Design and Development of Vibration Testing Fixtures

This paper deals with the Design of Vibration Testing Fixtures for Random Vibration loads as specified by the MIL 810 military standards. Following selection of the right material and configuration of the fixtures, CAD models are generated and numerically checked for natural frequencies and mode shapes using Finite Element Analysis. Based on these results, the response of the fixtures to the MIL 810 standard Random Vibration profile input is measured using Finite Element Analysis and the transmissibility is calculated.Finally, the fixture is tested experimentally for to the MIL 810 standard Random Vibration profile input and based on these values; transmissibility of the fixture is computed. The experimental result is compared to the Finite Element results and thus, found that the fixture can be used for testing missile packages at the Defense Research and Development Laboratory (DRDL), Hyderabad

Study of Liquid-Crystalline Behaviour of Aliphatic-Aromatic Polyamides Derived from Castor Oil Based Dimer Acid by DSC

ABSTRACT Aliphatic-aromatic polyamide of castor oil based dimer acid (DA) with pphenylenediamine (PPD) was characterized by differential scanning calorimetry. Thispolyamide exhibited interesting liquid-crystalline behavior which was quite unexpectedlooked at the structure of dimer acid moiety

Supplemental Oxygen Protects Heart Against Acute Myocardial Infarction

Myocardial infarction (MI), which occurs often due to acute ischemia followed by reflow, is associated with irreversible loss (death) of cardiomyocytes. If left untreated, MI will lead to progressive loss of viable cardiomyocytes, deterioration of cardiac function, and congestive heart failure. While supplemental oxygen therapy has long been in practice to treat acute MI, there has not been a clear scientific basis for the observed beneficial effects. Further, there is no rationale for the amount or duration of administration of supplemental oxygenation for effective therapy. The goal of the present study was to determine an optimum oxygenation protocol that can be clinically applicable for treating acute MI. Using EPR oximetry, we studied the effect of exposure to supplemental oxygen cycling (OxCy) administered by inhalation of 21–100% oxygen for brief periods (15–90 min), daily for 5 days, using a rat model of acute MI. Myocardial oxygen tension (pO2), cardiac function and pro-survival/apoptotic signaling molecules were used as markers of treatment outcome. OxCy resulted in a significant reduction of infarct size and improvement of cardiac function. An optimal condition of 30-min OxCy with 95% oxygen + 5% CO2 under normobaric conditions was found to be effective for cardioprotection

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.United States. Dept. of Defense (contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and Harvar

Common variants in CLDN2 and MORC4 genes confer disease susceptibility in patients with chronic pancreatitis

A recent Genome-wide Association Study (GWAS) identified association with variants in X-linked CLDN2 and MORC4 and PRSS1-PRSS2 loci with Chronic Pancreatitis (CP) in North American patients of European ancestry. We selected 9 variants from the reported GWAS and replicated the association with CP in Indian patients by genotyping 1807 unrelated Indians of Indo-European ethnicity, including 519 patients with CP and 1288 controls. The etiology of CP was idiopathic in 83.62% and alcoholic in 16.38% of 519 patients. Our study confirmed a significant association of 2 variants in CLDN2 gene (rs4409525—OR 1.71, P = 1.38 x 10-09; rs12008279—OR 1.56, P = 1.53 x 10-04) and 2 variants in MORC4 gene (rs12688220—OR 1.72, P = 9.20 x 10-09; rs6622126—OR 1.75, P = 4.04x10-05) in Indian patients with CP. We also found significant association at PRSS1-PRSS2 locus (OR 0.60; P = 9.92 x 10-06) and SAMD12-TNFRSF11B (OR 0.49, 95% CI [0.31–0.78], P = 0.0027). A variant in the gene MORC4 (rs12688220) showed significant interaction with alcohol (OR for homozygous and heterozygous risk allele -14.62 and 1.51 respectively, P = 0.0068) suggesting gene-environment interaction. A combined analysis of the genes CLDN2 and MORC4 based on an effective risk allele score revealed a higher percentage of individuals homozygous for the risk allele in CP cases with 5.09 fold enhanced risk in individuals with 7 or more effective risk alleles compared with individuals with 3 or less risk alleles (P = 1.88 x 10-14). Genetic variants in CLDN2 and MORC4 genes were associated with CP in Indian patients

Rapid assessment of facilitators and barriers related to the acceptance, challenges and community perception of daily regimen for treating tuberculosis in India

Introduction: The Revised National Tuberculosis Control Program (RNTCP) is the largest tuberculosis (TB) control program in the world based on Directly Observed Treatment Short-Course (DOTS) strategy. Globally, most countries have been using a daily regimen and in India a shift towards a daily regimen for TB treatment has already begun. The daily strategy is known to improve program coverage along with compliance. Such strategic shifts have both management and operational implications. We undertook a rapid assessment to understand the facilitators and barriers in adopting the daily regimen for TB treatment in three Indian states. Methods: In-depth interviews were planned across six districts of three purposively selected states of Maharashtra, Bihar and Sikkim, among health system personnel at various levels to identify their perspectives on adoption of a daily regimen for TB. These districts were sampled on the basis of TB notification rates. Thematic analysis of the qualitative data was undertaken. Results: 62 respondents were interviewed from these 6 districts. During the analysis, it was observed that an easily accessible, patient-centred and personalized outreach is an enabling factor for adherence to treatment. Lack of transportation facilities, out-of-pocket expenses and loss of wages for accessing DOTS at institutions are major identified barriers for treatment adherence at individual level. At program level, lack of trained service providers, poor administration of treatment protocols and inadequate supervision by health care providers and program managers are key factors that influence program outcomes. Conclusion: A major observation that emerged from the interviews is that the key to achieve a relapse-free cure is ensuring that a patient receives all doses of the prescribed treatment regimen. However, switching to a daily regimen makes adherence difficult and thus new strategies are needed for its implementation at patient and health provider levels. Most stakeholders appreciate the reasons for switching to a daily regimen. The stakeholders recognised the efforts of the Ministry of Health & Family Welfare (MoHFW) in spearheading the program. Strategies like the 99 DOTS call-centre approach may also further ensure treatment adherence

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice