62 research outputs found

    Prognostic impact of CD4-positive T cell subsets in early breast cancer : a study based on the FinHer trial patient population

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    Background: The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. Methods: The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. Results: High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29-0.67, P Conclusions: The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC.Peer reviewe

    A weighting approach for judging the effect of patient strata on high-dimensional risk prediction signatures

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    BACKGROUND: High-dimensional molecular measurements, e.g. gene expression data, can be linked to clinical time-to-event endpoints by Cox regression models and regularized estimation approaches, such as componentwise boosting, and can incorporate a large number of covariates as well as provide variable selection. If there is heterogeneity due to known patient subgroups, a stratified Cox model allows for separate baseline hazards in each subgroup. Variable selection will still depend on the relative stratum sizes in the data, which might be a convenience sample and not representative for future applications. Such effects need to be systematically investigated and could even help to more reliably identify components of risk prediction signatures. RESULTS: Correspondingly, we propose a weighted regression approach based on componentwise likelihood-based boosting which is implemented in the R package CoxBoost (https://github.com/binderh/CoxBoost). This approach focuses on building a risk prediction signature for a specific stratum by down-weighting the observations from the other strata using a range of weights. Stability of selection for specific covariates as a function of the weights is investigated by resampling inclusion frequencies, and two types of corresponding visualizations are suggested. This is illustrated for two applications with methylation and gene expression measurements from cancer patients. CONCLUSION: The proposed approach is meant to point out components of risk prediction signatures that are specific to the stratum of interest and components that are also important to other strata. Performance is mostly improved by incorporating down-weighted information from the other strata. This suggests more general usefulness for risk prediction signature development in data with heterogeneity due to known subgroups

    Influence of E-smoking liquids on human periodontal ligament fibroblasts

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    Introduction: Over the last years, electronic cigarettes (ECs) have become more popular, particularly in individuals who want to give up smoking tobacco. The aim of the present study was to assess the influence of the different e-smoking liquids on the viability and proliferation of human periodontal ligament fibroblasts. Method and materials: For this study six test solutions with components from ECs were selected: lime-, hazelnut- and menthol-flavored liquids, nicotine, propylene glycol, and PBS as control group. The fibroblasts were incubated up to 96 h with the different liquids, and cell viability was measured by using the PrestoBlue® reagent, the ATP detection and the migration assay. Fluorescence staining was carried out to visualize cell growth and morphology. Data were statistically analyzed by two-tailed one-way ANOVA. Results: The cell viability assay showed that the proliferation rates of the cells incubated with nicotine or the various flavored liquids of the e-cigarettes were reduced in comparison to the controls, though not all reductions were statistically significant. After an incubation of 96 h with the menthol-flavored liquid the fibroblasts were statistically significant reduced (p < 0.001). Similar results were found for the detection of ATP in fibroblasts; the incubation with menthol-flavored liquids (p < 0.001) led to a statistically significant reduction. The cell visualization tests confirmed these findings. Conclusion: Within its limits, the present in vitro study demonstrated that menthol additives of e-smoking have a harmful effect on human periodontal ligament fibroblasts. This might indicate that menthol additives should be avoided for e-cigarettes

    Early Validation of Automation Plant Control Software using Simulation Based on Assumption Modeling and Validation Use Cases

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    In automation plants, technical processes must be conducted in a way that products, substances, or services are produced reliably, with sufficient quality and with minimal strain on resources. A key driver in conducting these processes is the automation plant’s control software, which controls the technical plant components and thereby affects the physical, chemical, and mechanical processes that take place in automation plants. To this end, the control software of an automation plant must adhere to strict process requirements arising from the technical processes, and from the physical plant design. Currently, the validation of the control software often starts late in the engineering process in many cases – once the automation plant is almost completely constructed. However, as widely acknowledged, the later the control software of the automation plant is validated, the higher the effort for correcting revealed defects is, which can lead to serious budget overruns and project delays. In this article we propose an approach that allows the early validation of automation control software against the technical plant processes and assumptions about the physical plant design by means of simulation. We demonstrate the application of our approach on the example of an actual plant project from the automation industry and present it’s technical implementatio

    Changes in the probability of hysterectomy in the city of Mainz and Mainz-Bingen region, Germany

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    Abstract Background To assess the hysterectomy probability by calendar period and age, the overall and the age-specific prevalence of hysterectomy in women aged 30–65 years. Methods Baseline data (2005–2007) from the population-based MARZY study conducted in Mainz and Mainz-Bingen, Germany, were analysed. 6429 women aged 30–65 years were asked whether they had undergone a hysterectomy and the date and indication of the procedure. We calculated the 5-year age-specific prevalence of hysterectomy and estimated the probability of undergoing a hysterectomy combining two approaches: 1) Kaplan–Meier and 2) Inverse probability weighting (IPW). We assessed potential changes over calendar periods by simulating survival curves, having hysterectomy as the event, employing a Cox proportional hazard model. Results Data on hysterectomy were available for 4719 women. Of these, 961 (20.4%) had undergone a hysterectomy between 1960 and 2006. The hysterectomy prevalence was highest among the 60–64 year-olds (40.7%). The IPW-corrected probability of having a hysterectomy up to the age of 65 years was 36.4%. The age-specific probability of hysterectomy increased from 0.1% (20–24 years), peaking at 45–49 years (7.8%) and declining thereafter to less than 5% among women aged 50 and older. Over time, women were hysterectomised at an increasingly older age. Most hysterectomies (86.7%) were done due to benign disease. Conclusions A shift to older age at hysterectomy with an advancing calendar period likely reflects changes in clinical practice in Germany. Trial registration Landesärztekammer Rheinland-Pfalz: 837.438.03 (4100)

    Fluctuation of intraocular pressure in glaucoma patients before and after trabeculectomy with mitomycin C

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    Intraocular pressure (IOP) fluctuation is considered as a risk factor for glaucoma progression. We investigated IOP values and IOP fluctuation before and after trabeculectomy (TE) with mitomycin C (MMC) measured by 48-hour diurnal-nocturnal-IOP-profiles (DNP).Pre- and postoperative DNPs of 92 eyes undergoing primary TE with MMC were analysed. Each 48-hour IOP-profile involved 10 IOP measurements (8:00 a.m., 2:00 p.m., 6:00 p.m., and 9:00 p.m. in sitting and at 00:00 in supine position). The "preoperative DNP" was performed a few weeks before TE. The "postoperative DNP" was performed at least six months (range: 6 months-2 years) after TE. Mean IOP values and IOP fluctuations were calculated.After TE with MMC mean IOP was reduced from 16.94±3.83 to 11.26±3.77 mmHg at daytime and from 18.17±4.26 to 11.76±3.90 mmHg at night. At daytime mean IOP-fluctuation decreased from 8.61±4.19 to 4.92±2.52 mmHg, at night from 3.15±2.95 to 1.99±1.82 mmHg. Mean IOP was lower on the second day of the preoperative DNP. This effect was not present in the postoperative DNP. Preoperatively, IOP was controlled in all eyes with a mean of 3.22±0.94 antiglaucomatous agents. Postoperatively, IOP≤15 mmHg was achieved in 71.7%, IOP≤18 mmHg in 77.1% and a decrease in IOP of >30% in 47.8% without antiglaucomatous therapy. Postoperatively, pseudophakia was associated by a higher mean IOP-fluctuation compared to the phakic eyes.TE with MMC significantly reduces both mean IOP-values and IOP- fluctuations at day and night at least 6 months postoperatively. The effect of TE on the IOP fluctuation was less pronounced in pseudophakic eyes
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