Interleukin gene polymorphisms in age-related macular degeneration

[[abstract]]PURPOSE. To investigate polymorphisms in a candidate gene of interleukin (IL) in unrelated Taiwan Chinese patients with late age-related macular degeneration (AMD) and control subjects without AMD. METHODS. In this retrospective, case-control study, 312 unrelated Taiwan Chinese patients with late AMD and 180 age- and sex-matched control subjects were enrolled. Late AMD was classified as either atrophic (dry) or neovascular (wet) according to the International ARM Epidemiologic Study. Genomic DNA was prepared from peripheral blood obtained from all patients with AMD and control subjects. Polymerase chain reactions were used to analyze 14 single-nucleotide polymorphisms (SNPs) in candidate genes of 5 ILs: IL-1 beta(2q14): -511 T/C; IL-6 (7p21): -572 C/G and -596 G/A; IL-8 (4q13-q21): -251 A/T, +781 C/T, +1633 T/C, and +2767 A/T; IL-10 (1q31-q32): -592 A/C, -819 C/T, and -1082 G/A; and IL-18 (11q22.2-q22.3): +105 A/C, -137 C/G, -607 A/C, and -656 T/G. RESULTS. In the 312 patients with late AMD, dry AMD was diagnosed in 136 and wet AMD in 176. Among the 14 SNPs in the 5 IL genes studied, only the IL-8 +781 C/T SNP was significantly associated with wet AMD (T allele: 46% in wet AMD versus 28% in the control subjects, P = 1.03 x 10(-6), OR = 2.16, 95% CI = 1.58-2.94). The association analysis based on genotypes at both IL-8 +781 C/T and the CFH Y402H demonstrated that the IL-8 +781 C/T to AMD was not significant when analyzed conditional on the presence of the CFH Y402H C risk allele and vice versa. The IL-8 +781 C/T was in low linkage disequilibrium with CFH Y402H (D' = 0.02). CONCLUSIONS. The data suggest that Taiwan Chinese carriers of the IL-8 +781 T allele, independent of the CFH Y402H polymorphism, are at increased risk of developing wet AMD

Vascular endothelial growth factor gene 460 polymorphism is associated with pterygium formation in female patients

[[abstract]]Purpose: Pterygium is composed of proliferating fibrovascular tissue, and its formation and progression require neovascularization. Vascular endothelial growth factor (VEGF) is a specific mitogen for vascular endothelial cells and is essential for neovascularization. Recently, the VEGF-460 polymorphism was reported to be associated with increased VEGF basal promoter activity and with several fibrovascular diseases, such as proliferative diabetic retinopathy, endometriosis, and chronic renal disease. Therefore, this study evaluated the potential association between pterygium formation and VEGF-460 polymorphism. Methods: One hundred twenty-seven pterygium patients and 102 volunteers without pterygium were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to resolve the VEGF-460 genotypes of pterygium patients and normal controls. Results: There were no significant differences between pterygium and control groups in age, sex, and distribution of genotype and allelic frequency of VEGF-460 polymorphism. However, when results were stratified by sex, there were significant differences between female patients and controls in the distribution of genotype and allelic frequency of VEGF-460 polymorphism. Females who carried at least 1 C allele (C/C and C/T genotypes) had about a 2.5-fold increased risk of developing pterygium compared with those who carried the T/T genotype, and there was a significantly higher frequency of C/C and C/T genotypes in younger female patients than in older female patients. There were no differences between male patients and controls in the distribution of genotype and allelic frequency of the VEGF-460 polymorphism. Conclusions: VEGF-460C polymorphism is associated with pterygium formation in female patients. Females who carried the C allele have increased risk of developing pterygium at a younger age

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019.

BACKGROUND: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. METHODS: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). FINDINGS: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1-38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78-0·91) per female living with HIV in 2019, 0·99 male infections (0·91-1·10) for every female infection, and 1·02 male deaths (0·95-1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58-35·43, and a 39·66% decrease in deaths, 36·49-42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05-0·06) and the global incidence-to-mortality ratio was 1·94 (1·76-2·12). No regions met suggested thresholds for progress. INTERPRETATION: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. FUNDING: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at √s = 13 TeV

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” available online at: https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2 .A preprint of this article is available online at arXiv:2311.03261v2 [hep-ex] https://arxiv.org/abs/2311.03261v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-010 (CMS Public Pages)A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp → tH/A → tt¯c and pp → tH/A → tt¯u processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200-1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.SCOAP3

Search for long-lived heavy neutral leptons with lepton flavour conserving or violating decays to a jet and a charged lepton

A preprint version of the article is available at arXiv:2312.07484v3 [hep-ex], https://arxiv.org/abs/2312.07484 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-013 (CMS Public Pages)A search for long-lived heavy neutral leptons (HNLs) is presented, which considers the hadronic final state and coupling scenarios involving all three lepton generations in the 2-20 GeV HNL mass range for the first time. Events comprising two leptons (electrons or muons) and jets are analyzed in a data sample of proton-proton collisions, recorded with the CMS experiment at the CERN LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. A novel jet tagger, based on a deep neural network, has been developed to identify jets from an HNL decay using various features of the jet and its constituent particles. The network output can be used as a powerful discriminating tool to probe a broad range of HNL lifetimes and masses. Contributions from background processes are determined from data. No excess of events in data over the expected background is observed. Upper limits on the HNL production cross section are derived as functions of the HNL mass and the three coupling strengths VℓN to each lepton generation ℓ and presented as exclusion limits in the coupling-mass plane, as lower limits on the HNL lifetime, and on the HNL mass. In this search, the most stringent limit on the coupling strength is obtained for pure muon coupling scenarios; values of |VμN|2 > 5 (4) × 10−7 are excluded for Dirac (Majorana) HNLs with a mass of 10 GeV at a confidence level of 95% that correspond to proper decay lengths of 17 (10) mm.SCOAP3

Spatio-temporal analysis to identify determinants of Oncomelania hupensis infection with Schistosoma japonicum in Jiangsu province, China

With the successful implementation of integrated measures for schistosomiasis japonica control, Jiangsu province has reached low-endemicity status. However, infected Oncomelania hupensis snails could still be found in certain locations along the Yangtze river until 2009, and there is concern that they might spread again, resulting in the possible re-emergence of infections among people and domestic animals alike. In order to establish a robust surveillance system that is able to detect the spread of infected snails at an early stage, sensitive and reliable methods to identify risk factors for the establishment of infected snails need to be developed.; A total of 107 villages reporting the persistent presence of infected snails were selected. Relevant data on the distribution of infected snails, and human and livestock infection status information for the years 2003 to 2008 were collected. Spatio-temporal pattern analysis including spatial autocorrelation, directional distribution and spatial error models were carried out to explore spatial correlations between infected snails and selected explanatory factors.; The area where infected snails were found, as well as their density, decreased significantly between 2003 and 2008. Changes in human and livestock prevalences were less pronounced. Three statistically significant spatial autocorrelations for infected snails were identified. (i) The Moran's I of infected snails increased from 2004 to 2007, with the snail density increasing and the area with infected snails decreasing. (ii) The standard deviations of ellipses around infected snails were decreasing and the central points of the ellipses moved from West to East. (iii) The spatial error models indicated no significant correlation between the density of infected snails and selected risk factors.; We conclude that the contribution of local infection sources including humans and livestock to the distribution of infected snails might be relatively small and that snail control may limit infected snails to increasingly small areas ecologically most suitable for transmission. We provide a method to identify these areas and risk factors for persistent infected snail presence through spatio-temporal analysis, and a suggested framework, which could assist in designing evidence based control strategies for schistosomiasis japonica elimination