Higgs Boson Bounds in Three and Four Generation Scenarios

In light of recent experimental results, we present updated bounds on the lightest Higgs boson mass in the Standard Model (SM) and in the Minimal Supersymmetric extension of the Standard Model (MSSM). The vacuum stability lower bound on the pure SM Higgs boson mass when the SM is taken to be valid up to the Planck scale lies above the MSSM lightest Higgs boson mass upper bound for a large amount of SUSY parameter space. If the lightest Higgs boson is detected with a mass M_{H} < 134 GeV (150 GeV) for a top quark mass M_{top} = 172 GeV (179 GeV), it may indicate the existence of a fourth generation of fermions. The region of inconsistency is removed and the MSSM is salvagable for such values of M_{H} if one postulates the existence of a fourth generation of leptons and quarks with isodoublet degenerate masses M_{L} and M_{Q} such that 60 GeV 170 GeV.Comment: 7 pages, 4 figures. To be published in Physical Review

Mucoadhesive electrospun patch delivery of lidocaine to the oral mucosa and investigation of spatial distribution in tissue using MALDI-mass spectrometry imaging

Many oral mucosal conditions cause considerable and prolonged pain that to date has been difficult to alleviate via topical delivery, and the use of injection causes many patients dental anxiety and needle-prick pain. Therefore, developing a non-injectable drug delivery system as an alternative administration procedure may vastly improve the health and wellbeing of these patients. Recent advances in the development of mucoadhesive electrospun patches for the direct delivery of therapeutics to the oral mucosa offer a potential solution, but as yet, the release of local anaesthetics from this system and their uptake by oral tissue has not been demonstrated. Here, we demonstrate the fabrication of lidocaine-loaded electrospun fibre patches, drug release, and subsequent uptake and permeation through porcine buccal mucosa. Lidocaine HCl and lidocaine base were incorporated into the electrospun patches to evaluate the difference in drug permeation for the two drug compositions. Lidocaine released from the lidocaine HCl-containing electrospun patches was significantly quicker than from the lidocaine base patches, with double the amount of drug released from the lidocaine HCl patches in the first 15 minutes (0.16 ± 0.04 mg) compared to from the lidocaine base patches (0.07 ± 0.01 mg). The permeation of lidocaine from the lidocaine HCl electrospun patches through ex vivo porcine buccal mucosa was also detected in 15 minutes, whereas permeation of lidocaine from the lidocaine base patch was not detected. Matrix-assisted laser desorption ionisation – mass spectrometry imaging (MALDI-MSI) was used to investigate localisation of lidocaine within oral tissue. Lidocaine in solution as well as from the mucoadhesive patch penetrated into buccal mucosal tissue in a time-dependent manner and was detectable in the lamina propria after only 15 minutes. Moreover, the lidocaine released from lidocaine HCl electrospun patches retained biological activity, inhibiting veratridine-mediated opening of voltage-gated sodium channels in SH-SY5Y neuroblastoma cells. These data suggest that a mucoadhesive electrospun patch may be used as a vehicle for rapid uptake and sustained anaesthetic drug delivery and may reduce the need for injection

The Finite Temperature SU(2) Savvidy Model with a Non-trivial Polyakov Loop

We calculate the complete one-loop effective potential for SU(2) gauge bosons at temperature T as a function of two variables: phi, the angle associated with a non-trivial Polyakov loop, and H, a constant background chromomagnetic field. Using techniques broadly applicable to finite temperature field theories, we develop both low and high temperature expansions. At low temperatures, the real part of the effective potential V_R indicates a rich phase structure, with a discontinuous alternation between confined (phi=pi) and deconfined phases (phi=0). The background field H moves slowly upward from its zero-temperature value as T increases, in such a way that sqrt(gH)/(pi T) is approximately an integer. Beyond a certain temperature on the order of sqrt(gH), the deconfined phase is always preferred. At high temperatures, where asymptotic freedom applies, the deconfined phase phi=0 is always preferred, and sqrt(gH) is of order g^2(T)T. The imaginary part of the effective potential is non-zero at the global minimum of V_R for all temperatures. A non-perturbative magnetic screening mass of the form M_m = cg^2(T)T with a sufficiently large coefficient c removes this instability at high temperature, leading to a stable high-temperature phase with phi=0 and H=0, characteristic of a weakly-interacting gas of gauge particles. The value of M_m obtained is comparable with lattice estimates.Comment: 28 pages, 5 eps figures; RevTeX 3 with graphic

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction &lt; 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk