The flavor puzzle in multi-Higgs models

We reconsider the flavor problem in the models with two Higgs doublets. By studying two generation toy models, we look for flavor basis independent constraints on Yukawa couplings that will give us the mass hierarchy while keeping all Yukawa couplings of the same order. We then generalize our findings to the full three generation Standard Model. We find that we need two constraints on the Yukawa couplings to generate the observed mass hierarchy, and a slight tuning of Yukawa couplings of order 10%, much less than the Standard Model. We briefly study how these constraints can be realized, and show how flavor changing currents are under control for $K-\bar{K}$ mixing in the near-decoupling limit.Comment: 26 pages, typos are corrected, references are added, the final versio

May measurement month 2018: an analysis of blood pressure screening in the Philippines.

Building on the gains of May Measurement Month 2017 (MMM17), the Philippine Society of Hypertension once again took part in MMM18 to raise awareness of high blood pressure (BP) in the country and to harness opportunistic BP screening in detecting unaware hypertensive individuals and referring them for treatment. We followed the standard MMM18 protocol designed by the International Society of Hypertension, utilizing convenience sampling with volunteer investigators, taking three sitting BP measurements of volunteer adults (≥18 years). Basic data on demographic, lifestyle, and environmental factors were also taken. We analysed 177 176 screened individuals from the Philippines. Of these, 29.1% (51 527) had also participated in MMM17, whereas 68.8% (121 893) were new screenees; and 14.2% (25 232) had their BP taken for the first time ever. After multiple imputation, 39.0% (69 126) were hypertensive. Of these, 50.3% (34 795) were aware they were hypertensive. 49.9% (34 491) were on antihypertensive medication, 58.0% (20 010) of whom had controlled BP <140/90 mmHg. Only 28.9% of all participants with hypertension had controlled BP. Systolic BPs and diastolic BPs were significantly higher in the overweight and obese, in those receiving antihypertensive medications, in patients with diabetes, and significantly lower in pregnant women. MMM18 has again shown that opportunistic BP screening, harnessing volunteers, is a pragmatic public health measure to improve awareness and treatment rates of raised BP

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the <it>GNAS</it>1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly.</p> <p>Case presentation</p> <p>Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted.</p> <p>Conclusion</p> <p>Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base.</p

May Measurement Month 2017: an analysis of blood pressure screening in the Philippines-South-East Asia and Australasia

Cardiovascular diseases remain the Philippines' leading cause of mortality, with hypertension as a prevalent contributory risk factor. We took part in May Measurement Month 2017 (MMM17), a global initiative to raise awareness of high blood pressure (BP) and to serve as a temporary solution to the lack of screening programs worldwide. Following the standard MMM protocol, data for 271 604 screened individuals were submitted from the Philippines. After multiple imputation, 91 994 (34.3%) were hypertensive; 28 662 out of 205 158 participants (14.0%) not receiving treatment had hypertension; and of the 60 370 receiving treatment, 25 144 (41.6%) had uncontrolled BP. Blood pressures were significantly higher in the overweight and obese, current smokers, in participants receiving antihypertensive medication, those with previous myocardial infarction or stroke. The BP measurements were relatively lower when taken on the left arm, and in pregnant women. A slightly higher systolic BP was noted in participants who reported no alcohol intake. Blood pressures recorded during the weekends were highest, and the lowest readings were obtained on Tuesdays. MMM17 was the largest BP screening campaign conducted in the Philippines. Opportunistic BP screening, harnessing volunteers, are a cost-effective public health measure to improve awareness and treatment rates of raised BP. These may help provide additional information that can guide medical practitioners and health officials in drafting preventive and therapeutic measures to improve control rates and long-term outcomes of hypertensive individuals in the population

Coastal Upwelling Supplies Oxygen-Depleted Water to the Columbia River Estuary

Low dissolved oxygen (DO) is a common feature of many estuarine and shallow-water environments, and is often attributed to anthropogenic nutrient enrichment from terrestrial-fluvial pathways. However, recent events in the U.S. Pacific Northwest have highlighted that wind-forced upwelling can cause naturally occurring low DO water to move onto the continental shelf, leading to mortalities of benthic fish and invertebrates. Coastal estuaries in the Pacific Northwest are strongly linked to ocean forcings, and here we report observations on the spatial and temporal patterns of oxygen concentration in the Columbia River estuary. Hydrographic measurements were made from transect (spatial survey) or anchor station (temporal survey) deployments over a variety of wind stresses and tidal states during the upwelling seasons of 2006 through 2008. During this period, biologically stressful levels of dissolved oxygen were observed to enter the Columbia River estuary from oceanic sources, with minimum values close to the hypoxic threshold of 2.0 mg L−1. Riverine water was consistently normoxic. Upwelling wind stress controlled the timing and magnitude of low DO events, while tidal-modulated estuarine circulation patterns influenced the spatial extent and duration of exposure to low DO water. Strong upwelling during neap tides produced the largest impact on the estuary. The observed oxygen concentrations likely had deleterious behavioral and physiological consequences for migrating juvenile salmon and benthic crabs. Based on a wind-forced supply mechanism, low DO events are probably common to the Columbia River and other regional estuaries and if conditions on the shelf deteriorate further, as observations and models predict, Pacific Northwest estuarine habitats could experience a decrease in environmental quality

Neutrinoless double beta decay in seesaw models

We study the general phenomenology of neutrinoless double beta decay in seesaw models. In particular, we focus on the dependence of the neutrinoless double beta decay rate on the mass of the extra states introduced to account for the Majorana masses of light neutrinos. For this purpose, we compute the nuclear matrix elements as functions of the mass of the mediating fermions and estimate the associated uncertainties. We then discuss what can be inferred on the seesaw model parameters in the different mass regimes and clarify how the contribution of the light neutrinos should always be taken into account when deriving bounds on the extra parameters. Conversely, the extra states can also have a significant impact, cancelling the Standard Model neutrino contribution for masses lighter than the nuclear scale and leading to vanishing neutrinoless double beta decay amplitudes even if neutrinos are Majorana particles. We also discuss how seesaw models could reconcile large rates of neutrinoless double beta decay with more stringent cosmological bounds on neutrino masses.Comment: 34 pages, 5 eps figures and 1 axodraw figure. Final version published in JHEP. NME results available in Appendi

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions