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We carried out a retrospective study of acute gastroenteritis (AGE) outbreaks reported between 1 January 2015 and 31 December 2021 in Catalonia (Spain) to compare the incidence from 2015 to 2019 with that observed from 2020 to 2021. We observed a higher incidence rate of outbreaks during the prepandemic period (16.89 outbreaks/1,000,000 person-years) than during the pandemic period (6.96 outbreaks/1,000,000 person-years) (rate ratio (RR) 0.41; 95% confidence interval (CI) 0.34 to 0.51). According to the aetiology of the outbreak, those of viral aetiology decreased from 7.82 to 3.38 outbreaks/1,000,000 person-years (RR 2.31; 95% CI 1.72 to 3.12), and those of bacterial aetiology decreased from 5.01 to 2.78 outbreaks/1,000,000 person-years (RR 1.80; 95% CI 1.29 to 2.52). There was a great reduction in AGE outbreaks in Catalonia. This reduction may have been due to the effect of the nonpharmaceutical measures applied to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the collapse of the healthcare system and epidemiological surveillance services may also have had a strong influence.
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COVID-19 , Infecções por Caliciviridae , Gastroenterite , Norovirus , Humanos , Espanha/epidemiologia , Incidência , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , SARS-CoV-2 , Infecções por Caliciviridae/epidemiologia , Surtos de DoençasRESUMO
PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.
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Diabetes Mellitus , Hiperaldosteronismo , Humanos , Prevalência , Espanha/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Fatores de Risco , Hiperaldosteronismo/complicações , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/terapia , Sistema de RegistrosRESUMO
BACKGROUND: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance. PATIENTS AND METHODS: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy. Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and adverse events (AEs). RESULTS: Between May 2017 and February 2019, 155 patients were randomised (combination: 78; osimertinib: 77). At data cut-off of 22 February 2021, median follow-up was 33.8 months [interquartile range (IQR): 26.5-37.6 months] and 129 (83.2%) PFS events were reported in the intention-to-treat population. There was no difference in median PFS between the combination [15.4 months; 95% confidence interval (CI) 9.2-18.0 months] and osimertinib arm (12.3 months; 95% CI 6.2-17.2 months; stratified log-rank P = 0.83), [hazard ratio (HR) = 0.96; 95% CI 0.68-1.37]. Median OS was 24.0 months (95% CI 17.8-32.1 months) in the combination arm and 24.3 months (95% CI 16.9-37.0 months) in the osimertinib arm (stratified log-rank P = 0.91), (HR = 1.03; 95% CI 0.67-1.56). Exploratory analysis revealed a significant interaction of smoking history with treatment for PFS (adjusted P = 0.0052) with a HR of 0.52 (95% CI 0.30-0.90) for smokers, and 1.47 (95% CI 0.92-2.33) for never smokers. ORR was 55% in both arms and the median time to treatment failure was significantly shorter in the combination than in the osimertinib arm, 8.2 months versus 10.8 months, respectively (P = 0.0074). Safety of osimertinib and bevacizumab was consistent with previous reports with grade ≥3 treatment-related AEs (TRAEs) reported in 47% and 18% of patients on combination and osimertinib alone, respectively. CONCLUSIONS: No difference in PFS was observed between osimertinib plus bevacizumab and osimertinib alone. Grade ≥3 TRAEs were more common in patients on combination.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Compostos de Anilina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Superconductivity in infinite-layer nickelates holds exciting analogies with that of cuprates, with similar structures and 3d-electron count. Using resonant inelastic x-ray scattering, we studied electronic and magnetic excitations and charge density correlations in Nd_{1-x}Sr_{x}NiO_{2} thin films with and without an SrTiO_{3} capping layer. We observe dispersing magnons only in the capped samples, progressively dampened at higher doping. We detect an elastic resonant scattering peak in the uncapped x=0 compound at wave vector (â¼â ,0), remindful of the charge order signal in hole doped cuprates. The peak weakens at x=0.05 and disappears in the superconducting x=0.20 film. The role of the capping on the electronic reconstruction far from the interface remains to be understood.
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BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Demografia , Receptores ErbB/genética , Receptores ErbB/uso terapêutico , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Espanha/epidemiologiaRESUMO
Different factors affect the way dissolved organic matter (DOM) is processed in the ocean water column, including environmental conditions and the functional capabilities of the communities. Recent studies have shown that bathypelagic prokaryotes are metabolically flexible, but whether this versatility translates into a higher ability to process DOM has been barely explored. Here we performed a multifactorial transplant experiment to compare the growth, activity and changes in DOM quality in surface and bathypelagic waters inoculated with either surface or bathypelagic prokaryotic communities. The effect of nutrient additions to surface waters was also explored. Despite no differences in the cell abundance of surface and deep ocean prokaryotes were observed in any of the treatments, in surface waters with nutrients the heterotrophic production of surface prokaryotes rapidly decreased. Conversely, bathypelagic communities displayed a sustained production throughout the experiment. Incubations with surface prokaryotes always led to a significant accumulation of recalcitrant compounds, which did not occur with bathypelagic prokaryotes, suggesting they have a higher ability to process DOM. These contrasting abilities could be explained by the recruitment of a comparatively larger number of opportunistic taxa within the bathypelagic assemblages, which likely resulted in a broader community capability of substrate utilization.
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Archaea/metabolismo , Bactérias/metabolismo , Carbono/metabolismo , Metabolismo Energético/fisiologia , Compostos Orgânicos/metabolismo , Archaea/classificação , Bactérias/classificação , Processos Heterotróficos/fisiologia , Microbiota/fisiologia , Água do Mar/químicaRESUMO
Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.
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Astrócitos/ultraestrutura , Glicogênio , Ácido Láctico/administração & dosagem , Aprendizagem/fisiologia , Sinapses/metabolismo , Sinapses/ultraestrutura , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicogênio/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/ultraestrutura , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos , Sinapses/efeitos dos fármacosRESUMO
The sinking of organic particles formed in the photic layer is a main vector of carbon export into the deep ocean. Although sinking particles are heavily colonized by microbes, so far it has not been explored whether this process plays a role in transferring prokaryotic diversity from surface to deep oceanic layers. Using Illumina sequencing of the 16S rRNA gene, we explore here the vertical connectivity of the ocean microbiome by characterizing marine prokaryotic communities associated with five different size fractions and examining their compositional variability from surface down to 4,000 m across eight stations sampled in the Atlantic, Pacific, and Indian Oceans during the Malaspina 2010 Expedition. Our results show that the most abundant prokaryotes in the deep ocean are also present in surface waters. This vertical community connectivity seems to occur predominantly through the largest particles because communities in the largest size fractions showed the highest taxonomic similarity throughout the water column, whereas free-living communities were more isolated vertically. Our results further suggest that particle colonization processes occurring in surface waters determine to some extent the composition and biogeography of bathypelagic communities. Overall, we postulate that sinking particles function as vectors that inoculate viable particle-attached surface microbes into the deep-sea realm, determining to a considerable extent the structure, functioning, and biogeography of deep ocean communities.
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Microbiota/fisiologia , Modelos Biológicos , Microbiologia da Água , Oceanos e MaresRESUMO
Deep ocean microbial communities rely on the organic carbon produced in the sunlit ocean, yet it remains unknown whether surface processes determine the assembly and function of bathypelagic prokaryotes to a larger extent than deep-sea physicochemical conditions. Here, we explored whether variations in surface phytoplankton assemblages across Atlantic, Pacific and Indian ocean stations can explain structural changes in bathypelagic (ca. 4,000 m) free-living and particle-attached prokaryotic communities (characterized through 16S rRNA gene sequencing), as well as changes in prokaryotic activity and dissolved organic matter (DOM) quality. We show that the spatial structuring of prokaryotic communities in the bathypelagic strongly followed variations in the abundances of surface dinoflagellates and ciliates, as well as gradients in surface primary productivity, but were less influenced by bathypelagic physicochemical conditions. Amino acid-like DOM components in the bathypelagic reflected variations of those components in surface waters, and seemed to control bathypelagic prokaryotic activity. The imprint of surface conditions was more evident in bathypelagic than in shallower mesopelagic (200-1,000 m) communities, suggesting a direct connectivity through fast-sinking particles that escape mesopelagic transformations. Finally, we identified a pool of endemic deep-sea prokaryotic taxa (including potentially chemoautotrophic groups) that appear less connected to surface processes than those bathypelagic taxa with a widespread vertical distribution. Our results suggest that surface planktonic communities shape the spatial structure of the bathypelagic microbiome to a larger extent than the local physicochemical environment, likely through determining the nature of the sinking particles and the associated prokaryotes reaching bathypelagic waters.
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Plâncton , Água do Mar , Oceano Atlântico , Cilióforos , Dinoflagellida , Oceano Índico , Oceano Pacífico , Plâncton/genética , RNA Ribossômico 16S/genéticaRESUMO
A cross-sectional survey was carried out to estimate the seroprevalence of Coxiella burnetii in extensively grazed cattle and sheep from central Italy and to identify the related risk factors. Data on notified human Q fever cases in the area were also collected and described. A two-stage cluster sampling was performed. A total of 5083 animals (2210 cattle; 2873 sheep) belonging to 186 farms (92 herds; 94 flocks) were tested for the presence of antibodies against C. burnetii using a commercial enzyme-linked immunosorbent assay kit. The prevalence at the animal-level resulted three times higher in sheep compared to cattle (37.8% vs. 12.0%; χ2 = 270.10, P < 0.001). The prevalence at the herd-level was also higher in sheep than in cattle (87.2% vs. 68.5%; χ2 = 9.52, P < 0.01). The multivariate analysis showed a higher risk of seropositivity for cattle aged 67-107 months (OR 2.79, 95% CI 1.86-4.18), cattle >107 months of age (OR 2.07, 95% CI 1.36-3.14) and mixed breed cattle (OR 1.74, 95% CI 1.11-2.72). A herd size >92 animals was recognized as herd-level risk factor in cattle (OR 6.88, 95% CI 1.67-28.37). The risk of being seropositive was double in sheep belonging to flocks >600 animals (odds ratio (OR) 2.04, 95% CI 1.63-2.56). Sheep were confirmed to be the most exposed species. Nevertheless, the prevalence observed in cattle also suggests the potential involvement of this species in the circulation of the pathogen in the area. Seven confirmed human Q fever cases were reported. In five out of seven cases there was at least one exposed herd within a 5 km buffer. Even though the source of the infection was not identified, the possibility of C. burnetii circulating in the livestock and human population in the study area cannot be overlooked. The integration between veterinary and human surveillance will be crucial to understand the spread of this zoonosis and to support the adoption of appropriate control measures.
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Anticorpos Antibacterianos/sangue , Doenças dos Bovinos/epidemiologia , Coxiella burnetii/imunologia , Febre Q/epidemiologia , Febre Q/veterinária , Doenças dos Ovinos/epidemiologia , Animais , Bovinos , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Itália/epidemiologia , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , OvinosRESUMO
Cancer-related fatigue (CRF) is one of the most prolonged discomforts suffered by people who have had cancer. Seventy-eight to ninety-six percent of cancer patients experience fatigue, especially while undergoing treatment. CRF is related to insomnia, anxiety, depression, and also varies depending on age. However, little is known about the factors contributing to CRF and better understanding of determinants of CRF makes it easier to identify early patients at risk and in designing intervention planning. The aim of this study was to assess the influence of precipitating factors (diagnosis of breast cancer and other clinical aspects) and perpetuating factors (social network, quality of life, mental disorders) on the presence of chronic fatigue in women from our cultural context, by social class each other determinants. METHODS: It was carried out a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were data from the Brief Fatigue Inventory questionnaire and hospital medical records. The dependent variable was fatigue and the independent variables were age, social class, time since diagnoses, cohabitation, comorbidity, relapse, body mass index, mental health (anxiety and depression), social network, social support, and quality of life. RESULTS: Seventy-two percent of the women in the DAMA cohort reported moderate to severe fatigue. Risk of suffering from severe fatigue was greatest among individuals with low social class, those aged under 50 years, those with chronic disorders who had relapsed, and those with symptoms of anxiety and depression. In our study, CRF did not appear to be related to the stage of the cancer at diagnosis, or to the time since diagnosis. CONCLUSIONS: CRF is an element that the professionals responsible for the control and monitoring of women should take into account as another element to be taken into consideration.
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Neoplasias da Mama/epidemiologia , Fadiga/epidemiologia , Idoso , Ansiedade/epidemiologia , Ansiedade/psicologia , Neoplasias da Mama/psicologia , Estudos de Coortes , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Apoio Social , Fatores Socioeconômicos , Espanha/epidemiologia , Inquéritos e QuestionáriosRESUMO
Investigation of elementary excitations has advanced our understanding of many-body physics governing most physical properties of matter. Recently spin-orbit excitons have drawn much attention, whose condensates near phase transitions exhibit Higgs mode oscillations, a long-sought-after physical phenomenon [A. Jain, et al., Nat. Phys. 13, 633 (2017)NPAHAX1745-247310.1038/nphys4077]. These critical transition points, resulting from competing spin-orbit coupling (SOC), local crystalline symmetry, and exchange interactions, are not obvious in iridium-based materials, where SOC prevails in general. Here, we present results of resonant inelastic x-ray scattering on a spin-orbital liquid Ba_{3}ZnIr_{2}O_{9} and three other 6H-hexagonal perovskite iridates that show magnetism, contrary to the nonmagnetic singlet ground state expected due to strong SOC. Our results show that substantial hopping between closely placed Ir^{5+} ions within Ir_{2}O_{9} dimers in these 6H iridates modifies spin-orbit coupled states and reduces spin-orbit excitation energies. Here, we are forced to use at least a two-site model to match the excitation spectrum going in-line with the strong intradimer hopping. Apart from SOC, low-energy physics of iridates is thus critically dependent on hopping and may not be ignored even for systems having moderate hopping, where the excitation spectra can be explained using an atomic model. SOC, which is generally found to be 0.4-0.5 eV in iridates, is scaled in effect down to â¼0.26 eV for the 6H systems, sustaining the hope of achieving quantum criticality by tuning Ir-Ir separation.
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Equine infectious anaemia (EIA) is a disease with an almost worldwide distribution, with several outbreaks having been reported recently in European countries. In Italy, two regions, Lazio and Abruzzo, are considered as endemic areas for this disease. In nature, the EIA virus is mechanically transmitted by biting flies such as tabanids (Diptera: Tabanidae), although few studies have investigated the epidemiological implications. In the present study, several sites characterized by different levels of EIA prevalence were sampled. In sites with high tabanid populations, a seasonal succession of tabanid species with a dual-peak corresponding to early active species (i.e. in June to July) and late active species (i.e. in August to September) was clearly observed. Moreover, a positive correlation was found between EIA prevalence and tabanid abundance and species richness, suggesting that tabanid diversity might extend the duration of the seasonal transmission period of EIA. Further observations are required to better assess how vector diversity influence EIA transmission.
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Dípteros/fisiologia , Anemia Infecciosa Equina/epidemiologia , Insetos Vetores/fisiologia , Animais , Cavalos , Itália/epidemiologia , Dinâmica Populacional , Prevalência , Estações do AnoRESUMO
An end-station for resonant inelastic X-ray scattering and (resonant) X-ray emission spectroscopy at beamline ID20 of ESRF - The European Synchrotron is presented. The spectrometer hosts five crystal analysers in Rowland geometry for large solid angle collection and is mounted on a rotatable arm for scattering in both the horizontal and vertical planes. The spectrometer is optimized for high-energy-resolution applications, including partial fluorescence yield or high-energy-resolution fluorescence detected X-ray absorption spectroscopy and the study of elementary electronic excitations in solids. In addition, it can be used for non-resonant inelastic X-ray scattering measurements of valence electron excitations.
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At the end of 1998, universal hepatitis A+B vaccination of 12 year olds was introduced in Catalonia. The aim was to examine trends in hepatitis A during 2005-2015 and assess risk factors by age group. We carried out an observational epidemiological study of the incidence and risk factors of hepatitis A reported to the surveillance system. Information on exposure was recorded for each case for the 2-6 weeks before symptom onset. Spearman's coefficient was used to evaluate the trends of rates. The chi-square test was used to compare categorical. We studied 2621 hepatitis A cases; the age mean was 26.6 years (SD=18.2), and >50% of cases were in the 20-49 years age group. The incidence decreased from 3.28/100 000 in 2005 to 1.50/100 000 in 2015. The rate for women decreased over time (P = .008), but the reduction was not significant in men (P = .234). Men consistently had higher rates than women with the biggest difference being in the 20-34 years age group (rate 8.8 vs 2.8). The greatest risk factor was travel to an endemic country (42.1%) in the 0-19 years age group and male-to-male sexual contact (18.6%) in the 20-49 years age group. The case fatality rate in adults aged >49 years was 0.4%. In conclusion, the vaccination programme of preadolescents resulted in a reduction in hepatitis A cases. However, a significant amount of cases still appear in immigrants and men who have sex with men. Hepatitis A in adults is an emerging health problem that will require new strategies.
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Vacinas contra Hepatite A/administração & dosagem , Hepatite A/epidemiologia , Hepatite A/prevenção & controle , Programas de Imunização , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Epidemiológicos , Feminino , Vacinas contra Hepatite B/administração & dosagem , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mortalidade , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologia , Adulto JovemRESUMO
The temperature dependence of the excitation spectrum in NaOsO_{3} through its metal-to-insulator transition (MIT) at 410 K has been investigated using resonant inelastic x-ray scattering at the Os L_{3} edge. High-resolution (ΔEâ¼56 meV) measurements show that the well-defined, low-energy magnons in the insulating state weaken and dampen upon approaching the metallic state. Concomitantly, a broad continuum of excitations develops which is well described by the magnetic fluctuations of a nearly antiferromagnetic Fermi liquid. By revealing the continuous evolution of the magnetic quasiparticle spectrum as it changes its character from itinerant to localized, our results provide unprecedented insight into the nature of the MIT in NaOsO_{3} [J. G. Vale, S. Calder, C. Donnerer, D. Pincini, Y. G. Shi, Y. Tsujimoto, K. Yamaura, M. M. Sala, J. van den Brink, A. D. Christianson, and D. F. McMorrow, Phys. Rev. B 97, 184429 (2018)PRBMDO2469-995010.1103/PhysRevB.97.184429].
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SHANK3 (also called PROSAP2) genetic haploinsufficiency is thought to be the major cause of neuropsychiatric symptoms in Phelan-McDermid syndrome (PMS). PMS is a rare genetic disorder that causes a severe form of intellectual disability (ID), expressive language delays and other autistic features. Furthermore, a significant number of SHANK3 mutations have been identified in patients with autism spectrum disorders (ASD), and SHANK3 truncating mutations are associated with moderate to profound ID. The Shank3 protein is a scaffold protein that is located in the postsynaptic density (PSD) of excitatory synapses and is crucial for synapse development and plasticity. In this study, we investigated the molecular mechanisms associated with the ASD-like behaviors observed in Shank3Δ11-/- mice, in which exon 11 has been deleted. Our results indicate that Shank3 is essential to mediating metabotropic glutamate receptor 5 (mGlu5)-receptor signaling by recruiting Homer1b/c to the PSD, specifically in the striatum and cortex. Moreover, augmenting mGlu5-receptor activity by administering 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide ameliorated the functional and behavioral defects that were observed in Shank3Δ11-/- mice, suggesting that pharmaceutical treatments that increase mGlu5 activity may represent a new approach for treating patients that are affected by PMS and SHANK3 mutations.
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Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Benzamidas/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Pirazóis/farmacologia , Receptor de Glutamato Metabotrópico 5/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/metabolismo , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 22/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Éxons , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Proteínas de Arcabouço Homer/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Proteínas dos Microfilamentos , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Densidade Pós-Sináptica/metabolismo , Transdução de Sinais , Transmissão SinápticaRESUMO
BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. METHODS: The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. RESULTS: The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. CONCLUSIONS: Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Idoso , Doenças Mamárias/epidemiologia , Neoplasias da Mama/genética , Reações Falso-Positivas , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Fatores de Risco , Espanha/epidemiologiaRESUMO
A method to separate the non-resonant inelastic X-ray scattering signal of a micro-metric sample contained inside a diamond anvil cell (DAC) from the signal originating from the high-pressure sample environment is described. Especially for high-pressure experiments, the parasitic signal originating from the diamond anvils, the gasket and/or the pressure medium can easily obscure the sample signal or even render the experiment impossible. Another severe complication for high-pressure non-resonant inelastic X-ray measurements, such as X-ray Raman scattering spectroscopy, can be the proximity of the desired sample edge energy to an absorption edge energy of elements constituting the DAC. It is shown that recording the scattered signal in a spatially resolved manner allows these problems to be overcome by separating the sample signal from the spurious scattering of the DAC without constraints on the solid angle of detection. Furthermore, simple machine learning algorithms facilitate finding the corresponding detector pixels that record the sample signal. The outlined experimental technique and data analysis approach are demonstrated by presenting spectra of the Si L2,3-edge and O K-edge of compressed α-quartz. The spectra are of unprecedented quality and both the O K-edge and the Si L2,3-edge clearly show the existence of a pressure-induced phase transition between 10 and 24â GPa.
RESUMO
An end-station for X-ray Raman scattering spectroscopy at beamline ID20 of the European Synchrotron Radiation Facility is described. This end-station is dedicated to the study of shallow core electronic excitations using non-resonant inelastic X-ray scattering. The spectrometer has 72 spherically bent analyzer crystals arranged in six modular groups of 12 analyzer crystals each for a combined maximum flexibility and large solid angle of detection. Each of the six analyzer modules houses one pixelated area detector allowing for X-ray Raman scattering based imaging and efficient separation of the desired signal from the sample and spurious scattering from the often used complicated sample environments. This new end-station provides an unprecedented instrument for X-ray Raman scattering, which is a spectroscopic tool of great interest for the study of low-energy X-ray absorption spectra in materials under inâ situ conditions, such as inâ operando batteries and fuel cells, inâ situ catalytic reactions, and extreme pressure and temperature conditions.