Incidence, in-hospital case-fatality rates, and management practices in Puerto Ricans hospitalized with acute myocardial infarction

OBJECTIVE: There are extremely limited data on minority populations, especially Hispanics, describing the clinical epidemiology of acute coronary disease. The aim of this study is to examine the incidence rate of acute myocardial infarction (AMI), in-hospital case-fatality rate (CFR), and management practices among residents of greater San Juan (Puerto Rico) who were hospitalized with an initial AMI. METHODS: Our trained study staff reviewed and independently validated the medical records of patients who had been hospitalized with possible AMI at any of the twelve hospitals located in greater San Juan during calendar year 2007. RESULTS: The incidence rate (# per 100,000 population) of 1,415 patients hospitalized with AMI increased with advancing age and were significantly higher for older patients for men (198) than they were for women (134). The average age of the study population was 64 years, and women comprised 45% of the study sample. Evidence-based cardiac therapies, e.g., aspirin, beta blockers, ACE inhibitors/angiotensin receptor blockers, and statins, were used with 60% of the hospitalized patients, and women were less likely than men to have received these therapies (59% vs. 65%) or to have undergone interventional cardiac procedures (47% vs. 59%) (p \u3c 0.05). The in-hospital CFR increased with advancing age and were higher for women (8.6%) than they were for men (6.0%) (p \u3c 0.05). CONCLUSION: Efforts are needed to reduce the magnitude of AMI, enhance the use of evidence-based cardiac therapies, reduce possible gender disparities, and improve the short-term prognoses of Puerto Rican patients hospitalized with an initial AMI

Allelic frequency of DPYD genetic variants: implementation of a genotyping test in Mexican population

Background: Fluoropyrimidine-based (FP) chemotherapy is extensively used to treat solid cancers, including colorectal and breast cancer. A dihydropyrimidine dehydrogenase (DPD) enzyme deficiency, encoded by the dihydropyrimidine dehydrogenase (DPYD) gene, increases the risk of severe toxicity. FP toxicity affects about 30-40% of patients, which in some cases may be lethal. FPs have been used for over 50 years, and an estimated 2 million cancer patients are treated with FP drugs annually. In particular, FPs remain among the most effective drugs for treating GI malignancies, including colorectal cancer (CRC) (1.8 million), gastric (1 million), and pancreatic cancer (n=460,000). In Mexican oncology practice, FP and capecitabine chemotherapies are the most common drugs for gastrointestinal, head and neck, and breast tumors. DPYD genotyping aims to identify variants that lead to DPD deficiency. We implemented a seven-allelic genotyping test and analyzed the frequency in the Mexican population. Methods: We included seven DPYD variants: c.1129-5923C-\u3eG, c.2846A-\u3eT associated with increased risk toxicity (reduced activity), and c.1156G-\u3eT, c.1905+1G-\u3eA, c.1679T-\u3eG, c.1898delC, and c.299_302delTCAT associated with high risk for FP toxicity (no activity or significantly reduced activity). Genomic DNA was isolated from 280 subjects: 36 cancer patients and 244 non-cancer subjects. We analyzed DPYD variants by real-time PCR (c.1156G-\u3eT, c.2846A-\u3eT, and c.1129-5923C-\u3eG) and Sanger sequencing (c.1905+1G-\u3eA, c.1679T-\u3eG, c.1898delC and c.299_302delTCAT) The allele frequency was calculated for each variant. Results: For Sanger sequencing, primers were designed to amplify four variants. Amplified products of the expected size were obtained. Three variants were amplified using TaqMan probes and synthetic positive controls for both alleles. We found the c.1129-5923C\u3eG variant in the heterozygous state in 1% (n= 3), and the c.2846A\u3eT variant was found in 0.33% (n=1) of the participants. We did not found the rest of the variants in the Mexican population. Conclusions: The allele frequency for two of the seven analyzed variants (c.1129-5923C-\u3eG and the c.2846A\u3eT) was higher than reported for the global population (0.00476, and 0.005166). DPYD genotyping may help identify patients at higher risk of developing severe FP toxicity. Personalized medicine allows oncologists to modify the treatment before it begins

Agricultural intensification reduces selection of putative plant growth-promoting rhizobacteria in wheat

The complex evolutionary history of wheat has shaped its associated root microbial community. However, consideration of impacts from agricultural intensification has been limited. This study investigated how endogenous (genome polyploidization) and exogenous (introduction of chemical fertilizers) factors have shaped beneficial rhizobacterial selection. We combined culture-independent and -dependent methods to analyze rhizobacterial community composition and its associated functions at the root–soil interface from a range of ancestral and modern wheat genotypes, grown with and without the addition of chemical fertilizer. In controlled pot experiments, fertilization and soil compartment (rhizosphere, rhizoplane) were the dominant factors shaping rhizobacterial community composition, whereas the expansion of the wheat genome from diploid to allopolyploid caused the next greatest variation. Rhizoplane-derived culturable bacterial collections tested for plant growth-promoting (PGP) traits revealed that fertilization reduced the abundance of putative plant growth-promoting rhizobacteria in allopolyploid wheats but not in wild wheat progenitors. Taxonomic classification of these isolates showed that these differences were largely driven by reduced selection of beneficial root bacteria representative of the Bacteroidota phylum in allopolyploid wheats. Furthermore, the complexity of supported beneficial bacterial populations in hexaploid wheats was greatly reduced in comparison to diploid wild wheats. We therefore propose that the selection of root-associated bacterial genera with PGP functions may be impaired by crop domestication in a fertilizer-dependent manner, a potentially crucial finding to direct future plant breeding programs to improve crop production systems in a changing environment.Biotechnology and Biological Sciences Research Council (BBSRC)Rothamsted Research acknowledges strategic funding from the Biotechnology and Biological Sciences Research Council of the United Kingdom (BBSRC).This work was supported by the bilateral BBSRC-Embrapa grant on “Exploitation of the rhizosphere microbiome for sustainable wheat production” (BB/N016246/1); “Optimization of nutrients in soil-plant systems: How can we control nitrogen cycling in soil?” (BBS/E/C/00005196);.Institute Strategic Programmes “S2N – Soil to nutrition – Work package 1 – Optimizing nutrient flows and pools in the soil-plant-biota system” (BBS/E/C/000I0310) and “Growing Health Institute Strategic Programme [BB/X010953/1]; Work package 2: bio-inspired solutions for healthier agroecosystems: Understanding soil environments”(BBS/E/RH/230003B).The ISME Journa

Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study

Introduction: The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)). Methods: Histopathological alterations were systematically scored in skin biopsies of 53 consecutive SSc patients (dorsal forearm and upper inner arm) and 18 controls (upper inner arm). Clinical skin involvement was evaluated using the modified Rodnan skin score. In patients with lcSSc or dcSSc, associations of histopathological parameters with local clinical skin involvement were determined by generalised estimation equation modelling. Results: The hyalinised collagen score, the myofibroblast score, the mean epidermal thickness, the mononuclear cellular infiltration and the frequency of focal exocytosis differed significantly between biopsies with and without local clinical skin involvement. Except for mononuclear cellular infiltration, all of the continuous parameters correlated with the local clinical skin score at the dorsal forearm. Parakeratosis, myofibroblasts and intima proliferation were present in a minority of the SSc biopsies, but not in controls. No differences were found between lSSc and controls. Conclusions: Several histopathological parameters are linked to local clinical skin disease. SSc-specific histological alterations have a low diagnostic sensitivity

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

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

IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge

Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines IL-1β and IL-18 within the first 12 hours, while IL-1α expression continually increases over at least the first 48 hours. Strikingly, Il1r1-deficient mice are highly susceptible to pulmonary A. fumigatus challenge exemplified by robust fungal proliferation in the lung parenchyma. Enhanced susceptibility of Il1r1-deficient mice correlated with defects in leukocyte recruitment and anti-fungal activity. Importantly, IL-1α rather than IL-1β was crucial for optimal leukocyte recruitment. IL-1α signaling enhanced the production of CXCL1. Moreover, CCR2+ monocytes are required for optimal early IL-1α and CXCL1 expression in the lungs, as selective depletion of these cells resulted in their diminished expression, which in turn regulated the early accumulation of neutrophils in the lung after A. fumigatus challenge. Enhancement of pulmonary neutrophil recruitment and anti-fungal activity by CXCL1 treatment could limit fungal growth in the absence of IL-1α signaling. In contrast to the role of IL-1α in neutrophil recruitment, the inflammasome and IL-1β were only essential for optimal activation of anti-fungal activity of macrophages. As such, Pycard-deficient mice are mildly susceptible to A. fumigatus infection. Taken together, our data reveal central, non-redundant roles for IL-1α and IL-1β in controlling A. fumigatus infection in the murine lung