bluuebunny/crossref_metadata_2025 huggingface dataset:
A Sensitive and Robust Assay for Urokinase and Tissue-Type Plasminogen Activators (Upa and Tpa) and Their Inhibitor Type I (Pai-1) in Breast Tumor Cytosols
Authors: Grebenschikov N. , Geurts-Moespot A. , De Witte H. , Heuvel J. , Leake R. , Sweep F. , Benraad T.
Published: April 2018

uPA and PAI-1 are becoming established as amongst the most effective markers of poor prognosis for patients with node-negative breast cancer; tPA is an index of longer survival. This paper describes a sensitive ELISA for the measurement of uPA, tPA and PAI-1 in breast cancer cytosols. The structure of the assay involves coating Ab (sheep α-Chicken IgY), catching Ab (chicken α-analyte), tagging Ab (rabbit α-analyte) and detecting Ab (goat α-rabbit IgG) labelled with HRP. The assay has a high degree of accuracy and specificity. Comparison with the American Diagnostica kits shows the results’ equivalence for PAI-1 and tPA. For uPA the results of the assay were twice as high. The assay is sensitive and relatively inexpensive. It is the first published assay to yield strictly comparative values for uPA, tPA and PAI-1 in tissue extracts and is readily subject to external quality control.
How to Overcome the Disturbing Effects of Human Anti-Mouse Antibodies (Hama) on in Vitro Assays
Authors: Oltrogge J.B. , Baum R.P. , Lema K.N. , Donnerstag B. , Hör G.
Published: April 2018

The development of human anti-mouse antibodies (HAMA) is a common immune response in patients with ovarian carcinoma after repeated injections of murine anti-CA 125 monoclonal antibodies for immunoscintigraphy. As a tumor marker with significant diagnostic value CA 125 is routinely measured in the follow-up of tumor patients by immunoradiometric assays (IRMA) based on murine anti-CA 125 monoclonal antibodies. HAMA may cause false-positive findings in a CA 125-IRMA. In this report our group demonstrates a simple way of eliminating HAMA by protein A/G affinity chromatography allowing the reliable detection of the tumor marker CA 125 in the serum of patients with ovarian carcinoma.
Evaluation of Serum Carcinoembryonic Antigen Monitoring in the follow-up of Colorectal Cancer Patients with Metastatic Lymph Nodes and a Normal Preoperative Serum Level
Authors: Tobaruela E. , Enriquez J.M. , Diez M. , Camunas J. , Muguerza J. , Granell J.
Published: April 2018

The value of serial serum carcinoembryonic antigen (CEA) assay in the follow-up of colorectal cancer patients with metastatic lymph nodes and normal (≤ 5 ng/ml) preoperative CEA levels, was examined in this study. Thirty-eight patients were studied and compared with 22 patients with elevated CEA levels. The overall sensitivity of CEA for the diagnosis of recurrence was 36%. Postoperative CEA was strongly influenced by the site of recurrence. CEA monitoring showed the best results in patients who developed hepatic metastases (sensitivity 60%, specificity 94%, positive predictive value 60%, and negative predictive value 94%), and was ineffective for the detection of locoregional or pulmonary metastases. The results indicate that elevation of CEA in the postoperative course of these patients is an indicator of the presence of hepatic metastases. Postoperative CEA monitoring should not be omitted in Dukes C patients with normal preoperative levels, and is more reliable for the detection of liver metastases.
Tissue Polypeptide-Specific Antigen (Tps) Immunoassay in the Diagnosis and Clinical Staging of Prostatic Carcinoma. Comparison with Prostate-Specific Antigen (Psa)
Authors: Ceriani L. , Giovanella L. , Salvadore M. , Bono A.V. , Roncari G.
Published: April 2018

This experimental study investigated the potential role of Tissue Polypeptide-Specific Antigen (TPS) in comparison with Prostate-Specific Antigen (PSA) in the diagnosis and the clinical and pathological staging of prostate cancer. Serum TPS and PSA levels were determined in 128 patients (pts) with benign prostatic hypertrophy (BPH; Group 1) and in 92 pts with prostate cancer (Group 2). TPS was also measured in a control group of 100 healthy subjects. Normal cutoff values of 85 U/l for TPS and 4 ng/ml for PSA were determined on the basis of ROC curve analysis. The sensitivity, specificity and accuracy in the diagnosis of prostate cancer were 49%, 95% and 76% for TPS, and 84%, 90% and 87% for PSA. The combination of the two markers provided a higher accuracy (88%), improving the sensitivity of PSA, since 47% of patients with normal PSA had pathological levels of TPS. TPS showed an increase in sensitivity from low to higher stages of disease and, in patients with skeletal involvement, from small to larger numbers of bone metastases (Kruskal Wallis p < 0.0001). Nevertheless, TPS serum levels are not useful in the clinical staging of prostate cancer as they have a poorer performance than PSA. TPS was ineffective (ROC curve area=0.68) in predicting extraprostatic disease and demonstrated a reduced ability (area = 0.78) to identify skeletal involvement. Moreover, the combination of the two markers did not significantly improve the performance of PSA alone. The serum concentration of TPS in patients with localized tumors was not related to the degree of tumor cell differentiation evaluated by the Gleason score.

Conclusion

Our preliminary experience suggests that TPS in association with PSA may be useful at the time of diagnosis of prostate cancer. However, these preliminary data have to be confirmed by larger clinical trials and the role of this association in the clinical setting needs to be analyzed with an adequate evaluation of the cost-effectiveness ratio.
Detection of the Circulating Lung Cancer Marker Lcap with a New Monoclonal Antibody Trd-L1
Authors: Tsuji K. , Uwano T. , Yoshida Y. , Kikuchi K. , Okamoto T. , Yamamoto S. , Ichiki M. , Hayashi I. , Ohno T. , Kufe D.W.
Published: April 2018

Lung Cancer Associated Protein (LCAP) is a high molecular weight glycoprotein defined by the monoclonal antibody (MAb) DF-L1 prepared against a primary adenocarcinoma of the lung. Previous studies have demonstrated that LCAP circulates at elevated levels in patients with lung cancer. However, a suitable assay for monitoring LCAP levels has not been available. The present work describes the development of a double-determinant LCAP assay using MAb TRD-L1 as the capture antibody and MAb DF-L1 as the tracer. In 60 normal subjects, the mean LCAP level was 4.8 U/ml with 2 (3.3%) subjects having values >12 U/ml (mean + 2SDS). By contrast, 37 of 67 (55.2%) patients with lung cancer had LCAP levels >12 U/ml. Moreover, only 14 of 203 (6.9%) patients with benign lung disease had elevated levels. LCAP levels were most commonly elevated (62.7%) in patients with adenocarcinoma of the lung and with advanced disease. These results indicate that LCAP as detected by MAb TRD-L1 is a potentially useful marker for the evaluation of patients with lung cancer.
Histopathological and Prognostic Evaluation of Immunohistochemical Findings in Colorectal Cancer
Authors: Lorenzi M. , Vindigni C. , Minacci C. , Tripodi S.A. , Iroatulam A. , Petrioli R. , Francini G.
Published: April 2018

Many immunohistochemical studies have investigated the relationship between immunohistochemical characteristics and histopathological findings in colorectal tumors. One of the most extensively studied markers has been tissue CEA, although the prognostic significance of this and other antigens is still uncertain. The authors report results relative to three tumoral antigens (carcinoembryonic antigen, CEA; tissue polypeptide antigen, TPA, and carbohydrate antigen 19–9, CA 19–9) determined by immunohistochemical methods in tissue samples of 52 colorectal carcinomas. The relationship between the immunohistochemical characteristics of the neoplasms and the clinicopathologic parameters, as well as their influence on the prognosis of the patients, were examined. Positive CEA reaction has a significant relationship with grade of differentiation of the tumor while diffuse cellular expression of this antigen often indicates neoplasms extending beyond the intestinal wall and invading the lymph vessels. The number of tissue antigens expressed is significantly related to the extent of tumor spread through the intestinal wall. A greater incidence of recurrence and shorter disease-free interval and survival were observed in neoplasms that expressed tissue TPA antigen or more than one tissue antigens. In the present study the latter parameter has demonstrated to have independent prognostic significance for the disease-free interval. Immunohistochemical evaluation of antigens in colorectal carcinoma tissue shows a possible independent prognostic value of the antigenic heterogeneity of tumors, which could be related to their different biological behavior.
Lower Frequency of Sister Chromatid Exchanges and Altered Frequency of HLA B-region Alleles among Individuals with Sporadic Dysplastic Nevi
Authors: Illeni M.T. , Rovini D. , Di Lernia M. , Cascinelli N. , Ghidoni A.
Published: April 2018

Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes of 24 individuals, following diagnosis, and prior to surgical removal, of a sporadic dysplastic nevus (DN). Lower SCE values and variability were found in 23 sporadic DN individuals compared with controls (2.52+0.12 and 3.76±0.22 SCE/cell, respectively). These DN individuals, contrarily to healthy controls and some types of tumor patients whose cells are hypersensitive to mutagenic agents, did not show increased SCE rates as a consequence of cigarette smoking, alcohol consumption and diagnostic radiation treatments. These observations are in contrast with clinical evidence that similar lesions are both markers or risk and precursors of malignancy in individuals with multiple nevi, affected by the dysplastic nevus syndrome (DNS) or belonging to FMM (familial malignant melanoma) families. Three HLA class I alleles out of 72 tested were found more frequently in sporadic DN individuals compared with controls: B37 (p<0.05), B52 (p<0.01) and B70 (p<0.01). Whether the greater chromosomal stability (as shown by the SCE analysis), and/or the altered frequency of some HLA alleles could influence the chance of developing cutaneous malignancy in DN individuals is yet to be evaluated.
Reevaluation of the Usefulness of Systematic Bone Scanning in Initial Staging and follow-up of Small Cell Lung Carcinoma, Taking into Account the Serum Levels of Neuron-Specific Enolase
Authors: Gendreau V. , Montravers F. , Philippe C. , Talbot J.N.
Published: April 2018

The prescription of bone scans (BS) in the initial staging and follow-up of small cell lung carcinoma (SCLC) is a traditional attitude. The availability of the serum neuron-specific enolase (NSE) assay and budget limitations led us to evaluate retrospectively, in 57 patients, the consequences of a more selective attitude, namely to perform BS only in those patients with abnormal serum NSE levels. Both BS and NSE assays were performed in 47 patients referred for initial staging of SCLC; NSE levels were normal in 8 but in 2 of these cases (25%) secondary bone localizations with great clinical significance were discovered at BS. During follow-up, 59 BS were performed in conjunction with NSE assays; 45 NSE levels were in the normal range whereas 17 (38%) corresponding BS were suggestive of bone metastases. In conclusion, due to the frequent occurrence of false-negative results in patients with bone metastases, serum NSE levels proved to be useless in the selection for BS of patients suffering from SCLC.
Serum CA 15.3, CEA and ESR Patterns in Breast Cancer
Authors: Rubach M. , Szymendera J.J. , Kamińska J. , Kowalska M.
Published: April 2018

Serum CA 15.3, CEA and ESR were longitudinally determined in 298 patients with breast cancer during postsurgical follow-up and/or therapy. Observation lasted until the death of the patient or at least for three years. With regard to longitudinal serum markers and ESR curves, four different patterns have been identified: pattern I: the markers and ESR stayed at normal levels; pattern II: the markers and ESR decreased from a peak level; pattern III: the markers and ESR fluctuated widely; pattern IV: the markers and ESR increased steadily.

We have looked at overall survival (OS) and relapse-free survival (RFS) versus longitudinal CA 15.3, CEA and ESR patterns. Univariate Cox regression analysis showed that OS and RFS were significantly associated with all four patterns.
The Prognostic Significance of Increasing Marker Levels in Metastatic Breast Cancer Patients with Clinically Complete Remission, Partial Remission or Stable Disease
Authors: Van Dalen A. , Barak V. , Cremaschi A. , Gion M. , Molina R. , Namer M. , Stieber P. , Sturgeon C. , Einarsson R.
Published: April 2018

TPS, CA 15-3 and CEA were determined in metastatic breast cancer patients during treatment. After six months of follow-up the patients were divided into four groups according to the UICC criteria for treatment response. Forty-six patients with a more favorable prognosis (complete remission, partial remission or stable disease) were followed for an extended period.

In 30 of the 46 patients at least one marker had increased at the end of the six-month period by at least 25% (TPS in 54%, CA 15-3 in 20%, CEA in 20%). All these 30 patients subsequently developed progression. The prognostic sensitivity was 83%, 30% and 30%, respectively, for TPS, CA 15-3 and CEA. The combination of TPS and CA 15-3 showed a sensitivity of 96%. The median lead time was about 8 months for TPS and CA 15-3, but less than 50% of the patients showed a lead time for CA 15-3 as compared to TPS. We conclude that TPS and CA 15-3 determinations are helpful for the prediction of progression during the follow-up of breast cancer patients.
Progesterone Receptor Synthesis in Human Meningiomas: Relation to the Estrogen-Induced Proteins pS2 and Cathepsin-D and Influence of Epidermal Growth Factor, Forskolin and Phorbol Ester in vitro
Authors: Koehorst S.G.A. , Spapens M.E.D. , Van Der Kallen C.J.H. , Van'T Verlaat J.W. , Blaauw G. , Thijssen J.H.H. , Blankenstein M.A.
Published: April 2018

Autonomous expression of progesterone receptors (PR) in human meningiomas is well established. To evaluate whether, similar to progesterone receptors, other estrogen-inducible proteins are also autonomously expressed in meningiomas, concentrations of pS2 and cathepsin-D (Cath-D) were measured in 52 meningiomas. No pS2 protein was detectable in 52/52 tested meningiomas. The Cath-D protein was measurable in all 52 meningiomas, but the mean concentration of Cath-D in meningioma cytosols was 2.4-fold lower than that of a group of 54 breast tumors (p < 0.001). These results indicate that autonomous expression is a PR-related rather than an estrogen receptor-related phenomenon and, consequently, that estradiol is probably not responsible for PR synthesis in human meningiomas. To evaluate the role of other, non-estradiol-dependent signalling pathways in PR synthesis, the effects of EGF, Forskolin and phorbol ester on PR synthesis were tested in vitro. No PR was detectable after the addition of EGF to six different primary cultures. Forskolin and TPA addition caused a morphological change in meningioma cells, but did not induce PR or pS2 synthesis in two different primary meningioma cultures. We conclude that PR synthesis in human meningiomas cannot be triggered by switching on the signalling pathways activated by these growth factors.
A novel second subproblem for two arbitrary axes of robots
Authors: Wang Haixia , Lu Xiao , Zhang Ziye , Li Yuxia , Sheng Chunyang , Gao Li
Published: April 2018

The Paden–kahan subproblem is a simple and flexible method to solve the closed-form inverse resolution but limited by the geometrical structure of robots, which is very difficult to be kept because of processing and installation. Therefore, a closed-form solution on arbitrary configurations is an important issue in the field of robotic inverse kinematics. A novel second subproblem is firstly proposed in this study based on the product-of-exponentials model adapting to the two arbitrary axes without geometric constraints (parallel, vertical, disjoint, and so on). Furthermore, the algebraic methods involving the basic properties of the screw theory and Rodrigues’ rotation formula are employed for the solution, which makes the constraint equations of the second subproblem solvable for arbitrary configurations. This methodology can be applied to the inverse solutions of 5-degree-of-freedom robots that satisfies the Pieper criterion and can express the inverse solutions via two common formulas. Finally, the simulation and the real-world experiment demonstrated the accuracy of the method and the validity, respectively.
Evidence-based Practice: Making the Research Relevant to Your Situation—CLUE #4: Apply
Authors: Yonkaitis Catherine F. , Maughan Erin D.
Published: April 2018

Evidence-based practice (EBP) is often thought to be synonymous with research and literature. This article focuses on the fourth step in the EBP process: Apply. In this step, we fully integrate the EBP Venn diagram, which illustrates that EBP occurs at the intersection of evidence and data, clinical expertise and resources, and population’s values and cultures. Only when school nurses include each component into their practice decision will true EBP occur.
Moving an Evidence-Based Policy Agenda Forward: Leadership Tips From the Field
Authors: Garrett Teresa
Published: April 2018

Advancing evidence-based policy change is a leadership challenge that nurses should embrace. Key tips to ensure that evidence-based policy changes are successful at the individual, community, and population levels are offered to help nurses through the change process. The public trust in the nursing profession is a leverage point that should be used to advance the use of evidence, expedite change, and improve health for students and across communities.
Tracking public support for Japan’s remilitarization policies: An examination of elitist and pluralist governance
Authors: Madison Cory
Published: April 2018

Has Japan’s post-Second World War transformation into one of the most militarily capable nations been the result of 60 years of truly representative government? This research compares government-collected opinion polls to policy trends and actions, to determine whether the case of Japan’s remilitarization argues for or against the country’s democratic quality. For the purpose of this research, the size of Japan’s military and its legislative freedom to act as a more conventional military were considered the most pertinent militarization policies. Results indicated that those policies were consistently unjustified by measured opinion, suggesting elitist policy formation. However, other policy areas, such as Japan’s military budget, participation in UN peacekeeping, and national defense capability, have indicated a more pluralist model of policy formation. Therefore, results suggest that the country’s remilitarization has been the product of both elitist and pluralist governance.
Homeless Men Living in Transitional Housing: The BrainWise Program and Improvements in Executive Functions and Coping Self-Efficacy
Authors: Welsh Marilyn , Gorman Barry Patricia , Jacobs Amanda Atwater , Beddes Lindsay A.
Published: April 2018

We describe an innovative approach to teaching homeless men the critical thinking skills underlying adaptive decision making and self-regulation needed to bolster resilience in the face of multiple and complex personal challenges. Single men living in a transitional housing facility for the homeless were taught the BrainWise curriculum ( n = 210) along with other educational, career, and life skills programs, and tested 4 months later. This group was compared with a smaller control group ( n = 61) of men from the same and similar facilities. Outcomes were measured through self-reports of executive functions (Behavior Rating Inventory of Executive Function [BRIEF]), problem solving (Wasik Problem Solving Rating Scale [WPSRS]), coping (Coping Self-Efficacy [CSE]), and knowledge of the thinking skills taught through BrainWise (BrainWise Knowledge Survey [BKS]). All measures showed adequate internal consistency reliability and less strong, but significant, test–retest stability. As expected, self-reported skills in executive function, coping self-efficacy, problem solving, and BrainWise knowledge covaried in predictable ways. The attrition between the pretest and posttest was not predicted by any of the major outcome measures. The sample of 108 men in the Treatment Group who were still in the program 4 months later exhibited significant improvements on all BRIEF composites and subscales, CSE, and the BKS, but not on the WPSRS. In contrast, the remaining 37 Control Group men showed many fewer improvements in the BRIEF scores and a decrease in the WPSRS score. The results suggest the efficacy of BrainWise and measurement of these skills in the vulnerable population of homeless individuals; however, challenges of this type of research and limitations of this study are discussed.
PTSD and the War of Words
Authors: Chekroud Adam M. , Loho Hieronimus , Paulus Martin , Krystal John H.
Published: April 2018

Trauma-related symptoms among veterans of military engagement have been documented at least since the time of the ancient Greeks.1 Since the third edition of the Diagnostic and Statistical Manual in 1980, this condition has been known as posttraumatic stress disorder, but the name has changed repeatedly over the past century, including shell shock, war neurosis, and soldier’s heart. Using over 14 million articles in the digital archives of the New York Times, Associated Press, and Reuters, we quantify historical changes in trauma-related terminology over the past century. These data suggest that posttraumatic stress disorder has historically peaked in public awareness after the end of US military engagements, but denoted by a different name each time—a phenomenon that could impede clinical and scientific progress.
Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years
Authors: Rank Cecilie Utke , Toft Nina , Tuckuviene Ruta , Grell Kathrine , Nielsen Ove Juul , Frandsen Thomas Leth , Marquart Hanne Vibeke Hansen , Albertsen Birgitte Klug , Tedgård Ulf , Hallböök Helene , Ruud Ellen , Jarvis Kirsten Brunsvig , Quist-Paulsen Petter , Huttunen Pasi , Wartiovaara-Kautto Ulla , Jónsson Ólafur Gísli , Trakymiene Sonata Saulyte , Griškevičius Laimonas , Saks Kadri , Punab Mari , Schmiegelow Kjeld
Published: April 2018

Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P ≤ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.
Global optimization strategies for implementing 3D common-reflection-surface stack using the very fast simulated annealing algorithm: Application to real land data
Authors: Garabito German
Published: April 2018

The 3D common-reflection-surface (CRS) stack operator depends on eight kinematic wavefield attributes that must be extracted from the prestack data. These attributes are obtained by an efficient optimization strategy based on the maximization of the coherence measure of the seismic reflection events included by the CRS stacking operator. The main application of these kinematic attributes is to simulate zero-offset stacked data; however, they can also be used for regularization of the prestack data, prestack migration, and velocity model determination. The initial implementations of the 3D CRS stack used grid-search techniques to determine the attributes in several steps with the drawback that accumulated errors can deteriorate the final result. In this work, the global optimization very fast simulated annealing algorithm is used to search for the kinematic attributes by applying three optimization strategies for implementing CRS stacking: (1) simultaneous global search of five kinematic attributes of the 3D common-diffraction-surface stacking operator, (2) two-step global optimization strategy to first search for three attributes and then five attributes of the CRS stacking operator, and (3) simultaneous global search of eight kinematic attributes of the CRS operator. The proposed CRS stacking algorithms are applied to land data of the Potiguar Basin, Brazil. It is demonstrated that the one-step optimization strategy of the eight parameters produces the best results, however, with a higher computational cost.
Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal
Authors: Wang Shi-Yi , Dang Weixiong , Richman Ilana , Mougalian Sarah S. , Evans Suzanne B. , Gross Cary P.
Published: April 2018

Purpose

Prior studies examining cost effectiveness of the 21-gene assay (Oncotype DX [ODX]) for women with hormone receptor–positive, early-stage breast cancer have yielded disparate results. We aimed to explore why these analyses may have yielded different conclusions.

Methods

We conducted a systematic literature review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to which the structure of CEA modeling, the assumptions of the models, and the selection of input parameters influenced cost-effectiveness estimates. We also explored the prevalence of industry funding and whether industry funding was associated with study designs favoring ODX.

Results

We identified 27 analyses, 15 of which received industry funding. In 18 studies, the clinical characteristics (eg, tumor size and grade) commonly used to make chemotherapy decisions were not incorporated into simulation modeling; thus, these studies would favor ODX being cost effective and might not reflect clinical practice. Most studies ignored the heterogeneous effect of ODX on chemotherapy use; only five studies assumed that ODX would increase chemotherapy use for clinically low-risk patients but decrease chemotherapy use for clinically high-risk patients. No study used population-based joint distributions of ODX recurrence score and tumor characteristics, and 12 studies inappropriately assumed that chemotherapy would increase distant recurrence for the low recurrence score group; both approaches overestimated the benefits of ODX. Industry-funded studies tended to favor ODX; all five studies that reported ODX as being cost saving were industry funded. In contrast, two studies that reported an incremental cost-effectiveness ratio > $50,000 per quality-adjusted life-year were not funded by industry.

Conclusion

Although a majority of published analyses indicated that ODX is cost effective, they incorporated study designs that can increase the risk of bias.
Treatment of Stage IV Favorable Histology Wilms Tumor With Lung Metastases: A Report From the Children’s Oncology Group AREN0533 Study
Authors: Dix David B. , Seibel Nita L. , Chi Yueh-Yun , Khanna Geetika , Gratias Eric , Anderson James R. , Mullen Elizabeth A. , Geller James I. , Kalapurakal John A. , Paulino Arnold C. , Perlman Elizabeth J. , Ehrlich Peter F. , Malogolowkin Marcio , Gastier-Foster Julie M. , Wagner Elizabeth , Grundy Paul E. , Fernandez Conrad V. , Dome Jeffrey S.
Published: April 2018

Purpose

The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT.

Methods

Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR.

Results

Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% ( P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% ( P < .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P < .001) and 84.0% (95% CI, 79.4% to 88.6%; P < .001), respectively, in the predecessor NWTS-5 study.

Conclusion

Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.
Returning Individual Genetic Research Results to Research Participants: Uptake and Outcomes Among Patients With Breast Cancer
Authors: Bradbury Angela R. , Patrick-Miller Linda , Egleston Brian L. , Maxwell Kara N. , DiGiovanni Laura , Brower Jamie , Fetzer Dominique , Gaieski Jill Bennett , Brandt Amanda , McKenna Danielle , Long Jessica , Powers Jacquelyn , Stopfer Jill E. , Nathanson Katherine L. , Domchek Susan M.
Published: April 2018

Purpose

Understanding the outcomes of returning individual genetic research results to participants is critical because some genetic variants are found to be associated with health outcomes and have become available for clinical testing.

Materials and Methods

BRCA1/2-negative women with early-onset breast cancer, multiple primary cancers, or a family history of breast cancer who participated in a gene discovery cancer registry were offered the opportunity to learn their individual genetic research results of 24 breast cancer susceptibility genes with a genetic counselor after predisclosure genetic counseling. Outcomes included uptake of research results, knowledge, informed choice, psychosocial adjustment, uncertainty, satisfaction, and uptake of clinical confirmation testing.

Results

Four hundred two potential participants were contacted. One hundred ninety-four participants (48%) did not respond despite multiple attempts, and 85 participants (21%) actively or passively declined. One hundred seven participants (27%) elected for predisclosure counseling and were more likely to be younger, married, and white. Ninety percent of participants who had predisclosure counseling elected to receive their genetic research results, and 89% made an informed choice. Knowledge increased significantly after predisclosure counseling, and anxiety, intrusive cancer-specific distress, uncertainty, and depression declined significantly after receipt of results. General anxiety and intrusive cancer-specific distress declined significantly for both participants with a positive result and those with a negative result. Sixty-four percent of participants had clinical confirmation testing when recommended, including all participants with a mutation in a high-penetrance gene.

Conclusion

Uptake of genetic research results may be lower than anticipated by hypothetical reports and small select studies. Participants who elected to receive research results with genetic providers did not experience increases in distress or uncertainty, but not all patients return for confirmation testing.
Older Subjects With β-Cell Dysfunction Have an Accentuated Incretin Release
Authors: de Jesús Garduno-Garcia José , Gastaldelli Amalia , DeFronzo Ralph A , Lertwattanarak Raweewan , Holst Jens J , Musi Nicolas
Published: April 2018

Objective

Insulin secretion (IS) declines with age, which increases the risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older adults. IS is regulated by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is lower in older adults and that this decline is associated with β-cell dysfunction.

Research Design

A total of 40 young (25 ± 3 years) and 53 older (74 ± 7 years) lean nondiabetic subjects underwent a 2-hour oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided into three groups: young subjects with normal glucose tolerance (Y-NGT; n = 40), older subjects with normal glucose tolerance (O-NGT; n = 32), and older subjects with IGT (O-IGT; n = 21).

Main Outcome Measures

Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15 to 30 minutes. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity.

Results

Matsuda index, early phase ISR (0 to 30 minutes), and parameters of β-cell function were lower in O-IGT than in Y-NGT subjects but not in O-NGT subjects. GLP-1 concentrations were elevated in both older groups [GLP-1 area under the curve (AUC)0–120 was 2.8 ± 0.1 in Y-NGT, 3.8 ± 0.5 in O-NGT, and 3.7 ± 0.4 nmol/L∙120 minutes in O-IGT subjects; P < 0.05], whereas GIP secretion was higher in O-NGT than in Y-NGT subjects (GIP AUC0–120 was 4.7 ± 0.3 in Y-NGT, 6.0 ± 0.4 in O-NGT, and 4.8 ± 0.3 nmol/L∙120 minutes in O-IGT subjects; P < 0.05).

Conclusions

Aging is associated with an exaggerated GLP-1 secretory response. However, it was not sufficient to increase insulin first-phase release in O-IGT and overcome insulin resistance.
Combined use of two supervised learning algorithms to model sea turtle behaviours from tri-axial acceleration data
Authors: Jeantet L. , Dell'Amico F. , Forin-Wiart M. A. , Coutant M. , Bonola M. , Etienne D. , Gresser J. , Regis S. , Lecerf N. , Lefebvre F. , de Thoisy B. , Le Maho Y. , Brucker M. , Châtelain N. , Laesser R. , Crenner F. , Handrich Y. , Wilson R. , Chevallier D.
Published: April 2018

Accelerometers are becoming ever more important sensors in animal-attached technology, providing data that allow determination of body posture and movement and thereby helping elucidate behaviour in animals that are difficult to observe.We sought to validate the identification of sea turtle behaviours from accelerometer signals by deploying tags on the carapace of a juvenile loggerhead (Caretta caretta), an adult hawksbill (Eretmochelys imbricata) and an adult green turtle (Chelonia mydas) at Aquarium La Rochelle. We recorded tri-axial acceleration at 50Hz for each species for a full day while two fixed cameras recorded their behaviours. We identified behaviours from the acceleration data using two different supervised learning algorithms; Random Forest and Classification And Regression Tree (CART), treating the data from the adult animals as separate from the juvenile data. We achieved a global accuracy of 81.30% for the adult turtle CART model and 71.63% for the juvenile loggerhead, identifying 10 and 12 different behaviours, respectively. Equivalent figures were 86.96% for the hawksbill and green turtle Random Forest model and 79.49% for the loggerhead, for the same behaviours. The use of Random Forest combined with CART algorithms allowed us to understand the decision rules implicated in behaviour discrimination, and thus remove or group together some “confused” or underrepresented behaviours in order to get the most accurate models. This study is the first to validate accelerometer data to identify turtle behaviours and the approach can now be tested on other captive sea turtle species.
Przysłowie jako jednostka języka (w perspektywie tekstologii integralnej)
Authors: Wasiuta Sebastian
Published: April 2018

Proverb as a linguistic unit (from the perspective of integral text linguistics)

The paper presents arguments in favour of treating proverbs as text, and in consequence, as linguistic units. The starting point is the concept of integral text linguistics formulated by Jerzy Bartmiński and Stanisława Niebrzegowska-Bartmińska in their handbook Tekstologia (‘Text linguistics’, 2009). According to this theory, text is a supra-sentence linguistic unit, and the text of the parole plane corresponds to an abstract template of the langue plane. The argumentation that this paper presents in favour of regarding proverbs as text is based on an analysis of examples from the National Corpus of Polish which contain proverbs. It shows clearly that proverbs fulfill all of the requirements of textuality; among others, they are uniquely distinguished as a communicative whole, they receive a clear genre qualification, they have their senders and receivers, a clear communicative intent and a stylistic qualifier. The final part of the paper contains a proposition to describe proverbs as “minimal text”, and to separate the terms minimal text and prototypical text. Within this interpretation, a proverb is a prototypical minimal text that is different from both non-prototypical minimal texts, and from non-prototypical non-minimal long texts such as novels, as well as prototypical texts such as fables which tend to be longer (non-minimal).
Cechy słowotwórcze czasowników oznaczających zmianę pozycji ciała względem osi ciała
Authors: Witkowska Paulina
Published: April 2018

Word-formational features of verbs denoting change of position with respect to the axis of the body

The paper presents word-derivational features of verbs which co-occur with się and denote a change in the position of the body with respect to its vertical axis. The analysis shows how differences in the morphological structure of these verbs influence the manner in which the change of the position of the body proceeds. Moreover, the paper shows which elements of the meanings of verbs are carried by prefixes with which these verbs combine. The article also shows which of the morphological forms of the analysed verbs are primary, and what derivational relations hold between them and their derivatives.
Gatunkowe uwarunkowania znaczeń symbolicznych
Authors: Niebrzegowska-Bartmińska Stanisława
Published: April 2018

Genre conditioning of symbolic meanings

Folklore texts operate on two levels: inside the folk culture in combination with traditional beliefs and customs, and within the national culture as a point of reference and source of inspiration for writers and poets. Individual words also function on those two levels, as they can be understood ‘the literary way’ or ‘the folk way’. The paper presents two units of the vocabulary of the national language (jabłoń ‘apple tree’ and jabłko ‘apple’) which have fixed base meanings but which also accommodate additional senses on a higher semantic level and thus become the signifiant for a new sign. In folklore texts, depending on the genre, the images of apple tree and apple accept the symbolic senses of happy and fulfilled love (in love and courting songs), fertility and vitality (in wedding songs), of readiness for marriage and the stable, cosmic order (in wishing carols), of temptation and sin (in nativity plays), richness and ability to regenerate and renew life (in fairy tales), of the sense of security and parental care (in orphan songs), of the value of family home and proximity to the loved ones (in soldiers’ songs). These symbols can be explained using extralinguistic data (beliefs and customs) as the same senses can be expressed through words, rituals, or objects. The analysis reveals that the images of apple tree and apple serve to communicate values underlying the image of the world contained within the specific genre. The same images, transplanted to a different domain, outside of their particular social group, lose their value, become illegible, incomprehensible, and are viewed as merely a signal of folksiness.
Język jako wartość w „Tygodniku Ilustrowanym” w latach 1918–1928
Authors: Gabryś-Sławińska Monika
Published: April 2018

Language as a value in ”Tygodnik Ilustrowany” in the years 1918–28

In the years 1918–28, “Tygodnik Ilustrowany” offered its readers a new outlook on the issues of language and linguistics. Resigning from treating Polish as an argument in the struggle for national values, in the years 1920–25, the journal tried to present language as a value in its own right. In this period, it published the works of specialists such as Kryński and Lange. After a period of interest in the specificity of language, its secrets and mechanisms, one can observe a return to the instrumental treatment of Polish. Fixed in the journal’s tradition, the vision of language as subordinate to the fulfillment of specific goals reappears in the years 1926–28.
Jak mówimy, jakoś mówiąc? Formalne i semantyczne właściwości adwerbialnych uzupełnień quasi-imiesłowowego mówiąc
Authors: Kubicka Emilia
Published: April 2018

Formal and Semantic Characteristics of Adverbial Complements to Quasi-Adverbial mówiąc ‘Speaking’The paper presents the construction (jakoś) mówiąc ‘speaking (in some manner)’, against the background of metatextual expressions which serve the sender to comment on the utterance as it is created. The kind of this commentary depends on the filling of the valency slot opened by the quasi- -adverbial, i.e. on the meaning of the adverbial expression represented by the forms of adverbs (e.g. krótko ‘briefly’, inaczej ‘differently’, delikatniej ‘more subtly’, ściślej ‘more precisely’, wprost ‘bluntly’, ogólnie ‘generally’, szczerze ‘honestly’, poważnie ‘gravely’), adverbial expressions (e.g. z grubsza ‘roughly’, w skrócie ‘in short’, w cudzysłowie ‘in quotes’), the po _-u construction (e.g. po polsku ‘in Polish’, po ludzku ‘humanely’, po prostacku ‘in a boorish way’, po ludowemu ‘the folk way’, po sportowemu ‘the sport way’), and quasi-instrumentals (językiem _ ‘in the _ language’, słowami _ ‘with _ words’, żargonem _ ‘in the _ jargon’). The author shows how adverbials struggle to become independent from mówiąc, and presents their semantic classification based on two clearly separated groups: adverbials which project an evaluation of the communication (e.g. szczerze ‘honestly’, skromnie ‘humbly’, serio ‘seriously’, żartobliwie ‘facetiously’), and adverbials which name operations performed on the communication, i.e. modify its content (e.g. krótko ‘briefly’, ogólnie ‘generally’, precyzyjniej ‘more precisely’) or select a system of symbols (e.g. symbolicznie ‘symbolically’, po ludzku ‘humanely’, brutalnie ‘brutally’, fachowo ‘professionally’, po heglowsku ‘in a Hegelian manner’).
Wiedza kulturowa a opis leksykograficzny w jednojęzycznym słowniku języka polskiego
Authors: Czelakowska Anna
Published: April 2018

Cultural Information Versus Lexicographic Description in a Monolingual Dictionary of PolishThe paper speculates whether the lexicographic description in a general dictionary of Polish should contain explicit information about cultural knowledge petrified in the language. The author believes that this kind of commentary is important from the point of view of mediation between generations and cultures, and it can help create an active dictionary. An analysis of words from various fields (Wielkanoc ‘Easter’, szlachta ‘nobility’, dzwony ‘bell-bottoms’, bezpieka ‘security services’, orzeł ‘eagle’, magiel ‘mangle’, trzepak ‘carpet hanger’, and others) illustrates and justifies this desideratum, assuming that cultural information will be only partially connected with the semantic description. Such information should be incorporated in different fields within the microstructure of an entry, including material illustration. For many units, the introduction of an explanation in an extrasemantic section “cultural knowledge and competence” can be used as an alternative or supplementary solution.
Gość czy obcy? Od przekazu ewangelicznego (Mt 25, 31–46) do polskich przekładów biblijnych. Problemy ekwiwalencji
Authors: Koziara Stanisław , Przybylska Renata
Published: April 2018

Guest or Foreigner? From the Evangelical Message (Mt 25, 31-46) to the Polish Translations of the Bible. Problems of EquivalenceThe paper tries to draw attention to problems related to accurate conveyance in translation of certain forms and ideas contained in the Bible. It focuses on a fragment of the parable of the final judgment from the Gospel of St. Matthew (Mt 25, 31–46) which speaks about acts of love towards neighbours. Besides the evangelical command to care for the hungry, thirsty, naked, sick, and imprisoned, it contains an order to accept a FOREIGNER, described in the Greek and Latin text of the Bible as ksénos and hospes, respectively. The first goal of this paper is to attempt a reconstruction of the linguistic and cultural context in which those names for the FOREIGNER were used. The second, essential, goal is to philologically evaluate a collection of native equivalents of those foreign words which appear in 34 Polish translations of the Gospel of St. Matthew, from Old Polish to newer and contemporary renderings. The remarks presented in the paper are philological in nature and primarily refer to linguistic descriptive procedures, with a necessary utilization of certain findings in the fields of exegesis and Biblical hermenutics.
Polskie pantałyk i jego wschodniosłowiańskie, słowackie i morawskie odpowiedniki – uwagi o pochodzeniu
Authors: Stachowski Marek
Published: April 2018

Polish pantałyk and its Eastern Slavic, Slovak, and Moravian Counterparts. Remarks About the OriginThe Polish word pantałyk is only used in the expression zbić z pantałyku ‘put sb off his stride, confuse, upset, disconcert’ (lit. ‘strike sb off the pantałyk’). The original meaning and the etymology of the word have been unknown, and this is also valid for Moravian, Slovak and Eastern Slavonic. This author argues that it primarily was a riding term ‘crupper’, composed of a German loanword with a Slavonic suffix.
Słownictwo związane z obróbką lnu i tkactwem w gwarach Grodzieńszczyzny na tle gwar podlaskich
Authors: Konczewska Katarzyna
Published: April 2018

Flax Processing and Weaving Vocabulary in the Dialects of the Grodno Region, Against the Background of Podlasie DialectsFor the first time in the literature, the present paper compares flax processing and weaving vocabulary found strictly in the Polish–Belorussian borderland which was formerly part of a single Grodno county. The source material comprises well-known Polish lexicological works, and also a work on Grodno lexicon by Apanas Cychun which has not as yet been taken into consideration. Thanks to this, the paper notes lexemes unattested in previous corpora of dialectal vocabulary, and adds precision to the information contained in them.