PROS1 novel splice-site variant decreases protein S expression in patients from two families with thrombotic disease

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A viable A4A_4 3HDM theory of quark mass matrices

It is known that a three Higgs doublet model (3HDM)symmetric under an exact $A_4$ symmetry is not compatible with nonzero quark masses and/or non-block-diagonal CKM matrix. We show that a 3HDM with softly broken $A_4$ terms in the scalar potential does allow for a fit of quark mass matrices. Moreover, the result is consistent with $m_h=125\textrm{GeV}$ and the $h \rightarrow WW, ZZ$ signal. We also checked numerically that, for each point that passes all the constraints, the minimum is a global minimum of the potential.Comment: 21 pages, 10 Figures in PDF. Minor changes; matches version to be publishe

Multi-Higgs doublet models: the Higgs-fermion couplings and their sum rules

This is the second of a series of papers that explores the physical parameterization, sum rules and unitarity bounds arising from a non-minimal scalar sector of the Standard Model (SM) that consists of N Higgs doublets. In this paper, we focus on the structure and implication of the Yukawa interactions that couple the N scalar doublets to the SM fermions. We employ the charged Higgs basis, which is defined as the basis of scalar fields such that the neutral scalar field vacuum expectation value resides entirely in one of the N scalar doublet fields, and the charged components of the remaining N-1 scalar doublet fields are the physical (mass-eigenstate) charged Higgs fields. Based on the structure of the Yukawa Lagrangian of the model (and as a consequence of tree-level unitarity), one may deduce numerous sum rules, several of which have not appeared previously in the literature. These sum rules can be used to uncover intimate relations between the structure of the Higgs-fermion couplings and the scalar/gauge couplings. In particular, we show that the approximate alignment limit, in which the W+W- and ZZ couplings to the observed Higgs boson are approximately SM-like, imposes significant constraints on the Higgs-fermion couplings.Comment: 24 pages, 2 figures, 4 tables, uses jheppub.sty. Two typographical errors corrected, one clarification added and one reference updated in v

Fingerprinting the Type-Z three Higgs doublet models

There has been great interest in a model with three Higgs doublets in which fermions with a particular charge couple to a single and distinct Higgs field. We study the phenomenological differences between the two common incarnations of this so-called Type-Z 3HDM. We point out that the differences between the two models arise from the scalar potential only. Thus we focus on observables that involve the scalar self-couplings. We find it difficult to uncover features that can uniquely set apart the $Z_3$ variant of the model. However, by studying the dependence of the trilinear Higgs couplings on the nonstandard masses, we have been able to isolate some of the exclusive indicators for the $Z_2\times Z_2$ version of the Type-Z 3HDM. This highlights the importance of precision measurements of the trilinear Higgs couplings.Comment: 15 pages, 4 captioned figure

Is urinary density an adequate predictor of urinary osmolality?

Urinary density (UD) has been routinely used for decades as a surrogate marker for urine osmolality (U-osm). We asked if UD can accurately estimate U-osm both in healthy subjects and in different clinical scenarios of kidney disease. UD was assessed by refractometry. U-osm was measured by freezing point depression in spot urines obtained from healthy volunteers (N = 97) and in 319 inpatients with acute kidney injury (N = 95), primary glomerulophaties (N = 118) or chronic kidney disease (N = 106). UD and U-osm correlated in all groups (p < 0.05). However, a wide range of U-osm values was associated with each UD value. When UD was <= 1.010, 28.4% of samples had U-osm above 350 mOsm/kg. Conversely, in 61.6% of samples with UD above 1.020, U-osm was below 600 mOsm/kg. As expected, U-osm exhibited a strong relationship with serum creatinine (S-creat), whereas a much weaker correlation was found between UD and Screat. We found that UD is not a substitute for U-osm. Although UD was significantly correlated with U-osm, the wide dispersion makes it impossible to use UD as a dependable clinical estimate of U-osm. Evaluation of the renal concentrating ability should be based on direct determination of U-osm1

When Is the Best Moment to Assess the Ankle Brachial Index: Pre- or Post-Hemodialysis?

Background: Cardiovascular disease is an important cause of death in patients on dialysis. Peripheral arterial disease (PAD) is a prognostic factor for cardiovascular disease. The ankle brachial index (ABI) is a noninvasive method used for the diagnosis of PAD. The difference between ABI pre- and post-dialysis had not yet been formally tested, and it was the main objective of this study. Methods:The ABI was assessed using an automated oscillometric device in incident patients on hemodialysis. All blood pressure readings were taken in triplicate pre- and post-dialysis in three consecutive dialysis sessions (times 1, 2, and 3). Results: One hundred and twenty-three patients (85 men) aged 53 +/- 19 years were enrolled. We found no difference in ABI pre- and post-dialysis on the right or left side, and there was no difference in times 1, 2, and 3. In patients with a history of PAD, the ABI pre- versus post-dialysis were of borderline significance on the right side (p = 0.088). Conclusion: ABI measured pre- and post-dialysis presented low variability. The ABI in patients with a history of PAD should be evaluated with caution. The applicability of the current method in predicting mortality among patients on hemodialysis therefore needs further investigation. Copyright (C) 2012 S. Karger AG, Base

Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background: Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings: We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9-1.3) or abnormal (&lt;0.9 and &gt;1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions: An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ), Brazi