in the rat and the effects of treatment with the NaCh blocker and experimental neuroprotective agent RS100642 as compared to the prototype NaCh blocker mexiletine. The expression of Na(v) 1.1, Na(v) 1.2, Na(v) 1.3, Na(v) 1.7, Na(v) 1.8 and the housekeeping gene beta-actin were studied in vehicle or drug-treated rats at 6, 24 and 48 h post-MCAo using real-time quantitative RT-PCR. RS100642 (1 mg/kg), mexiletine (10 mg/kg), or vehicle (1 ml/kg) was injected (i.v.) at 30 min, 2, 4, and 6 h post-injury. Following MCAo only the Na(v) 1.1 and Na(v) 1.2 genes were significantly down-regulated in the ipsilateral hemisphere of the injured brains. RS100642 treatment significantly reversed the down-regulation of Na(v) 1.1 (but not Na(v) 1.2) at 24-48 h post-injury. Mexiletine treatment, on the other hand, had no significant effect on the down-regulation of either gene. These findings demonstrate that treatment with a neuroprotective dose of RS100642 significantly reverses the down-regulation of Na(v) 1.1 caused by ischemic brain injury and suggests that RS100642 selectively targets the Na(v) 1.1 Alpha-subunit of the NaCh. Furthermore, our findings strengthen the hypothesis that ischemic injury may produce selective depletion of voltage-gated NaChs, and suggest that the Na(v) 1.1 NaCh Alpha-subunit may play a key role in the neuronal injury/recovery process.

Animals↗

PubMed2003

DNA fragmentation in leukocytes following subacute low-dose nerve agent exposure.

The objective of the present study was to determine levels of DNA fragmentation in blood leukocytes from guinea pigs by single-cell gel electrophoresis (comet assay) after exposure to the chemical warfare nerve agent (CWNA), soman, at doses ranging from 0.1 LD50 to 0.4 LD50, once per day for either 5 or 10 days. Post-exposure recovery periods ranged from 0 to 17 days. Leukocytes were imaged from each animal, and the images analyzed by computer. Data obtained for exposure to soman demonstrated significant increases in DNA fragmentation in circulating leukocytes in CWNA-treated guinea pigs compared with saline-injected control animals at all doses and time points examined. Notably, significantly increased DNA fragmentation was observed in leukocytes 17 days after cessation of soman exposure. Our findings demonstrate that leukocyte DNA fragmentation assays may provide a sensitive biomarker for low-dose CWNA exposure.

Animals↗

PubMed2003

Shielding evaluation for IMRT implementation in an existing accelerator vault.

A formalism is developed for evaluating the shielding in an existing vault to be used for IMRT. Existing exposure rate measurements are utilized as well as a newly developed effective modulation scaling factor. Examples are given for vaults housing 6, 10 and 18 MV linear accelerators. The use of an 18 MV Siemens linear accelerator is evaluated for IMRT delivery with respect to neutron production and the effects on individual patients. A modified modulation scaling factor is developed and the risk of the incurrence of fatal secondary malignancies is estimated. The difference in neutron production between 18 MV Varian and Siemens accelerators is estimated using Monte Carlo results. The neutron production from the Siemens accelerator is found to be approximately 4 times less than that of the Varian accelerator resulting in a risk of fatal secondary malignancy occurrence of approximately 1.6% when using the SMLC delivery technique and our measured modulation scaling factors. This compares with a previously published value of 1.6% for routine 3D CRT delivery on the Varian accelerator.

Air Pollutants, Radioactive↗

PubMed2001

A genome-wide scan suggests a locus on chromosome 1q21-q23 contributes to normal variation in plasma cholesterol concentration.

To identify genes that influence plasma cholesterol, triglyceride, and high-density and low-density lipoproteins concentrations we conducted a genome-wide scan using 354 polymorphic markers spaced at 10-cM intervals in 75 obese but otherwise normal human families. The results of the genome scan using sibling pair analysis of quantitative phenotypes suggested that 1q21-q23 contains a locus that influences plasma cholesterol concentration. Chromosome 12 gave evidence of linkage to plasma triglyceride concentration (D12SPAH) and chromosomes 3, 6, 7, 10, 11, 17, and 20 yielded additional evidence of linkage for lipid phenotypes at lower levels of statistical significance. Allele sharing for markers near prominent candidate genes was either very weakly related or unrelated to sibling similarity for lipid concentrations. Together these results suggest that genes with important roles in regulating normal cholesterol and triglyceride concentrations do not coincide with the location of previously known candidate genes.

Adult↗

PubMed2001

A locus affecting obesity in human chromosome region 10p12.

AIMS/HYPOTHESIS: Obesity is a complex trait influenced by multiple genes. We evaluated linkage in three regions of human chromosome 10 previously linked to obesity-related phenotypes. METHODS: We conducted non-parametric linkage analysis of obesity-related phenotypes in cohorts of 170 European-American and 43 African-American families having extremely obese and normal weight subjects. RESULTS: We found support for linkage of an obesity phenotype (BMI > or = 27 kg/m2) in both cohorts, as well as in a combined analysis (European-American cohort, Z = 1.90, p = 0.03; African-American cohort, Z = 2.25, p = 0.014; combined cohort, Z = 2.55, p = 0.005). CONCLUSION/INTERPRETATION: These results confirm previous reports of linkage in French and German families. The consistency of results across these four cohorts supports the localization of a quantitative trait locus influencing obesity to human chromosome region 10p12.

Black People↗

PubMed2001

Nutrient preference and diet-induced adiposity in C57BL/6ByJ and 129P3/J mice.

Purified carbohydrates and fats are usually palatable to humans and other animals, and their consumption often induces weight gain and accumulation of fat. In this study, we examined consumption of complex carbohydrates (cornstarch and Polycose) and fats (soybean oil and margarine) in mice from two inbred strains, C57BL/6ByJ and 129P3/J. At lower concentrations of liquid nutrients tested using two-bottle tests, when the amounts consumed had negligible energy content, the C57BL/6ByJ mice had higher acceptance of Polycose and soybean oil. This was probably due to strain differences in chemosensory perception of Polycose and oil. At higher concentrations, the mice consumed a substantial part of their daily energy from the macronutrient sources, however, there were no or only small strain differences in nutrient consumption. These small differences were probably due to strain variation in body size. The two strains also did not differ in chow intake. Despite similar energy intakes, access to the nutrients resulted in greater body weight (BW) gain in the C57BL/6ByJ mice than in the 129P3/J mice. The diet-induced weight gain was examined in detail in groups of 2-month-old C57BL/6ByJ and 129P3/J mice given ether chow, or chow and margarine to eat. Access to margarine did not increase total energy consumption of either strain. It increased BW and adiposity of the C57BL/6ByJ mice, but only after they reached the age of approximately 3 months. There were no differences in BW and adiposity between control and margarine-exposed 129P3/J mice. The results suggest that diet-induced adiposity in the B6 mice depends on age and does not depend on hyperphagia.

Animals↗

PubMed2001

Leptin resistance is associated with extreme obesity and aggregates in families.

OBJECTIVE: To examine the determinants of plasma leptin levels and leptin resistance in a sample of extremely obese subjects and their relatives. DESIGN AND METHOD: We obtained plasma leptin values on 968 individuals from 218 families having both extremely obese and average weight members for obesity related variables. Multivariate regression analyses were used to identify predictors of both plasma leptin concentration and an index of leptin resistance. Family correlations and heritabilities were computed for plasma leptin and indices of leptin resistance. RESULTS: Body mass index and sex predicted 63% of the variance in plasma leptin. Extremely obese subjects were most likely and average weight subjects least likely to be leptin resistant. Both leptin and leptin resistance aggregated within families. CONCLUSION: Leptin resistance is strongly associated with extreme obesity and appears to be a heritable trait. The determination of its genetic causes will aid in understanding the role of leptin in common forms of human obesity.

Adult↗