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1.  How do respiratory state and measurement method affect bra size calculations? 
British Journal of Sports Medicine  2006;40(12):970-974.
Objectives
To investigate the effects of respiratory state and measurement method on bra size calculation.
Methods
The bra sizes of 16 large‐breasted women were measured during two respiratory states, end voluntary inspiration and relaxed voluntary expiration, and using two sizing methods, which were compared against subject‐reported bra sizes.
Results
Both respiratory state and measurement method significantly affected bra size estimations, whereby measuring chest circumference during inspiration increased both band and decreased cup size. However, whereas bra size calculated using the standard method differed significantly from subject‐reported bra size, cup size calculated using the breast hemi‐circumference method did not differ significantly from subject‐reported cup size.
Conclusions
As respiratory state significantly affects bra sizes, it should be standardised during bra size measurements. A more valid and reliable bra sizing method should be developed, possibly using the breast hemi‐circumference method for cup size estimations and raw under‐bust chest circumference values for band size.
doi:10.1136/bjsm.2005.025171
PMCID: PMC2577461  PMID: 17021004
2.  Breast size, bra fit and thoracic pain in young women: a correlational study 
Introduction
A single sample study was undertaken to determine the strength and direction of correlations between: a) breast size and thoracic spine or posterior chest wall pain; b) bra fit and thoracic spine or posterior chest wall pain and; c) breast size and bra fit, in thirty nulliparous women (18–26 years), with thoracic spine or posterior chest wall pain, who wore bras during daytime.
Measures
Pain (Short Form McGill Pain Questionnaire), bra size (Triumph International), bra fit (Triumph International).
Results
Most (80%) women wore incorrectly sized bras: 70% wore bras that were too small, 10% wore bras that were too large. Breast size was negatively correlated with both bra size (r = -0.78) and bra fit (r = -0.50). These results together indicate that large breasted women were particularly likely to be wearing incorrectly sized and fitted bras. Negligible relationships were found between pain and bra fit, and breast size and pain. Menstrual cycle stage was moderately positively correlated with bra fit (r = 0.32).
Conclusion
In young, nulliparous women, thoracic pain appears unrelated to breast size. Bra fit is moderately related to stage of menstrual cycle suggesting that this research may be somewhat confounded by hormonal changes or reproductive stage. Further research is needed to clarify whether there is a relationship between breast size or bra fit and thoracic pain in women during times of hormonal change.
doi:10.1186/1746-1340-16-1
PMCID: PMC2275741  PMID: 18339205
3.  Assessing the benefit:risk ratio of a drug - randomized and naturalistic evidence 
Randomized evidence from clinical trials and naturalistic evidence collected from pharmacoepidemiology and pharmacovigilance activities both contribute to the initial and continuous assessment of the benefits and risks of a drug, ie, the balance between therapeutic efficacy and safety risks. Benefit-risk assessment (BRA) mainly relies on a qualitative assessment of quantitative data. Current attempts to quantify BRA are reviewed and discussed, along with the expectations of regulatory authorities such as the Food and Drug Administration and the European Medicines Agency. No method provides a fully satisfactory solution regarding BRA, because it is difficult to reduce its multidimensional aspect to simple metrics, in a context where other therapeutic alternatives play a role. Consistency and transparency are key in this assessment, which is performed throughout the whole drug life cycle. BRA is mainly based on randomized clinical studies during clinical development, and it is continued and consolidated by naturalistic data once the drug is on the market.
PMCID: PMC3181998  PMID: 21842615
benefit risk; efficacy; safety; drug development; benefit:risk ratio; BRA
4.  A Simple Algorithm for Immediate Postmastectomy Reconstruction of the Small Breast—A Single Surgeon's 10-Year Experience 
Eplasty  2012;12:e55.
Introduction: Immediate small breast reconstruction poses challenges including limited potential donor site tissues, a thinner skin envelope, and limited implant choice. Few patients are suitable for autologous reconstruction while contralateral symmetrization surgery that often offsets the problem of obvious asymmetry in thin and small-breasted patients is often unavailable, too expensive, or declined by the patient. Methods: We reviewed 42 consecutive patients with mastectomy weights of 350 g or less (the lowest quartile of all reconstructions). Indications for the mastectomy, body mass index, bra cup size, comorbidity, reconstruction type, and complications were recorded. Results: A total of 59 immediate reconstructions, including 25 latissimus dorsi flaps, 23 implant-only reconstructions, 9 abdominal flaps, and 2 gluteal flaps, were performed in 42 patients. Of the 42 mastectomies, 4 were prophylactic. Forty-three percent of patients had immediate contralateral balancing surgery. The average mastectomy weight was 231 g (range, 74-350 g). Seven percent of implant-based reconstructions developed capsular contracture requiring further surgery. One free transverse rectus abdominus myocutaneous flap failed because of fulminant methicillin resistant staphylococcus aureus septicaemia. Discussion and Conclusion: Balancing contralateral surgery is key in achieving excellent symmetry in reconstruction small-breasted patients. However, many patients wish to avoid contralateral surgery, thus restricting a surgeon's reconstructive options. Autologous flaps, traditionally, had not been considered in thinner women because of inadequacy of donor site tissue, but in fact, often, as with larger-breasted patients, produce superior cosmetic results. We propose a simple algorithm for the reconstruction of small-breasted women (without resorting to super-complex microsurgery), which is designed to tailor the choice of reconstructive technique to the requirements of the individual patient.
PMCID: PMC3521473  PMID: 23308302
5.  Specific transcripts are elevated in Saccharomyces cerevisiae in response to DNA damage. 
Molecular and Cellular Biology  1984;4(11):2356-2363.
Differential hybridization has been used to identify genes in Saccharomyces cerevisiae displaying increased transcript levels after treatment of cells with UV irradiation or with the mutagen/carcinogen 4-nitroquinoline-1-oxide (NQO). We describe the isolation and characterization of four DNA damage responsive genes obtained from screening ca. 9,000 yeast genomic clones. Two of these clones, lambda 78A and pBR178C, contain repetitive elements in the yeast genome as shown by Southern hybridization analysis. Although the genomic hybridization pattern is distinct for each of these two clones, both of these sequences hybridize to large polyadenylated transcripts ca. 5 kilobases in length. Two other DNA damage responsive sequences, pBRA2 and pBR3016B, are single-copy genes and hybridize to 0.5- and 3.2-kilobase transcripts, respectively. Kinetic analysis of the 0.5-kilobase transcript homologous to pBRA2 indicates that the level of this RNA increases more than 15-fold within 20 min after exposure to 4-nitroquinoline-1-oxide. Moreover, the level of this transcript is significantly elevated in cells containing the rad52-1 mutation which are deficient in DNA strand break repair and gene conversion. These results provide some of the first evidence that DNA damage stimulates transcription of specific genes in eucaryotic cells.
Images
PMCID: PMC369065  PMID: 6440006
6.  Breast size and risk of type 2 diabetes mellitus 
Background
Elevated waist circumference and body mass index (BMI), both traditional measures of obesity, are accepted risk factors for type 2 diabetes mellitus. Girls who are obese experience earlier onset of puberty and possibly greater breast development. We sought to evaluate whether a woman's breast size in late adolescence is associated with an increased risk of type 2 diabetes mellitus in adulthood.
Methods
In conjunction with the ongoing Nurses' Health Study II, which began to study risk factors for breast cancer among women in 1989, we conducted a prospective cohort study involving 92 106 of the participants. We assessed the risk of type 2 diabetes mellitus in relation to self-reported bra cup sizes, categorized as ≤ A, B, C and ≥ D cups, among participants at age 20.
Results
The mean age of participants at baseline was 38.1 years. A total of 1844 new cases of type 2 diabetes mellitus arose at a mean age of 44.9 years during 886 443 person-years of follow-up. Relative to bra cup size ≤ A, the respective age-adjusted hazard ratios (and 95% confidence intervals [CIs]) were 2.30 (1.99–2.66) for B cup, 4.32 (3.71–5.04) for C cup and 4.99 (4.12–6.05) for ≥ D cup. Upon further adjustments for age at menarche, parity, physical activity, smoking status, diet, multivitamin use, family history of diabetes mellitus, BMI at age 18 and current BMI, the corresponding hazard ratios (and 95% CIs) were 1.37 (1.18–1.59) for B cup, 1.80 (1.53- 2.11) for C cup and 1.64 (1.34–2.01) for ≥ D cup. The addition of waist circumference to this model minimally changed the hazard ratios (and 95% CIs): 1.32 (1.14–1.53) for B cup, 1.71 (1.46–2.01) for C cup and 1.58 (1.29–1.94) for ≥ D cup.
Interpretation
A large bra cup size at age 20 may be a predictor of type 2 diabetes mellitus in middle-aged women. Whether this relation is independent of traditional indicators of obesity remains to be determined.
doi:10.1503/cmaj.071086
PMCID: PMC2211341  PMID: 18227448
7.  Cloning, nucleotide sequences, and identification of products of the Pseudomonas aeruginosa PAO bra genes, which encode the high-affinity branched-chain amino acid transport system. 
Journal of Bacteriology  1990;172(10):5531-5539.
A DNA fragment of Pseudomonas aeruginosa PAO containing genes specifying the high-affinity branched-chain amino acid transport system (LIV-I) was isolated. The fragment contained the braC gene, encoding the binding protein for branched-chain amino acids, and the 4-kilobase DNA segment adjacent to 3' of braC. The nucleotide sequence of the 4-kilobase DNA fragment was determined and found to contain four open reading frames, designated braD, braE, braF, and braG. The braD and braE genes specify very hydrophobic proteins of 307 and 417 amino acid residues, respectively. The braD gene product showed extensive homology (67% identical) to the livH gene product, a component required for the Escherichia coli high-affinity branched-chain amino acid transport systems. The braF and braG genes encode proteins of 255 and 233 amino acids, respectively, both containing amino acid sequences typical of proteins with ATP-binding sites. By using a T7 RNA polymerase/promoter system together with plasmids having various deletions in the braDEFG region, the braD, braE, braF, and braG gene products were identified as proteins with apparent Mrs of 25,500, 34,000, 30,000, and 27,000, respectively. These proteins were found among cell membrane proteins on a sodium dodecyl sulfate-polyacrylamide gel stained with Coomassie blue.
Images
PMCID: PMC526863  PMID: 2120183
8.  Genetic mapping of bra genes affecting branched-chain amino acid transport in Pseudomonas aeruginosa. 
Journal of Bacteriology  1983;153(3):1272-1281.
Pseudomonas aeruginosa PAO mutants defective in the transport systems for branched-chain amino acids were isolated and characterized. Two mutations in strains selected for trifluoroleucine resistance, braA300 and braB307, were mapped in the met-9020-dcu-9108 and the nar-9011-puuC10 region, respectively. The mutation loci in strains selected for azaleucine resistance, braC310 and bra-311 through bra-314, were all located near the fla genes, with an order of region I fla-bra-region II fla. Strains with braA300 showed a marked reduction in the high-affinity branched-chain amino acid transport system (LIV-I) and a considerable decrease in the lower-affinity system (LIV-II). Strains with braB307 were found to be defective in the LIV-II system. Strains selected for azaleucine resistance were all defective only in the LIV-I system and fell into three phenotypically distinct classes. Strains with braC310 produced a binding protein for leucine, isoleucine, valine, alanine, and threonine (LIVAT-BP) altered in binding ability, indicating that the braC gene is the structural one for the LIVAT-BP. Strains with bra-311 or bra-312 showed a complete loss of production of the LIVAT-BP. Strains with bra-313 or bra-314 produced normal levels of functional LIVAT-BP, suggesting that these mutations are located in a gene(s) other than braC.
Images
PMCID: PMC221773  PMID: 6402489
9.  Validation of Stereophotogrammetry of the Human Torso 
The objective of this study was to determine if measurements of breast morphology computed from three-dimensional (3D) stereophotogrammetry are equivalent to traditional anthropometric measurements obtained directly on a subject using a tape measure. 3D torso images of 23 women ranged in age from 36 to 63 who underwent or were scheduled for breast reconstruction surgery were obtained using a 3dMD torso system (3Q Technologies Inc., Atlanta, GA). Two different types (contoured and line-of-sight distances) of a total of nine distances were computed from 3D images of each participant. Each participant was photographed twice, first without fiducial points marked (referred to as unmarked image) and second with fiducial points marked prior to imaging (referred to as marked image). Stereophotogrammetry was compared to traditional direct anthropometry, in which measurements were taken with a tape measure on participants. Three statistical analyses were used to evaluate the agreement between stereophotogrammetry and direct anthropometry. Seven out of nine distances showed excellent agreement between stereophotogrammetry and direct anthropometry (both marked and unmarked images). In addition, stereophotogrammetry from the unmarked image was equivalent to that of the marked image (both line-of-sight and contoured distances). A lower level of agreement was observed for some measures because of difficulty in localizing more vaguely defined fiducial points, such as lowest visible point of breast mound, and inability of the imaging system in capturing areas obscured by the breast, such as the inframammary fold. Stereophotogrammetry from 3D images obtained from the 3dMD torso system is effective for quantifying breast morphology. Tools for surgical planning and evaluation based on stereophotogrammetry have the potential to improve breast surgery outcomes.
doi:10.4137/BCBCR.S6352
PMCID: PMC3076012  PMID: 21494398
three-dimensional; anthropometry; validation; breast; photogrammetry; stereophotogrammetry; surgical planning
10.  Does deep water running reduce exercise‐induced breast discomfort? 
British Journal of Sports Medicine  2007;41(12):879-883.
Aim
To establish whether exercise‐induced vertical breast displacement and discomfort in women with large breasts were reduced during deep water running compared to treadmill running.
Methods
Sixteen women (mean age  = 32 years, range 19–43 years; mean mass  = 74.1 kg, range 61–114 kg; mean height  = 1.7 m, range 1.61–1.74 m), who were professionally sized to wear a C+ bra cup, were recruited as representative of women with large breasts. After extensive familiarisation, vertical breast motion of the participants was quantified as they ran at a self‐selected stride rate on a treadmill and in 2.4 m deep water. Immediately after running, the subjects rated their breast discomfort and breast pain (visual analogue scale) and their perceived exertion (Borg scale). Breast discomfort, breast pain, perceived exertion, vertical breast displacement and vertical breast velocity were compared between the two experimental conditions.
Results
Exercise‐induced breast discomfort was significantly less and perceived exertion was significantly greater during deep water running relative to treadmill running. Although there was no significant between‐condition difference in vertical breast displacement, mean peak vertical breast velocity was significantly (p<0.05) less during deep water (upward mean (SD): 29.7 (14.0) cm.s‐1; downward: 31.1 (17.0) cm.s‐1) compared to treadmill running (upward mean (SD): 81.4 (21.7) cm.s‐1; downward: 100.0 (25.0) cm.s‐1).
Conclusion
Deep water running was perceived as a more strenuous but comfortable exercise mode for women with large breasts. Increased comfort was attributed to reduced vertical breast velocity rather than reduced vertical breast displacement.
doi:10.1136/bjsm.2007.036251
PMCID: PMC2658982  PMID: 17535854
11.  Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk 
British Journal of Cancer  2002;87(11):1246-1252.
Epidemiologists have established that women with small families, and particularly nulliparae, are prone to develop breast cancer later in life. We report that physiological mammary hypervascularity may be an intermediate reason against the background that breast-core vascularity is normal in pregnancy but pathological in the vascularisation of cancer. We examined breast ‘core’ vascularity in nulliparae during their potential reproductive life and in parous women after their last birth but before their menopause. Fifty clinically normal pre-menopausal non-pregnant women (100 breasts) were studied daily for one ‘luteal positive’ menstrual cycle. Their parity history varied from zero to five babies. Under controlled domestic conditions each wore a special electronic thermometric bra to automatically record breast ‘core’ temperature changes as a measure of mammary tissue blood flow. In the nulliparae there was a rise of breast vascularity throughout reproductive life. In the parous women, a year or so after each birth, breast vascularity was reset at a lower level than before the pregnancy; thereafter, as in nulliparae, there was progressive increase in mammary vascularity until the menopause.
British Journal of Cancer (2002) 87, 1246–1252. doi:10.1038/sj.bjc.6600600 www.bjcancer.com
© 2002 Cancer Research UK
doi:10.1038/sj.bjc.6600600
PMCID: PMC2408917  PMID: 12439713
breast; physiology; reproductive variables; cancer risk and epidemiology; chronobra
12.  Nonlinear Relationships between Weekly Walking Distance and Adiposity in 27,596 Women 
Introduction
Data from vigorously active women (runners) suggested that declines in adiposity with weekly running distance were nonlinear and dependent on whether the women are relatively lean or fat. The purpose of the current study is to assess the cross-sectional relationship between the amount of moderate-intensity physical activity (walking distance) and indicators of adiposity.
Methods
Cross-sectional analyses (i.e., quadratic polynomial regression, regression for percentiles of adiposity) of body mass index (BMI), body circumferences, and bra cup sizes in 27,596 women.
Results
The estimated percent reductions between walking 40–50 km/wk and <10 km/wk were greatest for BMI, intermediate for waist circumference and cup size, and least for hip and chest circumferences. The relationships of walking distance to BMI and body circumferences were all nonlinear (convex). In addition, the inverse relationship between weekly walking distance and adiposity was greatest at the highest percentile of BMI, body circumferences, and cup size, and least at the lowest percentiles. Thus, the decline in adiposity per kilometer per week increment in walking distance was greatest in overweight mostly sedentary women and least in lean active women. The decline in BMI per kilometer per week of exercise was greater in the walkers than previously reported for runners. However, based on the relationships between walking distance and percentiles of the BMI distribution reported here, we show that the majority of this difference is attributable to the leanness of the runners and greater fatness of the walker.
Conclusion
These data suggest that in women the greatest benefit of walking may be among the most obese and that at higher weekly distances the declines in weight associated with walking diminish. Whether these relationships are causal remains to be determined.
PMCID: PMC2813189  PMID: 16286858
exercise; body mass index; regional adiposity; waist circumference
13.  Prostate brachytherapy seed localization using a mobile c-arm without tracking 
The success of prostate brachytherapy depends on the faithful delivery of a dose plan. In turn, intraoperative localization and visualization of the implanted radioactive brachytherapy seeds enables more proficient and informed adjustments to the executed plan during therapy. Prior work has demonstrated adequate seed reconstructions from uncalibrated mobile c-arms using either external tracking devices or image-based fiducials for c-arm pose determination. These alternatives are either time-consuming or interfere with the clinical flow of the surgery, or both. This paper describes a seed reconstruction approach that avoids both tracking devices and fiducials. Instead, it uses the preoperative dose plan in conjunction with a set of captured images to get initial estimates of the c-arm poses followed by an auto-focus technique using the seeds themselves as fiducials to refine the pose estimates. Intraoperative seed localization is achieved through iteratively solving for poses and seed correspondences across images and reconstructing the 3D implanted seeds. The feasibility of this approach was demonstrated through a series of simulations involving variable noise levels, seed densities, image separability and number of images. Preliminary results indicate mean reconstruction errors within 1.2 mm for noisy plans of 84 seeds or fewer. These are attained for additive noise whose standard deviation of the 3D mean error introduced to the plan to simulate the implant is within 3.2 mm.
PMCID: PMC2801145  PMID: 20052296
Registration; Intraoperative Imaging; Image-Guided Therapy; Pelvic Procedures; Prostate Brachytherapy; Reconstruction
14.  Isolation of the braZ gene encoding the carrier for a novel branched-chain amino acid transport system in Pseudomonas aeruginosa PAO. 
Journal of Bacteriology  1991;173(6):1855-1861.
The braZ gene for a novel branched-chain amino acid transport system in Pseudomonas aeruginosa PAO was isolated and characterized. Determination of the nucleotide sequence showed that the braZ gene comprises 1,311 nucleotides specifying a protein of 437 amino acids. Hydropathy analysis suggested that the product is an integral membrane protein with 12 membrane-spanning segments. The amino acid sequence showed extensive homology to those of the braB and brnQ gene products, branched-chain amino acid carriers of P. aeruginosa and Salmonella typhimurium, respectively. By using the T7 RNA polymerase-promoter system, the braZ gene product was identified as a protein of an apparent Mr of 34,000 on a sodium dodecyl sulfate-polyacrylamide gel. Properties of the transport system encoded by braZ were studied by using P. aeruginosa PAO3537, defective in both the high- and low-affinity branched-chain amino acid transport systems (LIV-I and LIV-II, respectively). The transport system encoded by braZ was found to be another effective branched-chain amino acid transport system in P. aeruginosa PAO and was thus designated as LIV-III. This system is specific for isoleucine and valine, giving the same Km value of 12 microM for these amino acids. The system was found, however, to have a very low affinity for leucine, with a Km value of 150 microM, which contrasts with the substrate specificities of LIV-I and LIV-II.
Images
PMCID: PMC207713  PMID: 1900503
15.  Quality of Life of Ostomates with the Selected Factors in a Selected Hospital of Delhi with a View to Develop Guidelines for the Health Professionals 
Indian Journal of Palliative Care  2009;15(2):111-114.
Background:
A correlational survey to assess the quality of life (QoL) of ostomates with selected factors in a selected hospital of Delhi and to develop guidelines for the health professionals to improve QoL of ostomates was undertaken during the year 2005-2007. The objectives of the study were as follows: (1) To assess QoL of ostomates (2) To identify the factors associated with QoL of ostomates (3) To seek relationship between selected factors and QoL of ostomates (4) To develop guidelines for the health professionals to improve QoL of ostomates.
Materials and Methods:
The corelational survey was conducted on 50 ostomates from Surgical Oncology OPD of B.R.A. Institute Rotary Cancer Hospital, AIIMS, Delhi. Purposive sampling technique was employed to select the sample subjects. Structured interview schedule was prepared. Guidelines were prepared for health professionals to improve the quality of life of ostomates.
Result:
Majority of the ostomates possessed best quality of life. There was a significant association between QoL score of ostomates with age, sex, duration of surgery, education, income, and occupation. There was no significant association between QoL scores of ostomates and marital status and type of ostomy.
Conclusion:
This study conclude that nurses have a great role to play in the physical, psychological, economical, social, familial, and sexual aspects in the care of ostomates and to offer psychological support and empathy, to reinforce coping skills to promote an optimal QoL.also she has a great role to influence and educate all the aspects of care to the patients and their relatives. Their is a need to develop staff development program for nursing personnel in the clinical area in healthcare system.
doi:10.4103/0973-1075.58455
PMCID: PMC2902110  PMID: 20668588
Colostomy; Ostomates; Quality of life
16.  Prospective motion correction of high-resolution magnetic resonance imaging data in children 
NeuroImage  2010;53(1):139-145.
Motion artifacts pose significant problems for the acquisition and analysis of high-resolution magnetic resonance imaging data. These artifacts can be particularly severe when studying pediatric populations, where greater patient movement reduces the ability to clearly view and reliably measure anatomy. In this study, we tested the effectiveness of a new prospective motion correction technique, called PROMO, as applied to making neuroanatomical measures in typically developing school-age children. This method attempts to address the problem of motion at its source by keeping the measurement coordinate system fixed with respect to the subject throughout image acquisition. The technique also performs automatic rescanning of images that were acquired during intervals of particularly severe motion. Unlike many previous techniques, this approach adjusts for both in-plane and through-plane movement, greatly reducing image artifacts without the need for additional equipment. Results show that the use of PROMO notably enhances subjective image quality, reduces errors in Freesurfer cortical surface reconstructions, and significantly improves the subcortical volumetric segmentation of brain structures. Further applications of PROMO for clinical and cognitive neuroscience are discussed.
doi:10.1016/j.neuroimage.2010.06.017
PMCID: PMC3146240  PMID: 20542120
17.  Automatic segmentation of seeds and fluoroscope tracking (FTRAC) fiducial in prostate brachytherapy x-ray images 
C-arm X-ray fluoroscopy-based radioactive seed localization for intraoperative dosimetry of prostate brachytherapy is an active area of research. The fluoroscopy tracking (FTRAC) fiducial is an image-based tracking device composed of radio-opaque BBs, lines, and ellipses that provides an effective means for pose estimation so that three-dimensional reconstruction of the implanted seeds from multiple X-ray images can be related to the ultrasound-computed prostate volume. Both the FTRAC features and the brachytherapy seeds must be segmented quickly and accurately during the surgery, but current segmentation algorithms are inhibitory in the operating room (OR). The first reason is that current algorithms require operators to manually select a region of interest (ROI), preventing automatic pipelining from image acquisition to seed reconstruction. Secondly, these algorithms fail often, requiring operators to manually correct the errors. We propose a fast and effective ROI-free automatic FTRAC and seed segmentation algorithm to minimize such human intervention. The proposed algorithm exploits recent image processing tools to make seed reconstruction as easy and convenient as possible. Preliminary results on 162 patient images show this algorithm to be fast, effective, and accurate for all features to be segmented. With near perfect success rates and subpixel differences to manual segmentation, our automatic FTRAC and seed segmentation algorithm shows promising results to save crucial time in the OR while reducing errors.
doi:10.1117/12.844520
PMCID: PMC3438694  PMID: 22977294
segmentation; localization; C-arm; X-ray; fiducial; prostate brachytherapy
18.  RESPONSE LATENCY AS AN INDEX OF RESPONSE STRENGTH DURING FUNCTIONAL ANALYSES OF PROBLEM BEHAVIOR 
Dependent variables in research on problem behavior typically are based on measures of response repetition, but these measures may be problematic when behavior poses high risk or when its occurrence terminates a session. We examined response latency as the index of behavior during assessment. In Experiment 1, we compared response rate and latency to the first response under acquisition and maintenance conditions. In Experiment 2, we compared data from existing functional analyses when graphed as rate versus latency. In Experiment 3, we compared results from pairs of independent functional analyses. Sessions in the first analysis were terminated following the first occurrence of behavior, whereas sessions in the second analysis lasted for 10 min. Results of all three studies showed an inverse relation between rate and latency, indicating that latency might be a useful measure of responding when repeated occurrences of behavior are undesirable or impractical to arrange.
doi:10.1901/jaba.2011.44-51
PMCID: PMC3050468  PMID: 21541141
functional analysis; latency measures of responding
19.  Intraoperative 3-D Reconstruction of Prostate Brachytherapy Implants with Automatic Pose Correction 
Physics in medicine and biology  2011;56(15):5011-5027.
The success of prostate brachytherapy critically depends on delivering adequate dose to the prostate gland, and the capability of intraoperatively localizing implanted seeds provides potential for dose evaluation and optimization during therapy. REDMAPS is a recently reported algorithm that carries out seed localization by detecting, matching, and reconstructing seeds in only a few seconds from three acquired x-ray images. In this paper, we present an automatic pose correction (APC) process that is combined with REDMAPS to allow for both more accurate seed reconstruction and the use of images with relatively large pose errors. APC uses a set of reconstructed seeds as a fiducial and corrects the image pose by minimizing the overall projection error. The seed matching and APC are iteratively computed until a stopping condition is met. Simulations and clinical studies show that APC significantly improves the reconstructions with an overall average matching rate of ≥ 99.4%, reconstruction error of ≤ 0.5 mm, and the matching solution optimality of ≥ 99.8%.
doi:10.1088/0031-9155/56/15/022
PMCID: PMC3172706  PMID: 21772077
20.  Comparative analysis of traditional and coiled fiducials implanted during EUS for pancreatic cancer patients receiving stereotactic body radiation therapy 
Gastrointestinal endoscopy  2012;76(5):962-971.
Background
EUS-guided fiducial placement facilitates image-guided radiation therapy (IGRT).
Objective
To compare 2 types of commercially available fiducials for technical success, complications, visibility, and migration.
Design
Retrospective, single-center, comparative study.
Setting
Tertiary-care medical center.
Interventions
Traditional fiducials (TFs) (5-mm length, 0.8-mm diameter) and Visicoil fiducials (VFs) (10-mm length, 0.35-mm diameter) were compared. Fiducials were placed using linear 19-gauge (for TFs) or 22-gauge (for VFs) needles. A subjective visualization scoring system (0-2; 0 = not visible, 1 = barely visible, 2 = clearly visible) was used to assess visibility on CT. Fiducial migration was calculated as a change in interfiducial distance.
Main Outcome Measurements
Technical success, complications, visibility, and migration of 2 types of fiducials.
Results
Thirty-nine patients with locally advanced pancreatic cancer underwent EUS-guided placement of 103 fiducials (77 TFs, 26 VFs). The mean number of fiducials placed per patient was 2.66 (standard deviation 0.67) for the 19-gauge needle and 2.60 (standard deviation 0.70) for the 22-gauge needle (P = .83). No intra- or postprocedural complications were encountered. The median visibility score for TFs was significantly better than that for VFs, both when scores of 0 were and were not included (2.00, interquartile range [IQR] 2.00-2.00 vs 1.75, IQR 1.50-2.00, P = .009 and 2.00, IQR 2.00-2.00 vs 2.00, IQR 1.50-2.00, P < .0001, respectively). The mean migration was not significantly different between the 2 types of fiducials (0.8 mm [IQR 0.4-1.6 mm] for TFs vs 1.3 mm [IQR 0.6-1.5 mm] for VFs; P = .72).
Limitations
Retrospective, nonrandomized design.
Conclusions
Visibility was significantly better for TFs compared with VFs. The degree of fiducial migration was not significantly different for TFs and VFs. There was no significant difference in the mean number of fiducials placed, indicating a similar degree of technical difficulty for TF and VF deployment.
doi:10.1016/j.gie.2012.07.006
PMCID: PMC3578307  PMID: 23078921
21.  Regulation of canonical Wnt signaling by Brachury is essential for posterior mesoderm formation 
Developmental cell  2008;15(1):121-133.
SUMMARY
The T-box transcription factor Brachyury is essential for the formation of the posterior body in all vertebrates, although its critical transcriptional targets have remained elusive. Loss of function studies of mouse Brachyury and the zebrafish Brachyury ortholog Ntl indicated that Brachury plays a more significant role in higher vertebrates than lower vertebrates. We have identified a second zebrafish Brachyury ortholog (Bra), and show that a combined loss of Ntl and Bra recapitulates the mouse phenotype, demonstrating an ancient role for Brachyury in patterning all but the most anterior somites. Using cell transplantation we show that the only essential role for Brachury during somite formation is non cell-autonomous, and demonstrate that Ntl and Bra are required for and can induce expression of the canonical Wnts wnt8 and wnt3a. We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates.
doi:10.1016/j.devcel.2008.04.013
PMCID: PMC2601683  PMID: 18606146
22.  Horizontal Gene Transfer of PIB-Type ATPases among Bacteria Isolated from Radionuclide- and Metal-Contaminated Subsurface Soils 
Aerobic heterotrophs were isolated from subsurface soil samples obtained from the U.S. Department of Energy's (DOE) Field Research Center (FRC) located at Oak Ridge, Tenn. The FRC represents a unique, extreme environment consisting of highly acidic soils with cooccurring heavy metals, radionuclides, and high nitrate concentrations. Four hundred isolates obtained from contaminated soil were assayed for heavy metal resistance, and a smaller subset was assayed for tolerance to uranium. The vast majority of the isolates were gram-positive bacteria and belonged to the high-G+C- and low-G+C-content genera Arthrobacter and Bacillus, respectively. Genomic DNA from a randomly chosen subset of 50 Pb-resistant (Pbr) isolates was amplified with PCR primers specific for PIB-type ATPases (i.e., pbrA/cadA/zntA). A total of 10 pbrA/cadA/zntA loci exhibited evidence of acquisition by horizontal gene transfer. A remarkable dissemination of the horizontally acquired PIB-type ATPases was supported by unusual DNA base compositions and phylogenetic incongruence. Numerous Pbr PIB-type ATPase-positive FRC isolates belonging to the genus Arthrobacter tolerated toxic concentrations of soluble U(VI) (UO22+) at pH 4. These unrelated, yet synergistic, physiological traits observed in Arthrobacter isolates residing in the contaminated FRC subsurface may contribute to the survival of the organisms in such an extreme environment. This study is, to the best of our knowledge, the first study to report broad horizontal transfer of PIB-type ATPases in contaminated subsurface soils and is among the first studies to report uranium tolerance of aerobic heterotrophs obtained from the acidic subsurface at the DOE FRC.
doi:10.1128/AEM.72.5.3111-3118.2006
PMCID: PMC1472380  PMID: 16672448
23.  Time to Deterioration in Quality of Life Score as a Modality of Longitudinal Analysis in Patients with Breast Cancer 
The Oncologist  2011;16(10):1458-1468.
Definitions of time to deterioration in quality of life scores were examined as a modality of longitudinal quality of life assessment in breast cancer patients undergoing different surgical procedures, according to different cutoffs of the minimal clinically important difference.
Purpose.
This prospective multicenter study explored different definitions of time to deterioration (TTD) in quality of life (QoL) scores, according to different cutoffs of the minimal clinically important difference (MCID) as a modality for longitudinal QoL assessment in breast cancer patients.
Methods.
QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and BR-23 before surgery, after surgery, and 6 and 12 months later. The global health score, arm symptoms score (BRAS), and breast symptoms score were analyzed. For a given baseline score, QoL was considered to have deteriorated if this score decreased by ≥5 points at any time point after baseline. Analyses were repeated using an MCID of 10 points and taking the score after surgery as the reference score (to explore the occurrence of response shift). TTD was calculated using the Kaplan–Meier method and Cox regression was used to identify independent factors associated with TTD.
Results.
Two hundred thirty-five patients underwent axillary lymph node dissection (ALND), 222 underwent sentinel lymph node biopsy (SLNB), and 61 underwent SLNB plus ALND. Patients who underwent SLNB had a significantly longer TTD for the BRAS dimension than those who underwent ALND. Cox multivariate analyses showed that treatment using SLNB and age >59 years were independently associated with longer TTD for the BRAS, whereas surgery elsewhere than at the Centre Georges François Leclerc was associated with a shorter TTD.
Conclusion.
Exploration of different definitions of TTD in QoL provides meaningful longitudinal QoL results for clinicians.
doi:10.1634/theoncologist.2011-0085
PMCID: PMC3228064  PMID: 21948650
Quality of life; Longitudinal analysis; Methodology; Breast cancer
24.  Longitudinal Study of Mammary Epithelial and Fibroblast Co-Cultures Using Optical Coherence Tomography Reveals Morphological Hallmarks of Pre-Malignancy 
PLoS ONE  2012;7(11):e49148.
The human mammary gland is a complex and heterogeneous organ, where the interactions between mammary epithelial cells (MEC) and stromal fibroblasts are known to regulate normal biology and tumorigenesis. We aimed to longitudinally evaluate morphology and size of organoids in 3D co-cultures of normal (MCF10A) or pre-malignant (MCF10DCIS.com) MEC and hTERT-immortalized fibroblasts from reduction mammoplasty (RMF). This co-culture model, based on an isogenic panel of cell lines, can yield insights to understand breast cancer progression. However, 3D cultures pose challenges for quantitative assessment and imaging, especially when the goal is to measure the same organoid structures over time. Using optical coherence tomography (OCT) as a non-invasive method to longitudinally quantify morphological changes, we found that OCT provides excellent visualization of MEC-fibroblast co-cultures as they form ductal acini and remodel over time. Different concentrations of fibroblasts and MEC reflecting reported physiological ratios [1] were evaluated, and we found that larger, hollower, and more aspherical acini were formed only by pre-malignant MEC (MCF10DCIS.com) in the presence of fibroblasts, whereas in comparable conditions, normal MEC (MCF10A) acini remained smaller and less aspherical. The ratio of fibroblast to MEC was also influential in determining organoid phenotypes, with higher concentrations of fibroblasts producing more aspherical structures in MCF10DCIS.com. These findings suggest that stromal-epithelial interactions between fibroblasts and MEC can be modeled in vitro, with OCT imaging as a convenient means of assaying time dependent changes, with the potential for yielding important biological insights about the differences between benign and pre-malignant cells.
doi:10.1371/journal.pone.0049148
PMCID: PMC3495770  PMID: 23152864
25.  Tai Chi/ Yoga Effects on Anxiety, Heartrate, EEG and Math Computations 
Objective
To determine the immediate effects of a combined form of tai chi/yoga.
Design
38 adults participated in a 20-minute tai chi/yoga class. The session was comprised of standing tai chi movements, balancing poses and a short tai chi form and 10 minutes of standing, sitting and lying down yoga poses.
Main outcome measures
The pre- and post- tai chi/ yoga effects were assessed using the State Anxiety Inventory (STAI), EKG, EEG and math computations.
Results
Heartrate increased during the session, as would be expected for this moderate intensity exercise. Changes from pre to post session assessments suggested increased relaxation including decreased anxiety and a trend for increased EEG theta activity.
Conclusions
The increased relaxation may have contributed to the increased speed and accuracy noted on math computations following the tai chi/yoga class.
doi:10.1016/j.ctcp.2010.05.014
PMCID: PMC2950830  PMID: 20920810

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