Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles.

Drug development for tuberculosis is hindered by the methodological limitations in the definitions of patient outcomes, particularly the slow organism growth and difficulty in obtaining suitable and representative samples throughout the treatment. We developed target product profiles for biomarker assays suitable for early-phase and late-phase clinical drug trials by consulting subject-matter experts on the desirable performance and operational characteristics of such assays for monitoring of tuberculosis treatment in drug trials. Minimal and optimal criteria were defined for scope, intended use, pricing, performance, and operational characteristics of the biomarkers. Early-stage trial assays should accurately quantify the number of viable bacilli, whereas late-stage trial assays should match the number, predict relapse-free cure, and replace culture conversion endpoints. The operational criteria reflect the infrastructure and resources available for drug trials. The effective tools should define the sterilising activity of the drug and lower the probability of treatment failure or relapse in people with tuberculosis. The target product profiles outlined in this Review should guide and de-risk the development of biomarker-based assays suitable for phase 2 and 3 clinical drug trials.

COVID-19 Down Under: Australia's Initial Pandemic Experience.

The following case study aims to provide a broad overview of the initial Australian epidemiological situation of the novel coronavirus disease (COVID-19) pandemic. We provide a case presentation of Australia's current demographic characteristics and an overview of their health care system. The data we present on Australia's COVID-19 situation pertain to the initial wave of the pandemic from January through to 20 April 2020. The results of our study indicate the number of reported COVID-19 cases in Australia reduced, and Australia initially managed to successfully flatten the curve-from an initial doubling time of 3.4 days at the end of March 2020 to a doubling time of 112 days as of 20 April 2020. Using SEIR mathematical modelling, we investigate a scenario assuming infections increase once mitigation measures are lifted. In this case, Australia could experience over 15,000 confirmed cases by the end of April 2020. How Australia's government, health authorities and citizens adjust to preventative measures to reduce the risk of transmission as well as the risk of overburdening Australia's health care system is crucial. Our study presents the initial non-pharmaceutical intervention measures undertaken by the Australian health authorities in efforts to mitigate the rate of infection, and their observed and predicted outcomes. Finally, we conclude our study by presenting the observed and expected economic, social, and political disruptions Australians may endure as a result of the initial phase of the pandemic.

[Research Progress on Pathogenic Genes of Ph-like Acute Lymphoblastic Leukemia--Review].

Abstract　　Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL or BCR-ABL1-like ALL) is a kind of acute leukemia which has the similar gene expression profiles and manifests the biological behavior same to Ph-positive ALL, but lacks the BCR-ABL1 fusion gene. Ph-like ALL was involved in multiple abnormal changes of genomes, activating kinase and cytokine receptor signaling. This review focuses on the progress of classical genetic abnormalities of PH-like ALL in the JAK-STAT signaling, ABL kinase activation, TKI resistance in Ph-like ALL, SH2B3 gene inactivating mutation and IKZF1 gene abnormality. Besides, also summarizes the frontier progress of novel gene mutation (ATF7IP exon 9 fused with PDGFRB exon 11, PDGFRBC843G mutation caused by fusion of exon 11-23 of PDGFRB with exon 1-6 of AGGF1 gene) in recent years.

Singapore's Pandemic Preparedness: An Overview of the First Wave of COVID-19.

A global response to the rapid spread of the 2019 novel coronavirus disease (COVID-19) is imperative in order to reduce mortality and morbidity as well as preventing a country's health system from collapse. Singapore showed exceptional leadership in the containment of the spread of the virus, however through April 2020 the country experienced exponential growth in the number of infections, particularly migrant workers living in dormitories. The following historical case study provides an overview of Singapore's country profile, their healthcare system and the country's non pharmaceutical measures taken to mitigate and contain the spread of COVID-19 in the first few months of the pandemic. We explore the impact COVID-19 had on Singapore's economy at that time and the implications of the resultant social and political disruptions. We conclude our study by using mathematical modelling to explore confirmed COVID-19 cases in Singapore's local community and those living in dormitories and use this data to forecast the progression of the epidemic in Singapore given the non-pharmaceutical interventions in place at that time. Our results indicate the COVID-19 outbreak in Singapore increased 3-fold the initial doubling rate of 22.5 days in the first 2 months of the outbreak to 6.7 days in the 5th month; We note a faster doubling rate of 4.9 days for those living in dormitories compared to a doubling rate of 13.5 days for the rest of the community.