Social Distancing and SARS-CoV-2 Transmission Potential Early in the Epidemic in Finland.

BACKGROUND: Information about social mixing patterns under heavy social distancing is needed to model the impact of nonpharmaceutical interventions on SARS-CoV-2 transmission. METHODS: We conducted a survey on daily person-to-person contacts during the early phase of the SARS-CoV-2 epidemic in Finland, one month after strong social distancing measures had been introduced nationwide. We defined a contact as exchange of at least a few words in proximity of another person. We also considered physical ("skin-to-skin") contacts separately. Based on 3,171 reported contacts by 1,320 participants of 1-79 years of age, we estimated age-stratified contact matrices essential in modeling virus transmission. RESULTS: Compared with contacts during prepandemic conditions, as learned from the Finnish part of the Polymod study, there was a 72% (95% credible interval, CI = 71, 74) reduction in the daily number of all contacts and a 69% (95% CI = 66, 73) reduction in the daily number of physical contacts in April 2020. The largest reduction, of almost 90%, occurred in physical contacts by individuals more than 70 years of age. The estimated reduction in the transmission potential of the virus attributable solely to reduced contact frequencies varied between 59% (whole population; physical contacts; 95% CI = 52, 68) and 77% (over 20-year olds; physical contacts; 95% CI = 70, 89). CONCLUSIONS: We surmise that the large reduction in the daily numbers of social contacts in the early part of the SARS-CoV-2 epidemic in Finland was likely a major contributor to the steady decline of the epidemic in the country since early April.

Prognostic value of tumour budding in oesophageal cancer: a meta-analysis.

Recently, tumour budding (TB) has been suggested as a strong prognostic marker in oesophageal cancer. The aim of this systematic review is to test the prognostic value of TB in oesophageal cancer by a meta-analysis of previously published studies. We systematically reviewed the literature related to TB by using the bibliographic databases of Scopus, PubMed, and Web of Science. The search was limited to publications in the English language up to and including December 2014. There are 11 retrospective studies in which TB has been evaluated in oesophageal cancer. Two authors independently extracted the results from eligible studies. The meta-analysis of eligible studies revealed that TB is a significant prognosticator for overall survival in oesophageal cancer, with a risk ratio (RR) of 2.97 [95% confidence interval (CI) 1.81-4.85; P = 0.0023] in univariate analysis, and with an RR of 2.07 (95% CI 1.22-3.52; P = 0.017) in multivariate analysis. We conclude that a high TB score is a promising prognostic marker of poor survival in oesophageal cancer. Because of its simplicity, reproducibility and high predictive power, TB is strongly recommended to be included in the routine pathology report of oesophageal cancer.

Ant larvae as players in social conflict: relatedness and individual identity mediate cannibalism intensity.

Conflict arises among social organisms when individuals differ in their inclusive-fitness interests. Ant societies are excellent models for understanding how genetic relatedness mediates conflict intensity. However, although conflicts within colonies typically arise over offspring production, the role of larvae as actors in social conflict has received little attention. We develop and empirically test kin-selection theory of larval egg cannibalism in ant societies. Specifically, we investigate how selection for cannibalism is mediated by nestmate relatedness and larval sex in a mathematical model and then test the model's predictions by measuring cannibalism levels in eight ant species with varying nestmate relatedness. In line with our theoretical predictions, cannibalism levels in larvae were significantly influenced by relatedness and sex. Increased relatedness was associated with reduced levels of cannibalism, indicating that larval behavior is mediated by inclusive-fitness considerations. Levels of cannibalism were significantly higher in male larvae, and our model suggests that this is due to sex differences in the benefits of cannibalism. By examining the selfish interests of larvae and the constraints they face in a social environment, our study presents a novel perspective on conflict in ants and on the evolution of selfish elements in social systems in general.

Geographical variation in Plasmodium vivax relapse.

BACKGROUND: Plasmodium vivax has the widest geographic distribution of the human malaria parasites and nearly 2.5 billion people live at risk of infection. The control of P. vivax in individuals and populations is complicated by its ability to relapse weeks to months after initial infection. Strains of P. vivax from different geographical areas are thought to exhibit varied relapse timings. In tropical regions strains relapse quickly (three to six weeks), whereas those in temperate regions do so more slowly (six to twelve months), but no comprehensive assessment of evidence has been conducted. Here observed patterns of relapse periodicity are used to generate predictions of relapse incidence within geographic regions representative of varying parasite transmission. METHODS: A global review of reports of P. vivax relapse in patients not treated with a radical cure was conducted. Records of time to first P. vivax relapse were positioned by geographic origin relative to expert opinion regions of relapse behaviour and epidemiological zones. Mixed-effects meta-analysis was conducted to determine which geographic classification best described the data, such that a description of the pattern of relapse periodicity within each region could be described. Model outputs of incidence and mean time to relapse were mapped to illustrate the global variation in relapse. RESULTS: Differences in relapse periodicity were best described by a historical geographic classification system used to describe malaria transmission zones based on areas sharing zoological and ecological features. Maps of incidence and time to relapse showed high relapse frequency to be predominant in tropical regions and prolonged relapse in temperate areas. CONCLUSIONS: The results indicate that relapse periodicity varies systematically by geographic region and are categorized by nine global regions characterized by similar malaria transmission dynamics. This indicates that relapse may be an adaptation evolved to exploit seasonal changes in vector survival and therefore optimize transmission. Geographic patterns in P. vivax relapse are important to clinicians treating individual infections, epidemiologists trying to infer P. vivax burden, and public health officials trying to control and eliminate the disease in human populations.

Likelihood contrasts: a machine learning algorithm for binary classification of longitudinal data.

Machine learning methods have gained increased popularity in biomedical research during the recent years. However, very few of them support the analysis of longitudinal data, where several samples are collected from an individual over time. Additionally, most of the available longitudinal machine learning methods assume that the measurements are aligned in time, which is often not the case in real data. Here, we introduce a robust longitudinal machine learning method, named likelihood contrasts (LC), which supports study designs with unaligned time points. Our LC method is a binary classifier, which uses linear mixed models for modelling and log-likelihood for decision making. To demonstrate the benefits of our approach, we compared it with existing methods in four simulated and three real data sets. In each simulated data set, LC was the most accurate method, while the real data sets further supported the robust performance of the method. LC is also computationally efficient and easy to use.

HLA and non-HLA genes and familial predisposition to autoimmune diseases in families with a child affected by type 1 diabetes.

Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first- or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.

Ecological speciation in postglacial European whitefish: rapid adaptive radiations into the littoral, pelagic, and profundal lake habitats.

Understanding how a monophyletic lineage of a species diverges into several adaptive forms has received increased attention in recent years, but the underlying mechanisms in this process are still under debate. Postglacial fishes are excellent model organisms for exploring this process, especially the initial stages of ecological speciation, as postglacial lakes represent replicated discrete environments with variation in available niches. Here, we combine data of niche utilization, trophic morphology, and 17 microsatellite loci to investigate the diversification process of three sympatric European whitefish morphs from three northern Fennoscandian lakes. The morphological divergence in the gill raker number among the whitefish morphs was related to the utilization of different trophic niches and was associated with reproductive isolation within and across lakes. The intralacustrine comparison of whitefish morphs showed that these systems represent two levels of adaptive divergence: (1) a consistent littoral-pelagic resource axis; and (2) a more variable littoral-profundal resource axis. The results also indicate that the profundal whitefish morph has diverged repeatedly from the ancestral littoral whitefish morph in sympatry in two different watercourses. In contrast, all the analyses performed revealed clustering of the pelagic whitefish morphs across lakes suggesting parallel postglacial immigration with the littoral whitefish morph into each lake. Finally, the analyses strongly suggested that the trophic adaptive trait, number of gill rakers, was under diversifying selection in the different whitefish morphs. Together, the results support a complex evolutionary scenario where ecological speciation acts, but where both allopatric (colonization history) and sympatric (within watercourse divergence) processes are involved.

Estimating population-level coancestry coefficients by an admixture F model.

In this article, we develop an admixture F model (AFM) for the estimation of population-level coancestry coefficients from neutral molecular markers. In contrast to the previously published F model, the AFM enables disentangling small population size and lack of migration as causes of genetic differentiation behind a given level of F(ST). We develop a Bayesian estimation scheme for fitting the AFM to multiallelic data acquired from a number of local populations. We demonstrate the performance of the AFM, using simulated data sets and real data on ninespine sticklebacks (Pungitius pungitius) and common shrews (Sorex araneus). The results show that the parameterization of the AFM conveys more information about the evolutionary history than a simple summary parameter such as F(ST). The methods are implemented in the R package RAFM.

Dynamics of a sex-linked deleterious mutation in populations subject to sex reversal.

The heterogametic sex chromosomes (i.e. mammalian Y and avian W) do not usually recombine with the homogametic sex chromosomes which is known to lead into rapid degeneration of Y and W due to accumulation of deleterious mutations. On the other hand, some 96% of amphibian species have homomorphic, i.e. non-degenerate Y chromosomes. Nicolas Perrin's fountain-of-youth hypothesis states that this is a result of recombination between X and Y chromosomes in sex-reversed individuals. In this study, I model the consequences of such recombination for the dynamics of a deleterious mutation occurring in Y chromosomes. As expected, even relatively low levels of sex reversal help to purge deleterious mutations. However, the population-dynamic consequences of this depend on the type of selection that operates on the population undergoing sex reversal. Under fecundity selection, sex reversal can be beneficial for some parameter values, whereas under survival selection, it seems to be always harmful.

A new method to uncover signatures of divergent and stabilizing selection in quantitative traits.

While it is well understood that the pace of evolution depends on the interplay between natural selection, random genetic drift, mutation, and gene flow, it is not always easy to disentangle the relative roles of these factors with data from natural populations. One popular approach to infer whether the observed degree of population differentiation has been influenced by local adaptation is the comparison of neutral marker gene differentiation (as reflected in FST) and quantitative trait divergence (as reflected in QST). However, this method may lead to compromised statistical power, because FST and QST are summary statistics which neglect information on specific pairs of populations, and because current multivariate tests of neutrality involve an averaging procedure over the traits. Further, most FST-QST comparisons actually replace QST by its expectation over the evolutionary process and are thus theoretically flawed. To overcome these caveats, we derived the statistical distribution of population means generated by random genetic drift and used the probability density of this distribution to test whether the observed pattern could be generated by drift alone. We show that our method can differentiate between genetic drift and selection as a cause of population differentiation even in cases with FST=QST and demonstrate with simulated data that it disentangles drift from selection more accurately than conventional FST-QST tests especially when data sets are small.