Training and assessing convolutional neural network performance in automatic vascular segmentation using Ga-68 DOTATATE PET/CT.

To evaluate a convolutional neural network's performance (nnU-Net) in the assessment of vascular contours, calcification and PET tracer activity using Ga-68 DOTATATE PET/CT. Patients who underwent Ga-68 DOTATATE PET/CT imaging over a 12-month period for neuroendocrine investigation were included. Manual cardiac and aortic segmentations were performed by an experienced observer. Scans were randomly allocated in ratio 64:16:20 for training, validation and testing of the nnU-Net model. PET tracer uptake and calcium scoring were compared between segmentation methods and different observers. 116 patients (53.5% female) with a median age of 64.5 years (range 23-79) were included. There were strong, positive correlations between all segmentations (mostly r > 0.98). There were no significant differences between manual and AI segmentation of SUVmean for global cardiac (mean ± SD 0.71 ± 0.22 vs. 0.71 ± 0.22; mean diff 0.001 ± 0.008, p > 0.05), ascending aorta (mean ± SD 0.44 ± 0.14 vs. 0.44 ± 0.14; mean diff 0.002 ± 0.01, p > 0.05), aortic arch (mean ± SD 0.44 ± 0.10 vs. 0.43 ± 0.10; mean diff 0.008 ± 0.16, p > 0.05) and descending aorta (mean ± SD < 0.001; 0.58 ± 0.12 vs. 0.57 ± 0.12; mean diff 0.01 ± 0.03, p > 0.05) contours. There was excellent agreement between the majority of manual and AI segmentation measures (r ≥ 0.80) and in all vascular contour calcium scores. Compared with the manual segmentation approach, the CNN required a significantly lower workflow time. AI segmentation of vascular contours using nnU-Net resulted in very similar measures of PET tracer uptake and vascular calcification when compared to an experienced observer and significantly reduced workflow time.

Phylogenetic and transcriptional analysis of a strictosidine synthase-like gene family in Arabidopsis thaliana reveals involvement in plant defence responses.

Protein domains with similarity to plant strictosidine synthase-like (SSL) sequences have been uncovered in the genomes of all multicellular organisms sequenced so far and are known to play a role in animal immune responses. Among several distinct groups of Arabidopsis thaliana SSL sequences, four genes (AtSSL4-AtSSL7) arranged in tandem on chromosome 3 show more similarity to SSL genes from Drosophila melanogaster and Caenorhabditis elegans than to other Arabidopsis SSL genes. To examine whether any of the four AtSSL genes are immune-inducible, we analysed the expression of each of the four AtSSL genes after exposure to microbial pathogens, wounding and plant defence elicitors using real-time quantitative RT-PCR, Northern blot hybridisation and Western blot analysis with antibodies raised against recombinant AtSSL proteins. While the AtSSL4 gene was constitutively expressed and not significantly induced by any treatment, the other three AtSSL genes were induced to various degrees by plant defence signalling compounds, such as salicylic acid, methyl jasmonate and ethylene, as well as by wounding and exposure to the plant pathogens Alternaria brassicicola and cucumber mosaic virus. Our data demonstrate that the four SSL-coding genes are regulated individually, suggesting specific roles in basal (SSL4) and inducible (SSL5-7) plant defence mechanisms.

Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in Patients with Recurrent Glioblastoma.

BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit regions of diffusion restriction following the initiation of bevacizumab therapy. Studies suggest that these regions represent either diffusion-restricted necrosis or hypercellular tumor. This study explored postmortem brain specimens and a population analysis of overall survival to determine the identity and implications of such lesions. MATERIALS AND METHODS: Postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab with progressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. A receiver operating characteristic analysis was performed to define optimal ADC thresholds for differentiating tissue types. A retrospective population study was also performed comparing the overall survival of 64 patients with recurrent glioblastoma treated with bevacizumab. Patients were separated into 3 groups: no diffusion restriction, diffusion restriction that appeared and progressed within 5 months of bevacizumab initiation, and delayed or stable diffusion restriction. An additional analysis was performed assessing tumor O6-methylguanine-DNA-methyltransferase methylation. RESULTS: The optimal ADC threshold for differentiation of hypercellularity and necrosis was 0.736 × 10-3mm2/s. Progressively expanding diffusion restriction was pathologically confirmed to be coagulative necrosis surrounded by viable tumor. Progressive lesions were associated with the worst overall survival, while stable lesions showed the greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine-DNA-methyltransferase methylated tumors, none developed diffusion-restricted lesions. CONCLUSIONS: Progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. Stable lesions were, however, associated with increased overall survival. All lesions were associated with O6-methylguanine-DNA-methyltransferase unmethylated tumors.

Central lymphatic irradiation for stage III nodular malignant lymphoma: long-term results.

PURPOSE: To report the long-term results of central lymphatic irradiation for stage III nodular malignant lymphoma. PATIENTS AND METHODS: Between 1969 and 1985, 34 patients (26 with nodular poorly differentiated lymphoma, four with nodular mixed lymphocytic/histiocytic lymphoma, and four with nodular histiocytic lymphoma) were treated with central lymphatic irradiation. Median age of the group was 51 years (range, 30 to 73). There were 15 men and 19 women. Staging work-up included a physical examination and bone marrow biopsy in all patients. Seventy-four percent had a lymphangiogram (LAG) and 44% a laparotomy (LAP). Eighty-two percent had either a LAP or a LAG. Thirty-two patients were Ann Arbor stage IIIA and two were stage IIIB. All patients received lymphatic irradiation that encompassed cervical, supraclavicular, axillary, mediastinal, paraaortic, mesenteric, pelvic, and femoral lymphatics to total doses ranging from 20 to 30 Gy in 1.0- to 1.8-Gy fractions. Waldeyer's ring was initially treated in 17 patients. Follow-up information is available on all 34 patients. Median follow-up is 9 years, 8 months (range, 15 to 244 months). RESULTS: Life-table actuarial overall, disease-free, and cause-specific survival rates at 15 years are 28%, 40%, and 46%, respectively. Only one relapse was observed after 9 years. Disease-free survival was significantly improved in patients with five or fewer sites of involvement (P = .02). Age, sex, B symptoms, histology, and technique of irradiation were not prognostically significant. Salvage therapy, including further irradiation and/or chemotherapy, was delivered to 20 patients. Ten percent of these patients remain alive without evidence of disease. Toxicity data were available for the patients treated at the Medical College of Wisconsin (MCW). Radiation Therapy Oncology Group (RTOG) acute hematologic, gastrointestinal, and salivary toxicity scores were < or = 2 in 83% of patients. Late toxicity scores were < or = 2 in 96%. Persistent xerostomia was noted in 23% of patients who received initial treatment to Waldeyer's ring. CONCLUSION: These results suggest that initial comprehensive central lymphatic irradiation may be the preferred approach to achieve a durable relapse-free interval for this group of patients.

Arabidopsis mutants define an in vivo role for isoenzymes of aspartate aminotransferase in plant nitrogen assimilation.

Arabidopsis contains five isoenzymes of aspartate aminotransferase (AspAT) localized to the cytosol, chloroplast, mitochondria, or peroxisomes. To define the in vivo function of individual isoenzymes, we screened for Arabidopsis mutants deficient in either of the two major isoenzymes, cytosolic AAT2 or chloroplastic AAT3, using a native gel activity assay. In a screen of 8,000 M2 seedlings, three independent mutants deficient in cytosolic AAT2 (aat2) and two independent mutants deficient in chloroplastic AAT3 (aat3) were isolated. Mapping of aat2 and aat3 mutations and the five AspAT genes (ASP1-ASP5) established associations as follows: the mutation affecting aat2 maps with and cosegregates with ASP2, one of two expressed genes for cytosolic AspAT; the mutation affecting aat3 maps to the same location as the ASP5 gene encoding chloroplastic AspAT. Phenotypic analysis of the aat2 and aat3 mutants revealed a dramatic aspartate-related phenotype in one of the mutants deficient in cytosolic AAT2. The aat2-2 mutant displays an 80% reduction in levels of aspartate transported in the phloem of light-grown plants, and a 50% reduction in levels of asparagine transported in dark-adapted plants. These results indicate that cytosolic AAT2 is the major isoenzyme controlling aspartate synthesized for nitrogen transport in the light, and that this aspartate pool is converted to asparagine when plants are dark adapted.

Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

OBJECTIVE: The early detection of a rise in albumin excretion within the normal range could permit early intervention to prevent the development of microalbuminuria (MA) in genetically susceptible subjects with type 1 diabetes. In the Oxford Regional Prospective Study we prospectively examined urine albumin excretion during the first years after diagnosis of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1986 and 1995, 511 subjects aged < 16 years were recruited at diagnosis and followed for a median of 6 years (range 1-14). In 78 subjects (designated cases), an annual assessment of the albumin-to-creatinine ratio (ACR) in three morning first-void urine samples detected MA (males: ACR > or =3.5 mg/mmol, females: ACR > or =4.0 mg/mmol in two of three urine samples). In 63 of these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration. RESULTS: The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subjects than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, vs. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the ACR in the years before the onset of MA was higher in the microalbuminuric subjects than in the normoalbuminuric subjects (70% per year [37-149], n = 63, vs. 1% per year [-9 to 13], n = 396; P < 0.001). The mean HbA1c level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418). CONCLUSIONS: Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop MA. HbA1c is a determinant of risk for MA, but pubertal factors have a greater effect on rates of progression of urine albumin excretion during adolescence in this cohort.

Blood pressure does not rise before the onset of microalbuminuria in children followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study Group.

OBJECTIVE: To examine whether a rise in blood pressure could be detected before the onset of microalbuminuria (MA) in a cohort of children followed from diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: The Oxford Regional Prospective Study is an incident cohort study of children with type 1 diabetes aged (mean +/- SD) 9.8 +/- 3.7 years at diagnosis. Subjects were assessed annually from diagnosis, with measurement of HbA1c, arterial blood pressure (random zero), and three urine samples for estimation of the albumin/creatinine ratio. During follow-up, 63 of 494 children developed MA at one or more annual assessments and were designated as cases for a nested case-control study. Each case was matched for sex and age at diagnosis with two normoalbuminuric control subjects. Blood pressure (BP) data were compared at corresponding years of diabetes duration. RESULTS: Cases with MA were similar to normoalbuminuric control subjects with respect to age and BMI, but they had higher mean HbA1c levels (mean difference 1.1%, P < 0.001). In the years before the onset of MA, the diastolic BP standard deviation score (SDS) was significantly higher than zero in cases (mean 0.49, P < 0.001) and in control subjects (0.50, P < 0.001). No difference could be detected between cases and control subjects before the onset of MA in either systolic or diastolic BP (mean difference systolic -1.2 mmHg [95% CI -4.7 to 2.7], mean difference diastolic 0.1 mmHg [-2.4 to 2.6]). However, within the cases, the onset of MA was associated with elevations in systolic and diastolic BP SDSs (F = 16.1, P < 0.001; and F = 18.0, P < 0.001). BMI, but not HbA1c, was associated with systolic and diastolic BP SDSs in the subjects with MA (F = 0.6, P = 0.4; and F = 12.3, P = 0.001). However, the association of BP with MA remained signifcant for systolic BP (P = 0.001) and for diastolic BP (P < 0.001) after adjusting for BMI. CONCLUSIONS: A rise in systemic BP cannot be detected before the first appearance of MA in children with type 1 diabetes. BP rises concurrently with the onset of MA and is also closely related to BMI.

Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group.

OBJECTIVE: The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years. RESULTS: MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes. CONCLUSIONS: Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk.

Radioresponse of human astrocytic tumors across grade as a function of acute and chronic irradiation.

Astrocytomas make up the largest group of primary brain tumors of glial origin. Long term survival is rare with high grade tumors (grades 3 and 4), which recur despite subtotal resection, chemotherapy, and aggressive postoperative radiation therapy. In contrast, the 5-year survival for low grade astrocytomas (grades 1 and 2) following subtotal resection and postoperative radiotherapy approaches 50%. Variable sensitivity across grade may contribute to the difference in the behavior of these tumors. To investigate this possibility, the radioresponse of human glial tumors across grade as a function of the dose rate of irradiation was studied. Cell lines derived from a low grade astrocytoma (grade 1) and two high grade astrocytomas (grades 3 and 4) were established in culture. Clonal survival was determined following irradiation of the three cell lines with Cesium 137 gamma rays at high dose rate, 78 Gy/hr, and at low dose rate, range 14 cGy to 79 cGy/hr. The low grade astrocytoma was found to be more radiosensitive than either of the high grade tumors. The alpha/beta (Gy-1/Gy-2) values (linear quadratic model) were 0.35/0.082 for the grade 1 line and 0.20/0.036 and 0.30/0.045 for the grade 3 and 4, respectively. D0 (cGy) values (single-hit multi-target model) were 99, 144, and 117 for grades 1, 3, and 4, respectively. A dose rate effect was present for all three tumor lines irradiated from 14 cGy/hr to 78 Gy/hr. An inverse dose rate effect was also noted at 37 cGy/hr for each of the astrocytic lines. These findings may be useful in the development of strategies to treat astrocytic brain tumors which use high and/or low dose rate irradiation.

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

Continuous split course irradiation for stage I and II Hodgkin's disease: 20 year experience at the Medical College of Wisconsin.

Between January 1970 and December 1989, 153 consecutive patients with stage I or II Hodgkin's disease were treated at the Medical College of Wisconsin Affiliated Hospitals. Eighty-eight patients were clinically staged and 65 patients underwent staging laparotomy. Ninety-nine patients were treated using continuous split course irradiation (CSCI) technique. Overall survival (OS) at 5, 10, and 15 years was 89%, 79%, and 68%, respectively. Disease-free survival (DFS) at 5, 10, and 15 years was 75%, 72%, and 68%, respectively. No significant differences were found in OS or DFS when comparing pathologically and clinically staged patients or when comparing patients treated using CSCI with those treated with the standard technique. Patients treated using CSCI tended to complete therapy in a shorter time, without increased morbidity.

On the control of lipolysis in adipocytes.

The lipolytic reaction in adipocytes is one of the most important reactions in the management of bodily energy reserves, and dysregulation of this reaction may contribute to the symptoms of Type 2 diabetes mellitus. Yet, progress on resolving the molecular details of this reaction has been relatively slow. However, recent developments at the molecular level begin to paint a clearer picture of lipolysis and point to a number of unanswered questions. While HSL has long been known to be the rate-limiting enzyme of lipolysis, the mechanism by which HSL attacks the droplet lipids is not yet firmly established. Certainly, the immunocytochemical evidence showing the movement of HSL to the lipid droplet upon stimulation leaves little doubt that this translocation is a key aspect of the lipolytic reaction, but whether or not HSL phosphorylation contributes to the translocation, and at which site(s), is as yet unresolved. It will be important to establish whether there is an activation step in addition to the translocation reaction. The participation of perilipin A is indicated by the findings that this protein can protect neutral lipids within droplets from hydrolysis, but active participation in the lipolytic reaction is yet to be proved. Again, it will be important to determine whether mutations of serine residues of PKA phosphorylation sites of perilipins prevent lipolysis, and whether such modifications abolish the physical changes in the droplet surfaces that accompany lipolysis.

Combined lipase deficiency (cld/cld) in mice affects differently post-translational processing of lipoprotein lipase, hepatic lipase and pancreatic lipase.

Lipoprotein lipase (LPL) and hepatic lipase (HL), which act on plasma lipoproteins, belong to the same gene family as pancreatic lipase. LPL is synthesized in heart, muscle and adipose tissue, while HL is synthesized primarily in liver. LPL is also synthesized in liver of newborn rodents. The active form of LPL is a dimer, whereas that of HL has not been established. Combined lipase deficiency (CLD) is an autosomal recessive mutation (cld) in mice which impairs post-translational processing of LPL and HL. Cld/cld mice have very low LPL and HL activities (< 5% of normal), yet normal pancreatic lipase activity. They develop massive hypertriglyceridemia and die within 3 days after birth. The CLD mutation allows synthesis, glycosylation and dimerization of LPL, but blocks activation and secretion of the lipase. Thus, dimerization per se does not result in production of active LPL. Immunofluorescence studies showed that LPL is retained in endoplasmic reticulum (ER) in cld/cld cells. Translocation of Golgi components to ER by treatment with brefeldin A (BFA) enabled synthesis of active LPL in cultured cld/cld brown adipocytes. Thus, production of inactive LPL in cld/cld cells results from inability of the cells to transport LPL from ER. The CLD mutation allows synthesis and glycosylation of HL, but blocks activation of the lipase. Immunofluorescence studies located HL mostly outside of cells in liver, liver cell cultures and incubated adrenal tissue of normal and cld/cld mice and mostly inside of cells in liver cell cultures and adrenal tissues treated with monensin (to block secretion of protein). These findings demonstrate synthesis and secretion of HL by both liver and adrenal cells of normal and cld/cld mice. Thus, the CLD mutation allows secretion of inactive HL by liver and adrenals. However, it does not block synthesis or secretion of active pancreatic lipase. Our findings indicate that LPL, HL and pancreatic lipase, although closely related, are processed differently.

The role of dental prostheses in alveolar ridge squamous carcinomas.

BACKGROUND: Alveolar ridge squamous carcinomas develop in patients outside the usual constellation of risk factors. OBJECTIVE: To determine whether the use of dentures was a risk factor specific to patients with alveolar ridge carcinoma. DESIGN: Case-control method with a unique control group-a concurrent cohort of patients with head and neck cancer with primaries in the oropharynx, hypopharynx, and larynx. SETTING: Tertiary care hospital-based clinic. PATIENTS: Forty-one patients with squamous carcinomas centered on the maxillary or mandibular alveolar ridges. The control group was 175 concurrently seen patients with squamous carcinomas of the laryngopharynx for whom dental status was known. MAIN OUTCOME MEASURES: Age at diagnosis, sex, tobacco use, alcohol use, and denture use. RESULTS: Patients with alveolar ridge were more likely to be female, older, nonsmokers, and nondrinkers. The crude odds ratio of denture use in patients with alveolar ridge cancer was 2.28 (P=.03). Eliminating other confounding factors with logistic regression, the adjusted odds ratio dropped to 1.30 (P=.59). Among patients with alveolar ridge, smoking status correlated with age and gender: current smokers were on average 64.4 years old and 9 of 16 were men. Nonsmokers' average age was 79.1 years and 1 of 11 was a man. CONCLUSIONS: In this study, denture use was not an independent risk factor for alveolar ridge carcinomas. Among patients with little to no tobacco or alcohol exposure, the alveolar ridge carcinomas tended to occur in the elderly and in women.

Stage I and II Hodgkin's disease in the pediatric population. Long-term follow-up of patients staged predominantly clinically.

Between January 1, 1970, and December 31, 1990, 42 consecutive pediatric patients were treated at the Medical College of Wisconsin Affiliated Hospitals for early-stage Hodgkin's disease. Thirty patients were clinically staged. Twelve underwent staging laparotomy as a part of staging work-up. Thirty-one patients were treated with radiation therapy (RT) alone. Eleven were treated with combined chemotherapy and RT. For the entire group, overall survival at 5, 10, and 15 years was 98, 98, and 92%, respectively. Disease-free survival was 86, 86, and 79, respectively. There was no significant difference in overall survival or disease-free survival comparing clinically versus pathologically staged patients. There was a trend toward improved disease-free survival favoring pathologically staged patients; however, this difference did not reach statistical significance (p = 0.07). The long-term results of this series fail to show statistically significant superior disease-free or overall survival with surgical staging.

Effect of denaturants on the emulsifying activity of proteins.

The relationship between protein flexibility and emulsifying activity was investigated by disrupting disulfide bonds and/or noncovalent interactions of the protein. Oil-in-water emulsions using model proteins (apomyoglobin, beta-casein, alpha-casein, lysozyme, bovine serum albumin, kappa-casein, and beta-lactoglobulin) were made in the presence of chemical denaturants (dithiothreitol and/or urea). In most cases, the presence of denaturants enhanced emulsifying activity. The effect was protein-specific and depended on the relative importance of disulfide bonds and noncovalent interactions in stabilizing the native conformation of each protein. Implications for the design of novel protein emulsifiers are discussed.

A preliminary evaluation of the Colorado RETHINK Parenting and Anger Management program.

OBJECTIVE: The purpose was to report preliminary behavioral, social, and emotional results, and to project some potential economic results of a parenting and anger management program in a mountain state. METHOD: Following local and state-wide needs assessments, child abuse prevention was identified as the number two critical issue. An effective, research-based, preventive educational workshop program--RETHINK Parenting and Anger Management--was selected for testing and program evaluation. Measurable outcome objectives were written and assessments were developed and tested. A one-group pretest-posttest design with a convenience sample of parents was used for the study. Seventy-five of 99 parents completed pretests before and posttests after participating in the 6-week series of skill-enhancing workshops. RESULTS: Using a repeated measures analysis of variance, participants' group mean anger control levels increased (p = .016). Their family conflict levels fell (p = .006). Their overall anger levels fell (p = .000). Their violence levels fell, verbal aggression levels fell (p = .002). Their partners' violence levels also fell, verbal aggression levels fell (p = .004), and physical aggression levels fell (p = .032). In addition, participants reported increased knowledge levels (100%), improved attitudes (97.3%), improved behaviors (94.7%), and decreased unrealistic expectations of their children (69.3%). CONCLUSION: The findings suggest that professional preventive education specialists may now have an effective program to assist parents in managing their anger. Further research is encouraged. When parents participate in 6 weeks of skill building with well-trained professionals, positive changes in parenting and anger management are possible.

Oriented Gaussian mixture models for nonrigid 2D/3D coronary artery registration.

2D/3D registration of patient vasculature from preinterventional computed tomography angiography (CTA) to interventional X-ray angiography is of interest to improve guidance in percutaneous coronary interventions. In this paper we present a novel feature based 2D/3D registration framework, that is based on probabilistic point correspondences, and show its usefulness on aligning 3D coronary artery centerlines derived from CTA images with their 2D projection derived from interventional X-ray angiography. The registration framework is an extension of the Gaussian mixture model (GMM) based point-set registration to the 2D/3D setting, with a modified distance metric. We also propose a way to incorporate orientation in the registration, and show its added value for artery registration on patient datasets as well as in simulation experiments. The oriented GMM registration achieved a median accuracy of 1.06 mm, with a convergence rate of 81% for nonrigid vessel centerline registration on 12 patient datasets, using a statistical shape model. The method thereby outperformed the iterative closest point algorithm, the GMM registration without orientation, and two recently published methods on 2D/3D coronary artery registration.

First-line evaluation of coronary artery disease with coronary calcium scanning or exercise electrocardiography.

BACKGROUND: Although conventional (CAG) and computed tomography angiography (CTA) are reliable diagnostic modalities for exclusion of obstructive coronary artery disease (CAD), they are costly and with considerable exposure to radiation and contrast media. We compared the accuracy of coronary calcium scanning (CCS) and exercise electrocardiography (X-ECG) as less expensive and non-invasive means to rule out obstructive CAD. METHODS: In a rapid-access chest pain clinic, 791 consecutive patients with stable chest pain were planned to undergo X-ECG and dual-source CTA with CCS. According to the Duke pre-test probability of CAD patients were classified as low (<30%), intermediate (30-70%) or high risk (>70%). Angiographic obstructive CAD (>50% stenosis by CAG or CTA) was found in 210/791 (27%) patients, CAG overruling any CTA results. RESULTS: Obstructive CAD was found in 12/281 (4%) patients with no coronary calcium and in 73/319 (23%) with a normal X-ECG (p<0.001). No coronary calcium was associated with a substantially lower likelihood ratio compared to X-ECG; 0.11, 0.13 and 0.13 vs. 0.93, 0.55 and 0.46 in the low, intermediate and high risk group. In low risk patients a negative calcium score reduced the likelihood of obstructive CAD to less than 5%, removing the need for further diagnostic work-up. CCS could be performed in 754/756 (100%) patients, while X-ECG was diagnostic in 448/756 (59%) patients (p<0.001). CONCLUSIONS: In real-world patients with stable chest pain CCS is a reliable initial test to rule out obstructive CAD and can be performed in virtually all patients.