Estimation and worldwide monitoring of the effective reproductive number of SARS-CoV-2

The effective reproductive number; R; e; is a key indicator of the growth of an epidemic. Since the start of the SARS-CoV-2 pandemic, many methods and online dashboards have sprung up to monitor this number through time. However, these methods are not always thoroughly tested, correctly placed in time, or are overly confident during high incidence periods. Here, we present a method for timely estimation of; R; e; , applied to COVID-19 epidemic data from 170 countries. We thoroughly evaluate the method on simulated data, and present an intuitive web interface for interactive data exploration. We show that, in early 2020, in the majority of countries the estimated; R; e; dropped below 1 only after the introduction of major non-pharmaceutical interventions. For Europe the implementation of non-pharmaceutical interventions was broadly associated with reductions in the estimated; R; e; . Globally though, relaxing non-pharmaceutical interventions had more varied effects on subsequent; R; e; estimates. Our framework is useful to inform governments and the general public on the status of epidemics in their country, and is used as the official source of; R; e; estimates for SARS-CoV-2 in Switzerland. It further allows detailed comparison between countries and in relation to covariates such as implemented public health policies, mobility, behaviour, or weather data

Statistical Genetics and Evolution of Quantitative Traits

The distribution and heritability of many traits depends on numerous loci in the genome. In general, the astronomical number of possible genotypes makes the system with large numbers of loci difficult to describe. Multilocus evolution, however, greatly simplifies in the limit of weak selection and frequent recombination. In this limit, populations rapidly reach Quasi-Linkage Equilibrium (QLE) in which the dynamics of the full genotype distribution, including correlations between alleles at different loci, can be parameterized by the allele frequencies. This review provides a simplified exposition of the concept and mathematics of QLE which is central to the statistical description of genotypes in sexual populations. We show how key results of Quantitative Genetics such as the generalized Fisher's "Fundamental Theorem", along with Wright's Adaptive Landscape, emerge within QLE from the dynamics of the genotype distribution. We then discuss under what circumstances QLE is applicable, and what the breakdown of QLE implies for the population structure and the dynamics of selection. Understanding of the fundamental aspects of multilocus evolution obtained through simplified models may be helpful in providing conceptual and computational tools to address the challenges arising in the studies of complex quantitative phenotypes of practical interest.Comment: to appear in Rev.Mod.Phy

Pion Absorption Cross Section for ^2H and ^3He in the Delta-Isobar Region: A Phenomenological Connection

The absorption of \pi^+ on ^3He in the $\Delta$-region is evaluated with exact inclusion of the final state interaction among the three emerging protons. The absorption is described by a $\pi N \to \Delta$ vertex and a $N\Delta - NN$ transition t-matrix which are calculated from a phenomenological model for NN and \pi d reactions. In a calculation where the initial pion scattering effects are neglected, the predicted peaks of the pion absorption cross sections for ^2H and ^3He lie too high in energy in relation to the data. The effect of the final state three-nucleon interaction turns out to be too small for changing the magnitude and shifting the peak position of the total absorption cross section for ^3He. We demonstrate that the adjustment of the peak position for the deuteron cross section by small modifications of the $\Delta$-parameters, automatically leads to the correct peak position in ^3He.Comment: 12 pages, REVTeX, 10 PostScript figures, submitted to Phys. Rev.

Sampling bias and incorrect rooting make phylogenetic network tracing of SARS-COV-2 infections unreliable.

There is obvious interest in gaining insights into the epidemiology and evolution of the virus that has recently emerged in humans as the cause of the coronavirus disease 2019 (COVID-19) pandemic. The recent paper by Forster et al. (1), analyzed 160 SARS-CoV-2 full genomes available (https://www.gisaid.org/) in early March 2020. The central claim is the identification of three main SARS-CoV-2 types, named A, B, and C, circulating in different proportions among Europeans and Americans (types A and C) and East Asian (type B). According to a median-joining network analysis, variant A is proposed to be the ancestral type because it links to the sequence of a coronavirus from bats, used as an outgroup to trace the ancestral origin of the human strains. The authors further suggest that the “ancestral Wuhan B-type virus is immunologically or environmentally adapted to a large section of the East Asian population, and may need to mutate to overcome resistance outside East Asia”. There are several serious flaws with their findings and interpretation. First, and most obviously, the sequence identity between SARS-CoV-2 and the bat virus is only 96.2%, implying that these viral genomes (which are nearly 30,000 nucleotides long) differ by more than 1,000 mutations. Such a distant outgroup is unlikely to provide a reliable root for the network. Yet, strangely, the branch to the bat virus, in Figure 1 of the paper, is only 16 or 17 mutations in length. Indeed, the network seems to be mis-rooted because (see Supplementary Figure 4) a virus from Wuhan from week 0 (24th December 2019) is portrayed as a descendant of a clade of viruses collected in weeks 1-9 (presumably from many places outside China), which makes no evolutionary (2), nor epidemiological sense (3).N

Sensory Communication

Contains table of contents for Section 2, an introduction, reports on ten research projects and a list of publications.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Grant 5 R01 DC00270National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant 2 R01 DC00100National Institutes of Health Grant 7 R29 DC00428National Institutes of Health Grant 2 R01 DC00126U.S. Air Force - Office of Scientific Research Grant AFOSR 90-0200U.S. Navy - Office of Naval Research Grant N00014-90-J-1935National Institutes of Health Grant 5 R29 DC00625U.S. Navy - Office of Naval Research Grant N00014-91-J-145

Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Allergenicity assessment of genetically modified crops—what makes sense?

GM crops have great potential to improve food quality, increase harvest yields and decrease dependency on certain chemical pesticides. Before entering the market their safety needs to be scrutinized. This includes a detailed analysis of allergenic risks, as the safety of allergic consumers has high priority. However, not all tests currently being applied to assessing allergenicity have a sound scientific basis. Recent events with transgenic crops reveal the fallacy of applying such tests to GM crops

Sensory Communication

Contains table of contents on Section 2, an introduction, reports on eleven research projects and a list of publications.National Institutes of Health Grant 5 R01 DC00117National Institutes of Health Grant 5 R01 DC00270National Institutes of Health Contract 2 P01 DC00361National Institutes of Health Grant 5 R01 DC00100National Institutes of Health Contract 7 R29 DC00428National Institutes of Health Grant 2 R01 DC00126U.S. Air Force - Office of Scientific Research Grant AFOSR 90-0200U.S. Navy - Office of Naval Research Grant N00014-90-J-1935National Institutes of Health Grant 5 R29 DC00625U.S. Navy - Office of Naval Research Grant N00014-91-J-1454U.S. Navy - Office of Naval Research Grant N00014-92-J-181

[Avian cytogenetics goes functional] Third report on chicken genes and chromosomes 2015

High-density gridded libraries of large-insert clones using bacterial artificial chromosome (BAC) and other vectors are essential tools for genetic and genomic research in chicken and other avian species... Taken together, these studies demonstrate that applications of large-insert clones and BAC libraries derived from birds are, and will continue to be, effective tools to aid high-throughput and state-of-the-art genomic efforts and the important biological insight that arises from them