EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen Receptor–Positive Breast Cancer

Introduction Early stage estrogen receptor (ER)-positive breast cancer may be treated with chemotherapy in addition to hormone therapy. Currently available molecular signatures assess the risk of recurrence and the benefit of chemotherapy; however, these tests may have large intermediate risk groups, limiting their usefulness. Methods The EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded–based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis. Concordance index was used to measure the probability of prognostic score agreement with outcome. Results The EarlyR score and categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant recurrence-free interval in Affymetrix (categorical P = 3.5 × 10−14; continuous P = 8.8 × 10−15) and METABRIC (categorical P < 2.2 × 10−16; continuous P < 10−16) data sets of ER+ breast cancer. Similar results were observed for the breast cancer–free interval end point. At most 13% of patients were intermediate risk and at least 66% patients were low risk in both ER+ cohorts. The EarlyR score was significantly prognostic (distant recurrence-free interval; P < .001) in both lymph node–negative and lymph node–positive patients and was independent from clinical factors. EarlyR and surrogates of current molecular signatures were comparable in prognostic significance by concordance index. Conclusion The 5-gene EarlyR score is a robust prognostic assay that identified significantly fewer patients as intermediate risk and more as low risk than currently available assays. Further validation of the assay in clinical trial–derived cohorts is ongoing

Systematic Differences in Beliefs About Others in Strategic Interactions

Individuals' preferences for outcomes and their expectations about other players' choices that in uence the outcome govern strategic interactions. The common assumption that expectations about others are mutually consistent across players allows researchers to in- fer preferences from observed strategic decisions. In this paper, I show how players beliefs about other players choices systematically depart from this assumption and explain the consequences for the inference of preferences based on strategic choices. In the context of altruistic preferences, I document a relationship between an individ- ual's preferences and his (implicit or explicit) expectations of others' actions in modi ed dictator games. This relationship is beyond what false consensus or a simple correlation between beliefs and preferences can account for and is consistent with a more fundamental account of projection of preferences. I study the impact of systematic belief di erences on players strategic actions in a trust-dictator game. I show that preference incongruencies across di erent roles in a trust-dictator game are in line with preference projection. Finally, I demonstrate biases in the estimation of preferences from decisions in this strategic game under the assumption of mutually consistent beliefs.http://deepblue.lib.umich.edu/bitstream/2027.42/97023/1/1185_Orhun.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/97023/4/1185_Orhun2.pd

Facets of job satisfaction and work engagement

This study analyzes the relationship between the the facets of job satisfaction and the work engagement. Previous studies that focus on the linkages between work engagement and overall job satisfaction ignore the multi-faceted nature of job satisfaction construct. In this study, how job satisfaction facets are linked to three dimensions of work engagement - i.e. vigor, dedication and absorption- is discussed by drawing on the Social Exchange Theory. The cross-lagged data used in this study comes from the specialist lending division of a UK bank. The Linear Multiple Regression analyzes are run to test the proposed theoretical model. The results show that among all the job satisfaction facets, the ‘satisfaction with work itself’ is the key driver of all dimensions of work engagement i.e. vigor, dedication and absorption. The ‘satisfaction with conditions’ is negatively linked to absorption of employees in their work. This means that the employees with high workload might not be absorbed in their work. Finally, it is found that employees who are satisfied with the communication in their work are also absorbed in their work. This study contributes to our knowledge of the drivers of work engagement over time. The facets of job satisfaction as the drivers help us to have a comprehensive understanding of the link between the job satisfaction facets and work engagement. This study first contributes to the work engagement literature which has neglected the multi-dimensional approach of job satisfaction. This study also contributes to the limited number of work engagement studies conducted in service sector and in UK

Comparison of the accelerated and classic vaccination schedules against Hepatitis B: three-week Hepatitis B vaccination schedule provides immediate and protective immunity

BACKGROUND: Hepatitis B virus infection although preventable by vaccination remains an important health issue throughout the world due to its morbidity, mortality and economical losses. Early seroprotection is desirable for people at high risk of exposure. The aim of this study was to determine whether three-week hepatitis B vaccination (on days 0, 10 and 21) provide seroprotection or not. METHODS: The 120 subjects enrolled into the study were divided into two groups and vaccinated by the classic (months 0, 1, and 2) or the accelerated (days 0, 10, and 21) schedules and antibody response determined on days 30, 60, and 90 and, if below 10 mIU/ml(-1), again on day 180. For each individual in the classic group (B) three subjects were enrolled in the accelerated group (A). Recombinant hepatitis B vaccine (Gen-Hevac B, Pasteur) was given as 20 micrograms intramuscular injections via the deltoid muscle. A booster dose on day 365 was administered for each group. Family members of hepatitis B carriers and volunteer health personnel were enrolled into group A. To the B group only volunteers who wanted vaccination against hepatitis B were included. RESULTS: After three doses of vaccine, Anti-HBs titers reached protective levels in both groups. The number of vaccinees with seroprotective levels of Anti-HBs (≥10 mIU/ml(-1)) on day 30 was 53 (58.9%) in group A and 9 (30.0%) in group B (p < 0.05). On day 60, there was no difference between group A and B, with response rates of 84.4% (n = 76) and 80.0% (n = 24) respectively (p > 0.05). On day 90 there was no difference between group B and group A; with 26 (86.7%) and 79 (87.7%) responders respectively. In both groups those with Anti-HBs levels <10 mIU/ml(-1 )attained protective levels by day 180. CONCLUSION: In this study, the three-week vaccination provided protective antibody titers within a shorter time compared to the classic schedule. Therefore, in order to provide rapid antibody production against hepatitis B virus, the accelerated vaccination schedule seems to be a good preference

An application of quality function deployment for assessing the service quality performance of enterprises

Bu çalışmada, testere üreticisi bir işletmenin, müşterileri tarafından algılanan hizmet kalite performansını ölçmek ve kritik hizmet kalite karakteristiklerini tanımlamak amacıyla Kalite Fonksiyon Göçerimi (KFG) tekniği kullanılmıştır. Çalışma kapsamında, testere makinesini kullanan müşterilerin istek ve beklentilerinin tespit etmek ve işletmenin müşterilerine sunduğu kalite performansını ölçmek üzere bir anket çalışması yapılmıştır. Elde edilen verilere dayanarak Kalite Evi oluşturulmuştur. Çalışmanın sonuç ve değerlendirme kısmında, incelenen işletme için tespit edilen kritik hizmet kalite karakteristiklerine ve hizmet kalite performansına yer verilmiştir.&nbsp; In this study, a Quality Function Deployment technique is used to define the perceived customer quality performance and determine critical service quality characteristics in a saw production enterprise. Within the framework of the study, a questionnaire is used to determine the requirements and expectations of the costumers using the saw machine and measure the quality performance of the enterprise. Based on the collected data, a House of Quality is built. At the evaluation and conclusion section of the study, the defined critical service quality characteristics and service quality performance of the considered enterprise are presented.&nbsp

IRRIGATION SCHEDULING FOR WATERMELON WITH CROP WATER STRESS INDEX (CWSI)

This study was designed to evaluate different threshold values of crop water stress index (CWSI) to schedule irrigation for watermelon (Citrullus vulgaris) grown with drip irrigation Irrigations were started when CWSI values reached to 0.2, 0.4, 0.6, 0.8 and 1.0 (non-irrigation). The CWSI values were computed from measurements of canopy temperature, air temperature and vapor pressure defi cit. The total irrigations amount of 342, 280, 248 and 193 mm were applied to the 0.2, 0.4, 0.6 and 0.8 CWSI treatments, respectively. The maximum seasonal evapotranspiration (ET) as 412 mm was measured from 0.2 CWSI treatment. Irrigation levels signifi cantly affected fruit yield. Although the highest fruit yield (76.3 t ha-1) was obtained from the 0.2 CWSI treatment, the 0.4 and 0.6 of CWSI treatments were statistically in the same letter group with this treatment. Also, maximum water use effi ciency (WUE) and irrigation water use efficiency (IWUE) were obtained from 0.6 of CWSI treatment as 22.1 and 13.3 kg m-3, respectively. Therefore, based on these results, 0.6 of CWSI value should be used for irrigation time of watermelon under Tekirdag, Turkey conditions

Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals.

Background: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Methods: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. Results: Our study revealed significant uptrend in AM to PM FT4 ( Conclusion: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement

The effect of gamma irradiation on the structural properties of olivine

Gamma irradiation studies of (Mg0.905Fe0.095)2SiO4 olivine were performed using X-ray fluorescence method, X-ray diffraction, Raman and Mössbauer spectroscopy. The absorbed doses were 300, 600 and 1000 Gy. Small irradiation doses cause an increase of lattice vibrations and small deformation of both M1 and M2 octahedron. The observed effect is similar to the results expose to high temperature. However, the small deformation takes place only in unit cell of Olivine’s structure

Independent Validation of EarlyR Gene Signature in BIG 1-98: A Randomized, Double-Blind, Phase III Trial Comparing Letrozole and Tamoxifen as Adjuvant Endocrine Therapy for Postmenopausal Women with Hormone Receptor-Positive, Early Breast Cancer

Background EarlyR gene signature in estrogen receptor–positive (ER+) breast cancer is computed from the expression values of ESPL1, SPAG5, MKI67, PLK1, and PGR. EarlyR has been validated in multiple cohorts profiled using microarrays. This study sought to verify the prognostic features of EarlyR in a case-cohort sample from BIG 1–98, a randomized clinical trial of ER+ postmenopausal breast cancer patients treated with adjuvant endocrine therapy (letrozole or tamoxifen). Methods Expression of EarlyR gene signature was estimated by Illumina cDNA-mediated Annealing, Selection, and Ligation assay of RNA from formalin-fixed, paraffin-embedded primary breast cancer tissues in a case-cohort subset of ER+ women (N = 1174; 216 cases of recurrence within 8 years) from BIG 1–98. EarlyR score and prespecified risk strata (≤25 = low, 26–75 = intermediate, >75 = high) were “blindly” computed. Analysis endpoints included distant recurrence–free interval and breast cancer–free interval at 8 years after randomization. Hazard ratios (HRs) and test statistics were estimated with weighted analysis methods. Results The distribution of the EarlyR risk groups was 67% low, 19% intermediate, and 14% high risk in this ER+ cohort. EarlyR was prognostic for distant recurrence–free interval; EarlyR high-risk patients had statistically increased risk of distant recurrence within 8 years (HR = 1.73, 95% confidence interval = 1.14 to 2.64) compared with EarlyR low-risk patients. EarlyR was also prognostic of breast cancer–free interval (HR = 1.74, 95% confidence interval = 1.21 to 2.62). Conclusions This study confirmed the prognostic significance of EarlyR using RNA from formalin-fixed, paraffin-embedded tissues from a case-cohort sample of BIG 1–98. EarlyR identifies a set of high-risk patients with relatively poor prognosis who may be considered for additional treatment. Further studies will focus on analyzing the predictive value of EarlyR signature