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BACKGROUND Anastomotic leakage (AL), a severe complication following colorectal surgery, arises from defects at the anastomosis site. This study evaluates the feasibility of predicting AL using machine learning (ML) algorithms based on preoperative data. METHODS We retrospectively analyzed data including 21 predictors from patients undergoing colorectal surgery with bowel anastomosis at four Swiss hospitals. Several ML algorithms were applied for binary classification into AL or non-AL groups, utilizing a five-fold cross-validation strategy with a 90% training and 10% validation split. Additionally, a holdout test set from an external hospital was employed to assess the models' robustness in external validation. RESULTS Among 1244 patients, 112 (9.0%) suffered from AL. The Random Forest model showed an AUC-ROC of 0.78 (SD: ± 0.01) on the internal test set, which significantly decreased to 0.60 (SD: ± 0.05) on the external holdout test set comprising 198 patients, including 7 (3.5%) with AL. Conversely, the Logistic Regression model demonstrated more consistent AUC-ROC values of 0.69 (SD: ± 0.01) on the internal set and 0.61 (SD: ± 0.05) on the external set. Accuracy measures for Random Forest were 0.82 (SD: ± 0.04) internally and 0.87 (SD: ± 0.08) externally, while Logistic Regression achieved accuracies of 0.81 (SD: ± 0.10) and 0.88 (SD: ± 0.15). F1 Scores for Random Forest moved from 0.58 (SD: ± 0.03) internally to 0.51 (SD: ± 0.03) externally, with Logistic Regression maintaining more stable scores of 0.53 (SD: ± 0.04) and 0.51 (SD: ± 0.02). CONCLUSION In this pilot study, we evaluated ML-based prediction models for AL post-colorectal surgery and identified ten patient-related risk factors associated with AL. Highlighting the need for multicenter data, external validation, and larger sample sizes, our findings emphasize the potential of ML in enhancing surgical outcomes and inform future development of a web-based application for broader clinical use. more...

A 60-year-old female patient with longstanding left-sided ulcerative colitis presented with symptoms mimicking an acute flare and developed a colonic perforation shortly after starting steroid treatment. Following left hemicolectomy and Hartmann's procedure, rescue treatment with infliximab was started. Within a few days, the patient developed hepatic failure. Histology and immunohistochemistry of the specimen revealed extensive necrotizing herpes simplex virus colitis, and liver biopsy demonstrated herpes simplex virus hepatitis. Sixteen days after admission, the patient died from multiorgan failure. This compelling case of severe herpes simplex virus colitis raises awareness of a rare but potentially detrimental infection in patients with inflammatory bowel disease. more...

Background The costimulatory receptor 4-1BB (CD137, TNFRSF9) plays an important role in sustaining effective T cell immune responses and is investigated as target for cancer therapy. Systemic 4-1BB directed therapies elicit toxicity or low efficacy, which significantly hampered advancement of 4-1BB-based immunotherapy. Therefore, targeted delivery of 4-1BB agonist to the tumor side is needed for eliciting antitumor efficacy while avoiding systemic toxicity. Methods We analyzed the immunostimulatory properties of a fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL) by assessing tumor-infiltrating lymphocytes' (TIL) activity from patients with non-small cell lung cancer and epithelial ovarian cancer. Results Combination treatment with FAP-4-1BBL and T cell receptor stimulation by either anti-CD3 or T cell bispecific antibodies significantly enhanced TIL activation and effector functions, including T cell proliferation, secretion of proinflammatory cytokines and cytotoxicity. Notably, costimulation with FAP-4-1BBL led to de novo secretion of interleukin (IL)-13. This was associated with cytokine-mediated tumor cell apoptosis, which was partially dependent on IL-13 alpha 1/2 receptors and STAT6 phosphorylation. Conclusions Our study provides mechanistic insights into T cell stimulation induced by FAP-4-1BBL in primary human tumors and supports the investigation of FAP-4-1BBL compound in early clinical trials. more...

Background The costimulatory receptor 4-1BB (CD137, TNFRSF9) plays an important role in sustaining effective T cell immune responses and is investigated as target for cancer therapy. Systemic 4-1BB directed therapies elicit toxicity or low efficacy, which significantly hampered advancement of 4-1BB-based immunotherapy. Therefore, targeted delivery of 4-1BB agonist to the tumor side is needed for eliciting antitumor efficacy while avoiding systemic toxicity. Methods We analyzed the immunostimulatory properties of a fibroblast activation protein (FAP)-targeted 4-1BB agonist (FAP-4-1BBL) by assessing tumor-infiltrating lymphocytes' (TIL) activity from patients with non-small cell lung cancer and epithelial ovarian cancer. Results Combination treatment with FAP-4-1BBL and T cell receptor stimulation by either anti-CD3 or T cell bispecific antibodies significantly enhanced TIL activation and effector functions, including T cell proliferation, secretion of proinflammatory cytokines and cytotoxicity. Notably, costimulation with FAP-4-1BBL led to de novo secretion of interleukin (IL)-13. This was associated with cytokine-mediated tumor cell apoptosis, which was partially dependent on IL-13 alpha 1/2 receptors and STAT6 phosphorylation. Conclusions Our study provides mechanistic insights into T cell stimulation induced by FAP-4-1BBL in primary human tumors and supports the investigation of FAP-4-1BBL compound in early clinical trials. more...

PurposeThe National Mammography Database (NMD) contains nearly 20 million examinations from 693 facilities; it is the largest information source for use and effectiveness of breast imaging in the United States. NMD collects demographic, imaging, interpretation, biopsy, and basic pathology results, enabling facility and physician comparison for quality improvement. However, NMD lacks treatment and clinical outcomes data. The network of state cancer registries (CRs) contains detailed pathologic, treatment, and clinical outcomes data. This pilot study assessed electronic linkage of NMD and CR data at a multicenter institution as proof of concept.Materials and methodsWe obtained Quality Oversight Committee approval for this retrospective study. Data of patients diagnosed with breast cancer in 2014 and 2015 were retrieved from our NMD-approved radiology information system (RIS) and matched with reportable patients in our CR using social security number (SSN), first name (fname), last name (lname), and date of birth (DOB). Matching was repeated without SSN. Percentage and reasons for mismatch were evaluated.ResultsThe RIS query identified 1,316 patients. CR linkage was 99.2% successful (n = 1,305 of 1,316) using SSN, fname, lname, and DOB. Eleven mismatches included four CR case-finding failures, one NMD fname error, five nonreportable in the CR, and one with correct identifiers in both databases. Without SSN, linkage was 97.3% successful (n = 1,281 of 1,316); name errors accounted for 19 and DOB accounted for 5 additional mismatches.ConclusionUsing common data elements, linkage between the NMD and state CRs may be feasible and could provide critical outcomes information to advance accurate assessment of breast imaging in the United States. more...

BACKGROUND Postoperative ileus after colorectal surgery is a frequent problem that significantly prolongs hospital stay and increases perioperative costs. OBJECTIVE The aim was to evaluate the effect of standardized coffee intake on postoperative bowel movement after elective laparoscopic colorectal resection. DESIGN This is a prospective randomized controlled trial that was conducted between September 2014 and December 2016. SETTINGS This study was performed in a public cantonal hospital in Switzerland with accreditation for colon and rectum cancer surgery. PATIENTS Patients who underwent elective colorectal surgery were included. INTERVENTIONS Patients were randomly assigned either to the intervention group receiving coffee or the control group receiving tea. A total of 150 mL of the respective beverage was drunk 3 times per day every postoperative day until discharge. MAIN OUTCOME MEASURES The primary end point was time to first bowel movement. Secondary end points included the use of laxative, insertion of a nasogastric tube, length of hospital stay, and postoperative complications. RESULTS A total of 115 patients were randomly assigned: 56 were allocated to the coffee group and 59 to the tea group. After coffee intake, the first bowel movement occurred after a median of 65.2 hours versus 74.1 hours in the control group (intention-to-treat analysis; p = 0.008). The HR for earlier first bowel movement after coffee intake was 1.67 (p = 0.009). In the per-protocol analysis, hospital stay was shorter in the coffee group (6 d in the coffee group vs 7 d in the tea group; p = 0.043). LIMITATIONS The rate of protocol violation, mostly coffee consumption in the tea arm, was relatively high, even if patients were clearly instructed not to consume coffee if they were in the tea arm. CONCLUSIONS Coffee intake after elective laparoscopic colorectal resection leads to faster recovery of bowel function. Therefore, coffee intake represents a simple and effective strategy to pre more...

Purpose: The molecular chaperone heat shock protein 90 (HSP90) plays an important role in several types of tumors also participating in the modulation of the activity of receptor tyrosine kinases activity such as members of the Her family. We evaluated the significance of HSP90 and Her2 expression in colon cancer. Methods: HSP90 and Her2 expression was determined by immunohistochemistry and by fluorescence in situ hybridization (FISH) on 355 primary resected colon carcinomas. Results were correlated with pathologic features (Union for International Cancer Control (UICC) pTNM category, tumor localisation, tumor differentiation), additional molecular genetic characteristics (BRAF, KRAS mutational status, mismatch repair genes (MMR)), and survival. Results: HSP90 immunoreactivity was observed in various degrees. Fifty-one cases (14%) were positive for Her2 (score 2+ and 3+) with 16/43 cases with Her2 2+ staining pattern showing amplification of Her2 determined by FISH. There was a significant correlation between high HSP90 expression and Her2 overexpression (p = 0.011). High HSP90 expression was associated with earlier tumor stages (p = 0.019), absence of lymph node (p = 0.006), and absence of distant metastases (p = 0.001). Patients with high tumoral HSP90 levels had a better survival (p = 0.032), but this was not independent from other prognostic relevant pathologic parameters. Her2 expression was not associated with any of the investigated histopathological, molecular, or clinical parameters. Conclusions: High HSP90 levels are reflecting lower malignant potential in colon cancer. Her2 positivity can be observed in a small number of cases. Targeting HSP90 and/or Her2 may be an alternative therapeutic approach in colon cancer in a subset of patients. more...

Physical characteristics: Original contains color illustrations, 形態: カラー図版あり, Accepted: 2017-11-08

2009 erfolgte mit der 7. Edition die Neuauflage der TNM-Klassifikation für das kolorektale Karzinom. Durch die Einführung neuer Untergruppen sollte eine präzisere Prognosevorhersage ermöglicht werden. Gleichzeitig nahm die Komplexität erheblich zu. Zwischen 1990 und 2006 wurden 2.229 Patienten aufgrund eines kolorektalen Karzinoms am Klinikum rechts der Isar der TU München operiert. Anhand dieser Datensätze wurde die prognostische Güte der früheren sechsten TNM-Version, der aktuellen siebten TNM-Version sowie eines weiteren auf klinischen und histopathologischen Faktoren beruhenden Prognosemodells untersucht. Nur 7% aller Patienten wurden in der neuen TNM-Version in ein anderes Stadium umklassifiziert. Bis auf geringe Subgruppeneffekte zeigten sich keine relevanten Unterschiede der Prognosevorhersage zwischen sechster Version, siebter Version und dem unabhängigen Prognosemodell. Trotz höherer Komplexität erreicht die neue TNM-Klassifikation nicht das Ziel einer verbesserten Prognosevorhersage., In 2009, the 7th edition of the TNM classification for colorectal cancer was published, with the aim of improving prediction of prognosis. The complexity of the classification increased simultaneously. Between 1990 and 2006, 2.229 patients underwent colorectal cancer surgery at the Klinikum rechts der Isar, TU München. This data sets allowed comparison of the prognostic value of the former 6th, of the new 7th and of another prognosic model based on clinical and histopathological factors. Only 7% of all patients had a stage shift in the new TNM classification. Despite small effects in distinct subgroups, there was no relevant difference between the prediction of prognosis regarding the 6th and the 7th edition as well as the independent prognostic model. Despite increased complexity, the new TNM classification did not reach the aim of providing a better prognostic model. more...

Varying degrees of partial methylation are performed on the (111) surface of p-type Si in order to investigate the role of mixed surface functionality on the device’s overall properties. Current-voltage characteristics are acquired in nonaqueous regenerative photoelectrochemical cells with a variety of one-electron redox species. P-type and p/n+ electrodes are evaluated, allowing comparisons between devices where the energy barrier is set by the semiconductor-liquid interface and devices where the energy barrier is set by the buried junction with the heavily doped emitter layer. In contrast to fully methylated or entirely unprotected surfaces, the intermediately methylated devices exhibit mixed monolayers with a disparity in barrier height. Charge transfer across these interfaces is studied, and effects such as pinch-off are considered in the search for a threshold surface composition for acceptable device performance. more...

Varying degrees of partial methylation are performed on the (111) surface of p-type Si in order to investigate the role of mixed surface functionality on the device’s overall properties. Current-voltage characteristics are acquired in nonaqueous regenerative photoelectrochemical cells with a variety of one-electron redox species. P-type and p/n+ electrodes are evaluated, allowing comparisons between devices where the energy barrier is set by the semiconductor-liquid interface and devices where the energy barrier is set by the buried junction with the heavily doped emitter layer. In contrast to fully methylated or entirely unprotected surfaces, the intermediately methylated devices exhibit mixed monolayers with a disparity in barrier height. Charge transfer across these interfaces is studied, and effects such as pinch-off are considered in the search for a threshold surface composition for acceptable device performance. more...

Ziel der Dissertation war die Analyse der Daten von 1263 Patienten, die im Klinikum Rechts der Isar von 1982 – Mai 2006 aufgrund eines Rektumkarzinoms operiert wurden. Zudem wurden die Subkollektive von Patienten mit einem Stadium I und solche mit einem Stadium II/III hinsichtlich ihres Überlebens und relevanter Prognosefaktoren untersucht, sowie der Einfluss einer neoadjuvanten Radiochemotherapie. Es zeigte sich, dass sich die Prognose über den Zeitraum von 25 Jahren signifikant verbessert hat. Im klinischen Stadium II/III hat die konsequente Einführung der neoadjuvanten Radiochemotherapie sowie die chirurgische Optimierung durch Einführung der totalen mesorektalen Exzision zu einer signifikanten Reduktion der Lokalrezidivrate geführt., Aim of the study was to analyze the data of 1263 patients who having undergone surgery in Klinikum Rechts der Isar from 1982 to May 2006 concerning rectal cancer. Moreover, the subgroup of patients with rectal cancer with stage I and of those with a stage II/III was evaluated in terms of survival rate and relevant prognostic factors, and the influence of neoadjuvant radiochemotherapy. It was found that the prognosis of patients with rectal cancer over a period of 25 years has improved significantly. In clinical stage II/III, the systematic introduction of neoadjuvant chemoradiotherapy and the surgical improvement through the introduction of total mesorectal excision have resulted in a significant reduction of the local recurrence rate. more...

Varying degrees of partial methylation are performed on the (111) surface of p-type Si in order to investigate the role of mixed surface functionality on the device’s overall properties. Current-voltage characteristics are acquired in nonaqueous regenerative photoelectrochemical cells with a variety of one-electron redox species. P-type and p/n+ electrodes are evaluated, allowing comparisons between devices where the energy barrier is set by the semiconductor-liquid interface and devices where the energy barrier is set by the buried junction with the heavily doped emitter layer. In contrast to fully methylated or entirely unprotected surfaces, the intermediately methylated devices exhibit mixed monolayers with a disparity in barrier height. Charge transfer across these interfaces is studied, and effects such as pinch-off are considered in the search for a threshold surface composition for acceptable device performance. more...

Der Lymphknotenstatus und die Gesamtzahl resezierter Lymphknoten sind wichtige Prognosefaktoren beim kolorektalen Karzinom. Trotz der Empfehlung unserer Fachgesellschaften, dass mindestens 12 Lymphknoten reseziert werden sollten, unterscheiden sich die Daten zur Gesamtzahl resezierter Lymphknoten erheblich. Ziel der Studie war es, die prognostische Bedeutung des Lymphknotenquotienten (Verhältnis der Anzahl tumorinfiltrierter zur Anzahl resezierter Lymphknoten) zu untersuchen. Untersucht wurden klinische und histopathologische Daten von 3026 Patienten mit kolorektalem Karzinom, die zwischen 1982 und 2006 am Klinikum Rechts der Isar operiert wurden. Die statistisch berechneten Cut-off-Werte des Lymphknotenquotienten mit der höchsten prognostischen Diskrimination lagen bei 0,17, 0,41 und 0,69. Der Lymphknotenquotient führte zu einer feineren prognostischen Stratifizierung als die pN-Kategorie. In der multivariaten Analyse stellten sowohl der Lymphknotenquotient als auch die pN-Kategorie unabhängige prognostische Faktoren dar. Der Lymphknotenquotient sollte aufgrund seiner stärkeren prognostischen Stratifizierung stets angegeben werden., The lymph node status and the total number of resected lymph nodes are important prognostic factors in patients with colorectal cancer. In spite of the recommendation of our expert societies that at least a total number of 12 lymph nodes should be resected, studies still report large differences in lymph node numbers. The aim of the study was to examine the prognostic impact of lymph node ratio (relation of tumor-infiltrated to resected lymph nodes). The analysis contents the clinical and histopathological data of 3026 patients with colorectal cancer, who were operated at Klinikum Rechts der Isar between 1982 and 2006. The cut-off values for the highest prognostic differentiation of lymph node ratios were statistically calculated as 0.17, 0.41 and 0.69. The lymph node ratio had a better prognostic value than the pN category. Multivariate analysis identified both the lymph node ratio and the pN category as independent prognostic factors. Because of the further detailed prognostic stratification the lymph node ratio should always be reported. more...

Rationale and objectivesEvidence is inconsistent about whether radiologists' interpretive performance on a screening mammography test set reflects their performance in clinical practice. This study aimed to estimate the correlation between test set and clinical performance and determine if the correlation is influenced by cancer prevalence or lesion difficulty in the test set.Materials and methodsThis institutional review board-approved study randomized 83 radiologists from six Breast Cancer Surveillance Consortium registries to assess one of four test sets of 109 screening mammograms each; 48 radiologists completed a fifth test set of 110 mammograms 2 years later. Test sets differed in number of cancer cases and difficulty of lesion detection. Test set sensitivity and specificity were estimated using woman-level and breast-level recall with cancer status and expert opinion as gold standards. Clinical performance was estimated using women-level recall with cancer status as the gold standard. Spearman rank correlations between test set and clinical performance with 95% confidence intervals (CI) were estimated.ResultsFor test sets with fewer cancers (N = 15) that were more difficult to detect, correlations were weak to moderate for sensitivity (woman level = 0.46, 95% CI = 0.16, 0.69; breast level = 0.35, 95% CI = 0.03, 0.61) and weak for specificity (0.24, 95% CI = 0.01, 0.45) relative to expert recall. Correlations for test sets with more cancers (N = 30) were close to 0 and not statistically significant.ConclusionsCorrelations between screening performance on a test set and performance in clinical practice are not strong. Test set performance more accurately reflects performance in clinical practice if cancer prevalence is low and lesions are challenging to detect. more...

A completely updated, expanded edition of a longstanding and influential text on chemical thermodynamics Covers the logical foundations and interrelationships of thermodynamics and their application to problems that are commonly encountered by the chemist. Explanations of abstract concepts in a clear and simple, yet still rigorous fashion Logical arrangement of the material to facilitate learning, including worked out examples. Computational techniques, graphical, numerical, and analytical, are described fully and are used frequently, both in illustrative and in assigned problems. more...

A completely updated, expanded edition of a longstanding and influential text on chemical thermodynamics Covers the logical foundations and interrelationships of thermodynamics and their application to problems that are commonly encountered by the chemist. Explanations of abstract concepts in a clear and simple, yet still rigorous fashion Logical arrangement of the material to facilitate learning, including worked out examples. Computational techniques, graphical, numerical, and analytical, are described fully and are used frequently, both in illustrative and in assigned problems. more...

A completely updated, expanded edition of a longstanding and influential text on chemical thermodynamics Covers the logical foundations and interrelationships of thermodynamics and their application to problems that are commonly encountered by the chemist. Explanations of abstract concepts in a clear and simple, yet still rigorous fashion Logical arrangement of the material to facilitate learning, including worked out examples. Computational techniques, graphical, numerical, and analytical, are described fully and are used frequently, both in illustrative and in assigned problems. more...

ObjectiveUsing a combination of performance measures, we updated previously proposed criteria for identifying physicians whose performance interpreting screening mammography may indicate suboptimal interpretation skills.Materials and methodsIn this study, six expert breast imagers used a method based on the Angoff approach to update criteria for acceptable mammography performance on the basis of two sets of combined performance measures: set 1, sensitivity and specificity for facilities with complete capture of false-negative cancers; and set 2, cancer detection rate (CDR), recall rate, and positive predictive value of a recall (PPV1) for facilities that cannot capture false-negative cancers but have reliable cancer follow-up information for positive mammography results. Decisions were informed by normative data from the Breast Cancer Surveillance Consortium (BCSC).ResultsUpdated combined ranges for acceptable sensitivity and specificity of screening mammography are sensitivity≥80% and specificity≥85% or sensitivity 75-79% and specificity 88-97%. Updated ranges for CDR, recall rate, and PPV1 are: CDR≥6 per 1000, recall rate 3-20%, and any PPV1; CDR 4-6 per 1000, recall rate 3-15%, and PPV1≥3%; or CDR 2.5-4.0 per 1000, recall rate 5-12%, and PPV1 3-8%. Using the original criteria, 51% of BCSC radiologists had acceptable sensitivity and specificity; 40% had acceptable CDR, recall rate, and PPV1. Using the combined criteria, 69% had acceptable sensitivity and specificity and 62% had acceptable CDR, recall rate, and PPV1.ConclusionThe combined criteria improve previous criteria by considering the interrelationships of multiple performance measures and broaden the acceptable performance ranges compared with previous criteria based on individual measures. more...

AIM: VE1 is a monoclonal antibody detecting mutant BRAFV(600E) protein by immunohistochemistry. Here we aim to determine the inter-observer agreement and concordance of VE1 with mutational status, investigate heterogeneity in colorectal cancers and metastases and determine the prognostic effect of VE1 in colorectal cancer patients. METHODS: Concordance of VE1 with mutational status and inter-observer agreement were tested on a pilot cohort of colorectal cancers (n = 34), melanomas (n = 23) and thyroid cancers (n = 8). Two prognostic cohorts were evaluated (n = 259, Cohort 1 and n = 226, Cohort 2) by multiple-punch tissue microarrays. VE1 staining on preoperative biopsies (n = 118 patients) was compared to expression in resections. Primary tumors and metastases from 13 patients were tested for VE1 heterogeneity using a tissue microarray generated from all available blocks (n = 100 blocks). RESULTS: Inter-observer agreement was 100% (kappa = 1.0). Concordance between VE1 and V600E mutation was 98.5%. Cohort 1: VE1 positivity (seen in 13.5%) was associated with older age (p = 0.0175) and MLH1 deficiency (p < 0.0001). Cohort 2: VE1 positivity (seen in 12.8%) was associated with female gender (p = 0.0016), right-sided tumor location (p < 0.0001), higher tumor grade (p < 0.0001) and mismatch repair (MMR)-deficiency (p < 0.0001). In survival analysis, MMR status and postoperative therapy were identified as possible confounding factors. Adjusting for these features, VE1 was an unfavorable prognostic factor. Preoperative biopsy staining matched resections in all cases except one. No heterogeneity was found across any primary/metastatic tumor blocks. CONCLUSION: VE1 is highly concordant for V600E and homogeneously expressed suggesting staining can be analysed on resection specimens, preoperative biopsies, metastatic lesions and tissue microarrays. more...

BackgroundUpgrade rates of high-risk breast lesions after screening mammography were examined.MethodsThe Breast Cancer Surveillance Consortium registry was used to identify all Breast Imaging Reporting and Data System category 4 assessments followed by needle biopsies with high-risk lesions. Follow-up was performed for all women.ResultsHigh-risk lesions were found in 957 needle biopsies, with excision documented in 53%. Most (n = 685) were atypical ductal hyperplasia (ADH), 173 were lobular neoplasia, and 99 were papillary lesions. Upgrade to cancer varied with type of lesion (18% in ADH, 10% in lobular neoplasia, and 2% in papillary lesions). In premenopausal women with ADH, upgrade was associated with family history. Cancers associated with ADH were mostly (82%) ductal carcinoma in situ, and those associated with lobular neoplasia were mostly (56%) invasive. During a further 2 years of follow-up, cancer was documented in 1% of women with follow-up surgery and in 3% with no surgery.ConclusionsDespite low rates of surgery, low rates of cancer were documented during follow-up. Benign papillary lesions diagnosed on Breast Imaging Reporting and Data System category 4 mammograms among asymptomatic women do not justify surgical excision. more...

IL-23 is a heterodimeric cytokine involved in inflammatory diseases; its role in cancer progression is controversial. Here we analyse the expression of IL-23 subunits (p40 and p19) and IL-23R in colorectal cancer with regard to disease progression, clinical-pathological and molecular aspects. Immunohistochemistry for IL-23p19, IL-23p40, IL-23R and CD8 was performed on a multi-punch tissue microarray of 195 colorectal cancers (cohort 1), matched normal tissue, adenoma and lymph node metastases. Results were compared with clinical-pathological features and CD8+ T-cell counts, then validated on two patient cohorts (cohort 2: n=341, cohort 3: n=139). Cytoplasmic/membranous expression of IL-23 (p19 and p40 subunits) and IL-23R, respectively were over-expressed in carcinomas versus adenomas and normal tissues (p<0.0001) but were reduced in lymph node metastases (p<0.0001). Nuclear IL-23p19 expression was observed in 23.1% and was associated with early TNM stage (p=0.0186), absence of venous (p=0.0124) and lymphatic invasion (p=0.01493), favorable survival (p=0.014) and absence of distant metastasis (p=0.0146; specificity: 100%). This unexpected cellular localization was confirmed by cell fractionation. The beneficial effect of nuclear IL-23p19 was restricted to tumours with CD8+ high counts. Results were validated on Cohorts 2/3. This multicenter study underlines the possible CD8(+)--dependency and beneficial effect of nuclear IL-23p19 on overall patient survival. more...

PurposeTo develop criteria to identify thresholds for the minimally acceptable performance of physicians interpreting diagnostic mammography studies.Materials and methodsIn an institutional review board-approved HIPAA-compliant study, an Angoff approach was used to set criteria for identifying minimally acceptable interpretive performance for both workup after abnormal screening examinations and workup of a breast lump. Normative data from the Breast Cancer Surveillance Consortium (BCSC) was used to help the expert radiologist identify the impact of cut points. Simulations, also using data from the BCSC, were used to estimate the expected clinical impact from the recommended performance thresholds.ResultsFinal cut points for workup of abnormal screening examinations were as follows: sensitivity, less than 80%; specificity, less than 80% or greater than 95%; abnormal interpretation rate, less than 8% or greater than 25%; positive predictive value (PPV) of biopsy recommendation (PPV2), less than 15% or greater than 40%; PPV of biopsy performed (PPV3), less than 20% or greater than 45%; and cancer diagnosis rate, less than 20 per 1000 interpretations. Final cut points for workup of a breast lump were as follows: sensitivity, less than 85%; specificity, less than 83% or greater than 95%; abnormal interpretation rate, less than 10% or greater than 25%; PPV2, less than 25% or greater than 50%; PPV3, less than 30% or greater than 55%; and cancer diagnosis rate, less than 40 per 1000 interpretations. If underperforming physicians moved into the acceptable range after remedial training, the expected result would be (a) diagnosis of an additional 86 cancers per 100,000 women undergoing workup after screening examinations, with a reduction in the number of false-positive examinations by 1067 per 100,000 women undergoing this workup, and (b) diagnosis of an additional 335 cancers per 100,000 women undergoing workup of a breast lump, with a reduction in the number of false-posit more...

PurposeTo describe recruitment, enrollment, and participation in a study of US radiologists invited to participate in a randomized controlled trial of two continuing medical education (CME) interventions designed to improve interpretation of screening mammography.MethodsWe collected recruitment, consent, and intervention-completion information as part of a large study involving radiologists in California, Oregon, Washington, New Mexico, New Hampshire, North Carolina, and Vermont. Consenting radiologists were randomized to receive either a 1-day live, expert-led educational session; to receive a self-paced DVD with similar content; or to a control group (delayed intervention). The impact of the interventions was assessed using a preintervention-postintervention test set design. All activities were institutional review board approved and HIPAA compliant.ResultsOf 403 eligible radiologists, 151 of 403 (37.5%) consented to participate in the trial and 119 of 151 (78.8%) completed the preintervention test set, leaving 119 available for randomization to one of the two intervention groups or to controls. Female radiologists were more likely than male radiologists to consent to and complete the study (P = .03). Consenting radiologists who completed all study activities were more likely to have been interpreting mammography for 10 years or less compared to radiologists who consented and did not complete all study activities or did not consent at all. The live intervention group was more likely to report their intent to change their clinical practice as a result of the intervention compared to those who received the DVD (50% versus 17.6%, P = .02). The majority of participants in both interventions groups felt the interventions were a useful way to receive CME mammography credits.ConclusionsCommunity radiologists found interactive interventions designed to improve interpretative mammography performance acceptable and useful for clinical practice. more...

2009 erfolgte mit der 7. Edition die Neuauflage der TNM-Klassifikation für das kolorektale Karzinom. Durch die Einführung neuer Untergruppen sollte eine präzisere Prognosevorhersage ermöglicht werden. Gleichzeitig nahm die Komplexität erheblich zu. Zwischen 1990 und 2006 wurden 2.229 Patienten aufgrund eines kolorektalen Karzinoms am Klinikum rechts der Isar der TU München operiert. Anhand dieser Datensätze wurde die prognostische Güte der früheren sechsten TNM-Version, der aktuellen siebten TNM-Version sowie eines weiteren auf klinischen und histopathologischen Faktoren beruhenden Prognosemodells untersucht. Nur 7% aller Patienten wurden in der neuen TNM-Version in ein anderes Stadium umklassifiziert. Bis auf geringe Subgruppeneffekte zeigten sich keine relevanten Unterschiede der Prognosevorhersage zwischen sechster Version, siebter Version und dem unabhängigen Prognosemodell. Trotz höherer Komplexität erreicht die neue TNM-Klassifikation nicht das Ziel einer verbesserten Prognosevorhersage., In 2009, the 7th edition of the TNM classification for colorectal cancer was published, with the aim of improving prediction of prognosis. The complexity of the classification increased simultaneously. Between 1990 and 2006, 2.229 patients underwent colorectal cancer surgery at the Klinikum rechts der Isar, TU München. This data sets allowed comparison of the prognostic value of the former 6th, of the new 7th and of another prognosic model based on clinical and histopathological factors. Only 7% of all patients had a stage shift in the new TNM classification. Despite small effects in distinct subgroups, there was no relevant difference between the prediction of prognosis regarding the 6th and the 7th edition as well as the independent prognostic model. Despite increased complexity, the new TNM classification did not reach the aim of providing a better prognostic model. more...

PurposeThe aim of this study was to assess agreement of mammographic interpretations by community radiologists with consensus interpretations of an expert radiology panel to inform approaches that improve mammographic performance.MethodsFrom 6 mammographic registries, 119 community-based radiologists were recruited to assess 1 of 4 randomly assigned test sets of 109 screening mammograms with comparison studies for no recall or recall, giving the most significant finding type (mass, calcifications, asymmetric density, or architectural distortion) and location. The mean proportion of agreement with an expert radiology panel was calculated by cancer status, finding type, and difficulty level of identifying the finding at the patient, breast, and lesion level. Concordance in finding type between study radiologists and the expert panel was also examined. For each finding type, the proportion of unnecessary recalls, defined as study radiologist recalls that were not expert panel recalls, was determined.ResultsRecall agreement was 100% for masses and for examinations with obvious findings in both cancer and noncancer cases. Among cancer cases, recall agreement was lower for lesions that were subtle (50%) or asymmetric (60%). Subtle noncancer findings and benign calcifications showed 33% agreement for recall. Agreement for finding responsible for recall was low, especially for architectural distortions (43%) and asymmetric densities (40%). Most unnecessary recalls (51%) were asymmetric densities.ConclusionsAgreement in mammographic interpretation was low for asymmetric densities and architectural distortions. Training focused on these interpretations could improve the accuracy of mammography and reduce unnecessary recalls. more...

Our multi-team group (Los Alamos National Laboratories (LANL) and Children s Hospital Boston and Harvard Medical School) aims to develop the next-generation ultrasound (US) technology that combines the biomechanical aspects of cancer progression with advanced 3D image reconstruction. The UNM team will initially create imaging case studies that compare findings of common pathology and normal anatomy of the conventional modalities and US tomography. UNM will use this information for subsequent patients to validate or at least clarify the value of this new US tomography information. UNM will also supply Harvard with biopsy specimens for analysis of tissue structure and mechanics. Standard imaging that UNM will use for comparison with US tomography are magnification mammography, conventional mammography, conventional sonography, contrast enhanced MRI, and breast biopsies. Study participants will be selected after undergoing conventional work-up mammography. Patients will undergo high-resolution US with existing clinical sonography compared images from the US tomography device developed at LANL. more...

Ziel der Dissertation war die Analyse der Daten von 1263 Patienten, die im Klinikum Rechts der Isar von 1982 – Mai 2006 aufgrund eines Rektumkarzinoms operiert wurden. Zudem wurden die Subkollektive von Patienten mit einem Stadium I und solche mit einem Stadium II/III hinsichtlich ihres Überlebens und relevanter Prognosefaktoren untersucht, sowie der Einfluss einer neoadjuvanten Radiochemotherapie. Es zeigte sich, dass sich die Prognose über den Zeitraum von 25 Jahren signifikant verbessert hat. Im klinischen Stadium II/III hat die konsequente Einführung der neoadjuvanten Radiochemotherapie sowie die chirurgische Optimierung durch Einführung der totalen mesorektalen Exzision zu einer signifikanten Reduktion der Lokalrezidivrate geführt., Aim of the study was to analyze the data of 1263 patients who having undergone surgery in Klinikum Rechts der Isar from 1982 to May 2006 concerning rectal cancer. Moreover, the subgroup of patients with rectal cancer with stage I and of those with a stage II/III was evaluated in terms of survival rate and relevant prognostic factors, and the influence of neoadjuvant radiochemotherapy. It was found that the prognosis of patients with rectal cancer over a period of 25 years has improved significantly. In clinical stage II/III, the systematic introduction of neoadjuvant chemoradiotherapy and the surgical improvement through the introduction of total mesorectal excision have resulted in a significant reduction of the local recurrence rate. more...

Der Lymphknotenstatus und die Gesamtzahl resezierter Lymphknoten sind wichtige Prognosefaktoren beim kolorektalen Karzinom. Trotz der Empfehlung unserer Fachgesellschaften, dass mindestens 12 Lymphknoten reseziert werden sollten, unterscheiden sich die Daten zur Gesamtzahl resezierter Lymphknoten erheblich. Ziel der Studie war es, die prognostische Bedeutung des Lymphknotenquotienten (Verhältnis der Anzahl tumorinfiltrierter zur Anzahl resezierter Lymphknoten) zu untersuchen. Untersucht wurden klinische und histopathologische Daten von 3026 Patienten mit kolorektalem Karzinom, die zwischen 1982 und 2006 am Klinikum Rechts der Isar operiert wurden. Die statistisch berechneten Cut-off-Werte des Lymphknotenquotienten mit der höchsten prognostischen Diskrimination lagen bei 0,17, 0,41 und 0,69. Der Lymphknotenquotient führte zu einer feineren prognostischen Stratifizierung als die pN-Kategorie. In der multivariaten Analyse stellten sowohl der Lymphknotenquotient als auch die pN-Kategorie unabhängige prognostische Faktoren dar. Der Lymphknotenquotient sollte aufgrund seiner stärkeren prognostischen Stratifizierung stets angegeben werden., The lymph node status and the total number of resected lymph nodes are important prognostic factors in patients with colorectal cancer. In spite of the recommendation of our expert societies that at least a total number of 12 lymph nodes should be resected, studies still report large differences in lymph node numbers. The aim of the study was to examine the prognostic impact of lymph node ratio (relation of tumor-infiltrated to resected lymph nodes). The analysis contents the clinical and histopathological data of 3026 patients with colorectal cancer, who were operated at Klinikum Rechts der Isar between 1982 and 2006. The cut-off values for the highest prognostic differentiation of lymph node ratios were statistically calculated as 0.17, 0.41 and 0.69. The lymph node ratio had a better prognostic value than the pN category. Multivariate analysis identified both the lymph node ratio and the pN category as independent prognostic factors. Because of the further detailed prognostic stratification the lymph node ratio should always be reported. more...

Udgivelsesdato: 2010-Jan-26, Diagnostic mammography is the primary imaging modality to diagnose breast cancer. However, few studies have evaluated variability in diagnostic mammography performance in communities, and none has done so between countries. We compared diagnostic mammography performance in community-based settings in the United States and Denmark. The performance of 93,585 diagnostic mammograms from 180 facilities contributing data to the US Breast Cancer Surveillance Consortium (BCSC) from 1999 to 2001 was compared to that of all 51,313 diagnostic mammograms performed at Danish clinics in 2000. We used the imaging workup's final assessment to determine sensitivity, specificity and an estimate of accuracy: area under the receiver-operating characteristics (ROCs) curve (AUC). Diagnostic mammography had slightly higher sensitivity in the United States (85%) than in Denmark (82%). In contrast, it had higher specificity in Denmark (99%) than in the United States (93%). The AUC was high in both countries: 0.91 in United States and 0.95 in Denmark. Denmark's higher accuracy may result from supplementary ultrasound examinations, which are provided to 74% of Danish women but only 37% to 52% of US women. In addition, Danish mammography facilities specialize in either diagnosis or screening, possibly leading to greater diagnostic mammography expertise in facilities dedicated to symptomatic patients. Performance of community-based diagnostic mammography settings varied markedly between the 2 countries, indicating that it can be further optimized. more...

Udgivelsesdato: 2010-Jan-26, Diagnostic mammography is the primary imaging modality to diagnose breast cancer. However, few studies have evaluated variability in diagnostic mammography performance in communities, and none has done so between countries. We compared diagnostic mammography performance in community-based settings in the United States and Denmark. The performance of 93,585 diagnostic mammograms from 180 facilities contributing data to the US Breast Cancer Surveillance Consortium (BCSC) from 1999 to 2001 was compared to that of all 51,313 diagnostic mammograms performed at Danish clinics in 2000. We used the imaging workup's final assessment to determine sensitivity, specificity and an estimate of accuracy: area under the receiver-operating characteristics (ROCs) curve (AUC). Diagnostic mammography had slightly higher sensitivity in the United States (85%) than in Denmark (82%). In contrast, it had higher specificity in Denmark (99%) than in the United States (93%). The AUC was high in both countries: 0.91 in United States and 0.95 in Denmark. Denmark's higher accuracy may result from supplementary ultrasound examinations, which are provided to 74% of Danish women but only 37% to 52% of US women. In addition, Danish mammography facilities specialize in either diagnosis or screening, possibly leading to greater diagnostic mammography expertise in facilities dedicated to symptomatic patients. Performance of community-based diagnostic mammography settings varied markedly between the 2 countries, indicating that it can be further optimized. more...

As a leading edge center within the High Performance Computing Modernization Program (HPCMP), the Center for Computational Science (CCS) of the Naval Research Laboratory evaluates new high performance computing (HPC) assets. The center is currently evaluating two systems - an Altix 3700 running the SUSE Linus Enterprise Server (SLES) 10 operating systems and a Cray XD1. With respect to the Altix system, Naval Research Laboratory is looking at applications requiring large memory and testing the new Intel 10.0 compilers. For the XD1, we are examining the applicability of dual core processors and Field Programmable Gate Arrays (FPGAs) to HPC applications., The original document contains color images. All DTIC reproductions will be in black and white. Presented at the DoD High Performance Computer Modernization Program (HPCMP) Users Group Conference (USG)(2007): A Bridge to Future Defense held in Pittsburgh, PA on 18-21 June 2007. Published in Proceedings of the DoD High Performance Computer Modernization Program (HPCMP) Users Group Conference (USG), p328-333, June 2007. Publisher: IEEE Computer Society, Conference Publishing Services (CPS). ISBN 0-7695-3088-5 and ISBN 978-0-7695-3088-8. Sponsored in part by the Department of Defense. This article is from ADA488707 Proceedings of the HPCMP Users Group Conference 2007. High Performance Computing Modernization Program: A Bridge to Future Defense held 18-21 June 2007 in Pittsburgh, Pennsylvania more...

Since December 2002 the Naval Research Laboratory (NRL) has been evaluating an Altix 3000, the newest high performance computing system available from Silicon Graphics, Inc. (SCI). The Altix is a departure from the previous products from SGI in that instead of using MIPS processors and the IRIX operating system, the Altix uses the Intel Itanium IA-64 processor and SGI ProPack (based on Linux Red Hat) operating system. The Altix still has the brick concept of system configuration and the SGI NUMA link for the inter-module network for the shared memory. The Altix runs under a single image of the operating system and supports parallel programming through OpenMP, MPI, CoArray FORTRAN and an automatic parallelizing compiler. Various codes have been evaluated with respect to their ease of portability and their performance on the Altix as compared to other high performance computers., Presented at the DoD High Performance Computing Modernization Program (HPCMP) Users Group Conference (UGC), held in Williamsburg, Virginia on 7-11 June 2004. The original document contains color images. All DTIC reproductions will be in black and white. This article is from ADA492363 Proceedings of the HPCMP Users Group Conference 2004. more...

Arbetet är utfört åt skogsforskningsstationen Mógilsá som ligger strax norr om Reykjavik. Forskningen inom Mógilsá bedrivs inom delar av eller för hela Island med inriktning inom exempelvis dendrokronologi, proveniensförsök, och studier av insekter. Sedan 1900-talets början har inplantering av exotiska trädarter blivit allt vanligare och i en allt större skala. Syften med inplanteringen är bland andra att motverka jorderosion, bilda rekreationsområden och att skapa ytterligare arbetstillfällen på glesbygden. Under det senaste decenniet har allt större satsningar gjorts för nyplantering av skog på grund av lyckosamma resultat från tidigare planteringar. För att veta inom vilka områden som olika trädslag lämpar sig bäst är det av vikt att förstå vad som medverkar till en god eller dålig tillväxt. Viktiga faktorer att studera är bland andra jordarter, plantornas ursprung, dräneringsförhållanden, klimat och topografi. Syftet med detta arbete är att finna samband mellan topografiska faktorer samt tetraterm och tillväxt hos sitkagran (Picea sitchensis) och lärk (Larix sibirica och Larix sukaczewii). På uppdrag av Mógilsá modelleras dessutom en tetratermkarta fram vilken kan användas för kommande bruk inom skogsforskningen. Kartan utnyttjas i detta arbete för att finna samband mot tillväxt för sitkagran och lärk. De topografiska faktorerna är avstånd till hav, höjd över hav, aspekt, topex, sluttningslutning och markform. Aspekt är detsamma som sluttningsriktning och markformstyperna är konvex, konkav eller planmark. Topex kan beskrivas som ett topografiskt index för lä/skyl där närliggande och fjärrliggande områden mäts i åtta väderstrecksriktningar. Efter mätningar med klinometer adderas siffrorna ihop och blir mätpunktens topexvärde. Tetraterm är medeltemperaturen för månaderna juni, juli, augusti och september. Undersökningsområdet begränsas till dalsystemen på norra Island, under 300 meter över havet, där största delen av befolkningen bor. Tillväxt-, aspekt-, sluttning, This study was made in an attempt to give the forest research centre Mógilsá a produced tetratherm map and a better understanding of how topography and temperature influence the growth of two tree species. The digital tetratherm map model, covering the northern part of Iceland, was developed to investigate the correlation between tetratherm and the growth of Picea sitchensis and Larix (sukaczewii + sibirica). The study confirms the usefulness of digital terrain models in providing data for a lot of different factors and for the tetratherm model. Hopefully will this tetratherm map be used in future studies. Secondly, investigations were made correlating the growth of the two species against topographic factors representing height above sea level, distance to the sea, slope and topex. Thirdly, investigations were made comparing the aspect and the ground shape to the growth. The growth rate of Larix had strong significant correlations to the tetratherm and the distance to the sea- factors. Picea sitchensis has a correlation to tetratherm and topex. No other factors seemed to have any significant correlations against the growth rate. The only multiple correlation that showed any significance against the growth of Larix were distance to the sea and tetratherm. There were no significant multiple correlations when correlating the factors against the growth of Picea sitchensis. Picea sitchensis have the best growth on plane ground shapes while the ground shape does not seem to matter at all for Larix. The best growth of Picea sitchensis was indicated on south to north-westerly aspects while the best growth of Larix appeared to be suited on west to northerly aspects. Comparing the results to other studies and the origin of the species gave a lot of information and made it easier to understand why there were any or none regression. This really gives an understanding of why it is good to dig into tons of papers and books. Correlations were made comparing tetratherm against the more...

It Is certainly not news that the use of commercially-available-off-the-shelf (COTS) hardware and software is revolutionizing the acquisition process for new real time embedded systems. Designs using COTS hardware and software can be the only approach to meeting today's aggressive schedule and cost budgets, while lowering production risks. Using Open Systems is an attractive approach to inexpensively incorporate increased performance as technology improves. It is hard to imagine a program manager who would not want to try to take advantage of these benefits. DOD is not only encouraging, but also mandating the use of COTS hardware and software in the development of new and replacement (sub)systems to meet current budget constraints. However, the use of COTS must be carefully managed or the results of these benefits will disappear into a life cycle maintenance nightmare. There are several lessons that have been learned about the use of COTS that should be considered before planning a new program. The use of Commercial-Off the Shelf (COTS) hardware and software in real-time systems is not new. The author has been involved in developments using COTS in real-time systems since 1983 and he was hardly a pioneer. The use of COTS in real-time systems in the past was limited by technical considerations, operational suitability issues, and life cycle concerns. The lower cost of COTS was always attractive, but for most programs these limitations made its use impractical. The major performance hurdle to using COTS in Command and Control (C2) real-time applications was always that COTS hardware and its shrink-wrapped operating systems were not designed to handle the quantity of interrupts that C2 systems need to process in a timely fashion. As technology developed, it was possible to use intelligent controller cards to solve this technical issue. There were only a handful of vendors who started to design their products for the real-time market., Presented to the Joint Avionics and Weapons Systems Support Software and Simulation Conference. more...

The MRS symposium on In-Situ Patterning: Selective Area Deposition and Etching brought together a wide selection of microfabrication technologies and detailed studies of their enabling mechanisms. The common thread through the invited and contributed papers is the chemical and/or physical alteration of surfaces by the actions of ion, electron, or photon energy. The applications ranged from state-of-the-art lithographic techniques, to direct processing of semiconductor surfaces, aiming to obviate lithography in device fabrication. This direct processing encompasses patterned deposition of metallic conductors and insulating films, as well as local etching and doping of device structures. The work demonstrated in this symposium ranged from the detailed atomic behavior of treated surfaces, to nuts-and-bolts packaging techniques for the high-density descendants of today's printed circuit boards. more...

Spectral and magnetic studies on the cobalt(II), nickel(II), and copper(II) derivatives of the zinc containing metalloenzyme carboxypeptidase A (CPA) are reported and discussed. The absorption spectrum and magnetic moment of Co(II)-CPA are shown to be consistent with a five coordinate metal structure by comparison to the spectra and magnetic moments of a large number of pseudo-tetrahedral and five coordinate cobalt(II) complexes. The usefulness of magnetic susceptibility data in assigning coordination number for high-spin cobalt(II) metalloenzyme systems is demonstrated. The absorption spectrum and magnetic moment of Ni(II)-CPA are consistent only with an octahedral ground state geometry. The effect of substrate and inhibitor on the spectrum of Ni(II)-CPA was studied. The absorption and EPR spectra of Cu(II)-CPA were also investigated. A significant pseudo-tetrahedral distortion from planar coordination geometry is indicated for this derivative. The interaction of Cu(II)-CPA and the inhibitor sodium B-phenylpropionate was also studied. The results of these studies and especially those of Ni (II)-C PA do not agree with the predictions of the entatic state hypothesis. more...

Spectral and magnetic studies on the cobalt(II), nickel(II), and copper(II) derivatives of the zinc containing metalloenzyme carboxypeptidase A (CPA) are reported and discussed. The absorption spectrum and magnetic moment of Co(II)-CPA are shown to be consistent with a five coordinate metal structure by comparison to the spectra and magnetic moments of a large number of pseudo-tetrahedral and five coordinate cobalt(II) complexes. The usefulness of magnetic susceptibility data in assigning coordination number for high-spin cobalt(II) metalloenzyme systems is demonstrated. The absorption spectrum and magnetic moment of Ni(II)-CPA are consistent only with an octahedral ground state geometry. The effect of substrate and inhibitor on the spectrum of Ni(II)-CPA was studied. The absorption and EPR spectra of Cu(II)-CPA were also investigated. A significant pseudo-tetrahedral distortion from planar coordination geometry is indicated for this derivative. The interaction of Cu(II)-CPA and the inhibitor sodium B-phenylpropionate was also studied. The results of these studies and especially those of Ni (II)-C PA do not agree with the predictions of the entatic state hypothesis. more...

Spectral and magnetic studies on the cobalt(II), nickel(II), and copper(II) derivatives of the zinc containing metalloenzyme carboxypeptidase A (CPA) are reported and discussed. The absorption spectrum and magnetic moment of Co(II)-CPA are shown to be consistent with a five coordinate metal structure by comparison to the spectra and magnetic moments of a large number of pseudo-tetrahedral and five coordinate cobalt(II) complexes. The usefulness of magnetic susceptibility data in assigning coordination number for high-spin cobalt(II) metalloenzyme systems is demonstrated. The absorption spectrum and magnetic moment of Ni(II)-CPA are consistent only with an octahedral ground state geometry. The effect of substrate and inhibitor on the spectrum of Ni(II)-CPA was studied. The absorption and EPR spectra of Cu(II)-CPA were also investigated. A significant pseudo-tetrahedral distortion from planar coordination geometry is indicated for this derivative. The interaction of Cu(II)-CPA and the inhibitor sodium B-phenylpropionate was also studied. The results of these studies and especially those of Ni (II)-C PA do not agree with the predictions of the entatic state hypothesis. more...

The Defense Budget has come under attack recently as the source of a number of problems that the american economy faces. These problems range from unemployment to the size of the national debt. Because the defense portion of the budget is presently increasing while some non-defense programs are being reduced, the attacks are becoming more frequent. I think this is a natural reaction born out of frustration in trying to cope with the many facets of our economic problems; However, decreasing the military budget will only exacerbate our and the rest of the free world's problems. Critics of defense spending have resurrected the often debated issue of the trade- off between spending for national defense and spending for social programs, also known as the *Guns VS Butter debate. Their premise is that dollars spent on defense hardware come at the expense of basic social programs. History does not support this contention. The purpose of this presentation is first to identify the forces that drive the need for defense spending; second, to review the recent history of the American economy and the defense budget; and finally to provide some perspectives on the relative cost of defense. more...

This presentation covers four inter-related subjects: The growth of Soviet Power, How the Soviet threat drives quality and quantity of forces we need, The rationale for the president's decision on the B-1 and advanced technology bomber and some material to put defense spending in perspective by relating it to other U.S. expenditures. more...

This presentation covers several inter-related subjects: The Growth of Soviet Power; How the Soviet Threat drives the type of forces we need; and some material to put defense spending in perspective by relating it to other U.S. expenditures. more...

Complete assignments of the electronic spectra of stellacyanin, plastocyanin, and azurin have been made. Bands attributable to d-d transitions have been located in the near-infrared region for the first time, and their positions are consistent with a distorted tetrahedral geometry for the blue copper center. The kinetics of the electron transfer reactions of stellacyanin, azurin, and plastocyanin with Fe(EDTA)^(2-) and Co(phen)_3^(3+) have been studied. Kinetic parameters indicate that reduction of azurin and plastocyanin by Fe(EDTA)^(2-) occurs by long distance transfer to a buried blue copper center. However, the pathway for oxidation involves substantial protein rearrangement, thereby allowing contact of Co(phen)_3^(3+) with the copper ligands. In contrast, the blue copper center of stellacyanin is equally accessible in solution to redox agents. more...

Oxidation rates of 10 and 20 mil nickel-base superalloy wires, Rene 41 and Thoriated Nickel, were measured over the range 1600 F to 2000 F for up to 1000 minutes using gravimetric methods. Rene 41 wire oxidation was characterized by the rapid growth of A1203 caused by a high concentration gradient of aluminum. Formation of this protective A1203 scale resulted in much slower oxidation of chromium from the normal parabolic rates observed for 50 mil Rene 41 sheet. A theoretical analysis based on diffusion theory for cylindrical shapes was presented to explain the measured oxidation rates. TD Nickel oxidation exhibited a parabolic rate of reaction, controlled by the growth of NiO. Both alloys suffered increases in oxidation rates with increases in temperature. Oxidation of Rene 41 wire increased with the application of stress, while TD Nickel oxidation was insensitive to stress. Internal oxidation (A1203) of Rene 41 occurred, whereas the high density surface scale of TD Nickel and lack of alloys within its matrix prevented internal oxidation. Neither alloy appeared sensitive to a decrease in 02 partial pressure. more...

The magnetic susceptibilities of cobalt(II) and nickel(II) derivatives of carboxypeptidase A (CPA) follow the Curie law over a wide temperature range. The observed magnetic moments of Co(II)CPA and Ni(II)CPA are 4.77 ± 0.15 and 2.53 ± 0.10 Bohr Magnetons, respectively. The magnetic and spectral properties of Ni(II)CPA are consistent only with an octahedral ground-state geometry, whereas Co(II)CPA has a probable five-coordinate structure. The results establish ordinary metal-ion ground states for two metallocarboxypeptidase A derivatives which exhibit full peptidase activity. more...

Preparation of cobalt(II) derivatives of type 1 copper proteins has been extended to include bean plastocyanin and azurin from Pseudomonas aeruginosa. Fluorescence quenching data suggest that Co(II) binds to the type 1 site of both apoplastocyanin and apoazurin. Electronic absorption spectral measurements have been made for cobalt(II)-stellacyanin, cobalt(1I)-plastocyanin, and cobalt(II)-azurin. In each case two visible bands with moderate intensities and two rather strong ultraviolet absorption peaks are observed. The intensity pattern and the separation of the two ultraviolet bands in the Co(II) derivatives correspond closely to the two intense, low-lying absorption peaks in the analogous, type 1 copper proteins. The evidence suggests that the intense, two-band systems represent ligand-to-metal charge transfer transitions in both Cu(II) and Co(I1) derivatives. It is proposed that the transitions in each case originate in the 3p[pi] and 3p[sigma] orbitals of a cysteine sulfur ligand at the type 1 site. The visible absorption bands in the Co(II) derivatives are assigned to d-d transitions. The large <1> splitting observed indicates that the type 1 Co(II) site is of low symmetry. The d-d band pattern suggests that the high-spin Co(II) center is either distorted tetrahedral or five-coordinate. The observed band intensities are in much closer accord with the values for Co(II) complexes known to have distorted tetrahedral structures. more...

The magnetic susceptibilities of cobalt(II) and nickel(II) derivatives of carboxypeptidase A (CPA) follow the Curie law over a wide temperature range. The observed magnetic moments of Co(II)CPA and Ni(II)CPA are 4.77 ± 0.15 and 2.53 ± 0.10 Bohr Magnetons, respectively. The magnetic and spectral properties of Ni(II)CPA are consistent only with an octahedral ground-state geometry, whereas Co(II)CPA has a probable five-coordinate structure. The results establish ordinary metal-ion ground states for two metallocarboxypeptidase A derivatives which exhibit full peptidase activity. more...

Preparation of cobalt(II) derivatives of type 1 copper proteins has been extended to include bean plastocyanin and azurin from Pseudomonas aeruginosa. Fluorescence quenching data suggest that Co(II) binds to the type 1 site of both apoplastocyanin and apoazurin. Electronic absorption spectral measurements have been made for cobalt(II)-stellacyanin, cobalt(1I)-plastocyanin, and cobalt(II)-azurin. In each case two visible bands with moderate intensities and two rather strong ultraviolet absorption peaks are observed. The intensity pattern and the separation of the two ultraviolet bands in the Co(II) derivatives correspond closely to the two intense, low-lying absorption peaks in the analogous, type 1 copper proteins. The evidence suggests that the intense, two-band systems represent ligand-to-metal charge transfer transitions in both Cu(II) and Co(I1) derivatives. It is proposed that the transitions in each case originate in the 3p[pi] and 3p[sigma] orbitals of a cysteine sulfur ligand at the type 1 site. The visible absorption bands in the Co(II) derivatives are assigned to d-d transitions. The large <1> splitting observed indicates that the type 1 Co(II) site is of low symmetry. The d-d band pattern suggests that the high-spin Co(II) center is either distorted tetrahedral or five-coordinate. The observed band intensities are in much closer accord with the values for Co(II) complexes known to have distorted tetrahedral structures. more...