Mitochondrial variant enrichment from high-throughput single-cell RNA-seq resolves clonal populations

Reconstructing lineage relationships in complex tissues can reveal mechanisms underlying development and disease. Recent methods combine single-cell transcriptomics with mitochondrial DNA variant detection to establish lineage relationships in primary human cells, but are not scalable to interrogate complex tissues. To overcome this limitation, here we develop a technology for high-confidence detection of mitochondrial mutations from high-throughput single-cell RNA-sequencing. We use the new method to identify skewed immune cell expansions in primary human clonal hematopoiesis

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing >= 60 g/d with = 25 g/d with Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4 (62.3 (55.1�70.8) million) to 6.4 (58.3 (47.6�70.7) million), but is predicted to remain above the World Health Organization�s Global Nutrition Target of <5 in over half of LMICs by 2025. Prevalence of overweight increased from 5.2 (30 (22.8�38.5) million) in 2000 to 6.0 (55.5 (44.8�67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Author Correction: Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017 (Nature Medicine, (2020), 26, 5, (750-759), 10.1038/s41591-020-0807-6)

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s)

Risk: the ethics of a creative curriculum

Regulations in Higher Education, e.g. subject benchmarks, the qualifications framework (QAA) and the CATs system. play an important role in ensuring the quality of educational standards. They assure students that each CAT point they acquire has value and that ‘graduateness’ is of equal worth regardless of location or subject. In addition, a growing consumer ethos and the introduction of fees encourage students and their financial supporters to view Higher Education as a product. Whilst the student’s own motivation and input is still important, Universities are expected to deliver learning opportunities that maximise the likelihood of successful completion. Innovation and creativity do not sit comfortably within this paradigm. Delivering educational experiences where the outcome is uncertain, or where there are less clear and objective methods for measuring student achievement, presents a risk to educational standards and to student experience. This paper seeks to explore the relationship between risk, ethics and the introduction of creativity and innovation into the curriculum. It is generally accepted that university education should be challenging – encouraging the development of an enquiring mind that does not accept things at face value and the confidence to argue from an alterative viewpoint. These aspirations are related to notions of autonomy as espoused by J S Mill (1859) and others. Nurturing such attributes means respecting the autonomy of the student to make decisions, stand by them and to take responsibility for risk taking and its outcomes. It also means allowing lecturers to design courses that permit change, diversity of practice and risk taking. By contrast an unintended effect of the paradigm outlined above is a culture in which individual academic freedom is stifled by the need for conformity. Success may be measured by the averagely intelligent student, with average levels of motivation, achieving an award one point higher on the value added scale than they came with. The ethical principle of non-maleficence takes precedence such that the possibility of doing harm – to the student or University - outlaws risk taking behaviour in curriculum design and delivery. Utilitarian ethics (West 2004) is effective in surfacing such dilemmas. Its use in detailed analysis may help students and academics to plot the risks and benefits of innovative practice