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Purpose To evaluate the long-term effect of subthreshold nanosecond laser (SNL) treatment on progression to late age-related macular degeneration (AMD). Design Observational extension study of a randomized, sham-controlled trial. Participants Two hundred twelve participants with bilateral large drusen. Methods The Laser Intervention in the Early Stages of AMD (LEAD) study was a 36-month trial where participants were randomized to receive SNL or sham treatment in 1 eye at 6-monthly intervals up to 30 months. After the completion of the LEAD study, the 2 largest recruiting sites offered remaining participants an opportunity to enroll in a 24-month observational extension study. This study thus examined all participants from these 2 sites who were enrolled in the LEAD study at baseline, including the additional observational data. Main Outcome Measures Time to develop late AMD, defined on multimodal imaging, between those randomized the SNL or sham treatment. Results Overall, no significant difference was found in the rate of progression over a 60-month period in those randomized to the SNL compared with the sham group (adjusted hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.36–1.09; P = 0.098), similar to the findings at 36 months in the LEAD Study. However, evidence of treatment effect modification continued to emerge based on the coexistence of reticular pseudodrusen (RPD; P = 0.007, adjusted interaction). Namely, progression was slowed significantly with SNL treatment for those without coexistent RPD (adjusted HR, 0.34; 95% CI, 0.16–0.71; P = 0.004), but it was not significantly different for those with RPD (adjusted HR, 1.81; 95% CI, 0.67–4.88; P = 0.239). Conclusions A 24-month observational extension study to the LEAD Study confirmed that SNL treatment did not significantly reduce the overall rate of progression to late AMD in a cohort with intermediate AMD. However, the persistence of a potential beneficial treatment effect in those without coexistent RPD over a longer follow-up duration of an additional 24 months without additional treatment is encouraging. These findings provide further justification for future trials to examine the potential value of SNL treatment for slowing progression in intermediate AMD.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 km and 810 km from the beam source, is analyzed using an exposure of $12.51\times10^{20}$ protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of $121$ of neutral-current candidates are observed at the Far Detector, compared to a prediction of $122\pm11$(stat.)$\pm15$(syst.) assuming mixing between three active flavors. No evidence for $\bar{\nu}_{\mu}\rightarrow\bar{\nu}_{s}$ oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles ${\theta}_{24} < 25^{\circ}$ and ${\theta}_{34} < 32^{\circ}$ at the 90% C.L. for $0.05$eV$^{2} \leq \Delta m^{2}_{41} \leq 0.5$eV$^{2}$, the range of mass splittings that produces no significant oscillations at the Near Detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos., Comment: 8 pages, 4 figures

OBJECTIVE Studies of cancer screening have found that false positive screening events (FPSE) can affect worry about cancer risk and screening program use, we sought to further explore this. METHOD In a study of 1,100 women at high risk for ovarian cancer who participated in a previously published randomized controlled trial (RCT), we sought to explore whether worry might also influence the use of risk-reducing surgical procedures by women. Participants included 234 women with BRCA1/2 mutations and 866 women with high-risk pedigrees. We followed the women for up to 6 years. RESULTS Worry predicted risk reducing prophylactic bilateral salpingo-oophorectomy (pBSO) for both mutation carriers (HR = 1.74; p = .02), and women with high-risk pedigree (HR = 3.41; p < .001). FPSE also predicted subsequent pBSO among women with a high-risk pedigree (HR 2.31; p < .01). While screening may reduce worry among those who never receive a positive result, FPSE increase worry at least temporarily. Worry about ovarian cancer risk predicted use of preventative pBSO among high-risk women including those with BRCA1/2 mutations enrolled in an ovarian cancer-screening program. FPSE also predicted risk-reducing ovarian surgery among high-risk women without a known mutation at the time of screening program enrollment. CONCLUSIONS Physicians who offer screening should know that false positive results may increase use of pBSO, how this should effect clinical practice is unclear. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

This phase II study evaluated the toxicity and efficacy of docetaxel and carboplatin as salvage therapy in 36 patients with relapsed, platinum-sensitive ovarian cancer. The most common and significant toxicity was hematologic. The best response was seen in patients with ‡ 1-year remission before relapse. Background: The optimal therapy to treat relapsed, platinum-sensitive ovarian cancer remains elusive. Because most patients receive initial therapy with paclitaxel and platinum, there is a lack of cross-reaction of docetaxel and paclitaxel and retreatment with platinum is standard of care; we evaluated the toxicity and efficacy of docetaxel and carboplatin as salvage therapy for relapsed, platinum-sensitive ovarian cancer. Materials and Methods: This phase II study treated the first-relapsed, platinum-sensitive, stage III/IV ovarian cancer patients with docetaxel 80 mg/m 2 intravenous (IV) over 60 minutes followed by carboplatin area under the curve 6 IV over 30 minutes every 21 days, for 6 cycles. End points were toxicity, response rates, relapse rates, event-free survival, and survival rates. Results: Thirty-six patients were enrolled and 35 were evaluable. Twenty-three percent of patients were age � 70 years. A total of 170 cycles of therapy were given. Ten patients required dose reduction. Thirty-eight percent had a delay in starting subsequent planned cycles. Most delays were due to hematologic recovery. Hematologic toxicity was most common and significant; 77% grade 4 neutropenia. One patient died from typhilitis. Total complete remission (38%) and partial remission (27%) rate was 65%. Median time to progression was 261 days (60-717). Five (14%) patients remain alive without ovarian cancer, with median follow-up of 5.1 years. Patients who entered the study with � 12-month duration of initial remission had best response. Conclusion: The combination of docetaxel and carboplatin has toxicity, especially hematologic, and requires growth factor support and close monitoring for infections. Its role for treating ovarian cancer patients was better in patients in whom initial response to therapy was � 12 months.

Purpose A rat model was developed to enable direct administration of hyperpolarized 13C‐labeled molecules into a tumor‐supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism. Methods Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized 13C‐molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein. Spectroscopic data were obtained on a 7 Tesla preclinical scanner. Results Intra‐arterial infusion of hyperpolarized 13C‐pyruvate increased the pyruvate tumor signal by a factor of 4.6, compared with intravenous infusion, despite an approximately 7 times smaller total dose to the rat. Hyperpolarized glucose signal was detected at near‐physiological systemic blood concentration. Pyruvate to lactate but not glucose to lactate metabolism was detected in the tumor. Hyperpolarized 13C‐labeled combretastatin A1 diphosphate, a tumor vascular disrupting agent, showed an in vivo signal in the tumor. Conclusions The model maximizes tumor substrate/drug delivery and minimizes T1 relaxation signal losses in addition to systemic toxicity. Therefore, it permits metabolic studies of hyperpolarized substrates with relatively short T1 and opens up the possibility for preclinical studies of hyperpolarized drug molecules. Magn Reson Med 78:2116–2126, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

In this study, we used a multilevel analysis to examine how strike tactics influenced fans' support of the 1994-95 Major League Baseball player's strike. Strike tactics were discounted ticket prices for season games, replacement players in games, and picket lines of striking players. Tactics were varied within judgment scenarios (i.e., baseball game announcements) and fans' responses to scenarios were used as within-person variables to estimate tactic influences. Fans' perceptions of themselves (e.g., extent of fanship) and the strike situation (e.g., extent to which the dispute was perceived as a labor dispute) were used as between-person variables to predict individual differences in tactic influences. Results indicated that more replacement players has a positive influence on support for the strike and higher discounted prices had a negative influence on strike support. The influences of replacement players on judgments was not associated with individual differences, whereas the influence of discounted prices on judgments did show such differences. The findings were used to discuss implications for winning support from consumers in a professional entertainment workers' strike.

BACKGROUND: A phase 2 trial was conducted to determine the toxicity and efficacy of combined weekly topotecan and biweekly bevacizumab in patients with primary or secondary platinum-resistant ovarian, peritoneal, or fallopian tube cancer (OC). METHODS: Patients were treated with bevacizumab 10 mg/kg on days 1 and 15 and topotecan 4 mg/m2 on days 1, 8, and 15 of a 28-day cycle until progressive disease (PD) or excessive toxicity. The primary endpoint was progression-free survival (PFS); secondary objectives included overall survival (OS), objective response, and toxicity. RESULTS: Patients (N = 40) received a median of 8 treatment cycles. Toxicity was generally mild or moderate, with neutropenia (18%), hypertension (20%), gastrointestinal toxicity (18%), pain (13%), metabolic toxicity (15%), bowel obstruction (10%), and cardiotoxicity (8%) being the most common grade 3 and 4 adverse events. No bowel perforations, febrile neutropenia, or treatment-related deaths occurred. Median PFS and OS were 7.8 (95% confidence interval [CI], 3.0-9.4) and 16.6 months (95% CI, 12.8-22.9), with 22 (55%) patients progression-free for ≥6 months. Ten (25%) patients had partial response (PR), 14 (35%) had stable disease (SD), and 16 (40%) had PD. Patients treated with 2 prior regimens received greater benefit than patients treated with 1: PR/SD, 78.9% versus 42.9% (P = .03); median PFS, 10.9 versus 2.8 months (P = .08); median OS, 22.9 versus 12.8 months (P = .02). CONCLUSIONS: A weekly topotecan and biweekly bevacizumab combination demonstrates acceptable toxicity and encouraging efficacy in patients with platinum-resistant OC; further study is warranted. Cancer 2011;. © 2011 American Cancer Society.

In large asexual populations, clonal interference, whereby different beneficial mutations compete to fix in the population simultaneously, may be the norm. Results extrapolated from the spread of individual mutations in homogeneous backgrounds are found to be misleading in such situations: clonal interference severely inhibits the spread of beneficial mutations. In contrast with results gained in systems with just one mutation striving for fixation at any one time, the spatial structure of the population is found to be an important factor in determining the fixation probability when there are two beneficial mutations.

To evaluate the temporal stability of self-reported symptoms known to be associated with ovarian cancer.This report is a longitudinal analysis of symptom reporting from 123 women who participated in the Seattle-based Ovarian Cancer Early Detection Study (OCEDS). The OCEDS population includes women at increased risk of ovarian cancer based on a family history of cancer or a BRCA I/II mutation. Data on symptoms were collected at two time points using a Symptoms Index that included abdominal pain, pelvic pain, feeling full quickly, inability to eat normally, abdominal bloating, and increased abdominal size.There was a median of 101 days between the two time points, with a range of 72-332 days. The median age of the women was 51, with a range of 32-79 years. Abdominal bloating was the most commonly reported symptom at both time points. The symptom least commonly reported at the two time points was inability to eat normally. The Symptoms Index was negative at both time points for 86% of all women and positive at both time points for 2% of all women. There were no statistically significant patterns of change for symptom reporting between time points.The Symptoms Index and women's report of abdominal pain, pelvic pain, feeling full quickly, unable to eat normally, abdominal bloating, increased abdominal size were stable between two time points in this sample. These findings provide evidence that longitudinal measurements of symptoms reporting by women in a screening study are likely to be reliable.

Ovarian cancer is the second most common gynecologic malignancy in the U.S. Greater than 70% of women with ovarian cancer are diagnosed with advanced stage disease, in which the cure rates are only 20% to 30%, making it also the most deadly cancer.1 Fortunately, cure rates for those diagnosed when the disease is confined to the ovary are approximately 70% to 90%.2 Historically, the symptoms of ovarian cancer were thought to develop only after the disease had progressed to an advanced stage. However, recent research has shown that many women with early-stage disease report symptoms and the report of 1 of 3 symptoms that are new to an individual and occur frequently in ovarian cancer may serve to distinguish cancer cases from healthy women.3–5 Although ovarian cancer meets the World Heath Organization’s criteria of a disease that would benefit from screening,6 our current screening modalities have not been shown to reduce the morbidity or mortality of this disease. Currently, the American College of Obstetricians and Gynecologist and the U.S. Preventative Services Task Force recommend against screening for ovarian cancer in average-risk women. The National Institutes of Health (NIH) Consensus Panel on Ovarian Cancer statement also indicated that although currently available screening tests (CA 125 and transvaginal ultrasound [TVS]) should not be used for screening average-risk women outside of research trials, women with a family history of ovarian cancer (ie, those considered to be at an elevated risk) could reasonably choose to pursue screening using CA 125 and TVS. Despite uncertainty regarding the effectiveness of screening using current tests, screening for ovarian cancer was and is encouraged for those women at high risk for ovarian cancer because of a possible BRCA1/2 mutation and who have not chosen to pursue surgical risk reduction.7 Recently, a consensus statement concerning symptoms has come out to encourage the evaluation of ovarian cancer for women with certain symptoms associated with this disease. The effectiveness of several multimodal screening strategies for ovarian cancer using biomarkers (often CA 125) and TVS currently are being studied in several trials.8,9 These strategies generally include the annual (or more frequent) evaluation of blood biomarkers that might indicate the presence of a cancer. In these studies, TVS is generally a second screening tool for women who have positive biomarker results. Screening programs may or may not include the annual routine use of TVS as a first-line screen. Unfortunately, to our knowledge it is unclear how successful these various strategies for screening will be. Although TVS is a very sensitive test, when used as a first-line screen it produces a relatively high rate of false-positive results that require surgical follow-up and a rate of surgeries-per-cancer found that is unacceptable to most clinicians.10 When blood biomarkers are used for first-line screening, women with positive results generally do not go directly to surgery. Instead, TVS is generally used as a second screening step to identify women with false-positive marker results before surgical referral. When TVS is used as a second level of screening, the sensitivity of the multimodal screening program as a whole is limited by the sensitivity of the initial screening biomarker used. CA 125 has been used for this purpose. Unfortunately, CA 125 is elevated above reference levels in only approximately 50% of patients with clinically detectable, early-stage disease.2,11,12 Statistical efforts currently are under way to improve the performance of CA 125,13 as are studies of markers to be used in combination with CA 125 to trigger TVS as a second-stage screening test.14–16 Using a combination of markers to create a composite marker for use as an initial screen could improve the diagnostic performance of a 2-step screening program. In addition, the positive predictive value (PPV) of the screening program could be assured by the use of a second test such as TVS that would identify the majority of the false-positive results among the initial screening results. Efforts to combine CA 125 with other markers have included examinations of CA 125 with HE4, mesothelin, and other markers.14–17 Mesothelin18–21 and HE422,23 may be 2 of the most promising new ovarian cancer biomarkers currently under evaluation. Their diagnostic performance is known and they appear to complement CA 125. Briefly, mesothelin is an epithelial biomarker14 and HE4 is commonly found to be overexpressed in ovarian cancer tissue and elevated in the serum of patients with ovarian cancer.22–24 The current study presents a second report on the results of a study seeking to create a symptom index that could be used to differentiate women with undiagnosed ovarian cancer from healthy women and those with other gynecologic conditions. The prior report described the development of a symptom index in an exploratory dataset and analysis of the sensitivity and specificity of that index in a confirmatory dataset and with a general clinic control group.5 The symptom index thus developed consists of a decision-rule to be used in determining whether symptoms reported by a woman might suggest that she has ovarian cancer. Women reporting symptoms of pelvic or abdominal pain, bloating, increased abdominal size, difficulty eating, or feeling full quickly >12 times per month that have occurred for < 1 year are considered to have a positive symptom index.5 Few women (approximately 2%) in a general clinic sample report symptoms consistent with a positive index score. This report builds on our prior research by determining whether symptom reports might make an independent contribution to the prediction of ovarian cancer in a screening situation when data are also available on CA 125. We hypothesized that the symptom index would identify women with cancer who do not have elevated levels of CA 125 but might benefit from immediate TVS evaluation, and thus might add to the sensitivity of CA 125 and/or other biomarkers as an initial screening marker in a multistep screening strategy.

Background The accuracy of sentinel lymph node mapping has been shown in endometrial cancer, but studies to date have primarily focused on cohorts at low risk for nodal involvement. In our practice, we acknowledge the lack of benefit of lymphadenectomy in the low-risk subgroup and omit lymph node removal in these patients. Thus, our aim was to evaluate the feasibility and accuracy of sentinel node mapping in women at sufficient risk for nodal metastasis warranting lymphadenectomy and in whom the potential benefit of avoiding nodal procurement could be realized. Objective To evaluate the detection rate and accuracy of fluorescence-guided sentinel lymph node mapping in endometrial cancer patients undergoing robotic-assisted staging. Study Design One hundred twenty-three endometrial cancer patients undergoing sentinel lymph node sentinel node mapping using indocyanine green were prospectively evaluated. Two mL (1.0 mg/mL) of dye were injected into the cervical stroma divided between the 2−3 and 9−10 o'clock positions at the time of uterine manipulator placement. Before hysterectomy, the retroperitoneal spaces were developed and fluorescence imaging was used for sentinel node detection. Identified sentinel nodes were removed and submitted for touch prep intraoperatively, followed by permanent assessment with routine hematoxylin and eosin levels. Patients then underwent hysterectomy, bilateral salpingo-oophorectomy, and completion bilateral pelvic and periaortic lymphadenectomy based on intrauterine risk factors determined intraoperatively (tumor size >2 cm, >50% myometrial invasion, and grade 3 histology). Results Of 123 patients enrolled, at least 1 sentinel node was detected in 119 (96.7%). Ninety-nine patients (80%) had bilateral pelvic or periaortic sentinel nodes detected. A total of 85 patients met criteria warranting completion lymphadenectomy. In 14 patients (16%) periaortic lymphadenectomy was not feasible, and the mean number of pelvic nodes procured was 13 (6−22). Of the 71 patients undergoing pelvic and periaortic lymphadenectomy, the mean nodal count was 23.2 (8−51). Of patients undergoing lymphadenectomy, 10.6% had lymph node metastasis on final hematoxylin and eosin evaluation. Notably, the sentinel node was the only positive node in 44% of cases. There were no cases in which final pathology of the sentinel node was negative and metastatic disease was detected upon completion lymphadenectomy in the non-sentinel nodes (no false negatives), yielding a sensitivity of 100%. Of the 14 sentinel nodes ultimately found to harbor metastases, 3 were negative on touch prep, yielding a sensitivity of 78.6% for intraoperative detection of sentinel node involvement. In all 3 of the false-negative touch preps, final pathology detected a single micrometastasis (0.24 mm, 1.4 mm, 1.5 mm). As expected, there were no false-positive results, yielding a specificity of 100%. No complications related to sentinel node mapping or allergic reactions to the dye were encountered. Conclusion Intraoperative sentinel node mapping using fluorescence imaging with indocyanine green in endometrial cancer patients is feasible and yields high detection rates. In our pilot study, sentinel node mapping identified all women with Stage IIIC disease. Low false-negative rates are encouraging, and if confirmed in multi-institutional trials, this approach would be anticipated to reduce the morbidity, operative times, and costs associated with complete pelvic and periaortic lymphadenectomy.

Objective The purpose of this study was to define the rate of neoplasia in prophylactic surgical specimens with the use of a careful surgical and pathologic protocol in a prospective study of high-risk women who were undergoing risk-reducing salpingo-oophorectomy. Outcomes of interest were neoplasia that was identified in surgical specimens and clinical outcomes of women who were undergoing risk-reducing salpingo-oophorectomy. We hypothesized that older age and having a BRCA1 mutation would be predictors for tubal or ovarian neoplasia and that a careful surgical and pathologic protocol would lead to a low rate of subsequent primary peritoneal cancer. Study design A prospective tissue and research database enrolled patients who underwent risk-reducing salpingo-oophorectomy for prevention of ovarian cancer. Clinical and pathologic data were extracted for those patients after the initiation of a defined surgical and pathologic protocol in 1999. Results One hundred thirteen women met the high-risk criteria; 40 of the women (45%) who were tested had a deleterious mutation in BRCA1, and 22 women (25%) had a mutation in BRCA2. Seven women had ovarian or tubal neoplasia (6.2%). One woman had occult endometrial cancer. Age ≥45 years and having a BRCA1 or BRCA2 mutation were significant predictors of occult neoplasia. Two patients with neoplasia that was identified at risk-reducing salpingo-oophorectomy experienced recurrence. Three patients with BRCA1 mutations have subsequent new diagnoses of breast cancer. No patients had primary peritoneal cancer after risk-reducing salpingo-oophorectomy. Conclusion Age ≥45 years and mutations in BRCA1 or BRCA2 predict occult neoplasia in women who undergo risk-reducing salpingo-oophorectomy. A thorough pathologic and surgical protocol at the time of risk-reducing salpingo-oophorectomy may improve the risk of subsequent primary peritoneal cancer.

At the core of this effort is the requirement to answer the question of how many and what type of operators are needed to conduct a Battle Management Command and Control (BMC2) mission given the proposed capabilities of the E-10A. That is, define the organizational requirements for a future system before it is built. Based on detailed structured interviews, review of system design documents, and analysis of current Air Force systems, we created a comprehensive mission model as the analytical basis for a modeling and simulation study of operator tasks and task loading for the purpose of determining an optimal team structure for the E-10A. The final organizational design provides a detailed description of a proposed roles and responsibilities within the E-10A. The specification of a detailed model provides traceability of these recommendations and a high degree of transparency to support the system design process.

Based on the reduced morbidity seen in our retrospective study, we undertook a prospective, randomized trial to determine whether transposition of the sartorius muscle improves post-operative morbidity in women with squamous cell carcinoma of the vulva undergoing inguinal-femoral lymphadenectomy.Patients with squamous carcinoma of the vulva requiring inguinal-femoral lymphadenectomy were randomized to undergo sartorius transposition or not. All patients received perioperative antibiotics, DVT prophylaxis, and closed suction surgical site drainage. Outcomes assessed include wound cellulitis, wound breakdown, lymphocyst formation, lymphedema, and/or rehospitalization. Cohorts were compared using Fisher's exact test. Baseline characteristics were compared using Student's t test or Fischer's exact test as appropriate. Logistic regression was used to assess the impact of sartorius transposition, after adjusting for other factors.From June 1996 to December 2002, 61 patients underwent 99 inguinal-femoral lymphadenectomies, 28 with sartorius transposition, and 33 without. The mean (SD) age for controls and patients undergoing sartorius transposition was 63.5 (15.2) and 73.8 (13.7) years, respectively (P0.05). There were no statistically significant differences in BSA, tobacco use, co-morbid medical conditions, past surgical history, medication use, size of incision, duration of surgery, number of positive lymph nodes, pathologic stage, pathologic grade, pre- or postoperative hemoglobin, or length of hospitalization. There were no statistically significant differences in the incidence of wound cellulitis, wound breakdown, lymphedema, or rehospitalization. The incidence of lymphocyst formation was increased in the sartorius transposition group. After adjusting for age, however, the groups appeared similar.Sartorius transposition after inguinal-femoral lymphadenectomy does not reduce postoperative wound morbidity.

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late-stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20-45 normal female serum donors. These antigens include p53, NY-ESO-1, UBQLN1, HOXB6, TOP2A, putative helicase-RUVBL (RUVBL), HMBA-inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox-B7 and BRCA1. Real-time RT-PCR analysis showed that mRNA for HER2/neu and 3 SEREX-defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy.

The interconnected nature of the Army's Future Combat System provides an opportunity to use communication analysis as a viable evaluation method of both organizational efficiency and system design. In the current investigation, communications during teamin-the-loop experimentation were collected and analyzed for both content and flow patterns. Results suggest that players did not fully utilize the functionality of a common operating picture (COP) and new technology insertion did not achieve the desired effect within the organization. Requests for information and updates were frequently related to information that could have been found on the COP. The communication patterns suggested that the experimental organization was very much hierarchical, with little horizontal communications. That is, despite the influx of new systems, traditional operations were employed. In this study, communication data were successfully employed to assess operational effectiveness and the quality of system design.

Objective. Glassy cell carcinoma (GCC) of the cervix has traditionally been characterized as an aggressive histologic subtype with poor outcomes. An earlier series from our institution supported a grim prognostic outlook, demonstrating a survival rate of only 55% in women with stage I disease. We present a comparison of a contemporary series of patients with GCC. Methods. All cases of GCC treated from 1993 to 1999 identified by our tumor registry were reviewed for a variety of clinicopathologic features, treatment strategies, and outcome. Results. A total of 403 cases of invasive cancer of the cervix were identified. There were 22 patients with histologically confirmed GCC, representing only 5.4% of all cervical cancer diagnoses. Patients with GCC had an overall survival of 73% (16/22) and a disease-free survival of 64% (14/22). The incidence of stage I lesions was 64% (14/22). Overall survival of patients with stage I disease was 86% (12/14), with a disease-free survival of 71% (10/14) at a median follow-up of 28.5 months. Seven stage IB lesions were treated with surgery alone, whereas six received adjuvant radiation or chemoradiation following surgery. Two patients in each treatment group recurred, yielding an overall recurrence rate of 29% (4/14). However, of those who recurred with stage I disease, all 4 patients had two or more intermediate risk factors (lymph–vascular space invasion [LVSI], deep tumor invasion, or tumor size greater than 3 cm). Conclusions. Glassy cell carcinoma of the cervix appears to have a better prognosis than previously reported. We observed that intermediate risk histopathologic features identified in squamous cell cohorts are also predictive of a poorer outcome in patients with GCC. Thus, patients with LVSI, deep stromal invasion, and large tumor size are at the highest risk for pelvic relapse and should be candidates for adjuvant treatment.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν_μ disappearance and ν_e appearance data using the three-flavor formalism. We measure |Δm^2_(32)|=[2.28–2.46]×10^(−3) eV^2 (68% C.L.) and sin^2θ_(23)=0.35–0.65 (90% C.L.) in the normal hierarchy, and |Δm^2_(32)|=[2.32–2.53]×10^(−3) eV^2 (68% C.L.) and sin2θ23=0.34–0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ_(CP), the θ_(23) octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(μ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.28-2.46] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and |Δm(32)(2)| = [2.32-2.53] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ(CP), the θ(23} octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

Background: Serum markers are used before pelvic imaging to improve specificity and positive predictive value (PPV) of ovarian cancer multimodal screening strategies. Methods: We conducted a randomized controlled pilot trial to estimate surgical PPV of a “2 of 3 tests positive” screening rule, and to compare use of HE4 as a first-line (Arm 1) versus a second-line (Arm 2) screen, in women at high and elevated risk for epithelial ovarian cancer (EOC) at five study sites. Semiannual screening was offered to 208 women ages 25 to 80 years with deleterious BRCA germline mutations and to 834 women ages 35 to 80 years with pedigrees suggesting inherited susceptibility. Annual screening was offered to 130 women ages 45 to 80 years (Risk Group 3) with epidemiologic and serum marker risk factors. Rising marker levels were identified using the parametric empirical Bayes algorithm. Results: Both strategies yielded surgical PPV above 25%. Protocol-indicated surgery was performed in 6 women, identifying two ovarian malignancies and yielding a surgical PPV in both arms combined of 33% (95% confidence interval: 4%–78%), 25% in Arm 1 and 50% in Arm 2. Surgical consultation was recommended for 37 women (26 in Arm 1 and 11 in Arm 2). On the basis of 12 women with at least 2 of 3 tests positive (CA125, HE4, or imaging), an intent-to-treat analysis yielded PPV of 14% in Arm 1 and 20% in Arm 2. Conclusions: Positive screens were more frequent when HE4 was included in the primary screen. Impact: HE4 may be useful as a confirmatory screen when rising CA125 is used alone as a primary screen. Cancer Epidemiol Biomarkers Prev; 23(7); 1383–93. ©2014 AACR.

A systematic approach to developing design recommendations is described. It begins with the imposition of constraints on the solution space. Empirical results from domain research are then used as catalysts for conceptualizing new functions and designs. Where empirical data are not available, interviews are used to elicit issues of importance. This approach was used to develop design guidance for a prototype Navy command and control system.

The introduction of new technology, along with cost pressures to “do more with less,” are forcing organizations to re-engineer their team structures and processes. We have developed a systematic, formal, quantitative model-based approach for designing teams. The team model specifies tasks to be accomplished, interdependencies between tasks, resources available to accomplish the tasks, and a set of goals and constraints for the team. We optimize a multi-variable objective function to develop a team design that specifies the tasks performed and the resources controlled by each team member and the authority structure and communication links for the team. We are currently designing teams in a number of military domains—Joint Task Forces, Navy shipboard command centers, Air Force Air Operations Centers, and Air Force AW ACS teams. This paper will use examples from these domains to point out similarities and differences in the team-design problem across domains

The aim of this study was to evaluate the impact of total radiation dose on residual tumor and the prognostic significance of persistent disease in women with bulky, barrel-shaped cervical carcinoma who received definitive radiation followed by adjuvant hysterectomy.The medical records of 57 patients with bulky endophytic cervical carcinoma treated at the University of Washington between 1976 and 1997 were reviewed. All patients received external beam pelvic radiotherapy supplemented by intracavitary brachytherapy, followed by extrafascial hysterectomy 6 to 8 weeks later.The mean pretreatment tumor diameter was 5.9 cm, with a range of 4-9 cm. Total radiation dose to point A ranged from 5040 to 9700 cGy, and the mean for the group was 7966 cGy. Residual disease was present in 35 (61%) of the hysterectomy specimens. The frequency of cervical tumor sterilization correlated significantly with the mean radiation dose to point A (P = 0.016). Patients without histologic residual disease had a significantly improved outcome, with 95% of patients remaining clinically free of disease at last follow-up, versus 31% of those with residual disease (P0.001). As expected, the pelvic control rate was excellent (100%) in patients with complete tumor eradication compared to the group with residual tumor (44%). Those with no residual disease enjoyed a significantly improved survival compared to those with residual tumor (P0.001). Furthermore, a statistically significant higher survival was realized in patients harboring only microscopic residual compared to those with either macroscopically evident tumor residuum and/or positive surgical margins (P = 0.036).Higher radiation doses are associated with an improved likelihood of tumor eradication in the treatment of bulky, endophytic cervical cancer and complete tumor sterilization at adjuvant hysterectomy is predictive of significantly enhanced survival and pelvic control. The high rate of histologic tumor persistence in our series emphasizes the need for more efficacious therapies in patients with bulky endophytic cervical cancer and argues for escalation of radiation dose even when adjuvant hysterectomy is planned.

The purpose of this article is to describe the outcome of an arthroscopic examination and the pathology in symptomatic shoulders of 41 professional overhand throwing athletes. With the arm in the position of the relocation test, 100% of the subjects had either contact between the rotator cuff undersurface and the posterosuperior glenoid rim or osteochondral lesions. Other key findings included undersurface cuff fraying in 93%, posterosuperior labral fraying in 88%, and anterior labral fraying in 36% of the subjects. This study supports the concept of impingement of the posterior cuff undersurface with the posterosuperior glenoid rim in the overhand throwing athlete with shoulder pain.

Objectives. Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. Materials and methods. We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. Results. Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade ≥3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. Conclusions. Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

This paper describes a systematic, formal, quantitative approach for designing teams. The method develops a quantitative hierarchical mission or goal structure that specifies the parallelism, sequence, and structure of the tasks that must be accomplished in order to complete the team's mission. Using that quantitative task structure, we apply a systems engineering approach that describes organizational performance criteria as a multi-variable objective function to be optimized. We work closely with subject matter experts to develop the task structure and to specify the criteria to be optimized for the team (e.g., the distribution of workload among team members or the time needed to complete the mission). This process is iterative, with team designs produced, reviewed by domain experts, and modified. The method is currently being applied to two organizational design problems for Navy teams, and shows promise as a tool for human factors practitioners dealing with team design and organizational redesign issues.

BACKGROUND The routine use of extraperitoneal surgical staging prior to radiation therapy in patients with bulky or locally advanced cervical carcinoma remains controversial. METHODS A review was performed of 266 patients with cervical carcinoma who underwent extraperitoneal pelvic and paraaortic lymphadenectomy prior to receiving radiotherapy. Patients were divided into groups based on their lymph node status. Group A had negative lymph nodes; Group B had resected, microscopic lymph node metastases; Group C had macroscopically positive lymph nodes that were resectable at the time of surgery; and Group D had unresectable lymph nodes. All patients received standard radiotherapy utilizing external beam and brachytherapy. Patients with lymph node metastases received extended field irradiation. Survival probabilities were computed by the Kaplan-Meier product limits method with statistical significance determined by the Mantel-Cox log rank test. RESULTS Lymph node metastases were detected in 49% of patients. Five- and 10-year disease free survival rates were similar for all patients in Groups B and C. All patients in Group D recurred. There was a 10.5% incidence of severe radiation-related morbidity and a 1.1% incidence of treatment-related deaths. CONCLUSIONS Pretreatment extraperitoneal staging of patients with bulky or locally advanced cervical carcinoma may afford a survival benefit via the debulking of macroscopically positive lymph nodes without significantly increasing treatment-related morbidity or mortality. Cancer 1998;82:2241-2248. © 1998 American Cancer Society.

A current United States trend in alternative work schedules is to increase the length of the workday while decreasing the number of days in the work week. Referred to as compressed work schedules (CWS), they are popular amongst shiftworkers although the longer work shifts may be associated with increased fatigue and may create additional risk of accidents and health problems in the workplace. The specific aim of the current study is to evaluate a CWS to better understand its influence on the sleep and fatigue of shiftworkers. A 10 h day/14 h night rotating CWS was introduced to a fire department to replace an 8 h, three shift rotating schedule. This study is comprised of an assessment of a 10 h day/14 h night rotating CWS and an evaluation of the impact of a change in work schedules, comparing 8 h shifts to the extended work periods. The results of the current study revealed no significant differences between the compressed and non-compressed work schedules. Subjective measures of sleepiness and mood were shown to increase over the course of the extended work shifts. Despite the increase, the CWS is deemed acceptable because it did not negatively impact on the workers who participated to a greater extent than when they worked on the non-compressed schedule. Relevance to industry Approximately twenty present of all United States workers are employed on some form of shiftwork. Previous research has demonstrated that negative outcomes may be associated with shiftwork, especially nightwork. The current study aims to evaluate a compressed work schedule, one that may minimize the deleterious impact of night and shiftwork.

Background. Malignant transformation of endometriosis is an infrequent complication of endometriosis. Extragonadal disease is uncommon. Case. 55-year-old female presented with postmenopausal bleeding. Physical examination revealed a 2-cm polypoid lesion at the posterior vaginal apex, which was found to be a moderately differentiated invasive adenocarcinoma. Final pathology at the time of definitive surgery demonstrated a clear cell adenocarcinoma of the vagina arising in vaginal endometriosis. Conclusion. Vaginal endometriosis may lead to the development of cancer. Malignancy arising in endometriotic foci is rare, but most commonly occurs in the ovary. We report a case of clear cell malignancy arising in vaginal endometriosis, adding to only seven cases previously reported. Risk factors include unopposed estrogen and obesity, but it may occur in the absence of either.

BACKGROUND Tumor angiogenesis is essential for solid tumor growth. Yet, the importance of any particular factor in neoplastic proliferation is poorly defined. This study examines the clinical significance of increased expression of one of the angiogenic factors, vascular endothelial growth factor (VEGF), in early stage ovarian carcinoma. METHODS Tumor specimens from 68 patients with International Federation of Gynecology and Obstetrics Stage I and II ovarian carcinoma were evaluated for VEGF expression. Antisense and corresponding sense (control) RNA probes were transcribed from the pCR™II construct (Invitrogen, San Diego, CA), which contained human VEGF cDNA. The antisense probe was designed to include a highly conserved region of the VEGF coding sequence and thus detect all known variants. After in situ hybridization, sections were assessed for overexpression of VEGF. RESULTS Twenty-nine of the tumor samples overexpressed VEGF, whereas 39 specimens did not. In patients whose tumors demonstrated elevated VEGF expression, 25% were without evidence of disease recurrence at last follow-up. In contrast, 75% of the patients whose tumors did not overexpress VEGF were without evidence of disease at last follow-up (P 108 months for the VEGF negative group (P 120 months for the VEGF negative group (P 0.05). Assignment to a high risk group, as defined by the Gynecologic Oncology Group of the National Cancer Institute, was somewhat predictive of a shorter relapse free interval (P = 0.056). In a multivariate analysis, however, only elevated VEGF expression was associated with poorer survival. CONCLUSIONS In this analysis, patients with early stage ovarian carcinoma with increased VEGF expression had a poorer prognosis. Further study of VEGF may ultimately lead to identification of patients with high risk lesions whose tumor biology portends a worse prognosis and who therefore may benefit from aggressive adjuvant therapy. Cancer 1997; 80:98-106. © 1997 American Cancer Society.

Background: Human epididymis protein 4 (HE4) is approved for clinical use with CA125 to predict epithelial ovarian cancer in women with a pelvic mass or in remission after chemotherapy. Previously reported reference ranges for HE4 are inconsistent. Methods: We report positivity thresholds yielding 90%, 95%, 98%, and 99% specificity for age-defined populations of healthy women for HE4, CA125, and Risk of Ovarian Malignancy Algorithm (ROMA), a weighted average of HE4 and CA125. HE4 and CA125 were measured in 1,780 samples from 778 healthy women aged >25 years with a documented deleterious mutation, or aged >35 years with a significant family history. Effects on marker levels of a woman's age, ethnicity, and epidemiologic characteristics were estimated, as were the population-specific means, variances, and within- and between-woman variances used to generate longitudinal screening algorithms for these markers. Results: CA125 levels were lower with Black ethnicity (P = 0.008). Smoking was associated with higher HE4 (P = 0.007) and ROMA (P < 0.019). Continuous oral contraceptive use decreased levels of CA125 (P = 0.041), and ROMA (P = 0.12). CA125 was lower in women age ≥55, and HE4 increased with age (P < 0.01), particularly among women age ≥55. Conclusions: Because of the strong effect of age on HE4, thresholds for HE4 are best defined for women of specific ages. Age-specific population thresholds for HE4 for 95% specificity ranged from 41.4 pmol/L for women age 30 to 82.1 pmol/L for women age 80. Impact: Incorporation of serial marker values from screening history reduces personalized thresholds for CA125 and HE4 but is inappropriate for ROMA. Cancer Epidemiol Biomarkers Prev; 21(11); 2087–94. ©2012 AACR.

The present evaluation was conducted to assess whether crews can cope and adapt to a restricted living and work environment. Two United States Coast Guard small boat stations with similar environmental conditions, mission profiles, and workload levels were selected for this evaluation. At one station, shore-side facilities were replaced with a 50-foot live-aboard boat (NORCREW). The second station, maintained shore-side facilities (COMP). Survey and daily log data on human factors variables, which have been used to predict adaptation to work environments, were collected from 18 crew members. Analysis of these data did not reveal any significant adverse psychophysiological effects associated with the live-aboard concept. Data revealed time-of-day effects consistent with conventional thought and chronobiological theory which leads the authors to conclude that the live aboard concept does not appear to disrupt circadian cycles. Overall, the consistent failure to detect any differences between NORCREW and COMP on human factors variables clearly suggests that further consideration of this concept is warranted.

A current trend in alternative work schedules is to increase the length of the workday while decreasing the number of days in the work week. These “compressed” work schedules are popular amongst shiftworkers, in part because of longer periods of non-work days. The current research is an attempt to add to the short list of long-term evaluations of compressed work schedules. A change in work schedules from an 8 hour rotating shift schedule to a rotating 10 hour day/14 hour night operating schedule in a fire department was studied. Multiple measures were used to address a variety of outcomes associated with the new schedule. From the significant increase in satisfaction with their work schedule, it is clear that the new shift schedule is well liked by the fire fighters. Reasons for the satisfaction include significant changes in usual sleep length, a decrease in being tired or sleepy at work and an increase in free time benefits. Other results are discussed in the paper. In conclusion, the use of a compressed work schedule is beneficial when workers are allowed to sleep on the job, however, generalizations to other workplaces must be limited. Use of these popular work schedules should be limited to applications which incorporate a systematic evaluation of the new work schedule.

Fatigue has often been viewed as a simple variable that is positively correlated with time on task in the workplace and is produced mainly by physical activity. However, shiftwork researchers have demonstrated time-of-day differences for variables including sleepiness and mood, thereby challenging this notion of fatigue. Using a within-subjects design, the present study advances this research by searching for differences in time-of-day interactions in firefighters' sleep length, sleepiness, and mood ratings as a function of shift. We examined reductions in sleep length associated with shiftwork and used sleepiness and mood scales to assess the effects of these reductions. Participants completed surveys throughout a complete cycle of their shift schedule. The study showed that firefighters working on a rotating S-h shift schedule will sleep less and will report lower positive mood scores, higher negative mood scores, and greater sleepiness ratings on the night shift. Additionally, it was shown that over the course of a shift (two weeks), firefighters were unable to adapt to changes in their sleep schedule. Finally, the significant interactions that were observed challenge the historical, singular notion of fatigue.

Two cases of complex fracture dislocation of the calcaneus having an unusual pattern of injury are described. The cases exhibit the following special characteristics: (1) fracture dislocation of the calcaneus where the primary fracture line separates the calcaneus into an anteromedial fragment that maintains its normal relationship to the talus and a posterolateral fragment that is dislocated from the subtalar joint. This posterolateral fragment moves laterally and lies adjacent to the fibula; (2) a secondary fracture line separating the lateral portion of the posterior facet from the tuberosity of the calcaneus. Both fragments are dislocated from their normal anatomical position; (3) talar tilt as shown on AP view of the ankle caused by inversion of the talus due to rupture of the lateral collateral ligament. Also, the posterolateral fragments impinging on the fibula pushes the heel downward and contributes to the talar tilt; (4) involvement of the calcaneocuboid joint; (5) dislocation of the peroneal tendons. This fracture pattern is unusual and has not been described before. Recognition of this unusual injury with subsequent and proper management may prevent major disability to the patient. Conservative treatment by casting or early range of motion is contraindicated. Closed reduction should be attempted immediately, and if not successful, a lateral approach with open reduction and internal fixation is the treatment of choice for this complex injury.

In summary, a case of Ewing's tumor of the proximal phalanx of the long finger of the right hand was presented. This case is unusual because of its location as well as the unusually long clinical course before the correct diagnosis was made. The major point to be stressed is that Ewing's tumor may initially present with a "benign" appearance mimicking a bone cyst [17] or angioma [12]. Timely follow-up of so-called benign lesions, particularly when recurrent swelling occurs, would help in avoiding prolonged delays in diagnosis.

A procedure is described for the detection and direct enumeration of the number of particles that can potentially be released from wiping materials. The technique involves the use of a scanning electron microscope (SEM) to count the particles from a wiper, first by releasing them in deionized water and then filtering the entirety of the liquid through a submicron membrane filter. To obtain an accurate count, the filtration must produce a normal distribution of particles on the filter, and hence the details of the filtering technique must be performed in a very precise manner. The counting of the particles on the filter is accomplished by scanning a statistically representative number of fields and averaging the number of particles per field. The results can then be checked for statistical precision and accuracy. Our criterion for successful measurement was ± 10% accuracy at a 95% confidence level. We believe that the SEM method described in this article is sensitive enough to quantify very low levels of total particle burden without succumbing to the variability and limitations encountered with other enumeration techniques. Typically, this technique enables the accurate counting of particles of all shapes from below 0.1 μm to hundreds of micrometers. In addition, the SEM technique allows for morphologic identification of particles as well as chemical identification if an energy-dispersive x-ray system (EDS) is employed.

Locomotive engineers (train drivers) on irregular work schedules reported a general coffee consumption rate higher than that reported by a comparison sample of permanent shift factory workers. The present study examines the impact of this consumption on workday and non-workday sleep behaviour and mood ratings. Twenty-seven engineers and their spouses each completed daily logs for 30 consecutive days. Daily logs were then sorted into workday and non-workday categories. Workday sleep length was significantly shorter than non-workday sleep length for both engineers and spouses. For the engineers only, coffee consumption on workdays was higher than on non-workdays. This increased coffee consumption was correlated with longer sleep latency, increased negative mood, and decreased positive mood on both work and non-workdays. This was not true for spouses. These results may be related to a days-off carry-over effect of caffeine or a general consumption behaviour characteristic.

We propose to construct and deploy a fine-grained detector in the Fermilab NOvA 2 GeV narrow-band neutrino beam. In this beam, the detector can make unique contributions to the measurement of quasi-elastic scattering, neutral-current elastic scattering, neutral-current {pi}{sup 0} production, and enhance the NOvA measurements of electron neutrino appearance. To minimize cost and risks, the proposed detector is a copy of the SciBar detector originally built for the K2K long baseline experiment and used recently in the SciBooNE experiment.