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Background and aims Clinical trials have shown that intensive low-density lipoprotein cholesterol (LDL-C) lowering improves cardiovascular outcomes among patients with atherosclerotic cardiovascular disease (ASCVD), but data are limited in real clinical practice, particularly for patients with ASCVD informing different territories. Methods FRENA was a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We compared the incidence of recurrent events in patients with sustained LDL-C levels As of December 2018, 1182 patients were eligible for this study. Among them, 172 (14.5%) had mean LDL-C levels = 70 mg/dl; the rate ratio was 0.61 (95% CI, 0.39-0.92), p = 0.019. On multivariable analysis, patients with LDL-C levels

Standards on tissue banking determine the need of microbiological monitoring during critical steps (recovery, processing, storage, and transplantation). This information will be useful for both discarding contaminated tissues or risk analysis (in case of recipient infection). In this study, we show the case of a multiorgan-multitissue donor colonized by Candida auris. This microorganism is characterized by multidrug resistance, with higher transmissibility and severe outcome. Some of the microbiological cultures from arteries tested positive for this microorganism, but it was not cultured in samples from musculoskeletal tissues and corneas. No recipient case of infection transmission by Candida species was observed (organs and cornea). The implementation of active surveillance protocol for C. auris detection in critical care units (as source of tissue donors) has been suggested as a part of our hospitals' infection control policy.

The aim was to develop a predictive model of infection by multidrug-resistant microorganisms (MDRO). A national, retrospective cohort study was carried out including all patients attended for an infectious disease in 54 Spanish Emergency Departments (ED), in whom a microbiological isolation was available from a culture obtained during their attention in the ED. A MDRO infection prediction model was created in a derivation cohort using backward logistic regression. Those variables significant at p < 0.05 assigned an integer score proportional to the regression coefficient. The model was then internally validated by k-fold cross-validation and in the validation cohort. A total of 5460 patients were included; 1345 (24.6%) were considered to have a MDRO infection. Twelve independent risk factors were identified in the derivation cohort and were combined into an overall score, the ATM (assessment of threat for MDRO) score. The model achieved an area under the curve-receiver operating curve of 0.76 (CI 95% 0.74-0.78) in the derivation cohort and 0.72 (CI 95% 0.70-0.75) in the validation cohort (p = 0.0584). Patients were then split into 6 risk categories and had the following rates of risk: 7% (0-2 points), 16% (3-5 points), 24% (6-9 points), 33% (10-14 points), 47% (15-21 points), and 71% (> 21 points). Findings were similar in the validation cohort. Several patient-specific factors were independently associated with MDRO infection risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were related to an increased risk for MDRO infection. This clinical prediction rule could be used by providers to identify patients at high risk and help to guide antibiotic strategy decisions, while accounting for clinical judgment.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388. ispartof: CANADIAN MEDICAL ASSOCIATION JOURNAL vol:191 issue:9 pages:E247-E256 ispartof: location:Canada status: published

Background Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk. Methods In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin= 0.3 mg/dl within 48 hours of surgery, or >= 50% within 7 days of surgery. Results Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted threshold group compared with the liberal-threshold group; P

The relationship between humans and the insect pests of cultivated plants may be considered to be an indirect coevolutionary process, i.e., an arms race. Over time, humans have developed several strategies to minimize the negative impacts of insects on agricultural production. However, insects have made adaptive responses via the evolution of resistance to insecticides, and more recently against Bacillus thuriengiensis. Thus, we need to continuously invest resources in the development of new strategies for crop protection. Recent advances in genomics have demonstrated the possibility of a new weapon or strategy in this war, i.e., gene silencing, which involves blocking the expression of specific genes via mRNA inactivation. In the last decade, several studies have demonstrated the effectiveness of this strategy in the control of different species of insects. However, several technical difficulties need to be overcome to transform this potential into reality, such as the selection of target genes, the concentration of dsRNA, the nucleotide sequence of the dsRNA, the length of dsRNA, persistence in the insect body, and the life stage of the target species where gene silencing is most efficient. This study analyzes several aspects related to the use of gene silencing in pest control and it includes an overview of the inactivation process, as well as the problems that need to be resolved to transform gene silencing into an effective pest control method.

Gemcitabine and erlotinib have shown a survival benefit in the first-line setting in metastatic pancreatic cancer (mPC). The aim of this study was to assess whether combining capecitabine (C) with gemcitabine + erlotinib (GE) was safe and effective versus GE in patients with mPC.

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists must deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers several specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved. (C) 2017 The Authors. Published by Elsevier Ltd.

Background Intensive Care to facilitate Organ Donation (ICOD) may help to increase the donor pool. We describe the Spanish experience with ICOD. Methods Achieving Comprehensive Coordination in Organ Donation (ACCORD)-Spain consisted of an audit of the donation pathway from patients who died as a result of a devastating brain injury (possible donors) in 68 hospitals during November 1, 2014, to April 30, 2015. We focused on possible donors whose families were interviewed to discuss organ donation once intensive care with a therapeutic purpose was deemed futile and brain death (BD) was a likely outcome. Results Of the 1970 possible donors in ACCORD-Spain, in 257, the family was interviewed once the decision had been made not to intubate/ventilate (n = 105), with the patient under intubation/ventilation outside of the intensive care unit (n = 59), or with the patient intubated/ventilated within the intensive care unit (n = 93). Consent to ICOD was obtained in 174 cases. Consent was higher when the donor coordinator participated in the interview (odds ratio, 2.32; 95% confidence interval, 1.33-4.11; P = 0.003). One hundred thirty-one patients developed BD, of whom 117 transitioned to actual donation after BD. Of the 35 patients who did not develop BD, 2 transitioned to actual donation after circulatory death. Sixteen patients subject to ICOD were finally medically unsuitable organ donors. ICOD contributed to 24% of the 491 actual donors registered in ACCORD-Spain. Conclusions Despite the complexity of the interview, the majority of families consented to ICOD. Estimating the probability of BD and assessing medical suitability are additional challenges of the practice. ICOD represents a clear opportunity to increase the donor pool and ensures organ donation is posed at every end-of-life care pathway.

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors. Methods and Materials: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT . Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy. Results: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT. Conclusions: According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted. (C) 2016 Elsevier Inc. All rights reserved.

Objective: To evaluate the activity and safety profile of panitumumab in combination with paclitaxel in patients with recurrent or metastatic SCCHN. Materials and methods: The VECTITAX phase II, open-label, multicenter study included patients with confirmed metastatic and/or recurrent SCCHN deemed to be untreatable by surgery or radiotherapy and ECOG PS = 0-1. All patients received paclitaxel (80 mg/m(2)/week) and panitumumab (6 mg/kg/2 weeks) until disease progression or unacceptable toxicity. EQ-5D-3L and visual analogic scale (VAS) were used to evaluate impact on quality of life (QoL). Results: The study included 40 patients (ITT population): (median age: 61 years; 87% male). Previous treatment: 29 patients (73%) had undergone surgery, 34 (85%) had received prior radiotherapy and 23 (58%) prior systemic treatment for locally advanced disease. Confirmed response was observed in 19 patients (48%) which was a complete response in 15% of patients. Stable disease was observed in 11 patients (28%). Disease control rate was 75%. Median progression-free survival was 7.5 months (95% CI: 4.9-8.3) and median overall survival 9.9 months (95% CI: 7.9-16.3). Most frequent grade 3-4 adverse events were skin rash (25%); asthenia (17%); neurotoxicity (15%); hypomagnesemia (10%); neutropenia (10%). Permanent discontinuation of panitumumab or paclitaxel due to adverse events was required in 10 (25%) and 13 patients (33%), respectively. There was one toxic death due to febrile neutropenia. Patient-reported QoL was preserved with no decline of median VAS scores. Conclusion: Panitumumab and paclitaxel is an active combination, providing promising outcomes with preservation of the QoL and a favorable safety profile. (EudraCT: 2010-018898-37; NCT01264328). (C) 2016 Published by Elsevier Ltd.

Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are beta-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of beta-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of beta-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

The CERN Axion Solar Telescope (CAST) has finished its search for solar axions with 3^He buffer gas, covering the search range 0.64 eV < m_a, 5 pages, 2 figures. Last version uploaded

Background The present report compares prognosis in hospitalized cases with the H1N1 pandemic virus in two seasons. Methods Two series of hospitalized patients with laboratory-confirmed H1N1 pandemic influenza have been compared: 813 in the season 2009-2010 and 707 in the season 2010-2011. A detailed history of variables preceding hospital admission and during hospitalization was obtained by interview and clinical charts. A combined endpoint of death admission to intensive care was used as outcome due to the low number of deaths. Logistic regression was applied in the analysis for adverse outcome. Results Patients of the second season had different characteristics than in the first one (older, more underlying conditions, more malfunctioning organs and more symptoms). Patients with H1N1 pandemic virus when hospitalized were more frequently directly admitted to ICU during the 2010-2011 season than in the previous season (RR = 2.10; 95% confidence intervals CI, 1.55-2.85), as a consequence of a higher presence of sepsis and respiratory distress. These patients also showed during hospitalization a higher risk of ICU admission or death (RR = 3.22, 95% CI, 2.15-4.83). After adjusting for the differences in risk factors of adverse outcome, patients in the second season showed a higher risk of ICU admission and/or in-hospital death odds ratio (OR = 3.77, 95% CI, 2.30-6.18). Conclusion Hospitalized patients with H1N1 pandemic influenza during the second season were more severely affected at hospital admission and showed a worse prognosis than in previous season, independently of the differences found at hospital admission.

Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009-2010 pandemic wave and 2010-2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8-62) in all patients and 43% (95% CI 2-78) in patients aged 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65-90) in all patients and 76% (95% CI 46-90) in patients aged 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38-72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza.

The International Axion Observatory (IAXO) is a next generation axion helioscope aiming at a sensitivity to the axion-photon coupling of a few 10^{-12} GeV^{-1}, i.e. 1-1.5 orders of magnitude beyond sensitivities achieved by the currently most sensitive axion helioscope, the CERN Axion Solar Telescope (CAST). Crucial factors in improving the sensitivity for IAXO are the increase of the magnetic field volume together with the extensive use of x-ray focusing optics and low background detectors, innovations already successfully tested at CAST. Electron-coupled axions invoked to explain the white dwarf cooling, relic axions, and a large variety of more generic axion-like particles (ALPs) along with other novel excitations at the low-energy frontier of elementary particle physics could provide additional physics motivation for IAXO., Comment: 6 pages, 1 figure, Contribution to the 8th Patras Workshop on Axions, WIMPs and WISPs, Chicago, IL, USA, 2012

Axion helioscopes aim at the detection of solar axions through their conversion into x-rays in laboratory magnetic fields. The use of low background x-ray detectors is an essential component contributing to the sensitivity of these searches. Here we review the recent advances on Micromegas detectors used in the CERN Axion Solar Telescope (CAST) and proposed for the future International Axion Observatory (IAXO). The most recent Micromegas setups in CAST have achieved background levels of 1.5$\times10^{-6}$\ckcs, a factor of more than 100 lower than the ones obtained by the first generation of CAST detectors. This improvement is due to the development of active and passive shielding techniques, offline discrimination techniques allowed by highly granular readout patterns, as well as the use of radiopure detector components. The status of the intensive R&D to reduce the background levels will be described, including the operation of replica detectors in test benches and the detailed Geant4 simulation of the detector setup and the detector response, which has allowed the progressive understanding of background origins. The best levels currently achieved in a test setup operating in the Canfranc Underground Laboratory (LSC) are as low as $\sim10^{-7}$\ckcs, showing the good prospects of this technology for application in the future IAXO., 26 pages, 21 figures

Background: The pneumococcal conjugate vaccine (PCV) might prevent hospitalizations in children because of the role of Streptococcus pneumoniae in the complications of influenza infection. We investigated the benefit of PCV vaccination in preventing influenza hospitalization in children

Background. In most seasons, the influenza vaccine is effective in preventing influenza, but it is not clear whether it is equally effective in preventing mild and severe cases. We designed a case-control study to compare the effectiveness of the influenza vaccine in preventing outpatient, inpatient, and severe or fatal cases of laboratory-confirmed influenza. Methods. Hospitalized patients (n = 691) with laboratory-confirmed influenza in the 2010-2011 season recruited in 29 Spanish hospitals were individually matched by age, admission/visit date, and province with an outpatient with laboratory-confirmed influenza and an outpatient control. Severe cases were considered those patients admitted to intensive care units or who died in the hospital (n = 177). We compared the influenza vaccine status of controls and outpatient cases, inpatient cases, and severe cases using conditional logistic regression adjusted for potential confounding factors. Severe and nonsevere inpatient influenza cases were compared using unconditional logistic regression. Vaccine effectiveness was (1 - odds ratio) x 100. Results. Vaccine effectiveness was 75% (adjusted odds ratio [AOR], 0.25; 95% confidence interval [CI],.16-.39) in preventing influenza outpatient cases, 60% (AOR, 0.40; 95% CI,.25-.63) in preventing influenza-associated hospitalizations, and 89% (AOR, 0.11; 95% CI,.04-.37) in preventing severe cases. In inpatients, influenza vaccination was associated with a lower risk of severe influenza (AOR, 0.42; 95% CI,.22-.80). Conclusions. Influenza vaccination prevented influenza cases and hospitalizations and was associated with a better prognosis in inpatients with influenza. The combined effect of these 2 mechanisms would explain the high effectiveness of the vaccine in preventing severe cases due to influenza.

The International Axion Observatory (IAXO) is a new generation axion helioscope aiming at a sensitivity to the axion-photon coupling of g(alpha gamma) >~ few x 10-12 GeV**-1}, i.e. 1 - 1.5 orders of magnitude beyond the one currently achieved by CAST. The project relies on improvements in magnetic field volume together with extensive use of x-ray focusing optics and low background detectors, innovations already successfully tested in CAST. Additional physics cases of IAXO could include the detection of electron-coupled axions invoked to explain the white dwarf cooling, relic axions, and a large variety of more generic axion-like particles (ALPs) and other novel excitations at the low-energy frontier of elementary particle physics. This contribution is a summary of our recent paper \cite{Irastorza:2011gs}., Proc. of Patras Workshop on Axions, WIMPs and WISPs, 98 - 101; DESY-PROC-2011-04; ISSN 1435-8077

The emergence and pandemic spread of a new strain of influenza A (H1N1) virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1) virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1) 2009 were determined to be obesity (BMI >= 40, with an odds-ratio [OR] 14.27), hematological neoplasia (OR 10.71), chronic heart disease, COPD (OR 5.16) and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds) were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88) and high risk conditions raise this value markedly (OR 6.43). The risk of hospitalization increased proportionally when for two (OR 2.08) or for three or more (OR 4.86) risk factors were simultaneously present

Prepared for submission to JCAP We study the feasibility of a new generation axion helioscope, the most ambitious and promising detector of solar axions to date. We show that large improvements in magnetic field volume, x-ray focusing optics and detector backgrounds are possible beyond those achieved in the CERN Axion Solar Telescope (CAST).

The molecular epidemiology of HIV-1 is constantly changing, mainly as a result of human migratory flows and the high adaptive ability of the virus. In recent years, Spain has become one of Europe's main destinations for immigrants and one of the western European countries with the highest rates of HIV-positive patients. Using a phylogeographic approach, we have analyzed the relationship between HIV-1 variants detected in immigrant and native populations of the urban area of Madrid. Our project was based on two coincidental facts. First, resistance tests were extended to naive and newly diagnosed patients, and second, the Spanish government legislated the provision of legal status to many immigrants. This allowed us to obtain a large data set (n = 2,792) from 11 Madrid hospitals of viral pol sequences from the two populations, and with this unique material, we explored the impact of immigration in the epidemiological trends of HIV-1 variants circulating in the largest Spanish city. The prevalence of infections by non-B HIV-1 variants in the studied cohort was 9%, rising to 25% among native Spanish patients. Multiple transmission events involving different lineages and subsubtypes were observed in all the subtypes and recombinant forms studied. Our results also revealed strong social clustering among the most recent immigrant groups, such as Russians and Romanians, but not in those groups who have lived in Madrid for many years. Additionally, we document for the first time the presence of CRF47_BF and CRF38_BF in Europe, and a new BG recombinant form found in Spaniards and Africans is tentatively proposed. These results suggest that the HIV-1 epidemic will evolve toward a more complex epidemiological landscape.

The CAST (CERN Axion Solar Telescope) experiment is searching for axions, an hypothetical particle that emerges as a possible solution to the well known CP violation problem in strong interactions. CAST is using a decommissioned LHC dipole magnet able to track the Sun as a possible source of solar axions, and to convert them to X-rays photons detectable with low background X-ray detectors. CAST continues its data taking period scanning masses up to 1eV. This thesis presents the data obtained with a Micromegas detector for the scanned axion mass range up to 0.64eV. The working principle, characterization and analysis of the Micromegas detectors operating in CAST are detailed in this work. Moreover, the last detector data corresponding to the new data taking period, with 3He gas inside the bores, was used to obtain a preliminar and conservative upper limit on the axion-photon coupling for the new axion mass range explored, g_{a\gamma} < 2.44 10^{-10} GeV^{-1}., Comment: PhD. Thesis

Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type beta-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution. Antimicrobial agents should not be considered only as selectors for efficient mechanisms of resistance but also as diversifying agents of the evolutionary trajectories. Different trajectories were identified using a combination of phylogenetic reconstructions and directed mutagenesis analyses, indicating that such an approach might be useful to fulfill the desirable goal of predicting evolutionary trajectories in antimicrobial resistance.

A novel read-out architecture has been developed for the Micromegas detector. The anode element is made of a resistive layer on a ceramic substrate. The detector part is entirely separated from the read-out element. Without significant loss, signals are transmitted by capacitive coupling to the read-out pads. The detector provides high gas gain, good energy resolution and the resistive layer assures spark protection to the electronics. This assembly could be combined with modern pixel array electronic ASICs. This readout organization is free on how the pixels are designed, arranged and connected. We present first results taken with a MediPix read-out chip., 10 pages, 10 figures

CAST (CERN Axion Solar Telescope) is a helioscope looking for axions coming from the solar core to the Earth. The experiment, located at CERN, is based on the Primakoff effect and uses a magnetic field of 9 Tesla provided by a decommissioned LHC magnet. CAST is able to follow the Sun during sunrise and sunset and therefore three X-ray detectors are mounted on both ends of the magnet waiting for a photon from axion-to-photon conversion due to the Primakoff effect. During its first phase, which concluded in 2004, CAST has been looking for axions with masses up to 0.02 eV. CAST’ s second phase manages to re-establish the coherence needed to scan for axions with masses up to 1.16 eV by using a buffer gas. This technique enables the experiment to look into the theoretical regions for axions. During the years 2005 and 2006, the use of 4He in CAST has already provided coherence in order to look for axions with masses up to 0.4 eV.

The Spherical gaseous detector (or Spherical Proportional Counter, SPC) is a novel type of par- ticle detector, with a broad range of applications. Its main features include a very low energy threshold independent of the volume (due to its very low capacitance), a good energy resolution, robustness and a single detection readout channel, in its simplest version. Applications range from radon emanation gas monitoring, neutron flux and gamma counting and spectroscopy to dark matter searches, in particular low mass WIMPs and coherent neutrino scattering measure- ment. Laboratories interested in these various applications share expertise within the NEWS (New Experiments With Sphere) network. SEDINE, a low background prototype installed at underground site of Laboratoire Souterrain de Modane is currently being operated and aims at measuring events at very low energy threshold, around 100 eV. We will present the energy cali- bration with 37Ar, the surface background reduction, the measurement of detector background at sub-keV energies, and show anticipated sensitivities for light dark matter search., 5 pages, 3 figures

The CERN Axion Solar Telescope (CAST) searches for a -> gamma conversion in the 9 T magnetic field of a refurbished LHC test magnet that can be directed toward the Sun. Two parallel magnet bores can be filled with helium of adjustable pressure to match the x-ray refractive mass m(gamma) to the axion search mass m(a). After the vacuum phase (2003-2004), which is optimal for m(a) less than or similar to 0.02 eV, we used He-4 in 2005-2007 to cover the mass range of 0.02-0.39 eV and He-3 in 2009-2011 to scan from 0.39 to 1.17 eV. After improving the detectors and shielding, we returned to He-4 in 2012 to investigate a narrow m(a) range around 0.2 eV ("candidate setting" of our earlier search) and 0.39-0.42 eV, the upper axion mass range reachable with He-4, to "cross the axion line" for the KSVZ model. We have improved the limit on the axion-photon coupling to g(a gamma) < 1.47 x 10(-10) GeV-1 (95% C.L.), depending on the pressure settings. Since 2013, we have returned to the vacuum and aim for a significant increase in sensitivity.

This Letter of Intent describes IAXO, the International Axion Observatory, a proposed 4th generation axion helioscope. As its primary physics goal, IAXO will look for axions or axion-like particles (ALPs) originating in the Sun via the Primakoff conversion of the solar plasma photons. In terms of signal to background ratio, IAXO will be about 4-5 orders of magnitude more sensitive than CAST, which means that this instrument will reach sensitivity to axion-photon couplings down to a few $\times 10^{-12}$ GeV$^{-1}$. IAXO has the potential for the discovery of axions and other ALPs, since it will deeply enter into unexplored parameter space. At the very least it will firmly exclude a large region of this space of high cosmological and astrophysical relevance. In particular it will probe a large fraction of the high mass part (1 meV to 1 eV) of the QCD axion allowed window. Additional physics cases for IAXO include the possibility of detecting solar axions produced by mechanisms mediated by the axion-electron coupling $g_{ae}$ with sensitivity $-$for the first time$-$ to values of $g_{ae}$ not previously excluded by astrophysics. IAXO follows the conceptual layout of an enhanced axion helioscope, with a purpose-built 8-coils toroidal superconducting magnet. All the eight 60-cm diameter magnet bores are equipped with focusing x-ray optics, able to focus the signal photons into $\sim$0.2 cm$^2$ spots that are imaged by ultra-low-background Micromegas x-ray detectors. The magnet is built into a structure with elevation and azimuth drives the will allow for solar tracking for $\sim$12 h each day. All the enabling technologies exists, there is no need for development. All the needed know-how is present in the proponent groups. Potential additional physics cases for IAXO to be developed in the future are the search of axionic dark radiation, relic cold dark matter axions or the realization of microwave light-shining-through wall setups, as well as the search of more specific models of weakly interacting sub-eV particles (WISPs) at the low energy frontier of particle physics. IAXO has the potential to serve as a multi-purpose facility for generic axion and ALP research in the next decade.

The CERN Axion Solar Telescope has finished its search for solar axions with He-3 buffer gas, covering the search range 0.64 eV less than or similar to ma less than or similar to 1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of g(a gamma) less than or similar to 3.3 x 10(-10) GeV-1 at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of g(a gamma), for example by the currently discussed next generation helioscope International AXion Observatory.

This article presents a cross-cultural study of the relationship among the subsistence strategies, the environmental setting and the food sharing practices of 22 modern small-scale societies located in America (n = 18) and Siberia (n = 4). Ecological, geographical and economic variables of these societies were extracted from specialized literature and the publicly available D-PLACE database. The approach proposed comprises a variety of quantitative methods, ranging from exploratory techniques aimed at capturing relationships of any type between variables, to network theory and supervised-learning predictive modelling. Results provided by all techniques consistently show that the differences observed in food sharing practices across the sampled populations cannot be explained just by the differential distribution of ecological, geographical and economic variables. Food sharing has to be interpreted as a more complex cultural phenomenon, whose variation over time and space cannot be ascribed only to local adaptation.