An Information Theoretic, Microfluidic-Based Single Cell Analysis Permits Identification of Subpopulations among Putatively Homogeneous Stem Cells

An incomplete understanding of the nature of heterogeneity within stem cell populations remains a major impediment to the development of clinically effective cell-based therapies. Transcriptional events within a single cell are inherently stochastic and can produce tremendous variability, even among genetically identical cells. It remains unclear how mammalian cellular systems overcome this intrinsic noisiness of gene expression to produce consequential variations in function, and what impact this has on the biologic and clinical relevance of highly ‘purified’ cell subgroups. To address these questions, we have developed a novel method combining microfluidic-based single cell analysis and information theory to characterize and predict transcriptional programs across hundreds of individual cells. Using this technique, we demonstrate that multiple subpopulations exist within a well-studied and putatively homogeneous stem cell population, murine long-term hematopoietic stem cells (LT-HSCs). These subgroups are defined by nonrandom patterns that are distinguishable from noise and are consistent with known functional properties of these cells. We anticipate that this analytic framework can also be applied to other cell types to elucidate the relationship between transcriptional and phenotypic variation

Estimates of number of children and adolescents without access to surgical care.

OBJECTIVE: To estimate how many children and adolescent worldwide do not have access to surgical care. METHODS: We estimated the number of children and adolescents younger than 19 years worldwide without access to safe, affordable and timely surgical care, by using population data for 2017 from the United Nations and international data on surgical access in 2015. We categorized countries by World Bank country income group and obtained the proportion of the population with no access to surgical care from a study by the Lancet Commission on Global Surgery. FINDINGS: An estimated 1.7 billion (95% credible interval: 1.6-1.8) children and adolescents worldwide did not have access to surgical care in 2017. Lack of access occurred overwhelmingly in low- and middle-income countries where children and adolescents make up a disproportionately large fraction of the population. Moreover, 453 million children younger than 5 years did not have access to basic life-saving surgical care. According to Lancet Commission on Global Surgery criteria, less than 3% of the paediatric population in low-income countries and less than 8% in lower-middle-income countries had access to surgical care. CONCLUSION: There were substantial gaps in the availability of surgical services for children worldwide, particularly in low- and middle-income countries. Future research should focus on developing specific measures for assessing paediatric surgical access, delivery and outcomes and on clarifying how limited surgical access in the poorest parts of the world affects child health, especially mortality in children younger than 5 years

Extremes of age are associated with differences in the expression of selected pattern recognition receptor genes and ACE2, the receptor for SARS-CoV-2: implications for the epidemiology of COVID-19 disease.

BackgroundOlder aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes.MethodsUsing a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2.ResultsExtremes of age are associated with increased expression of selected PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins.ConclusionsAssessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels

Estimates of Treatable Deaths Within the First 20 Years of Life from Scaling Up Surgical Care at First-Level Hospitals in Low- and Middle-Income Countries.

BACKGROUND: Surgical care is an important, yet often neglected component of child health in low- and middle-income countries (LMICs). This study examines the potential impact of scaling up surgical care at first-level hospitals in LMICs within the first 20 years of life. METHODS: Epidemiological data from the global burden of disease 2019 Study and a counterfactual method developed for the disease control priorities; 3rd Edition were used to estimate the number of treatable deaths in the under 20 year age group if surgical care could be scaled up at first-level hospitals. Our model included three digestive diseases, four maternal and neonatal conditions, and seven common traumatic injuries. RESULTS: An estimated 314,609 (95% UI, 239,619-402,005) deaths per year in the under 20 year age group could be averted if surgical care were scaled up at first-level hospitals in LMICs. Most of the treatable deaths are in the under-5 year age group (80.9%) and relates to improved obstetrical care and its effect on reducing neonatal encephalopathy due to birth asphyxia and trauma. Injuries are the leading cause of treatable deaths after age 5 years. Sixty-one percent of the treatable deaths occur in lower middle-income countries. Overall, scaling up surgical care at first-level hospitals could avert 5·1% of the total deaths in children and adolescents under 20 years of age in LMICs per year. CONCLUSIONS: Improving the capacity of surgical services at first-level hospitals in LMICs has the potential to avert many deaths within the first 20 years of life

Estimates of Treatable Deaths Within the First 20 Years of Life from Scaling Up Surgical Care at First-Level Hospitals in Low- and Middle-Income Countries.

BackgroundSurgical care is an important, yet often neglected component of child health in low- and middle-income countries (LMICs). This study examines the potential impact of scaling up surgical care at first-level hospitals in LMICs within the first 20 years of life.MethodsEpidemiological data from the global burden of disease 2019 Study and a counterfactual method developed for the disease control priorities; 3rd Edition were used to estimate the number of treatable deaths in the under 20 year age group if surgical care could be scaled up at first-level hospitals. Our model included three digestive diseases, four maternal and neonatal conditions, and seven common traumatic injuries.ResultsAn estimated 314,609 (95% UI, 239,619-402,005) deaths per year in the under 20 year age group could be averted if surgical care were scaled up at first-level hospitals in LMICs. Most of the treatable deaths are in the under-5 year age group (80.9%) and relates to improved obstetrical care and its effect on reducing neonatal encephalopathy due to birth asphyxia and trauma. Injuries are the leading cause of treatable deaths after age 5 years. Sixty-one percent of the treatable deaths occur in lower middle-income countries. Overall, scaling up surgical care at first-level hospitals could avert 5·1% of the total deaths in children and adolescents under 20 years of age in LMICs per year.ConclusionsImproving the capacity of surgical services at first-level hospitals in LMICs has the potential to avert many deaths within the first 20 years of life