Shut and re-open: the role of schools in the spread of COVID-19 in Europe

From The Royal Society via Jisc Publications RouterHistory: accepted 2020-12-02, pub-electronic 2021-05-31, pub-print 2021-07-19Article version: VoRPublication status: PublishedFunder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100004440; Grant(s): 202562/Z/16/ZFunder: Royal Society; Id: http://dx.doi.org/10.13039/501100000288; Grant(s): 202562/Z/16/ZFunder: Department for Health and Social CareFunder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024; Grant(s): 2019 Novel Coronavirus (COVID-19) rapid researchFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MC UU 00002/11We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden and German states as case studies. By comparing the growth rates in daily hospitalizations or confirmed cases under different interventions, we provide evidence that school closures contribute to a reduction in the growth rate approximately 7 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. In countries where community transmission is generally low, such as Denmark or Norway, a large-scale reopening of schools while controlling or suppressing the epidemic appears feasible. However, school reopening can contribute to statistically significant increases in the growth rate in countries like Germany, where community transmission is relatively high. In all regions, a combination of low classroom occupancy and robust test-and-trace measures were in place. Our findings underscore the need for a cautious evaluation of reopening strategies. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’

Shut and re-open: the role of schools in the spread of COVID-19 in Europe.

Funder: Department for Health and Social CareWe investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden and German states as case studies. By comparing the growth rates in daily hospitalizations or confirmed cases under different interventions, we provide evidence that school closures contribute to a reduction in the growth rate approximately 7 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. In countries where community transmission is generally low, such as Denmark or Norway, a large-scale reopening of schools while controlling or suppressing the epidemic appears feasible. However, school reopening can contribute to statistically significant increases in the growth rate in countries like Germany, where community transmission is relatively high. In all regions, a combination of low classroom occupancy and robust test-and-trace measures were in place. Our findings underscore the need for a cautious evaluation of reopening strategies. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'

The Effect of Genetic and Environmental Variation on Genital Size in Male Drosophila: Canalized but Developmentally Unstable

The genitalia of most male arthropods scale hypoallometrically with body size, that is they are more or less the same size across large and small individuals in a population. Such scaling is expected to arise when genital traits show less variation than somatic traits in response to factors that generate size variation among individuals in a population. Nevertheless, there have been few studies directly examining the relative sensitivity of genital and somatic traits to factors that affect their size. Such studies are key to understanding genital evolution and the evolution of morphological scaling relationships more generally. Previous studies indicate that the size of genital traits in male Drosophila melanogaster show a relatively low response to variation in environmental factors that affect trait size. Here we show that the size of genital traits in male fruit flies also exhibit a relatively low response to variation in genetic factors that affect trait size. Importantly, however, this low response is only to genetic factors that affect body and organ size systemically, not those that affect organ size autonomously. Further, we show that the genital traits do not show low levels of developmental instability, which is the response to stochastic developmental errors that also influence organ size autonomously. We discuss these results in the context of current hypotheses on the proximate and ultimate mechanisms that generate genital hypoallometry

FOXO Regulates Organ-Specific Phenotypic Plasticity In Drosophila

Phenotypic plasticity, the ability for a single genotype to generate different phenotypes in response to environmental conditions, is biologically ubiquitous, and yet almost nothing is known of the developmental mechanisms that regulate the extent of a plastic response. In particular, it is unclear why some traits or individuals are highly sensitive to an environmental variable while other traits or individuals are less so. Here we elucidate the developmental mechanisms that regulate the expression of a particularly important form of phenotypic plasticity: the effect of developmental nutrition on organ size. In all animals, developmental nutrition is signaled to growing organs via the insulin-signaling pathway. Drosophila organs differ in their size response to developmental nutrition and this reflects differences in organ-specific insulin-sensitivity. We show that this variation in insulin-sensitivity is regulated at the level of the forkhead transcription factor FOXO, a negative growth regulator that is activated when nutrition and insulin signaling are low. Individual organs appear to attenuate growth suppression in response to low nutrition through an organ-specific reduction in FOXO expression, thereby reducing their nutritional plasticity. We show that FOXO expression is necessary to maintain organ-specific differences in nutritional-plasticity and insulin-sensitivity, while organ-autonomous changes in FOXO expression are sufficient to autonomously alter an organ's nutritional-plasticity and insulin-sensitivity. These data identify a gene (FOXO) that modulates a plastic response through variation in its expression. FOXO is recognized as a key player in the response of size, immunity, and longevity to changes in developmental nutrition, stress, and oxygen levels. FOXO may therefore act as a more general regulator of plasticity. These data indicate that the extent of phenotypic plasticity may be modified by changes in the expression of genes involved in signaling environmental information to developmental processes

A Switch in the Control of Growth of the Wing Imaginal Disks of Manduca sexta

Background: Insulin and ecdysone are the key extrinsic regulators of growth for the wing imaginal disks of insects. In vitro tissue culture studies have shown that these two growth regulators act synergistically: either factor alone stimulates only limited growth, but together they stimulate disks to grow at a rate identical to that observed in situ. It is generally thought that insulin signaling links growth to nutrition, and that starvation stops growth because it inhibits insulin secretion. At the end of larval life feeding stops but the disks continue to grow, so at that time disk growth has become uncoupled from nutrition. We sought to determine at exactly what point in development this uncoupling occurs. Methodology: Growth and cell proliferation in the wing imaginal disks and hemolymph carbohydrate concentrations were measured at various stages in the last larval instar under experimental conditions of starvation, ligation, rescue, and hormone treatment. Principal Findings: Here we show that in the last larval instar of M. sexta, the uncoupling of nutrition and growth occurs as the larva passes the critical weight. Before this time, starvation causes a decline in hemolymph glucose and trehalose and a cessation of wing imaginal disks growth, which can be rescued by injections of trehalose. After the critical weight the trehalose response to starvation disappears, and the expression of insulin becomes decoupled from nutrition. After the critical weight the wing disks loose their sensitivity to repression by juvenile hormone, and factors from the abdomen, bu

New Frontiers for Organismal Biology

Understanding how complex organisms function as integrated units that constantly interact with their environment is a long-standing challenge in biology. To address this challenge, organismal biology reveals general organizing principles of physiological systems and behavior—in particular, in complex multicellular animals. Organismal biology also focuses on the role of individual variability in the evolutionary maintenance of diversity. To broadly advance these frontiers, cross-compatibility of experimental designs, methodological approaches, and data interpretation pipelines represents a key prerequisite. It is now possible to rapidly and systematically analyze complete genomes to elucidate genetic variation associated with traits and conditions that define individuals, populations, and species. However, genetic variation alone does not explain the varied individual physiology and behavior of complex organisms. We propose that such emergent properties of complex organisms can best be explained through a renewed emphasis on the context and life-history dependence of individual phenotypes to complement genetic data.Organismic and Evolutionary Biolog

New Applications of Gamma Spectroscopy: Characterization Tools for D&D Process Development, Inventory Reduction Planning & Shipping, Safety Analysis & Facility Management During the Heavy Element Facility Risk Reduction Program

Novel applications of gamma ray spectroscopy for D&D process development, inventory reduction, safety analysis and facility management are discussed in this paper. These applications of gamma spectroscopy were developed and implemented during the Risk Reduction Program (RPP) to successfully downgrade the Heavy Element Facility (B251) at Lawrence Livermore National Laboratory (LLNL) from a Category II Nuclear Facility to a Radiological Facility. Non-destructive assay in general, gamma spectroscopy in particular, were found to be important tools in project management, work planning, and work control (''Expect the unexpected and confirm the expected''), minimizing worker dose, and resulted in significant safety improvements and operational efficiencies. Inventory reduction activities utilized gamma spectroscopy to identify and confirm isotopics of legacy inventory, ingrowth of daughter products and the presence of process impurities; quantify inventory; prioritize work activities for project management; and to supply information to satisfy shipper/receiver documentation requirements. D&D activities utilize in-situ gamma spectroscopy to identify and confirm isotopics of legacy contamination; quantify contamination levels and monitor the progress of decontamination efforts; and determine the point of diminishing returns in decontaminating enclosures and glove boxes containing high specific activity isotopes such as {sup 244}Cm and {sup 238}Pu. In-situ gamma spectroscopy provided quantitative comparisons of several decontamination techniques (e.g. TLC-free Stripcoat{trademark}, Radiac{trademark} wash, acid wash, scrubbing) and was used as a part of an iterative process to determine the appropriate level of decontamination and optimal cost to benefit ratio. Facility management followed a formal, rigorous process utilizing an independent, state certified, peer-reviewed gamma spectroscopy program, in conjunction with other characterization techniques, process knowledge, and historical records, to provide information for work planning, work prioritization, work control, and safety analyses (e.g. development of hold points, stop work points); and resulted in B251 successfully achieving Radiological status on schedule. Gamma spectroscopy helped to define operational approaches to achieve radiation exposure ALARA, e.g. hold points, appropriate engineering controls, PPE, workstations, and time/distance/shielding in the development of ALARA plans. These applications of gamma spectroscopy can be used to improve similar activities at other facilities

Standards of lithium monitoring in mental health trusts in the UK

<p>Abstract</p> <p>Background</p> <p>Lithium is a commonly prescribed drug with a narrow therapeutic index, and recognised adverse effects on the kidneys and thyroid. Clinical guidelines for the management of bipolar affective disorder published by The National Institute for Health and Clinical Excellence (NICE) recommend checks of renal and thyroid function before lithium is prescribed. They further recommend that all patients who are prescribed lithium should have their renal and thyroid function checked every six months, and their serum lithium checked every three months. Adherence to these recommendations has not been subject to national UK audit.</p> <p>Methods</p> <p>The Prescribing Observatory for Mental Health (POMH-UK) invited all National Health Service Mental Health Trusts in the UK to participate in a benchmarking audit of lithium monitoring against recommended standards. Data were collected retrospectively from clinical records and submitted electronically.</p> <p>Results</p> <p>436 clinical teams from 38 Trusts submitted data for 3,373 patients. In patients recently starting lithium, there was a documented baseline measure of renal or thyroid function in 84% and 82% respectively. For patients prescribed lithium for a year or more, the NICE standards for monitoring lithium serum levels, and renal and thyroid function were met in 30%, 55% and 50% of cases respectively.</p> <p>Conclusions</p> <p>The quality of lithium monitoring in patients who are in contact with mental health services falls short of recognised standards and targets. Findings from this audit, along with reports of harm received by the National Patient Safety Agency, prompted a Patient Safety Alert mandating primary care, mental health and acute Trusts, and laboratory staff to work together to ensure systems are in place to support recommended lithium monitoring by December 2010.</p

A Role for Drosophila dFoxO and dFoxO 5′UTR Internal Ribosomal Entry Sites during Fasting

One way animals may cope with nutrient deprivation is to broadly repress translation by inhibiting 5′-cap initiation. However, under these conditions specific proteins remain essential to survival during fasting. Such peptides may be translated through initiation at 5′UTR Internal Ribosome Entry Sites (IRES). Here we show that the Drosophila melanogaster Forkhead box type O (dFoxO) transcription factor is required for adult survival during fasting, and that the 5′UTR of dfoxO has the ability to initiate IRES-mediated translation in cell culture. Previous work has shown that insulin negatively regulates dFoxO through AKT-mediated phosphorylation while dFoxO itself induces transcription of the insulin receptor dInR, which also harbors IRES. Here we report that IRES-mediated translation of both dFoxO and dInR is activated in fasted Drosophila S2 cells at a time when cap-dependent translation is reduced. IRES mediated translation of dFoxO and dInR may be essential to ensure function and sensitivity of the insulin signaling pathway during fasting

The Effects of Larval Nutrition on Reproductive Performance in a Food-Limited Adult Environment

It is often assumed that larval food stress reduces lifetime fitness regardless of the conditions subsequently faced by adults. However, according to the environment-matching hypothesis, a plastic developmental response to poor nutrition results in an adult phenotype that is better adapted to restricted food conditions than one having developed in high food conditions. Such a strategy might evolve when current conditions are a reliable predictor of future conditions. To test this hypothesis, we assessed the effects of larval food conditions (low, improving and high food) on reproductive fitness in both low and high food adults environments. Contrary to this hypothesis, we found no evidence that food restriction in larval ladybird beetles produced adults that were better suited to continuing food stress. In fact, reproductive rate was invariably lower in females that were reared at low food, regardless of whether adults were well fed or food stressed. Juveniles that encountered improving conditions during the larval stage compensated for delayed growth by accelerating subsequent growth, and thus showed no evidence of a reduced reproductive rate. However, these same individuals lost more mass during the period of starvation in adults, which indicates that accelerated growth results in an increased risk of starvation during subsequent periods of food stress