Evaluation of the efficacy and safety of text messages targeting adherence to cardiovascular medications in secondary prevention: the txt2heart Colombia randomised controlled trial (Preprint)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in the world. Prevalence is estimated at around 100 million patients worldwide. There is evidence that antiplatelet agents and antihypertensive medication reduce the risk of new vascular events in this population, but treatment adherence is very low. Objective: We developed an intervention based on behavioral modification techniques delivered via mobile short message services (SMS) to increase the adherence to pharmacologic treatment on patients with prior history of ASCVD. Methods: We conducted a randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular event such as acute myocardial infarction, unstable angina, cerebrovascular disease or peripheral artery disease in one centre in Colombia. Patients randomized to the intervention arm were assigned to receive SMS daily for the first 4 weeks, five SMS on week 5: three SMS per week from week 6, and one SMS from 8th week until 52nd week. Patients in the control arm received a monthly SMS reminding them of the next study appointment, requesting information about changes in phone number, thanking them for participating in the study and reminding them of the importance of the study. Primary endpoint was change in Low Density Lipoprotein-Cholesterol (LDL-C) and the secondary endpoints were change in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure. Medication adherence was measured with the Medication Adherence Report Scale (MARS 5), mortality and new cardiac hospitalization were assessed at one year end point. A logistic regression analysis and bivariate testing was performed. Results: Nine hundred and thirty patients were randomized, 805 (87%) completed follow up, and were analyzed for the primary endpoint. There was no difference between arms in change of LDL-C at 12 months (P=.41). or for any of the secondary outcomes. No adverse events were reported. Conclusions: In our study we did not find evidence that a behavior modification intervention delivered by SMS improved LDL-C, blood pressure levels or adherence at 12 months. More research is needed to evaluate whether different SMS strategies including personalized messages and with different timing are effective; future studies should include mixed methods to understand better why, for whom and in which context (e.g. health system, social environment) SMS interventions work (or not) to improve adherence in patients with ASCVD. Clinical Trial: Clinicaltrial.gov NCT03098186. Date of registration: March 31st 201

Vertical Binocular Disparity is Encoded Implicitly within a Model Neuronal Population Tuned to Horizontal Disparity and Orientation

Primary visual cortex is often viewed as a “cyclopean retina”, performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D) disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea), the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans

Definition of a temporal distribution index for high temporal resolution precipitation data over Peninsular Spain and the Balearic Islands: the fractal dimension; and its synoptic implications

Precipitation on the Spanish mainland and in the Balearic archipelago exhibits a high degree of spatial and temporal variability, regardless of the temporal resolution of the data considered. The fractal dimension indicates the property of self-similarity, and in the case of this study, wherein it is applied to the temporal behaviour of rainfall at a fine (10-min) resolution from a total of 48 observatories, it provides insights into its more or less convective nature. The methodology of Jenkinson & Collison which automatically classifies synoptic situations at the surface, as well as an adaptation of this methodology at 500 hPa, was applied in order to gain insights into the synoptic implications of extreme values of the fractal dimension. The highest fractal dimension values in the study area were observed in places with precipitation that has a more random behaviour over time with generally high totals. Four different regions in which the atmospheric mechanisms giving rise to precipitation at the surface differ from the corresponding above-ground mechanisms have been identified in the study area based on the fractal dimension. In the north of the Iberian Peninsula, high fractal dimension values are linked to a lower frequency of anticyclonic situations, whereas the opposite occurs in the central region. In the Mediterranean, higher fractal dimension values are associated with a higher frequency of the anticyclonic type and a lower frequency of the advective type from the east. In the south, lower fractal dimension values indicate higher frequency with respect to the anticyclonic type from the east and lower frequency with respect to the cyclonic type

Influence of the Temperature and the Genotype of the HSP90AA1 Gene over Sperm Chromatin Stability in Manchega Rams

The present study addresses the effect of heat stress on males' reproduction ability. For that, we have evaluated the sperm DNA fragmentation (DFI) by SCSA of ejaculates incubated at 37°C during 0, 24 and 48 hours after its collection, as a way to mimic the temperature circumstances to which spermatozoa will be subject to in the ewe uterus. The effects of temperature and temperature-humidity index (THI) from day 60 prior collection to the date of semen collection on DFI were examined. To better understand the causes determining the sensitivity of spermatozoa to heat, this study was conducted in 60 males with alternative genotypes for the SNP G/C−660 of the HSP90AA1 promoter, which encode for the Hsp90α protein. The Hsp90α protein predominates in the brain and testis, and its role in spermatogenesis has been described in several species. Ridge regression analyses showed that days 29 to 35 and 7 to 14 before sperm collection (bsc) were the most critical regarding the effect of heat stress over DFI values. Mixed model analyses revealed that DFI increases over a threshold of 30°C for maximum temperature and 22 for THI at days 29 to 35 and 7 to 14 bsc only in animals carrying the GG−660 genotype. The period 29–35 bsc coincide with the meiosis I process for which the effect of the Hsp90α has been described in mice. The period 7–14 bsc may correspond with later stages of the meiosis II and early stages of epididymal maturation in which the replacement of histones by protamines occurs. Because of GG−660 genotype has been associated to lower levels of HSP90AA1 expression, suboptimal amounts of HSP90AA1 mRNA in GG−660 animals under heat stress conditions make spermatozoa DNA more susceptible to be fragmented. Thus, selecting against the GG−660 genotype could decrease the DNA fragmentation and spermatozoa thermal susceptibility in the heat season, and its putative subsequent fertility gainsPublishe

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Keep off the grass?:Cannabis, cognition and addiction

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.This work was supported by grants from the US National Institutes of Health to L.H.P. (AA020404, AA006420, AA022249 and AA017447) and by grants from the UK Medical Research Council to H.V.C. and C.J.A.M. (G0800268; MR/K015524/1)

First Measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary-Black-hole Merger GW170814

We present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in ${H}_{0}={75}_{-32}^{+40}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find {H}_{0 {78}_{-24}^{+96}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1} (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

High-resolution spatio-temporal analyses of drought episodes in the western Mediterranean basin (Spanish mainland, Iberian Peninsula)

12 Pags.- 6 Figs.- 1 Tabl. © The Author(s) 2018. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The purpose of this research was to identify major drought events on the Spanish mainland between 1961 and 2014 by means of two drought indices, and analyze the spatial propagation of drought conditions. The indices applied were the standardized precipitation index (SPI) and the standardized evaporation precipitation index (SPEI). The first was calculated as standardized anomalies of precipitation at various temporal intervals, while the second examined the climatic balance normalized at monthly scale, incorporating the relationship between precipitation and the atmospheric water demand. The daily meteorological data from Spanish Meteorological Archives (AEMet) were used in performing the analyses. Within the framework of the DESEMON project, original data were converted into a high spatial resolution grid (1.1 km2) following exhaustive quality control. Values of both indices were calculated on a weekly scale and different timescales (12, 24 and 36 months). The results show that during the first half of the study period, the SPI usually returned a higher identification of drought areas, while the reverse was true from the 1990s, suggesting that the effect from atmospheric evaporative demand could have increased. The temporal propagation from 12- to 24-month and 36-month timescales analyzed in the paper seems to be a far from straightforward phenomenon that does not follow a simple rule of time lag, because events at different temporal scales can overlap in time and space. Spatially, the propagation of drought events affecting more than 25% of the total land indicates the existence of various spatial gradients of drought propagation, mostly east–west or west–east, but also north–south have been found. No generalized episodes were found with a radial pattern, i.e., from inland to the coast.This work is supported by the projects CGL2014-52135-C03-01, CGL2014-52135-C3-3-R and PCIN-2015-220, financed by the Spanish Government, Ministry of the Economy and Finance and FEDER, IMDROFLOOD financed by the Water Works 2014 co-funded call of the European Commission, INDECIS, financed by the ERA-NET Cofund for Climate Services of the European Research Area for Climate Services, and the Regional Government of Aragón DGA-FSE (Grupo de Investigación Consolidado ‘Clima, Agua, Cambio Global y Sistemas Naturales’). Celia Salinas is a FPI-PhD student supported by the Ministry of the Economy and Finance. Miquel Tomas-Burguera was supported by the predoctoral FPU program 2013 (Ministry of Education, Culture and Sport).Peer reviewe