Remote ischaemic preconditioning in the settings of cardiac bypass surgery and coronary angioplasty

Myocardial revascularisation in the form of coronary artery bypass surgery (CABG) and percutaneous coronary interventions (PCI) are the two important treatment strategies in combating ischaemic heart disease. There have been tremendous improvements in many aspects of these revascularisation methods over the years. However both these forms of revascularisation can have a deleterious effect on the myocardium while its vascularity is re-established. This revascularisation induced myocardial injury is one of the prognostically important deleterious effects. Consequently, many therapeutic strategies are being studied which can cardioprotect and reduce peri-operative myocardial injury during CABG and peri-procedural myocardial injury during PCI. We evaluate Remote ischaemic preconditioning, a cardioprotective strategy, for its effect on myocardial revascularisation methods of PCI and CABG. In the PCI settings, the beneficial effect of remote ischaemic preconditioning in patients undergoing elective PCI has now been established. However its role in patients admitted with Non ST elevation acute coronary syndrome (NSEACS) and undergoing urgent PCI is still unknown. This group of patients particularly has increased peri-procedural myocardial injury due to their soft coronary plaque and thrombi. In the CABG settings, remote preconditioning has been shown reduce perioperative myocardial injury in non diabetic patients. There are no clinical studies looking at the beneficial effect of remote preconditioning in diabetic cohort of patients undergoing CABG. In animal models, diabetic myocardium is known to possess higher threshold for preconditioning, albeit still possible to precondition. As diabetic patients, are more vulnerable for myocardial injury during CABG and also tolerate the injury relatively poorly compared to their non diabetic counterparts, it is important to explore for cardioprotective strategies to be applied to this high risk diabetic population. The two clinical studies in this thesis evaluate the effect of remote ischemic preconditioning in a) reducing peri-procedural myocardial injury in patients with NSTEACS undergoing urgent percutaneous intervention and b) reducing peri-operative myocardial injury in type 2 diabetic patients undergoing coronary artery bypass surgery

Vacuum Alignment in SUSY A4 Models

In this note we discuss the vacuum alignment in supersymmetric models with spontaneously broken flavour symmetries in the presence of soft supersymmetry (SUSY) breaking terms. We show that the inclusion of soft SUSY breaking terms can give rise to non-vanishing vacuum expectation values (VEVs) for the auxiliary components of the flavon fields. These non-zero VEVs can have an important impact on the phenomenology of this class of models, since they can induce an additional flavour violating contribution to the sfermion soft mass matrix of right-left (RL) type. We carry out an explicit computation in a class of SUSY A4 models predicting tri-bimaximal mixing in the lepton sector. The flavour symmetry breaking sector is described in terms of flavon and driving supermultiplets. We find non-vanishing VEVs for the auxiliary components of the flavon fields and for the scalar components of the driving fields which are of order m_{SUSY} x and m_{SUSY}, respectively. Thereby, m_{SUSY} is the generic soft SUSY breaking scale which is expected to be around 1 TeV and is the VEV of scalar components of the flavon fields. Another effect of these VEVs can be the generation of a mu term.Comment: 23 pages; added a new section on the relation to Supergravity; version accepted for publication in JHE

Ultraviolet Completion of Flavour Models

Effective Flavour Models do not address questions related to the nature of the fundamental renormalisable theory at high energies. We study the ultraviolet completion of Flavour Models, which in general has the advantage of improving the predictivity of the effective models. In order to illustrate the important features we provide minimal completions for two known A4 models. We discuss the phenomenological implications of the explicit completions, such as lepton flavour violating contributions that arise through the exchange of messenger fields.Comment: 18 pages, 8 figure

R-parity violation in SU(5)

We show that judiciously chosen R-parity violating terms in the minimal renormalizable supersymmetric SU(5) are able to correct all the phenomenologically wrong mass relations between down quarks and charged leptons. The model can accommodate neutrino masses as well. One of the most striking consequences is a large mixing between the electron and the Higgsino. We show that this can still be in accord with data in some regions of the parameter space and possibly falsified in future experiments.Comment: 30 pages, 1 figure. Revised version. To appear in JHE

On the nature of the fourth generation neutrino and its implications

We consider the neutrino sector of a Standard Model with four generations. While the three light neutrinos can obtain their masses from a variety of mechanisms with or without new neutral fermions, fourth-generation neutrinos need at least one new relatively light right-handed neutrino. If lepton number is not conserved this neutrino must have a Majorana mass term whose size depends on the underlying mechanism for lepton number violation. Majorana masses for the fourth generation neutrinos induce relative large two-loop contributions to the light neutrino masses which could be even larger than the cosmological bounds. This sets strong limits on the mass parameters and mixings of the fourth generation neutrinos.Comment: To be published. Few typos corrected, references update

Dynamical R-parity Breaking at the LHC

In a class of extensions of the minimal supersymmetric standard model with (B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity symmetry is an essential and dynamical requirement for successful gauge symmetry breaking. Two consequences of these models are: (i) a new kind of R-parity breaking interaction that protects proton stability but adds new contributions to neutrinoless double beta decay and (ii) an upper bound on the extra gauge and parity symmetry breaking scale which is within the large hadron collider (LHC) energy range. We point out that an important prediction of such theories is a potentially large mixing between the right-handed charged lepton ($e^c$) and the superpartner of the right-handed gauge boson ($\widetilde W_R^+$), which leads to a brand new class of R-parity violating interactions of type $\widetilde{\mu^c}^\dagger\nu_\mu^c e^c$ and \widetilde{d^c}^\dagger\u^c e^c. We analyze the relevant constraints on the sparticle mass spectrum and the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note the "smoking gun" signals for such models to be lepton flavor/number violating processes: $pp\to \mu^\pm\mu^\pm e^+e^-jj$ (or $\tau^\pm\tau^\pm e^+e^-jj$) and $pp\to\mu^\pm e^\pm b \bar{b} jj$ (or $\tau^\pm e^\pm b \bar{b} jj$) without significant missing energy. The predicted multi-lepton final states and the flavor structure make the model be distinguishable even in the early running of the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde

Dark matter scenarios in the minimal SUSY B-L model

We perform a study of the dark matter candidates of a constrained version of the minimal R-parity-conserving supersymmetric model with a gauged $U(1)_{B-L}$. It turns out that there are four additional candidates for dark matter in comparison to the MSSM: two kinds of neutralino, which either correspond to the gaugino of the $U(1)_{B-L}$ or to a fermionic bilepton, as well as "right-handed" CP-even and -odd sneutrinos. The correct dark matter relic density of the neutralinos can be obtained due to different mechanisms including new co-annihilation regions and resonances. The large additional Yukawa couplings required to break the $U(1)_{B-L}$ radiatively often lead to large annihilation cross sections for the sneutrinos. The correct treatment of gauge kinetic mixing is crucial to the success of some scenarios. All candidates are consistent with the exclusion limits of Xenon100.Comment: 45 pages, 22 figures; v2: extended discussion of direct detection cross section, matches published versio

Single-Scale Natural SUSY

We consider the prospects for natural SUSY models consistent with current data. Recent constraints make the standard paradigm unnatural so we consider what could be a minimal extension consistent with what we now know. The most promising such scenarios extend the MSSM with new tree-level Higgs interactions that can lift its mass to at least 125 GeV and also allow for flavor-dependent soft terms so that the third generation squarks are lighter than current bounds on the first and second generation squarks. We argue that a common feature of almost all such models is the need for a new scale near 10 TeV, such as a scale of Higgsing or confinement of a new gauge group. We consider the question whether such a model can naturally derive from a single mass scale associated with supersymmetry breaking. Most such models simply postulate new scales, leaving their proximity to the scale of MSSM soft terms a mystery. This coincidence problem may be thought of as a mild tuning, analogous to the usual mu problem. We find that a single mass scale origin is challenging, but suggest that a more natural origin for such a new dynamical scale is the gravitino mass, m_{3/2}, in theories where the MSSM soft terms are a loop factor below m_{3/2}. As an example, we build a variant of the NMSSM where the singlet S is composite, and the strong dynamics leading to compositeness is triggered by masses of order m_{3/2} for some fields. Our focus is the Higgs sector, but our model is compatible with a light stop (with the other generation squarks heavy, or with R-parity violation or another mechanism to hide them from current searches). All the interesting low-energy mass scales, including linear terms for S playing a key role in EWSB, arise dynamically from the single scale m_{3/2}. However, numerical coefficients from RG effects and wavefunction factors in an extra dimension complicate the otherwise simple story.Comment: 32 pages, 3 figures; version accepted by JHE

Ventricular Arrhythmia Burden in Patients With Heart Failure and Cardiac Resynchronization Devices: The Importance of Renal Function

Background: Chronic kidney disease (CKD) is a risk factor for arrhythmias in patients with heart failure (HF). However, the effects of CKD on ventricular arrhythmia (VA) burden in patients with cardiac resynchronization therapy and defibrillator (CRT‐D) devices in a primary prevention setting are unknown. Objective: To determine whether baseline CKD is associated with increased risk of VA in patients implanted with primary prevention CRT‐D devices. Methods and Results: In this retrospective study, 199 consecutive primary prevention CRT‐D recipients (2005–2010) were stratified by estimated glomerular filtration rate (eGFR) levels prior to device implantation with 106 (53.2%) ≥CKD III (eGFR III as the only predictor of sustained VA in this group (adjusted hazard ratio [HR] 2.92, CI = 1.39–6.1, P = 0.004). Conclusion: Baseline CKD is a strong independent risk factor for VA in primary prevention CRT‐D recipients. Further understanding of the underlying arrhythmogenic mechanisms relating to CKD may be of interest to allow appropriate correction and prevention. Device programming in this cohort may need to reflect this increased risk

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE