Discriminaci?n de precios como mecanismo para promover la demanda de servicios de entretenimiento en el consumidor adulto joven

La presente tesis es una investigaci?n aplicada que tiene como objetivo general dise?ar un modelo de discriminaci?n de precios, al cual se ha llegado luego de realizar un modelo econom?trico que permite predecir el gasto de los consumidores adultos j?venes en actividades de entretenimiento por semana y compararlo con el gasto promedio de este grupo etario, lo que permite calificar a estas personas en diversos grupos para el otorgamiento de un precio diferenciado (descuento sobre precio de lista). El modelo propuesto puede ser de gran utilidad para las empresas del sector entretenimiento que cuentan con capacidad instalada subutilizada, y costos marginales cercanos a cero, ya que el incremento de uno o m?s consumidores adicionales incrementar?a sus beneficios, pues mejorar?a sus ingresos sin tener implicancias significativas en sus costos totales de operaci?n

Functional heterogeneity of POMC neurons relies on mTORC1 signaling.

Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A pair of TESS planets spanning the radius valley around the nearby mid-M dwarf LTT 3780

We present the confirmation of two new planets transiting the nearby mid-M dwarf LTT 3780 (TIC 36724087, TOI-732, $V=13.07$, $K_s=8.204$, $R_s$=0.374 R$_{\odot}$, $M_s$=0.401 M$_{\odot}$, d=22 pc). The two planet candidates are identified in a single TESS sector and are validated with reconnaissance spectroscopy, ground-based photometric follow-up, and high-resolution imaging. With measured orbital periods of $P_b=0.77$ days, $P_c=12.25$ days and sizes $r_{p,b}=1.33\pm 0.07$ R$_{\oplus}$, $r_{p,c}=2.30\pm 0.16$ R$_{\oplus}$, the two planets span the radius valley in period-radius space around low mass stars thus making the system a laboratory to test competing theories of the emergence of the radius valley in that stellar mass regime. By combining 63 precise radial-velocity measurements from HARPS and HARPS-N, we measure planet masses of $m_{p,b}=2.62^{+0.48}_{-0.46}$ M$_{\oplus}$ and $m_{p,c}=8.6^{+1.6}_{-1.3}$ M$_{\oplus}$, which indicates that LTT 3780b has a bulk composition consistent with being Earth-like, while LTT 3780c likely hosts an extended H/He envelope. We show that the recovered planetary masses are consistent with predictions from both photoevaporation and from core-powered mass loss models. The brightness and small size of LTT 3780, along with the measured planetary parameters, render LTT 3780b and c as accessible targets for atmospheric characterization of planets within the same planetary system and spanning the radius valley.Comment: Accepted to AJ. 8 figures, 6 tables. CSV file of the RV measurements (i.e. Table 2) are included in the source cod

K2-291b:A rocky super-Earth in a 2.2 day orbit

K2-291 (EPIC 247418783) is a solar-type star with a radius of R_star = 0.899 $\pm$ 0.034 R_sun and mass of M_star=0.934 $\pm$ 0.038 M_sun. From K2 C13 data, we found one super-Earth planet (R_p = 1.589+0.095-0.072 R_Earth) transiting this star on a short period orbit (P = 2.225177 +6.6e-5 -6.8e-5 days). We followed this system up with adaptive-optic imaging and spectroscopy to derive stellar parameters, search for stellar companions, and determine a planet mass. From our 75 radial velocity measurements using HIRES on Keck I and HARPS-N on Telescopio Nazionale Galileo, we constrained the mass of EPIC 247418783b to M_p = 6.49 $\pm$ 1.16 M_Earth. We found it necessary to model correlated stellar activity radial velocity signals with a Gaussian process in order to more accurately model the effect of stellar noise on our data; the addition of the Gaussian process also improved the precision of this mass measurement. With a bulk density of 8.84+2.50-2.03 g cm-3, the planet is consistent with an Earth-like rock/iron composition and no substantial gaseous envelope. Such an envelope, if it existed in the past, was likely eroded away by photo-evaporation during the first billion years of the star's lifetime.Comment: Accepted to AJ, 15 pages, 8 figure

An Ultra-short Period Rocky Super-Earth with a Secondary Eclipse and a Neptune-like Companion around K2-141

Ultra-short period (USP) planets are a class of low mass planets with periods shorter than one day. Their origin is still unknown, with photo-evaporation of mini-Neptunes and in-situ formation being the most credited hypotheses. Formation scenarios differ radically in the predicted composition of USP planets, it is therefore extremely important to increase the still limited sample of USP planets with precise and accurate mass and density measurements. We report here the characterization of an USP planet with a period of 0.28 days around K2-141 (EPIC 246393474), and the validation of an outer planet with a period of 7.7 days in a grazing transit configuration. We derived the radii of the planets from the K2 light curve and used high-precision radial velocities gathered with the HARPS-N spectrograph for mass measurements. For K2-141b we thus inferred a radius of $1.51\pm0.05~R_\oplus$ and a mass of $5.08\pm0.41~M_\oplus$, consistent with a rocky composition and lack of a thick atmosphere. K2-141c is likely a Neptune-like planet, although due to the grazing transits and the non-detection in the RV dataset, we were not able to put a strong constraint on its density. We also report the detection of secondary eclipses and phase curve variations for K2-141b. The phase variation can be modeled either by a planet with a geometric albedo of $0.30 \pm 0.06$ in the Kepler bandpass, or by thermal emission from the surface of the planet at $\sim$3000K. Only follow-up observations at longer wavelengths will allow us to distinguish between these two scenarios.Comment: 16 pages, 10 figures., accepted for publication in A

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362