Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections

Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with subcutaneous protein immunization to improve protection against influenza A virus infections using a mouse model. We found enhanced long-term protection with ecCpG compared to scCpG as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with influenza A virus infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against influenza A virus infection

Evaluation of Cognitive and Functional Status Among Survivors of Sepsis in a Tertiary Care Hospital in South India (CAFDASS)

INTRODUCTION: Sepsis is a life-threatening state and continues to be a major challenge for health care institutions. Sepsis syndrome is a frequent cause of intensive care admissions and may even develop in patients admitted to the ICU for other reasons. There has been decrease in in-hospital mortality rate of patients admitted with sepsis from 27.8 percent during the period 1979 through 1984, to 17.9 percent during the period 1995 through 2000. Thus, despite favorable mortality outcomes, an accurate reflection of treatment success of a sepsis survivor depends on the person’s ability to get back to normal life and activity. This not only depends on his physical function but also mental alertness and cognitive capabilities. OBJECTIVES: Primary objective of this study is to measure the change in cognitive function and functional ability in survivors of Sepsis up to 3 months after discharge. Secondary objective of this study is to compare outcomes in both groups and identify factors which may have contributed to poorer outcome. METHODS: This was a prospective observational cohort study of patients admitted and discharged with a diagnosis of sepsis and survivors were followed up 3 months after discharge. Baseline physical and cognitive evaluation was assessed prior to discharge using WHODAS 2 and the RetroBCRS questionnaires and was reassessed withWHODAS-2 and BCRS questionnaire at 3 months follow up. 130 patients were included in the study and statistical analysis was done using paired t-test to evaluate cognitive and physical decline in sepsis survivors and bivariate analyses was done to assess variables that resulted in poorer outcome. RESULTS: Study showed significant decline in physical and cognitive function at 3 months follow up in patients following discharge, with 31.8% and 27.2% increase in scores of assessments as compared to baseline values respectively. Age above 60 years, underlying chronic obstructive airway disease, SOFA score of more than 2, moderate or higher grade of acute respiratory distress syndrome and developing in hospital critical illness polyneuropathy and bed sores were variables which were associated with greater decline in physical and cognitive functioning of patients at 3 months follow up

Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice

Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Rα, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα449F). Thymic precursors were reduced in number in IL-7Rα449F mice, but in marked contrast to IL-7Rα−/− knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Rα449F mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449 independent and insufficient for IL-7–mediated maintenance of CD8 memory

Photometric Catalogue of Quasars and Other Point Sources in the Sloan Digital Sky Survey

We present a catalogue of about 6 million unresolved photometric detections in the Sloan Digital Sky Survey Seventh Data Release classifying them into stars, galaxies and quasars. We use a machine learning classifier trained on a subset of spectroscopically confirmed objects from 14th to 22nd magnitude in the SDSS {\it i}-band. Our catalogue consists of 2,430,625 quasars, 3,544,036 stars and 63,586 unresolved galaxies from 14th to 24th magnitude in the SDSS {\it i}-band. Our algorithm recovers 99.96% of spectroscopically confirmed quasars and 99.51% of stars to i $\sim$21.3 in the colour window that we study. The level of contamination due to data artefacts for objects beyond $i=21.3$ is highly uncertain and all mention of completeness and contamination in the paper are valid only for objects brighter than this magnitude. However, a comparison of the predicted number of quasars with the theoretical number counts shows reasonable agreement.Comment: 16 pages, Ref. No. MN-10-2382-MJ.R2, accepted for publication in MNRAS Main Journal, April 201

Automated Galaxy Morphology: A Fourier Approach

We use automated surface photometry and pattern classification techniques to morphologically classify galaxies. The two-dimensional light distribution of a galaxy is reconstructed using Fourier series fits to azimuthal profiles computed in concentric elliptical annuli centered on the galaxy. Both the phase and amplitude of each Fourier component have been studied as a function of radial bin number for a large collection of galaxy images using principal component analysis. We find that up to 90 percent of the variance in many of these Fourier profiles may be characterized in as few as 3 principal components and their use substantially reduces the dimensionality of the classification problem. We use supervised learning methods in the form of artificial neural networks to train galaxy classifiers that detect morphological bars at the 85-90 percent confidence level and can identify the Hubble type with a 1-sigma scatter of 1.5 steps on the 16-step stage axis of the revised Hubble system. Finally, we systematically characterize the adverse effects of decreasing resolution and S/N on the quality of morphological information predicted by these classifiers.Comment: Accepted to Astrophysical Journal, 43 pages, 12 figure

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome