Running minimal flavor violation

We consider the flavor structure of the minimal supersymmetric standard model (MSSM) in the framework of `minimal flavor violation' (MFV). We show that, if one imposes the MFV structure at some scale, to a good accuracy the MFV decomposition works at all other scales. That is, quantum effects can be described by running coefficients of the MFV decomposition. We find that the coefficients get driven to non-trivial fixed points.Comment: 13 pages, 12 figure

Shape-specific characterization of colorectal adenoma growth and transition to cancer with stochastic cell-based models

Colorectal adenoma are precursor lesions on the pathway to cancer. Their removal in screening colonoscopies has markedly reduced rates of cancer incidence and death. Generic models of adenoma growth and transition to cancer can guide the implementation of screening strategies. But adenoma shape has rarely featured as a relevant risk factor. Against this backdrop we aim to demonstrate that shape influences growth dynamics and cancer risk. Stochastic cell-based models are applied to a data set of 197,347 Bavarian outpatients who had colonoscopies from 2006-2009, 50,649 patients were reported with adenoma and 296 patients had cancer. For multi-stage clonal expansion (MSCE) models with up to three initiating stages parameters were estimated by fits to data sets of all shapes combined, and of sessile (70% of all adenoma), peduncular (17%) and flat (13%) adenoma separately for both sexes. Pertinent features of adenoma growth present themselves in contrast to previous assumptions. Stem cells with initial molecular changes residing in early adenoma predominantly multiply within two-dimensional structures such as crypts. For these cells mutation and division rates decrease with age. The absolute number of initiated cells in an adenoma of size 1 cm is small around 10(3), related to all bulk cells they constitute a share of about 10(−5). The notion of very few proliferating stem cells with age-decreasing division rates is supported by cell marker experiments. The probability for adenoma transiting to cancer increases with squared linear size and shows a shape dependence. Compared to peduncular and flat adenoma, it is twice as high for sessile adenoma of the same size. We present a simple mathematical expression for the hazard ratio of interval cancers which provides a mechanistic understanding of this important quality indicator. We conclude that adenoma shape deserves closer consideration in screening strategies and as risk factor for transition to cancer

Radiatively induced flavour violation in the general two-Higgs doublet model with Yukawa alignment

The most general two Higgs doublet model contains new sources of flavour violation that are usually in conflict with the experimental constraints. One possibility to suppress the exotic contribution to the flavour changing neutral currents consists on imposing the alignment of the Yukawa couplings. This condition presumably holds at a high-energy scale and is spoiled by the radiative corrections. We compute in this letter the size of the radiatively induced flavour violating Higgs couplings at the electroweak scale. These also yield the absolute lower bound on the size of the exotic contributions to the flavour changing neutral currents in any two Higgs doublet model, barring cancellations and the existence of discrete symmetries. We show that these contributions are well below the experimental bounds in large regions of the parameter space.Comment: 15 pages, 2 figure

Simulating the dynamics of atherosclerosis to the incidence of myocardial infarction, applied to the KORA population

Analyzing epidemiological data with simplified mathematical models of disease development provides a link between the time-course of incidence and the underlying biological processes. Here we point out that considerable modeling flexibility is gained if the model is solved by simulation only. To this aim, a model of atherosclerosis is proposed: a Markov Chain with continuous state space which represents the coronary artery intimal surface area involved with atherosclerotic lesions of increasing severity. Myocardial infarction rates are assumed to be proportional to the area of most severe lesions. The model can be fitted simultaneously to infarction incidence rates observed in the KORA registry, and to the age-dependent prevalence and extent of atherosclerotic lesions in the PDAY study. Moreover, the simulation approach allows for non-linear transition rates, and to consider at the same time randomness and inter-individual heterogeneity. Interestingly, the fit revealed significant age dependence of parameters in females around the age of menopause, qualitatively reproducing the known vascular effects of female sex hormones. For males, the incidence curve flattens for higher ages. According to the model, frailty explains this flattening only partially, and saturation of the disease process plays also an important role. This study shows the feasibility of simulating subclinical and epidemiological data with the same mathematical model. The approach is very general and may be extended to investigate the effects of risk factors or interventions. Moreover, it offers an interface to integrate quantitative individual health data as assessed, for example, by imaging

Breast cancer radiotherapy and the risk of acute coronary events - insights from a process oriented model

BACKGROUND AND PURPOSE: Acute coronary events (ACEs) are considered the most important side effect of radiotherapy (RT) for breast cancer but underlying mechanisms still have to be identified. Process oriented models mathematically describe the development of disease and provide a link between mechanisms and subsequent risk. Here, this link is exploited to learn about the underlying mechanisms from the observed age-time patterns of ACE risk. MATERIALS AND METHODS: A process oriented model of atherosclerosis and subsequent ACEs was applied to a contemporary breast cancer cohort of 810 patients with measurements of coronary artery calcification. Patients with prior ischemic heart disease were excluded. The process oriented model describes disease development as a series of different stages. Different variants of the model were fitted to the data. In each variant, one stage was assumed to be accelerated in relation to mean heart dose. RESULTS: During a mean follow up of 9.1 years, 25 ACEs occurred. The model reproduced the prevalence and associated risk of coronary calcifications. Mean heart dose significantly improved the fit only when implemented as affecting a late stage of atherosclerosis on already existing, complicated lesions (achieving p = 0.007). This can be understood by atherosclerosis being a slowly progressing disease. Therefore, an increase of ACEs few years after RT requires advanced atherosclerosis at the time of RT. CONCLUSION: Risk of ACE increases within few years in patients with advanced atherosclerosis at RT. Therefore, patients should be assessed for cardiovascular risk, and also elderly patients need to be considered for heart sparing techniques

Longitudinal atherosclerotic changes after radio(chemo)therapy of hypopharyngeal carcinoma

Background Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up. Methods Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2 months to 4.5 years. For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records. Results Total plaque volume rose from 0.25 cm3 before to 0.33 cm3 after therapy but this was not significant (p = 0.26). The mean number of plaques increased from 5.7 to 8.1 (p = 0.002), and the intima media thickened from 1.17 mm to 1.35 mm (p = 0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter. Conclusion Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear

Constraints on the rare tau decays from mu --> e gamma in the supersymmetric see-saw model

It is now a firmly established fact that all family lepton numbers are violated in Nature. In this paper we discuss the implications of this observation for future searches for rare tau decays in the supersymmetric see-saw model. Using the two loop renormalization group evolution of the soft terms and the Yukawa couplings we show that there exists a lower bound on the rate of the rare process mu --> e gamma of the form BR(mu --> e gamma) > C BR(tau --> mu gamma) BR(tau --> e gamma), where C is a constant that depends on supersymmetric parameters. Our only assumption is the absence of cancellations among the high-energy see-saw parameters. We also discuss the implications of this bound for future searches for rare tau decays. In particular, for large regions of the mSUGRA parameter space, we show that present B-factories could discover either tau --> mu gamma or tau --> e gamma, but not both.Comment: 39 pages, 7 figures. Typos corrected, references adde