Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation ...within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.
In 2005 and 2006, outbreaks of Fusarium keratitis associated with soft contact lens use occurred in multiple U.S. states and Puerto Rico. A case-control study conducted by the Centers for Disease ...Control and Prevention (CDC) showed a significant association between infections and the use of one particular brand of lens solution. To characterize the full spectrum of the causal agents involved and their potential sources, partial DNA sequences from three loci (RPB2, EF-1α, and nuclear ribosomal rRNA) totaling 3.48 kb were obtained from 91 corneal and 100 isolates from the patient's environment (e.g., contact lens and lens cases). We also sequenced a 1.8-kb region encoding the RNA polymerase II second largest subunit (RPB2) from 126 additional pathogenic isolates to better understand how the keratitis outbreak isolates fit within the full phylogenetic spectrum of clinically important fusaria. These analyses resulted in the most robust phylogenetic framework for Fusarium to date. In addition, RPB2 nucleotide variation within a 72-isolate panel was used to design 34 allele-specific probes to identify representatives of all medically important species complexes and 10 of the most important human pathogenic Fusarium in a single-well diagnostic assay, using flow cytometry and fluorescent microsphere technology. The multilocus data revealed that one haplotype from each of the three most common species comprised 55% of CDC's corneal and environmental isolates and that the corneal isolates comprised 29 haplotypes distributed among 16 species. The high degree of phylogenetic diversity represented among the corneal isolates is consistent with multiple sources of contamination.
To confirm in a cohort recruited in 1999-2001 our finding in a cohort recruited in 1992-1994 relating type 2 diabetes (T2D) to late-onset Alzheimer's disease (LOAD).
Participants were 1,488 persons ...aged 65 years and older without dementia at baseline from New York City. T2D was ascertained by self-report. Dementia and LOAD were ascertained by standard research procedures. Proportional hazard regression was used for analyses relating T2D and LOAD.
The prevalence of T2D was 17%. There were 161 cases of dementia and 149 cases of LOAD. T2D was related to dementia (hazard ratio = 1.7; 95% confidence interval = 1.4-2.9) and LOAD (1.6; 1.0-2.6) after adjustment for age, sex, education, ethnic group and apolipoprotein E ε4. This association was weaker when only AD - excluding cases of mixed dementia - was considered (hazard ratio = 1.3; 95% confidence interval = 0.8-2.2).
T2D is associated with LOAD. Cerebrovascular disease may be an important mediator.
Background. Compounding pharmacies often prepare parenteral nutrition (PN) and must adhere to rigorous standards to avoid contamination of the sterile preparation. In March 2011, Serratia marcescens ...bloodstream infections (BSIs) were identified in 5 patients receiving PN from a single compounding pharmacy. An investigation was conducted to identify potential sources of contamination and prevent further infections. Methods. Cases were defined as S. marcescens BSIs in patients receiving PN from the pharmacy between January and March 2011. We reviewed case patients' clinical records, evaluated pharmacy compounding practices, and obtained epidemiologically directed environmental cultures. Molecular relatedness of available Serratia isolates was determined by pulsed-field gel electrophoresis (PFGE). Results. Nineteen case patients were identified; 9 died. The attack rate for patients receiving PN in March was 35%. No case patients were younger than 18 years. In October 2010, the pharmacy began compounding and filtersterilizing amino acid solution for adult PN using nonsterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. S. marcescens was identified from a pharmacy water faucet, mixing container, and opened amino acid powder. These isolates were indistinguishable from the outbreak strain by PFGE. Conclusions. Compounding of nonsterile amino acid components of PN was initiated due to a manufacturer shortage. Failure to follow recommended compounding standards contributed to an outbreak of S. marcescens BSIs. Improved adherence to sterile compounding standards, critical examination of standards for sterile compounding from nonsterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks.
Changes to the efficiency and integrity of swallowing mechanisms are inevitable in Parkinson disease (PD); however, it remains unclear how many people with PD are at risk of dysphagia. The aim of ...this study was to establish the frequency of impaired swallowing in people with PD and the relationship between swallowing performance and indicators of disease progression.
A community-based and hospital-based cohort of 137 individuals with PD were asked to drink 150 ml of water as quickly as possible while in an 'off drug' state.
Thirty-one (23%) patients could not completely drink the full 150 ml. Swallowing rate (ml/sec) fell to more than 1 SD below published norms for 115 (84%) patients and to more than 2SD below for 44 (32%) individuals. There were moderate correlations between rate of swallowing and disease severity, depression and cognition, but not between swallowing speed and disease duration. There was poor correlation between subjective reports of dysphagia and performance on the water swallow test.
Swallowing problems are frequent in PD. Self-report of 'no difficulty' is not a reliable indicator of swallowing ability. Studies employing more-objective assessment of aspiration risk to compare with water swallow test performance are advocated.
Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime ...cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups.
A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L.
Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 95% CI £282,811 to £299,451 by D'Amico and £292,736 95% CI £284,074 to £297,719 by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 95% CI £258,630 to £285,474 by D'Amico and £271,933 95% CI £237,864 to £287,784 by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 95% CI £280,781 to £296,281) for men younger than 65 and radical radiotherapy (£201,311 95% CI £195,161 to £205,049) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings.
Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model.
Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).
Here, we present a measurement of gravitational lensing over 1500deg2 of the Southern sky using SPT-3G temperature data at 95 GHz and 150 GHz taken in 2018. The lensing amplitude relative to a ...fiducial Planck 2018 Lambda cold dark matter ( Λ CDM ) cosmology is found to be 1.020±0.060 , excluding instrumental and astrophysical systematic uncertainties. We conduct extensive systematic and null tests to check the robustness of the lensing measurements, and report a minimum-variance combined lensing power spectrum over angular multipoles of 50<L<2000 , which we use to constrain cosmological models. When analyzed alone and jointly with primary cosmic microwave background (CMB) spectra within the Λ CDM model, our lensing amplitude measurements are consistent with measurements from SPT-SZ, SPTpol, ACT, and Planck. Incorporating loose priors on the baryon density and other parameters including uncertainties on a foreground bias template, we obtain a 1σ constraint on σ8 Ω m 0.25=0.595±0.026 using the SPT-3G 2018 lensing data alone, where σ8 is a common measure of the amplitude of structure today and Ω m is the matter density parameter. Combining SPT-3G 2018 lensing measurements with baryon acoustic oscillation (BAO) data, we derive parameter constraints of σ8=0.810±0.033 , S8≡σ8 ( Ω m /0.3 ) 0.5= 0.836±0.039 , and Hubble constant H0=68.8-1.6+1.3km s -1Mpc-1 . Our preferred S8 value is higher by 1.6 to 1.8σ compared to cosmic shear measurements from DES-Y3, HSC-Y3, and KiDS-1000 at lower redshift and smaller scales. We combine our lensing data with CMB anisotropy measurements from both SPT-3G and Planck to constrain extensions of Λ CDM . Using CMB anisotropy and lensing measurements from SPT-3G only, we provide independent constraints on the spatial curvature of Ω K=0.014-0.026+0.023 (95% C.L.) and the dark energy density of Ω Λ =0.722-0.026+0.031 (68% C.L.). When combining SPT-3G lensing data with SPT-3G CMB anisotropy and BAO data, we find an upper limit on the sum of the neutrino masses of Σmν<0.30eV (95% C.L.). Due to the diferent combination of angular scales and sky area, this lensing analysis provides an independent check on lensing measurements by ACT and Planck.
This paper reviews ultrasound segmentation methods, in a broad sense, focusing on techniques developed for medical B-mode ultrasound images. First, we present a review of articles by clinical ...application to highlight the approaches that have been investigated and degree of validation that has been done in different clinical domains. Then, we present a classification of methodology in terms of use of prior information. We conclude by selecting ten papers which have presented original ideas that have demonstrated particular clinical usefulness or potential specific to the ultrasound segmentation problem
PDF
