712 research outputs found

    Complexity in the hybridization physics revealed by depth-resolved photoemission spectroscopy of single crystalline novel Kondo lattice systems, CeCuX2_2 (X = As/Sb)

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    We investigate the electronic structure of a novel Kondo lattice system CeCuX2 (X = As/Sb) employing high resolution depth-resolved photoemission spectroscopy of high quality single crystalline materials. CeCuSb2 and CeCuAs2 represent different regimes of the Doniach phase diagram exhibiting Kondo-like transport properties and CeCuSb2 is antiferromagnetic (TN ~ 6.9 K) while CeCuAs2_2 does not show long-range magnetic order down to the lowest temperature studied. In this study, samples were cleaved in ultrahigh vacuum before the photoemission measurements and the spectra at different surface sensitivity establish the pnictogen layer having squarenet structure as the terminated surface which is weakly bound to the other layers. Cu 2p and As 2p spectra show spin-orbit split sharp peaks along with features due to plasmon excitations. Ce 3d spectra exhibit multiple features due to the hybridization of the Ce 4f/5d states with the valence states. While overall lineshape of the bulk spectral functions look similar in both the cases, the surface spectra are very different; the surface-bulk difference is significantly weaker in CeCuAs2 compared to that observed in CeCuSb2. A distinct low binding energy peak is observed in the Ce 3d spectra akin to the scenario observed in cuprates and manganites due to the Zhang-Rice singlets and/or high degree of itineracy of the conduction holes. The valence band spectra of CeCuSb2_2 manifest highly metallic phase. In CeCuAs2, intensity at the Fermi level is significantly small suggesting a pseudogap-type behavior. These results bring out an interesting scenario emphasizing the importance and subtlety of hybridization physics underlying the exoticity of this novel Kondo system

    Layer-resolved electronic behavior in a Kondo lattice system, CeAgAs2

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    We investigate the electronic structure of an antiferromagnetic Kondo lattice system CeAgAs2 employing hard x-ray photoemission spectroscopy. CeAgAs2, an orthorhombic variant of HfCuSi2 structure, exhibits antiferromagnetic ground state, Kondo like resistivity upturn and compensation of magnetic moments at low temperatures. The photoemission spectra obtained at different photon energies suggest termination of the cleaved surface at cis-trans-As layers. The depth-resolved data show significant surface-bulk differences in the As and Ce core level spectra. The As 2p bulk spectrum shows distinct two peaks corresponding to two different As layers. The peak at higher binding energy correspond to cis-trans-As layers and is weakly hybridized with the adjacent Ce layers. The As layers between Ce and Ag-layers possess close to trivalent configuration due to strong hybridization with the neighboring atoms and the corresponding feature appear at lower binding energy. Ce 3d core level spectra show multiple features reflecting strong Ce-As hybridization and strong correlation. Intense f0 peak is observed in the surface spectrum while it is insignificant in the bulk. In addition, we observe a features at binding energy lower than the well-screened feature indicating the presence of additional interactions. This feature becomes more intense in the bulk spectra suggesting it to be a bulk property. Increase in temperature leads to a spectral weight transfer to higher binding energies in the core level spectra and a depletion of spectral intensity at the Fermi level as expected in a Kondo material. These results reveal interesting surface-bulk differences, complex interplay of intra- and inter-layer covalency, and electron correlation in the electronic structure of this novel Kondo lattice system

    Respiratory syncytial virus infection among children younger than 2 years admitted to a paediatric intensive care unit with extended severe acute respiratory infection in ten Gavi-eligible countries: the RSV GOLD—ICU Network study

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    Background Patient-level data on life-threatening respiratory syncytial virus (RSV) infection in children in low-income and lower-middle-income countries (LMICs) are scarce, and this scarcity might limit demand for RSV interventions in LMICs who rely on support from Gavi, the Vaccine Alliance. We aimed to describe the characteristics of RSV-positive children younger than 2 years who were admitted to paediatric intensive care units (PICUs) with extended severe acute respiratory infection (eSARI) in Gavi-eligible countries. Methods The RSV GOLD—ICU Network study is a 2-year prospective, multicountry, observational study of children younger than 2 years admitted to a PICU with eSARI. The study was conducted at 12 referral hospitals in Bolivia, Cameroon, The Gambia, Ghana, Haiti, Mozambique, Nepal, Nigeria, Sudan, and Tanzania. For comparison with a high-income country, patients were also included from two referral hospitals in the Netherlands. Children were eligible for inclusion if they were aged between 4 days and 2 years, admitted to a PICU, and met the WHO eSARI definition. RSV infection was confirmed within 72 h of PICU admission via a molecular point-of-care test at LMIC study sites and via a PCR test at the Dutch study sites. Clinical data were extracted from admission charts of patients; underlying conditions that were identified at admission were classified as comorbidities. Socioeconomic and demographic data were collected via a written, structured, parental questionnaire. Findings Between April 28, 2021, and Sept 30, 2023, we included 2118 children who were admitted to a PICU with eSARI in the ten participating countries. 614 (29·0%; range 23·0–38·2) of 2118 children tested positive for RSV and 608 were included in descriptive analyses as six medical files were lost at one study site and data could not be retrieved. Among all 608 children infected with RSV, 379 (62%) were male and 229 (38%) were female. Median age at testing was 3·0 months (IQR 1·3–7·7). 30 (5%) of 608 children died from RSV infection. RSV fatality occurred at seven of ten participating LMIC study sites and was highest in Tanzania (seven [27%] of 26 children). Median age at testing of children who died with RSV infection was 1·8 months (IQR 1·1–4·2).Interpretation To our knowledge, this is the first prospective, multicountry study reporting data from children admitted to a PICU with life-threatening RSV infection in Gavi-eligible countries. As there is no access to intensive care for most children in LMICs, RSV prevention is urgently needed

    Deletion of Porcn in Mice Leads to Multiple Developmental Defects and Models Human Focal Dermal Hypoplasia (Goltz Syndrome)

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    Focal Dermal Hypoplasia (FDH) is a genetic disorder characterized by developmental defects in skin, skeleton and ectodermal appendages. FDH is caused by dominant loss-of-function mutations in X-linked PORCN. PORCN orthologues in Drosophila and mice encode endoplasmic reticulum proteins required for secretion and function of Wnt proteins. Wnt proteins play important roles in embryo development, tissue homeostasis and stem cell maintenance. Since features of FDH overlap with those seen in mouse Wnt pathway mutants, FDH likely results from defective Wnt signaling but molecular mechanisms by which inactivation of PORCN affects Wnt signaling and manifestations of FDH remain to be elucidated.We introduced intronic loxP sites and a neomycin gene in the mouse Porcn locus for conditional inactivation. Porcn-ex3-7flox mice have no apparent developmental defects, but chimeric mice retaining the neomycin gene (Porcn-ex3-7Neo-flox) have limb, skin, and urogenital abnormalities. Conditional Porcn inactivation by EIIa-driven or Hprt-driven Cre recombinase results in increased early embryonic lethality. Mesenchyme-specific Prx-Cre-driven inactivation of Porcn produces FDH-like limb defects, while ectodermal Krt14-Cre-driven inactivation produces thin skin, alopecia, and abnormal dentition. Furthermore, cell-based assays confirm that human PORCN mutations reduce WNT3A secretion.These data indicate that Porcn inactivation in the mouse produces a model for human FDH and that phenotypic features result from defective WNT signaling in ectodermal- and mesenchymal-derived structures

    RNA viruses in community-acquired childhood pneumonia in semi-urban Nepal; a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Pneumonia is among the main causes of illness and death in children <5 years of age. There is a need to better describe the epidemiology of viral community-acquired pneumonia (CAP) in developing countries.</p> <p>Methods</p> <p>From July 2004 to June 2007, we examined nasopharyngeal aspirates (NPA) from 2,230 cases of pneumonia (World Health Organization criteria) in children 2 to 35 months old recruited in a randomized trial of zinc supplementation at a field clinic in Bhaktapur, Nepal. The specimens were examined for respiratory syncytial virus (RSV), influenza virus type A (InfA) and B (InfB), parainfluenza virus types 1, 2 and 3 (PIV1, PIV2, and PIV3), and human metapneumovirus (hMPV) using a multiplex reverse transcriptase polymerase chain reaction (PCR) assay.</p> <p>Results</p> <p>We identified 919 virus isolates in 887 (40.0%) of the 2,219 NPA specimens with a valid PCR result, of which 334 (15.1%) yielded RSV, 164 (7.4%) InfA, 129 (5.8%) PIV3, 98 (4.4%) PIV1, 93 (4.2%) hMPV, 84 (3.8%) InfB, and 17 (0.8%) PIV2. CAP occurred in an epidemic pattern with substantial temporal variation during the three years of study. The largest peaks of pneumonia occurrence coincided with peaks of RSV infection, which occurred in epidemics during the rainy season and in winter. The monthly number of RSV infections was positively correlated with relative humidity (<it>r</it><sub><it>s </it></sub>= 0.40, <it>P </it>= 0.01), but not with temperature or rainfall. An hMPV epidemic occurred during one of the three winter seasons and the monthly number of hMPV cases was also associated with relative humidity (<it>r</it><sub><it>s </it></sub>= 0.55, <it>P </it>= 0.0005).</p> <p>Conclusion</p> <p>Respiratory RNA viruses were detected from NPA in 40% of CAP cases in our study. The most commonly isolated viruses were RSV, InfA, and PIV3. RSV infections contributed substantially to the observed CAP epidemics. The occurrence of viral CAP in this community seemed to reflect more or less overlapping micro-epidemics with several respiratory viruses, highlighting the challenges of developing and implementing effective public health control measures.</p

    Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

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    Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Funding: Bill & Melinda Gates Foundation

    Global, regional, and national burden of tuberculosis, 1990–2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study

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    Background Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016. Methods We analysed 15 943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate. Findings Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05–10·16) and the number of tuberculosis deaths was 1·21 million (1·16–1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01–1·89) and the number of tuberculosis deaths was 0·24 million (0·16–0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (–1·3% [–1·5 to −1·2]) than mortality did (–4·5% [–5·0 to −4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was −4·0% (–4·5 to −3·7) and mortality was −8·9% (–9·5 to −8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality). Interpretation If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV
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