Minimal Flavour Violation and Multi-Higgs Models

We propose an extension of the hypothesis of Minimal Flavour Violation (MFV) to general multi-Higgs Models without the assumption of Natural Flavour Conservation in the Higgs sector. We study in detail under what conditions the neutral Higgs couplings are only functions of $V_{CKM}$ and propose a MFV expansion for the neutral Higgs couplings to fermions.Comment: 16 pages, no figures. References adde

Theory and phenomenology of two-Higgs-doublet models

We discuss theoretical and phenomenological aspects of two-Higgs-doublet extensions of the Standard Model. In general, these extensions have scalar mediated flavour changing neutral currents which are strongly constrained by experiment. Various strategies are discussed to control these flavour changing scalar currents and their phenomenological consequences are analysed. In particular, scenarios with natural flavour conservation are investigated, including the so-called type I and type II models as well as lepton-specific and inert models. Type III models are then discussed, where scalar flavour changing neutral currents are present at tree level, but are suppressed by either specific ansatze for the Yukawa couplings or by the introduction of family symmetries. We also consider the phenomenology of charged scalars in these models. Next we turn to the role of symmetries in the scalar sector. We discuss the six symmetry-constrained scalar potentials and their extension into the fermion sector. The vacuum structure of the scalar potential is analysed, including a study of the vacuum stability conditions on the potential and its renormalization-group improvement. The stability of the tree level minimum of the scalar potential in connection with electric charge conservation and its behaviour under CP is analysed. The question of CP violation is addressed in detail, including the cases of explicit CP violation and spontaneous CP violation. We present a detailed study of weak basis invariants which are odd under CP. A careful study of spontaneous CP violation is presented, including an analysis of the conditions which have to be satisfied in order for a vacuum to violate CP. We present minimal models of CP violation where the vacuum phase is sufficient to generate a complex CKM matrix, which is at present a requirement for any realistic model of spontaneous CP violation.Comment: v3: 180 pages, 506 references, new chapter 7 with recent LHC results; referee comments taken into account; submitted to Physics Report

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Computer-based system to assess efficacy of stuttering therapy techniques

This paper presents a computer-based system tool used to assess efficacy of stuttering therapy techniques. The software assists Speech-Language Pathologist (SLP) in determining suitable techniques for each client. The project implements Digital Signal Processing (DSP)techniques to analyze speech signals and incorporates standard speech fluency shaping techniques that can be used as part of fluency rehabilitation regimen. The software provides real-time visual and audio feedbacks for clients to be aware of their speech patterns. It provides self training aid for clients that motivates them to practice at home. The software runs under Windows XP on a computer equipped with multimedia capabilities. Real-time visual and audio displays enable the clients to compare their average magnitude profiles (AMPs) with clinician’s and alter their speech to match clinician’s AMP. The start and end alignment, maximum magnitude and duration of two AMPs are compared. A score is assigned to each category. The software is developed using Microsoft Visual C++ 6.0. Software is designed as graphic user interface (GUI), which makes therapy user friendly. Three techniques that are implemented in the project have been decided through the discussion with SLP in Hospital Sultanah Aminah (HSA). The techniques are Shadowing, using a Metronome (Taping) and Delayed Auditory Feedback (DAF). This project is done in collaboration with HSA where the hospital assists in the clinical trial

From “book view” to “field view”: Social anthropological constructions of the Indian village

The “book view” of rural India of the title is that of Indologists and Orientalists, constructed from Hindu scriptures and the historical record. In the post-Independence period this was gradually replaced by the “field view” of sociologists and anthropologists, based on participant observation. Their studies threw new light on the nature of the village community, particularly in relation to caste, gender and political faction. The work is important in the context of development since traditional society was, and remains, in a state of flux. One important result of the “field view”, however, is that India's villages appear to have been well integrated into the broader economy and society for a very long period of time, rather than being isolated communities. While recognizing this important contribution, the problems of participant observation are discussed in this paper, notably the possibility that the social and economic background of those engaged might itself induce bias into the results. This is a fundamental issue and indeed one which has not escaped the attention of the major writers themselves.