Rheumatoid arthritis as underlying cause of death in 31 countries, 1987-2011: Trend analysis of WHO mortality database

Objective To examine trends in rheumatoid arthritis (RA) as an underlying cause of death (UCD) in 31 countries across the globe during 1987-2011. Methods Data on mortality and population were collected from the World Health Organization mortality database and the United Nations. Age-standardized mortality rates (ASMR) were calculated by means of direct standardization. We applied joinpoint regression analysis for trend analysis. Between-country disparities were examined using between-country variance, and Gini coefficient. Due to low numbers of deaths, we smoothed our ASMR using a three-year moving average. The changes in number of RA deaths between 1987 and 2011 were decomposed using two counterfactual scenarios. Results The absolute number of deaths with RA registered as UCD declined from 9281 (0.12% of all-cause deaths) in 1987 to 8428 in 2011 (0.09% of all-cause deaths). The mean ASMR declined from 7.1/million person-years in 1987-89 to 3.7 in 2009-11 (48.2% reduction). Reduction of 25% or more in ASMR occurred in 21 countries while a corresponding increase was observed in 3 countries. There was a persistent reduction in RA mortality and, on average, the ASMR declined by 3.0% per year. The absolute and relative between-country disparities declined over the study period.CONCLUSION: Mortality rates attributable to RA have declined globally. However, there were substantial between-country disparities in RA mortality, though the disparities decreased over time. Population aging combined with fall in RA mortality may lead to an increase in the economic burden of disease that should be taken into consideration in policy-making. This article is protected by copyright. All rights reserved

Near-field optical spectroscopy and microscopy of self-assembled GaN∕AlN nanostructures

The spatial distribution and emission properties of small clusters of GaNquantum dots in an AlN matrix are studied using high-resolution electron and optical microscopy. High-resolution transmission electron microscopy reveals near vertical correlation among the GaNdots due to a sufficiently thin AlN spacer layer thickness, which allows strain induced stacking. Scanning electron and atomic force microscopy show lateral coupling due to a surface roughness of ∼50–60nm. Near-field photoluminescence in the illumination mode (both spatially and spectrally resolved) at 10K revealed emission from individual dots, which exhibits size distribution of GaNdots from localized sites in the stacked nanostructure. Strong spatial localization of the excitons is observed in GaNquantum dots formed at the tip of self-assembled hexagonal pyramid shapes with six [101¯1¯] facets

Absolute photoionization cross section measurements of the Kr I-isoelectronic sequence

Photoionization spectra have been recorded in the 4s, 4p and 3d resonance regions for the Kr Iisoelectronic sequence using both the dual laser produced plasma technique (at DCU) to produce photoabsorption spectra, and the merged ion beam and synchrotron radiation technique (at ASTRID) to measure absolute photoionization cross sections. Profile parameters are compared for the 4s − np resonances of Rb+ and Sr2+. Many new 4p " ns, md transitions are identified with the aid of Hartree-Fock calculations, and consistent quantum defects are observed for the various ns and md Rydberg series. Absolute single and double photoionization cross sections recorded in the 3d region for Rb+ and Sr2+ ions show preferential decay via double photoionization. This is only the second report where both the DLP technique and the merged beam technique have been used simultaneously to record photoionization spectra, and the advantages of both techniques (i.e. better resolution in the case of DLP and values for absolute photoionization cross sections in the case of the merged beam technique) are highlighted

Vacuum-ultraviolet photoabsorption imaging system for laser plasma plume diagnostics

We describe a recently designed and constructed system based on a 1 m normal incidence vacuum monochromator with corrected (toroidal) optics that produces a wavelength tuneable and collimated vacuum-ultraviolet (VUV) (λ=30–100 nm) beam. The VUV continuum source is a laser-generated gold plasma. The primary function of the system is the measurement of time resolved “images” or spatial distributions of photoabsorption/photoionization in expanding laser plasma plumes. This is achieved by passing the beam through the sample of interest (in our case a second synchronised plasma) and recording the “footprint” of the attenuated beam on a charge coupled device. Using this VUV photoabsorption imaging or “shadowgraphy” technique we track and extract column density distributions in expanding plasma plumes. We can also measure the plume front velocity. We have characterized the system, particularly in relation to spectral and spatial resolution and the experimental results meet very well the expectations from ray tracing done at the design phase. We present first photoabsorption images and column density distributions of laser produced Ca plumes from the system

Molecular Epidemiology of HIV-1 Subtypes in India: Origin and Evolutionary History of the Predominant Subtype C

This thesis describes the translational genomics of HIV-1subtype C in India from its origin to therapeutic response with the aim to improve our knowledge for better therapeutic and preventive strategies to combat HIV/AIDS. In a systemic approach, we identified the molecular phylogeny of HIV-1 subtypes circulating in India and the time to most recent common ancestors (tMRCA) of predominant HIV-1 subtype C strains. Additionally, this thesis also studied drug resistance mutations in children, adolescents and adults, the role of host factors in evolution of drug resistance, and population dynamics of viremia and viral co-receptor tropism in perinatal transmission. Finally, the long term therapeutic responses on Indian national first-line antiretroviral therapy were also studied. In Paper I, we reported an increase in the HIV-1 recombinant forms in the HIV-1 epidemiology using a robust subtyping methodology. While the study confirmed HIV- 1 subtype C as a dominant subtype, its origin was dated back to the early 1970s from a single or few genetically related strains from South Africa, whereafter, it has evolved independently. In Paper II, the lethal hypermutations due to the activity of human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (hA3G) was significantly associated with antiretroviral therapy (ART) failure in Indian HIV-1 subtype C patients. The presence of M184I and M230I mutations were observed due to the editing of hA3G in the proviral compartment but stop codons were also found in the open reading frames and the same drug resistance mutations were absent in plasma virus. Therefore, it is unlikely that the viral variants which exhibit hypermutated sequences and M184I and/or M230I will mature and expand in vivo and hence are unlikely to have any clinical significance. The high concordance of drug resistance genotyping in the plasma and proviral compartments in therapy-naïve patients, gives weight to the idea of using whole blood for surveillance of drug resistance mutations which precludes logistic challenges of cold chain transport. In Papers III and IV, we identified a substantial proportion of HIV-1 subtype C perinatally-infected older children who had a high burden of plasma viremia but also had high CD4+ T-cell counts. In addition, older children with HIV-1 subtype C infection presented a high prevalence of predicted X4 and R5/X4 tropic strains which indicates that HIV-1 subtype C strains required longer duration of infection and greater disease progression to co-receptor transition from R5- to X4-tropic strains (IV). Our studies also indicate that transmitted drug resistance is low among Indian HIV-1 infected children, adolescents (III) and adults (II). In Paper V, in a longitudinal cohort study, a good long-term response to the Indian national first-line therapy for a median of nearly four years with 2.8% viral failure, indicating the overall success of the Indian ART program. Our study also showed that three immunologically well patients with virological rebound and major viral drug resistance mutations (M184V, K103N and Y181C) during one study visit had undetectable viral load at their next visit. These findings suggest that use of multiple parameters like patients’ immunological (CD4+ T-cell count), virological (viral load) and drug resistance data should all be used to optimize the treatment switch to second line therapy. In conclusion, this translational genomics study enhances our knowledge about the HIV-1 subtype C strains circulating in India which are genetically distinct from prototype African subtype C strains. Considerably more research using appropriate models need to be performed to understand the phenotypic and biological characteristics of these strains to guide efficient disease intervention and management strategies

Examining sex differences in knee pain: the Multicenter Osteoarthritis Study

SummaryObjectiveTo determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA).Design and methodsA cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren–Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA).ResultsWomen reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21–0.31, P < 0.0001–0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16–0.22, P < 0.0001–0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10–0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32–0.52, P < 0.0001–0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45–0.62, P = 0.0006–0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31–0.57, P = 0.0013–0.0361). Results using WOMAC were similar.ConclusionsWomen reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences