HLA‐associated relative risks of type 1 (insulin‐dependent) diabetes mellitus were analysed in population‐based Swedish patients and controls aged 0–34 years. The age dependence of HLA‐associated relative risks was assessed by likelihood ratio tests of regression parameters in separate logistic regression models for each HLA category. The analyses demonstrated an attenuation with increasing age at onset in the relative risk for the positively associated DQB1*0201‐A1*0502/B1*0302‐A1*0301 (DQ2/8) genotype (P=0.02) and the negatively associated DQB1*0602‐A1*0102 (DQ6.2) haplotype (P=0.004). At birth, DQ6.2‐positive individuals had an estimated relative risk of 0.03, but this increased to 1.1 at age 35 years. Relative risks for individuals with DQ genotype 8/8 or 8/X or DQ genotype 2/2 or 2/X, where X is any DQ haplotype other than 2, 8 or 6.2, were not significantly age‐dependent. An exploratory analysis of DQ haplotypes other than 2, 8 and 6.2 suggested that the risk of type 1 diabetes increases with age for DQB1*0604‐A1*0102 (DQ6.4) and that the peak risk for the negatively associated DQB1*0301‐A1*0501 haplotype is at age 18 years. There was also weak evidence that the risk for DQB1*0303‐A1*0301 (DQ9), which has a positive association in the Japanese population, may decrease with age. We speculate that HLA‐DQ alleles have a significant effect on the rate of beta cell destruction, which is accelerated in DQ2/8‐positive individuals and inhibited, but not completely blocked, in DQ6.2‐positive individuals.
The outbreak of the COVID-19 pandemic has had a major impact on the health and well-being of people with its long-term effect on lung function and oxygen uptake. In this work, we present a unique approach to augment the phosphorescence signal from phosphorescent gold(III) complexes based on a surface plasmon-coupled emission platform and use it for designing a ratiometric sensor with high sensitivity and ultrafast response time for monitoring oxygen uptake in SARS-CoV-2-recovered patients. Two monocyclometalated Au(III) complexes, one having exclusively phosphorescence emission (λPL = 578 nm) and the other having dual emission, fluorescence (λPL = 417 nm) and phosphorescence (λPL = 579 nm), were studied using the surface plasmon-coupled dual emission (SPCDE) platform for the first time, which showed 27-fold and 17-fold enhancements, respectively. The latter complex having the dual emission was then used for the fabrication of a ratiometric sensor for studying the oxygen quenching of phosphorescence emission with the fluorescence emission acting as an internal standard. Low-cost poly (methyl methacrylate) (PMMA) and biodegradable wood were used to fabricate the microfluidic chips for oxygen monitoring. The sensor showed a high sensitivity with a limit of detection ∼ 0.1%. Furthermore, real-time oxygen sensing was carried out and the response time of the sensor was calculated to be ∼0.2 s. The sensor chip was used for monitoring the oxygen uptake in SARS-CoV-2-recovered study participants, to assess their lung function post the viral infection.
In this study, we develop a mathematical model incorporating age-specific transmission dynamics of COVID-19 to evaluate the role of vaccination and treatment strategies in reducing the size of COVID-19 burden. Initially, we establish the positivity and boundedness of the solutions of the non controlled model and calculate the basic reproduction number and do the stability analysis. We then formulate an optimal control problem with vaccination and treatment as control variables and study the same. Pontryagin’s Minimum Principle is used to obtain the optimal vaccination and treatment rates. Optimal vaccination and treatment policies are analysed for different values of the weight constant associated with the cost of vaccination and different efficacy levels of vaccine. Findings from these suggested that the combined strategies (vaccination and treatment) worked best in minimizing the infection and disease induced mortality. In order to reduce COVID-19 infection and COVID-19 induced deaths to maximum, it was observed that optimal control strategy should be prioritized to the population with age greater than 40 years. Varying the cost of vaccination it was found that sufficient implementation of vaccines (more than 77 %) reduces the size of COVID-19 infections and number of deaths. The infection curves varying the efficacies of the vaccines against infection were also analysed and it was found that higher efficacy of the vaccine resulted in lesser number of infections and COVID induced deaths. The findings would help policymakers to plan effective strategies to contain the size of the COVID-19 pandemic.
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