Frailty models

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Regenerative amplification of ultrashort laser pulses with thulium- and holmium-doped materials

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Unobserved heterogeneity in a model with cure fraction applied to breast cancer

We suggest a cure-mixture model to analyze bivariate time-to-event data, as motivated by the paper of Chatterjee and Shih (2001, Biometrics 57, 779 - 786), but with a simpler estimation procedure and the correlated gamma-frailty model instead of the shared gamma-frailty model. This approach allows us to deal with left truncated and right censored lifetime data and accounts for heterogeneity as well as for an insusceptible (cure) fraction in the study population. We perform a simulation study to evaluate the properties of the estimates in the proposed model and apply it to breast cancer incidence data for 5,857 Swedish female monozygotic and dizygotic twin pairs from the so-called old cohort of the Swedish Twin Registry. This model is used to estimate the size of the susceptible fraction and the correlation between the frailties of the twin partners. Possible extensions, advantages and limitations of the proposed method are discussed.Sweden, breast, cancer, correlation, survival, twins

Flying Qualities of Otto Lilienthal's Large Biplane

The paper describes full-scale balance tests, which have proven structural integrity and longitudinal static stability of an authentic replica of Otto Lilienthal's Large Biplane glider. In addition to that, the replica, built after patent drawings, photographs, and textual descriptions by the Otto-Lilienthal-Museum, was towed using a rope winch and finally flown downhill without rope or guide wires. The tests allow for the assessment of the aircraft's controllability and stability not only during steady flight, but also during takeoff, landing, and on the occasion of wind gusts. A brief description of the design parameters and applied methods is given along with force and moment data gained from balance measurements as well as the evaluation of a limited set of data acquired during flight, including speed, duration, and distances flown

Association Between VEGF Expression and Diffusion Weighted Imaging in Several Tumors—A Systematic Review and Meta-Analysis

To date, only a few studies have investigated relationships between Diffusion-weighted imaging (DWI) and Vascular endothelial growth factor (VEGF) expression in tumors. The reported results are contradictory. The aim of the present analysis was to review the published results and to perform a meta-analysis regarding associations between apparent diffusion coefficients (ADC) derived from DWI and VEGF expression. MEDLINE library was screened for relationships between ADC and VEGF expression up to January 2019. Overall, 14 studies with 578 patients were identified. In 10 studies (71.4%) 3 T scanners were used and in four studies (28.6%) 1.5 T scanners. Furthermore, seven studies (50%) had a prospective design and seven studies (50%) had a retrospective design. Most frequently, prostate cancer, followed by rectal cancer, cervical cancer and esophageal cancer were identified. The pooled correlation coeffcient of all tumors was r = 0.02 [95% CI 0.26–0.21]. ADC values derived from routinely acquired DWI do not correlate with VEGF expression in various tumors. Therefore, DWI is not sensitive enough to reflect angiogenesis-related microstructure of tumors

Apparent Diffusion Coefficient for Distinguishing Between Malignant and Benign Lesions in the Head and Neck Region: A Systematic Review and Meta-Analysis

Background: The purpose of the present meta-analysis was to provide evident data about use of apparent diffusion coefficient (ADC) values for distinguishing malignant and benign lesions in the head and neck region. Material and Methods: MEDLINE and Scopus databases were screened for associations between ADC and malignancy/benignancy of head and neck lesions up to December 2018. Overall, 22 studies met the inclusion criteria. The following data were extracted: authors, year of publication, study design, number of patients/lesions, lesion type, mean value, and standard deviation of ADC. The primary endpoint of the systematic review was the analysis of the association between lesion nature and ADC values. The methodological quality of the involved studies was checked according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument. The meta-analysis was undertaken by using RevMan 5.3 software. DerSimonian and Laird random-effects models with inverse-variance weights were used without further correction to account for the heterogeneity between the studies. Mean ADC values including 95% confidence intervals were calculated separately for benign and malignant lesions. Results: The acquired 22 studies comprised 1,227 lesions. Different malignant lesions were diagnosed in 818 cases (66.7%) and benign lesions in 409 cases (33.3%). The mean ADC value of the malignant lesions was 1.04 × 10−3 mm2 /s, and the mean value of the benign lesions was 1.46 × 10−3 mm2 /s. Lymphomas and sarcomas showed the lowest calculated mean ADC values, 0.7 and 0.79 × 10−3 mm2 /s, respectively. Adenoid cystic carcinomas had the highest ADC values (1.5 × 10−3 mm2 /s). None of the analyzed malignant tumors had mean ADC values above 1.75 × 10−3 mm2 /s. Conclusion: ADC values play a limited role in distinguishing between malignant and benign lesions in the head and neck region. It may be only suggested that lesions with mean ADC values above 1.75 × 10−3 mm2 /s are probably benign. Further large studies are needed for the analysis of the role of diffusion-weighted imaging (DWI)/ADC in the discrimination of benign and malignant lesions in the head and neck region

Ultrafast switching with nonlinear optics in thin films

We demonstrate a novel, to the best of our knowledge, concept for an all-optical switch based on the optical Kerr effect in optical interference coatings. The utilization of the internal intensity enhancement in thin film coatings as well as the integration of highly nonlinear materials enable a novel approach for self-induced optical switching. The paper gives insight into the design of the layer stack, suitable materials, and the characterization of the switching behavior of the manufactured components. A modulation depth of 30% could be achieved, which prepares the way for later applications in mode locking

Genetic analysis of cause of death in a bivariate lifetime model with dependent competing risks

A mixture model in multivariate survival analysis is presented, whereby heterogeneity among subjects creates divergent paths for the individual's risk of experiencing an event (i.e., disease), as well as for the associated length of survival. Dependence among competing risks is included and rendered testable. This method is an extension of the bivariate correlated gamma-frailty model. It is applied to a data set on Danish twins, for whom cause-specific mortality is known. The use of multivariate data solves the identifiability problem which is inherent in the competing risk model of univariate lifetimes. We analyse the in uence of genetic and environmental factors on frailty. Using a sample of 1470 monozygotic (MZ) and 2730 dizygotic (DZ) female twin pairs, we apply five genetic models to the associated mortality data, focusing particularly on death from coronary heart disease (CHD). Using the best fitting model, the inheritance risk of death from CHD was 0.39 (standard error 0.13). The results from this model are compared with the results from earlier analysis that used the restricted model, where the independence of competing risks was assumed. Comparing both cases, it turns out, that heritability of frailty on mortality due to CHD change substantially. Despite the inclusion of dependence, analysis confirms the significant genetic component to an individual's risk of mortality from CHD. Whether dependence or independence is assumed, the best model for analysis with regard to CHD mortality risks is an AE model, implying that additive factors are responsible for heritability in susceptibility to CHD. The paper ends with a discussion of limitations and possible further extensions to the model presented.

Flight testing Otto Lilienthal's experimental monoplane

Free flights and tethered flights were performed using an authentic replica of Otto Lilienthal's experimental monoplane, the "Vorflügelapparat", achieving flight distances of more than 100m. The flight stability, controllability and performance of the design has been verified through balance measurements using a 1:5 scaled wind tunnel test