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Objective To describe a cross-institutional approach to verify the Abbott ARCHITECT SARS-CoV-2 antibody assay and to document the kinetics of the serological response. Methods We conducted analytical performance evaluation studies using the Abbott ARCHITECT SARS-CoV-2 antibody assay on 5 Abbott ARCHITECT i2000 automated analyzers at 2 academic medical centers. Results Within-run and between-run coefficients of variance (CVs) for the antibody assay did not exceed 5.6% and 8.6%, respectively, for each institution. Quantitative and qualitative results agreed for lithium heparin plasma, EDTA-plasma and serum specimen types. Results for all SARS-CoV-2 IgG-positive and -negative specimens were concordant among analyzers except for 1 specimen at 1 institution. Qualitative and quantitative agreement was observed for specimens exchanged between institutions. All patients had detectable antibodies by day 10 from symptom onset and maintained seropositivity throughout specimen procurement. Conclusions The analytical performance characteristics of the Abbott ARCHITECT SARS-CoV-2 antibody assay within and between 2 academic medical center clinical laboratories were acceptable for widespread clinical-laboratory use.

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5–7 (AUC 0.76 vs. 0.56) and Gleason scores of 8–10 (AUC 0.74 vs. 0.47). With Gleason scores (8–10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.

2059 Background: BPM 31510-IV is a drug-lipid conjugate nanodispersion containing oxidized Coenzyme Q10 (CoQ10) in clinical development for glioblastoma multiforme (GBM). In a recently concluded Phase 1 study of BPM 31510-IV (NCT03020602), in addition to safety and tolerability, longitudinal pharmacodynamic samples (20 samples/cycle of 28 days) were collected at various times in patient’s refractory to radiation, temozolomide, and bevacizumab. Methods: Comprehensive multi-omic (proteomic, lipidomic, metabolomic) profiles were generated from buffy coat (proteomics only), plasma, and urine matrices. These data were further analyzed using bAIcis, a Bayesian statistics based artificial intelligence (AI) software, creating causal networks linking clinical information and endpoints to molecular composition of diverse biomatrices of patients prior to, as well as during, treatment with BPM 31510-IV. Twelve subjects comprised the intent to treat population (ITT) which were stratified across days of treatment (DR1; ≤28 days; DLT period; n=6) and (DR2, OS; >28 days; n=6). Bayesian networks and regression analysis were performed on the outputs of the analysis. Molecular analyte panels (combination of proteins, lipids, and metabolites) descriptive of progression free survival (PFS), adverse events (possibly/probably related to BPM 31510-IV), and of overall survival (OS) were generated. Results: Significant alteration (p

There is a need and desire to push low voltage point-of-load voltage regulators (POL VRs) to higher switching frequencies. The main reason for this is to increase power density. Silicon MOSFET-based solutions are rapidly approaching their technology limits and are not capable of providing multi-MHz switching frequency for high current (>10A) applications. Gallium Arsenide (GaAs) field effect transistors (FETs) can switch much faster, enabling cost-effective, high-current, high switching frequency POL VRs. Recent advances in GaAs technologies have enabled the demonstration of 5MHz VRs and provide a path to even higher frequency (>50MHz) Power Supply in Package (PSiP) solutions. The high-speed GaAs power FETs are the “engine” to enable efficient high switching frequency POL VRs, but certain key elements must be designed appropriately to realize the desired performance. The gate driver and power path impedances must be minimized. To do this, a high level of integration is required, thus packaging is a critical element. New embedded die packaging solutions enable this high level of integration, dramatically reducing key parasitic impedances that can otherwise throttle performance, while also facilitating very compact multi-chip modules.

Granular power is a well-known approach to achieve fast dynamic voltage and frequency scaling (DVFS) for SoCs. For effective granular power the voltage regulators (VRs) must be very small and very fast. Conventional MOSFET-based VRs cannot achieve these goals without significant compromise in efficiency and/or current capability. Fortunately, compound semiconductors can help alleviate this issue. Gallium Arsenide (GaAs) has superior switching attributes versus silicon and Gallium Nitride (GaN) for the voltages of interest (

Objectives: The purpose of this study was to determine whether a correlation exists between a panel of immunohistochemical stains (consisting of estrogen receptor (ER), progesterone receptor (PR) and wild type p53 (p53)) and nodal status in women with endometrioid endometrial cancer. Methods: Three hundred forty-three women underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, bilateral pelvic and para-aortic lymph node dissection performed. All tumors were stained for ER, PR and p53. This panel was compared to the patient’s nodal status and other clinic-pathologic factors. All data was collected from the patients’ charts. Results: One hundred eight patients had grade 1 tumors (83.3% node negative), one hundred forty three had grade 2 (86.6% node negative), and seventy had grade 3 (74.3% node negative). One hundred thirty six patients (39.6%) had tumors that were positive for ER, PR and negative for p53. Twenty eight patients (8.1%) had tumors that were negative for ER, PR and positive for p53. One hundred seventy nine patients (52.1%) had tumors that had mixed staining. Only 6 (4.4%) patients with ER+, PR+, p53– tumors had positive node nodes (P = 0.005). None of the sixty patients with grade 1 tumors that stained ER+, PR+, p53– had positive nodes found. Conclusion: In women with grade 1 disease, no positive nodes were found if the tumors stained positively for ER and PR and negatively for p53. Further studies will look at staining in diagnostic biopsies specimens and their correlation with nodal status.

Background The purpose of this study was to determine whether vascular endothelial growth factor (VEGF) expression in tumors correlates with the incidence of an elevated prothrombin time (PT), specifically an international normalized ratio (INR) ≥ 1.4, in patients undergoing primary surgical cytoreduction for ovarian cancer. Methods INRs were obtained on all patients perioperatively. VEGF expression was determined by immunostaining of tumor specimens using published protocols. Results One hundred patients underwent surgical cytoreduction. Sixty-seven percent of patients had postoperative INR of 1.4 or greater. INRs of greater than or equal to 1.8 were found in 5% of patients. INR elevation was independent of mean estimated blood loss (EBL) with the EBL in the patients with INRs ≥ 1.4 not significantly different than the EBL in the patients with INRs

A new GaAs power switching device, the gFET™ switch was introduced at APEC 2013. This paper describes devices developed since APEC 2013 including depletion mode devices with nominal on resistances of 7, 14 and 40 MΩ as well as an enhancement mode device with a nominal on resistance of 40 MΩ. The enhancement mode device is particularly well suited for use as a control switch in buck converters. The paper also describes the development of SPICE models from the experimental data.

BACKGROUND Mutations in p53 are the most common genetic alterations in human malignancies. Expression of its protein product has been linked to decreased survival rate in ovarian carcinoma. Less is known about the importance of p21 expression. The purpose of this study was to determine the value of the combination of p21 and p53 expression in patients with epithelial ovarian malignancies. METHODS One hundred three consecutive patients with epithelial ovarian carcinoma were studied using snap-frozen tissue specimens. Immunohistochemical staining utilizing the pAb1801 monoclonal antibody to p53 and NCL-WAF-1 monoclonal antibody to p21 was performed. Image analysis was used to determine whether nuclear staining for either antibody was present. In addition to p21 and p53, International Federation of Gynecology and Obstetrics stage, grade, histology, level of cytoreduction, and DNA index were analyzed as prognostic factors. Univariate and multivariate analyses was performed. RESULTS One hundred three patients were observed for more than 5 years. Immunohistochemical staining for p21 and p53 were significantly inversely related (P = 0.041). Among the patients whose tumors showed p21 staining but no p53 staining, there were no recurrences and all patients were alive at 5-year follow-up. The 5-year survival rate for these patients was significantly better than for the patients with other combinations of p21/p53 staining (P < 0.0001). The DNA index between these 2 groups was not significantly different (P = 0.057). Multivariate analysis shows the combination of p21 and p53 (P = 0.013) staining to be more valuable as a prognostic indicator than either p53 (P = 0.015) or p21 (P = 0.5) alone. CONCLUSIONS This study confirms the importance of the combination of p21 and p53 nuclear staining in patients with ovarian carcinoma. Cox regression analysis revealed combination of p21 positive and p53 negative to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than either p21 or p53 alone. Cancer 2001;92:781–6. © 2001 American Cancer Society.

Objective. MIB-1, a monoclonal antibody to the Ki-67 antigen, has presumptively been shown to be predictive of recurrent disease in patients with endometrial cancer. In order to more conclusively establish whether MIB-1 staining can be used as a prognostic indicator of recurrent disease or survival, a larger group of patients with a minimum follow-up of 5 years was analyzed. Methods. The tumors from 147 consecutive patients receiving primary surgical therapy for endometrial carcinoma were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. Patients were followed for a minimum of 60 months. In addition to MIB-1 staining, histologic type, stage, grade, depth of invasion, lymphovascular space invasion, and peritoneal cytology were evaluated as prognostic indicators. Results. Twenty-five of 147 patients died during the study period. MIB-1 staining was not significantly elevated in advanced (stage II, III, and IV) as opposed to early (stage I) carcinomas ( P = 0.38). In patients whose tumor MIB-1 staining was less than 33.0%, no deaths occurred. By multivariate analysis, only MIB-1 staining ( P P = 0.005), and LVI ( P = 0.005) were shown to be independent prognostic indicators predictive of survival. Conclusion. In this series of 147 consecutive patients with endometrial carcinoma, the monoclonal antibody MIB-1 was shown to be an independent prognostic indicator of 5-year survival. This follow-up further validates the previous work regarding the significance and potential usefulness of MIB-1 as a prognostic indicator.

One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. The purpose of this article was to build upon the authors' previous work with p53 and determine whether p53 was a prognostic indicator of 5-year survival.One hundred thirty-seven consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis. All patients were evaluable for 5-year survival.One hundred three patients had endometrioid adenocarcinoma; 6, adenosquamous carcinoma; 14, papillary serous carcinoma; 10, clear cell carcinoma; and 4, undifferentiated carcinoma. p53 expression ranged from 0.0 to 58.2% positive nuclear area with a mean of 11.5% (median 2.6%) for the cohort. For the patients with endometrioid carcinoma, the mean p53 expression was 7.1% while for the nonendometrioid tumors it was 24.6% (P0.001). Fifty-nine of the 103 endometrioid tumors (57.3%) stained positive for p53 while 32 of the 34 nonendometrioid (94.1%) tumors stained positive (P0.001). Increasing histologic grade correlated with an increasing p53 expression (P = 0.003). The percentage of tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.003). However, mean p53 expression did not differ between early (stage I) and advanced (stage II, III, and IV) cancers (P = 0.088). Utilizing 5-year survival as the endpoint for multivariate analysis, FIGO stage (P = 0.0028) and p53 expression (P0.001) were the only independent prognostic indicators found.p53 expression is more commonly found in nonendometrioid than in endometrioid adenocarcinoma of the endometrium. It, along with FIGO stage, is an independent prognostic indicator of 5-year survival.

Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain.Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls.Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls.This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli.

Cohen, Yale E., Greg L. Miller, and Eric I. Knudsen. Forebrain pathway for auditory space processing in the barn owl. J. Neurophysiol. 79: 891–902, 1998. The forebrain plays an important role in many aspects of sound localization behavior. Yet, the forebrain pathway that processes auditory spatial information is not known for any species. Using standard anatomic labeling techniques, we used a “top-down” approach to trace the flow of auditory spatial information from an output area of the forebrain sound localization pathway (the auditory archistriatum, AAr), back through the forebrain, and into the auditory midbrain. Previous work has demonstrated that AAr units are specialized for auditory space processing. The results presented here show that the AAr receives afferent input from Field L both directly and indirectly via the caudolateral neostriatum. Afferent input to Field L originates mainly in the auditory thalamus, nucleus ovoidalis, which, in turn, receives input from the central nucleus of the inferior colliculus. In addition, we confirmed previously reported projections of the AAr to the basal ganglia, the external nucleus of the inferior colliculus (ICX), the deep layers of the optic tectum, and various brain stem nuclei. A series of inactivation experiments demonstrated that the sharp tuning of AAr sites for binaural spatial cues depends on Field L input but not on input from the auditory space map in the midbrain ICX: pharmacological inactivation of Field L eliminated completelyauditory responses in the AAr, whereas bilateral ablation of the midbrain ICX had no appreciable effect on AAr responses. We conclude, therefore, that the forebrain sound localization pathway can process auditory spatial information independently of the midbrain localization pathway.

The perceived function of wild-type p53 is suppression of cell proliferation. An alteration in the p53 tumor suppressor gene is a common defect in human malignancies. The purpose of this study was to prospectively determine whether p53 expression, as quantified by image analysis, was related to traditional prognostic indicators as well as survival in patients epithelial ovarian cancer.Eighty-three consecutive patients with epithelial ovarian cancer had their p53 expression studied by immunohistochemical staining and quantified by image analysis. Unless otherwise noted, p53 expression was reported as the percentage positive nuclear area staining.The mean follow-up was 37 months (median, 30 months; range 24-55 months). In patients with serous carcinomas of the ovary, the mean p53 expression was 29.4%, whereas in patients with other histologies, the mean was 10.5% (P0.001). The tumors of patients with stage III or IV tumors stained significantly higher (mean 28. 7%) than the tumors of patients with stage I or II disease (mean 8. 36%) (P0.001). The tumors of patients with disease which could be optimally cytoreduced stained significantly lower (mean 23.0%) than the tumors of patients whose disease was unable to be optimally cytoreduced (mean 28.6%) (P = 0.041). Utilizing survival as the endpoint for multivariate analysis, FIGO stage (P = 0.006), p53 expression (P = 0.046), and the level of cytoreduction (P0.001) were independent prognostic indicators.Image analysis allows quantitative measurements of p53 staining. p53 staining is significantly higher in advanced-stage, high-grade tumors which are unable to be cytoreduced than in early-stage, low-grade tumors which can be optimally cytoreduced. p53 expression is an independent prognostic indicator of survival in patients with epithelial ovarian carcinomas.

The history of power electronics has been characterized by progress mainly based on improved switching devices. SCRs opened the door to modern power electronics. The silicon MOSFET made possible incredible density and efficiency. However, the silicon MOSFET is running out of steam. SiC and GaN are very promising for higher voltages [1] but are poorly suited for low-voltage switches that are so widely used in POL converters. Recently Sarda Technologies has developed a way to make a practical, low cost GaAs high electron mobility transistor (HEMT) for this application. These devices, known as gFET™ switches, offer low on-resistance, essentially negligible capacitance, and sub-nanosecond switching times. This paper describes the construction of these devices, how they operate, and presents the measured electrical characteristics of the prototype devices.

Background Endometrial carcinoma is the most common gynecologic malignancy in developed countries, affecting an estimated 140,000 women. More than 32,000 women will be diagnosed with endometrial cancer this year in the United States, and approximately 6,000 will die from this disease. Methods Twenty consecutive patients, surgically treated, with advanced endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, as well as FIGO stage, grade, and histology. DI was determined using image analysis. Results Ten of the 20 patients had recurrence of their disease within the 3-year observation period of the study. A DI of ≥ 1.2 strongly predicted recurrence of disease (P = 0.002). Increasing histologic grade and an increasing DI were related (P = 0.01). Conclusion Independent of other prognostic indicators, including lymphovascular space invasion, depth of invasion, and histologic type, a tumor with a DI of ≥ 1.2, had a significantly increased chance of recurring within the 3-year observation period. © 1996 Wiley-Liss, Inc.

Background: Endometrial carcinoma is the most common gynecologic malignancy in developed countries. Stage, grade, DNA index, histologic type, depth of invasion, steroid receptor status, and the presence of positive peritoneal cytology have all been linked to survival. The monoclonal antibody MIB-1 reacts with the same antigen as Ki-67 giving an estimate of proliferation index. The authors investigated whether MIB-1 staining, using image analysis, could be used as a prognostic indicator of recurrence in endometrial carcinoma. Methods: The tumors from 39 consecutive patients receiving primary surgical therapy for endometrial cancer were evaluated with the MIB-1 monoclonal antibody. Proliferation index was quantified by image analysis. The patients were followed for a median of 34 months and their charts were reviewed to determine recurrence, histologic type, grade, stage, depth of invasion, and status of peritoneal cytology. Results: Eleven of the 39 patients had recurrence of their disease within the 3-year observation period of this study. Overall, 22 patients had stage I disease, 3 patients had stage II disease, 12 patients had stage III disease, and 2 patients had stage IV disease. MIB-1 staining was not significantly elevated in advanced (stage III and IV) as opposed to early (stage I and II) cancers ( P = 0.558). Elevated MIB-1 staining was associated with an increased incidence of recurrence within 24 months of diagnosis ( P = 0.002). Patients whose tumors had MIB-1 staining of greater than or equal to 39.0% had an increased chance of recurring over patients whose tumors stained less than 39.0% ( P = 0.003). Conclusion: In this series of 39 patients with endometrial cancers, MIB-1 monoclonal antibody staining was shown to be a prognostic indicator of recurrence.

One of the most common genetic alterations to occur in human cancers is an alteration of the p53 tumor suppressor gene. Although endometrial cancer is the most common gynecologic malignancy in the United States, any connection between it and p53 is just beginning to be explored.Forty-six consecutively surgically treated patients with endometrial cancer had their p53 expression studied by immunoperoxidase staining and quantified by image analysis.Thirty-five patients had endometrioid adenocarcinomas, 3 had adenosquamous carcinomas, 3 had papillary serous carcinomas, 3 had clear cell carcinomas, and 2 had undifferentiated carcinomas. p53 expression ranged from 0.0 to 55.8% with a mean of 10.7% for the cohort. For the patients with endometrioid carcinomas, the mean p53 expression was 3.9%, while for those with more aggressive histologies it was 32.4% (P0.001). Sixteen of the 35 endometrioid tumors (45.7%) stained positive for p53, while 11 of the remaining 12 (91.2%) tumors with more aggressive histologies stained positive (P0.01). Increasing histologic grade correlated with an increasing p53 expression (P = 0.006). The percentage of patient tumors expressing p53 was found to be higher in FIGO stage II, III, and IV than in FIGO stage I cancer (P = 0.01). However, the mean p53 expression was not different between early (stage 1) and advanced (stage 11, III, and IV) cancers (P = 0.55). Utilizing recurrence as the endpoint for multivariate analysis, FIGO stage and p53 expression were the only independent prognostic indicators found.p53 expression is more common in more aggressive histologic subtypes than in endometrioid adenocarcinomas. It is an independent prognostic indicator of disease recurrence.

Purpose: Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer.Materials and Methods: Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis.R...

Argument theorists have long been concerned with the explanation of practical everyday argument. Since Stephen Toulmin's The Uses of Argument,(1) the study of argument fields has become a theme in argumentation theories that examine arguments in social space.(2) Responding to analytic philosophers, Toulmin posited that formal logic was an inadequate system for explaining engaged argumentative practices of social agents. Because claims of universal rationality inevitably fail to explain arguments in their real world context, Toulmin argued that different logical types of propositions correspond to different human arenas, metaphorically referred to as "fields." From this perspective argument theorists could delineate among fields by examining the systems of argumentative forms successfully employed in social fields. The study of argument fields, therefore, allowed for the systematic inquiry and consideration of argument without having to make universal claims. This view offered a practical step toward the recognition of the dynamics of social authority in particular social contexts.(3) In Human Understanding, Toulmin recasted the discussion of fields to include a schemata more analogous to academic disciplines.(4) From this perspective, a field is defined as a more formal organization based on subject matter. The institutional or disciplinary framework is the arena in which the participants apply arguments. Both of these approaches to the study of practical argumentation have generated useful scholarly debates about the definition and purpose of argument fields and the goal of argumentation studies. While the assumption that arguments are based on fields seems to be accepted uniformly by argument scholars, this insight has yet to yield a coherent critical theory of everyday argumentative practices within fields.(5) Despite the heuristic value, the argument field literature has not provided a concrete descriptive or critical method to guide inquiry. We have isolated three problems limiting the formulation of a critical theory of argument fields. First, argument theorists have not defined argument fields in a way in which both the internal logic of argumentative utterances and the external organization constraining those utterances are adequately taken into account. Second, the literature on fields has virtually ignored the dynamic discursive struggles for epistemic legitimacy in social fields in favor of a more evolutionary conception of epistemic development. Third, research into fields has failed to reconcile the riced for sociological description with its overarching disciplinary preference for normative criticism. The call to reconcile such problems in field theory is not unique to this essay. We agree with Pamela Benoit's claim that the conceptual confusion has contributed to a set of articles that construct "critical" appraisals lacking a central theoretical focus.(6) This lack of correspondence between theory and practice also caused Raymie McKerrow to question "whether the 'theory' undergirding field research has provided a sufficiently powerful critical vocabulary for the explication of arguments."(7) This essay argues that the integration of Pierre Bourdieu's theory of social practice to argument field theory provides an answer to the persistent problems confronting scholars interested in a critical social theory of argument. LIMITATIONS OF ARGUMENT FIELD LITERATURE The first practical obstacle to the formation of a coherent critical theory of argument fields is the lack of a theoretical consensus regarding the defining characteristics of an argument field. Examining the general characteristics of argument fields is useful and some degree of conceptual "fuzziness" is needed to allow argument fields to account for the diversity of argument types and settings.(8) However, current field definitions have failed to resolve adequately the tension between fields as "logical types" or as "disciplines," impeding the goal of explaining practical argumentative practices. …

Background. Thirty percent of patients with clinical Stage A nonseminomatous testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a previous retrospective study at Indiana University, the combination of tumor proliferation rates by flow cytometry and histopathologic evaluation defined risk groups for occult metastatic disease in these patients with clinical Stage A NSGCT. A new immunohistochemical proliferation marker (MIB-1) was therefore used to assess growth fraction in combination with histopathology in an effort to predict pathologic stage in patients with clinical Stage A NSGCT. Methods. Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node dissection at Indiana University were histopathologically evaluated. Formalin fixed, paraffin embedded tissue sections were immunohistochemically stained using a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67 (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method based on microwave oven heating of paraffin sections. Results. MIB-1 immunohistochemical staining showed significant differences in mean values between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients with pathologic Stage B NSGCT P = 0.0032). The negative predictive value for patients with pathologic Stage A disease was 87% using a cut-off of 80% or less MIB-1 positively stained cells. A combined approach, using the absolute volume of embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (⩾ 80%) was able to define a group of 30% of all patients who were at extremely low risk for occult metastatic disease. Conclusions. MIB-1 immunostaining in combination with histopathology aided in defining a low risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk for metastasis. The risk factors need to be tested in a prospective clinical trial to determine if they are potentially useful in assigning therapy to individual patients. Cancer 1995;75:844-50.

The authors were aware of no published studies in which the performance characteristics of first-year National Collegiate Athletic Association Division I collegiate football players were reported. From 2003 to 2006, 73 freshman and 12 transfer football recruits were tested before twice-a-day practices for bench press (BP), squat (SQ), power clean (PC), vertical jump (VJ), calculated jump power (CP), treadmill endurance capacity (Vo2peak), and maximal treadmill time (MTT). Individuals were grouped by player position for descriptive statistical analysis. As a group, offensive linemen (OL), defensive linemen (DL), linebackers (LB), tight ends (TE), and running backs (RB) averaged 152.8 kg for BP, 210.5 kg for SQ, 127.3 kg for PC, and 224.2 W for CP. These values were 22% to 30% higher than those for quarterbacks (QB), wide receivers (WR), defensive backs (DB), and kickers (K), who together averaged 120.2 kg for BP, 163.4 kg for SQ, 104.6 kg for PC, and 172.4 W for CP. Quarterbacks, WR, DB, and K as a group showed the highest MTT (13:13 m.s) and Vo2peak values (47.24 mL.kg.min), 15% to 20% higher than those for OL, DL, LB, RB, and TE, who averaged 11:27 m.s for MTT and 39.51 mL.kg.min for Vo2peak. Running backs, TE, LB, DB, and WR averaged 82.56 cm for VJ, which was 14% higher than that for DL, QB, K, and OL, who averaged 72.72 cm. On the basis of average resting blood pressure, 23.5% (20 players) were categorized as hypertensive (i.e., >/=140/90 mm Hg), 54% (46 players) as prehypertensive (i.e., 120-139/80-89 mm Hg), and 22.5% (19 players) as normal (i.e.

Endothelial phenotypes derived from different pulmonary vascular segments have markedly different permeability response to inflammatory agonists, but their responses to mechanical strain have not been characterized. Therefore, we evaluated the effect of cyclical stretch on cell shape, cell membrane wounding, and junctional beta-catenin in rat pulmonary artery (RPAEC) and microvascular (RPMVEC) endothelial cell monolayers. After 24 h of 24% uniaxial strain at 40 cycles/min, RPAEC but not RPMVEC reoriented transverse to the axis of strain. Total beta-catenin increased in RPAEC but decreased in RPMVEC. Transient plasma membrane wounding was produced by cyclical biaxial strain of 34% or by scratching of monolayers with a needle and was indicated by retention of lysine fixable fluorescent 70 kDa dextran. Junctional beta-catenin was quantified by fluorescence intensity and image analysis. beta-catenin fluorescence was significantly lower in wounded cells than in adjacent uninjured cells in both phenotypes, and the decrease was significantly greater in RPAEC compared to RPMVEC in both scratched (57% vs. 30%) and stretched (55% vs. 37%) cells. Using immunoprecipitation, VE-cadherin-associated beta-catenin decreased significantly in RPAEC (61%) but E-cadherin-associated beta-catenin was not significantly decreased in RPMVEC after 34% biaxial cyclical strain. These data suggest that RPAEC more readily remodel cell-cell adhesions during cyclical stretch than RPMVEC and that a reduced intercellular adhesion adjacent to wounded cells could serve as transvascular leak sites in both phenotypes.

Background Prognostic markers for pancreas cancer, such as CEA, CA19-9, ploidy analysis, and S-phase determination using flow cytometry, have not been consistently predictive. We chose to evaluate nuclear proliferation, as measured by the MIB-1 monoclonal antibody and digital image analysis, as a prognostic marker in pancreatic carcinoma, and compare the findings with DNA ploidy and S-phase analysis. MIB-1 identifies the Ki67 antigen present in nuclei of cells in all phases of the cell cycle except G0. Methods We retrospectively reviewed 33 patients with pancreatic adenocarcinoma resected for cure between 1989 and 1994 with available fixed tissue. Sectioned tissue was stained with MIB-1, and the number of positively stained nuclei determined and expressed as a MIB-1 labeling index (LI) by quantitative image analysis. Disaggregated nuclei were analyzed by flow cytometry using standard techniques. Results MIB-1 LI for pancreas cancers was heterogeneous within and between cancers. The MIB-1 LI for the cancers was 28 ± 15 (median 29). There was no correlation between survival and MIB-1 expression ( R 2 = 0.03). Likewise, there was no correlation between MIB-1 LI and percentage of cells in S-phase, G 2 /M, or total proliferating cells (S+G 2 /M; R 2 = 0.01), nor was there a difference between MIB-1 LI and ploidy ( P = 0.88). Conclusions We conclude that in our patient population, nuclear proliferation in pancreatic cancer, as determined by expression of Ki67 nuclear antigen, does not appear to correlate with survival and is not a useful prognostic marker. Despite intuitive thoughts to the contrary, there is no correlation between cell cycle analysis as determined by flow cytometry and Ki67 expression in pancreas cancer. Current methods of assessing prognosis after curative resection of cancer of the pancreas, including lymph node and margin status, tumor size, and possibly DNA ploidy as determined by flow cytometry, are not augmented by the assessment of nuclear proliferation by image analysis using the MIB-1 monoclonal antibody.

Binaural acoustic cues such as interaural time and level differences (ITDs and ILDs) are used by many species to determine the locations of sound sources. The relationship between cue values and locations in space is frequency dependent and varies from individual to individual. In the current study, we tested the capacity of neurons in the forebrain localization pathway of the barn owl to adjust their tuning for binaural cues in a frequency-dependent manner in response to auditory experience. Auditory experience was altered by raising young owls with a passive acoustic filtering device that caused frequency-dependent changes in ITD and ILD. Extracellular recordings were made in normal and device-reared owls to characterize frequency-specific ITD and ILD tuning in the auditory archistriatum (AAr), an output structure of the forebrain localization pathway. In device-reared owls, individual sites in the AAr exhibited highly abnormal, frequency-dependent variations in ITD tuning, and across the population of sampled sites, there were frequency-dependent shifts in the representation of ITD. These changes were in a direction that compensated for the acoustic effects of the device on ITD and therefore tended to restore a normal representation of auditory space. Although ILD tuning was degraded relative to normal at many sites in the AAr of device-reared owls, the representation of frequency-specific ILDs across the population of sampled sites was shifted in the adaptive direction. These results demonstrate that early auditory experience shapes the representation of binaural cues in the forebrain localization pathway in an adaptive, frequency-dependent manner.

p53 is the most common tumor suppressor gene involved with human malignancies. Mutations in p53 are present in approximately 50% of human malignancies. bcl-2 is a protooncogene. Expression of its protein product is related to better prognosis in several malignancies.One hundred and three patients with epithelial ovarian carcinoma were studied. Immunohistochemical staining using the pAb1801 monoclonal antibody to p53 and the anti-bcl-2 124 monoclonal antibody to bcl-2 was performed. Image analysis was used to measure percentage positive nuclear area staining of mutant p53. In addition to bcl-2 and p53, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. Univariate as well as Cox regression analysis was performed.One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO stage I disease, 4 stage II, 59 stage III, and 20 stage IV. Immunohistochemical staining for mutant p53 was not significantly related to DNA index (P = 0.99) but was related to increasing FIGO stage (P0.001) and increasing histologic grade (P = 0.039). Using Cox regression analysis, increased mutant p53 staining was an independent predictor of survival in these patients (P = 0.0032), along with stage (P0. 0001) and level of cytoreduction (P0.0001). Although by itself bcl-2 was not an independent prognostic indicator (P = 0.18), the combination of p53 and bcl-2 was independently predictive of survival (P = 0.038).This study confirms the authors' earlier report on the importance of p53 as a prognostic indicator of survival in ovarian carcinoma. Cox regression analysis reveals mutant p53 staining to be a better independent indicator of prognosis and survival in patients with ovarian carcinoma than the combination of bcl-2 and p53.

Objective. Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiologic stress. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors in patients with endometrial carcinoma. Methods. One hundred fifty-three consecutive patients with endometrial carcinoma were studied. Slides were prepared from fresh tissue. HSP27 was analyzed using a semiquantitative measurement. Patient records were examined for FIGO stage, grade, depth of myometrial invasion, histology, lymphovascular space invasion, time to recurrence, and survival. Results. The mean follow-up was 53 months (median 56 months, range 30–68 months). Endometrioid tumors showed significantly higher HSP27 staining than nonendometrioid tumors ( P = 0.005). Patients alive at the conclusion of this study had significantly higher mean HSP27 staining than patients who were deceased ( P P = 0.02), FIGO stage ( P = 0.014), and lymphovascular space invasion ( P = 0.046) to be independently predictive of survival. Conclusion. HSP27 staining is significantly higher in endometrioid than nonendometrioid tumors. HSP27 staining is an independent prognostic indicator in patients with endometrial carcinoma, the most common gynecologic malignancy in the United States.

Anaerobic microbial dechlorination is an important step in the detoxification and elimination of polychlorinated biphenyls (PCBs), but a microorganism capable of coupling its growth to PCB dechlorination has not been isolated. Here we describe the isolation from sediment of an ultramicrobacterium, strain DF-1, which is capable of dechlorinating PCBs containing double-flanked chlorines added as single congeners or as Aroclor 1260 in contaminated soil. The isolate requires Desulfovibrio spp. in coculture or cell extract for growth on hydrogen and PCB in mineral medium. This is the first microorganism in pure culture demonstrated to grow by dehalorespiration with PCBs and the first isolate shown to dechlorinate weathered commercial mixtures of PCBs in historically contaminated sediments. The ability of this isolate to grow on PCBs in contaminated sediments represents a significant breakthrough for the development of in situ treatment strategies for this class of persistent organic pollutants.

bcl-2 is a protein which prohibits programmed cell death. The purpose of this study was to determine whether bcl-2 staining was related to traditional prognostic factors and/or recurrence in patients with endometrial carcinoma.One hundred twenty consecutively surgically treated patients with endometrial carcinoma had their tumors studied immunohistochemically for bcl-2 staining.The mean follow-up of the patients was 53 months with a median of 56 months (range 30 to 68 months). bcl-2 staining was positive in 44.0% of patients with endometrioid carcinomas and in 23. 1% of patients with nonendometrioid carcinomas (P0.001). Increasing depth of invasion (P = 0.014), grade (P = 0.011), and FIGO stage (P = 0.018) were each correlated with decreasing bcl-2 staining. bcl-2 staining was positive in 44.1% of patients whose tumors showed no lymphovascular space invasion and in 11.1% of patients with lymphovascular space invasion (P0.001). Only 1 of 26 patients with recurrent disease had persistence of bcl-2 staining. Multivariate analysis revealed FIGO stage (P = 0.0051), histologic grade (P = 0.050), and lack of staining for bcl-2 (P = 0.012) to be independent predictors of recurrence.bcl-2 persistence is more common in endometrioid than in nonendometrioid adenocarcinomas of the endometrium. It appears to be inversely correlated with the universally recognized prognostic factors of depth of invasion, histologic grade, and FIGO stage. Lack of bcl-2 persistence was an independent predictor of recurrence of disease. This group of patients continues to be followed to determine the role of bcl-2 persistence or lack of persistence as a predictor of 5-year survival of patients with endometrial carcinoma.

Objective. Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The purpose of this study was to determine prospectively whether HSP27 was associated with known prognostic factors as well as survival in patients with epithelial ovarian carcinoma. Methods. Ninety-nine patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction, and survival. Results. Immunohistochemical staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant difference in HSP27 staining was found in relation to FIGO stage ( P = 0.013). HSP27 staining was found to be an independent predictor of 2-year survival in these patients ( P = 0.041). Conclusion. The level of HSP27 significantly decreases as the FIGO stage increases and is an independent prognostic indicator of survival in patients with epithelial ovarian carcinoma.

The annual American Society for Nutritional Sciences/American Society for Clinical Nutrition Public Information Committee symposium for 2005 titled "Dietary Reference Intakes (DRIs) for Food Labeling" served as a platform to address the use of DRIs in food labeling, a change that could affect the processing of foods and supplements and the nutrient intakes of consumers. Speakers from science, industry, trade organizations, and the government came together to provide critical thinking about the most appropriate DRI values to use in food labeling. The proceedings of the symposium cover consumer perspectives on food labels, the regulatory process for revising labeling relative to the DRIs, the food industry's perspective on the use of the new DRIs in food labeling, and differing opinions on whether to use Recommended Dietary Allowances or Estimated Average Requirements to set Daily Values.

Texture is a descriptive property of a surface distinct from color and shape. Image analysis allows gray-scale images to have their optical texture measured and analyzed. The authors, utilizing image analysis, prospectively studied Markov texture parameters to determine their relevance as prognostic indicators of disease recurrence in endometrial cancer.Seventy-four consecutive patients, surgically treated, with endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as 21 Markov parameters. DI and the Markov parameters were quantified using image analysis.Median follow-up for the study population was 31 months with a range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12 patients died from disease during the observation period of the study. Eleven Markov parameters showed significant correlation with increasing FIGO stage (P0.05), while 14 Markov parameters showed significant correlation with survival (P0.05). Three Markov parameters, difference entropy (P = 0.025), information measure B (P = 0.01), and diagonal moment (P = 0.046), were demonstrated to be independent prognostic indicators along with the more traditional prognostic indicators, stage (P = 0.006), grade (P = 0.029), and depth of myometrial invasion (P = 0.03).Image analysis is able to quantify optical texture. Utilizing bivariate correlations and multivariate analysis, three of these parameters were demonstrated to be independent prognostic indicators in endometrial cancer, specifically difference entropy, information measure B, and diagonal moment.

Background: Steroid receptor status as a prognostic indicator in gynecologic malignancies has been a focus of study for almost 20 years. Although shown to be of importance in assessing prognosis in some patients with endometrial cancer, their importance in assessing prognosis in patients with serous cystadenocarcinoma of the ovary is not established. Methods: All cases of stage IIIc serous cystadenocarcinoma of the ovary operated on by the gynecologic oncology service from January 1, 1981, through December 31, 1989, were evaluated for their estrogen and progesterone receptor status, time to recurrence, length of survival, and level of primary cytoreduction as well as FIGO stage, grade, and histology. Fresh tissue was obtained and frozen at the time of surgery for the steroid assays. Results: Ninety-six patients who had optimal primary cytoreductive surgery for their stage IIIc serous cystadenocarcinomas of the ovary and had their estrogen and progesterone receptor status established were found. Patients with an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein were shown to have a better mean survival (41 months) than patients with estrogen receptor levels greater than 10 fmol/mg cytosol protein (34 months) ( P = 0.015). Five-year survival in the former group (38 patients) was 39.5% while 5-year survival in the latter group (58 patients) was 10.3% ( P = 0.001). The was no correlation between progesterone status and survival ( P > 0.05) in that same cohort of patients. Conclusions: In patients with optimally cytoreduced stage IIIc serous cystadenocarcinoma of the ovary, an estrogen receptor level of less than or equal to 10 fmol/mg cytosol protein may be indicative of a better prognosis. Progesterone receptor status does not appear to affect survival.

Malignant mixed mesodermal tumors of the ovary occur in less than 1% of cases of ovarian cancer. They have a dismal prognosis and the most effective type of therapy is still not known. All cases of malignant mixed mesodermal tumor of the ovary between January 1, 1985 and May 1, 1994 operated on by the gynecologic oncology service are the subject of this report. Data were obtained from the hospital and office records of the patients. Nine patients who had their primary surgery by the gynecologic oncology service were found to have the diagnosis of malignant mixed mesodermal tumor of the ovary. Homologous tumors were found in five patients and heterologous tumors in four. Homologous tumors (mean survival 15.2 months) showed a better survival than heterologous tumors (mean survival 6.5 months; P = 0.001). An elevated estrogen receptor status was shown to correspond to longer survival (P < 0.0001). Six specimens were considered to be estrogen receptor positive and three were receptor negative. The mean survival in those patients who had a positive estrogen receptor status, 13.7 months, with a median of 7.5 months was significantly higher than those who were not positive, 6.7 months (P = 0.019) with a median of 6.25 months. All specimens were progesterone receptor negative. Malignant mixed mesodermal tumors of the ovary have a dismal prognosis, no effective therapy, and controversial prognostic indicators. Increasing estrogen receptor status appeared to correlate with longer mean survival. Larger, multi-institutional studies need to be done to determine the overall significance of these findings.