Hidden in Plain Sight: Subgroup Shifts Escape OOD Detection

The safe application of machine learning systems in healthcare relies on valid performance claims. Such claims are typically established in a clinical validation setting designed to be as close as possible to the intended use, but inadvertent domain or population shifts remain a fundamental problem. In particular, subgroups may be differently represented in the data distribution in the validation compared to the application setting. For example, algorithms trained on population cohort data spanning all age groups may be predominantly applied in elderly people. While these data are not “out-of distribution”, changes in the prevalence of different subgroups may have considerable impact on algorithm performance or will at least render original performance claims invalid. Both are serious problems for safely deploying machine learning systems. In this paper, we demonstrate the fundamental limitations of individual example out-of-distribution detection for such scenarios, and show that subgroup shifts can be detected on a population-level instead. We formulate population-level shift detection in the framework of statistical hypothesis testing and show that recent state-of-the-art statistical tests can be effectively applied to subgroup shift detection in a synthetic scenario as well as real histopathology images

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive

Marginal fit of dental restorations and the periodontium in Swiss army recruits | Restaurationsrandschlusse und Parodont bei Schweizer Rekruten.

The present study analyzed the relationship between periodontal health adjacent to filled and unfilled tooth sites in young men (recruits). The status of oral health of 419 Swiss army recruits, aged 19 to 20 years was assessed by determining Plaque Index (PI), Retention Index (RI) and Gingival Index (GI) as well as Pocket Probing Depth (PPD) and Probing Attachment Loss (PAL). In addition, the level of alveolar bone was measured using digitized bite-wing radiographs with an enlargement of 4.5x. Filling margins were assessed and the distance between the alveolar bone crest and the cemento-enamel junction (CEJ) measured to the nearest one tenth of a millimeter. These data were compared with the clinical parameters. A total of 8'050 sites were examined. 765 or 9.5 of the sites in the posterior area were filled. 119 of them showed filling overhangs larger than 0.2 mm. Thus, 1.5 % of the examined sites had a significant overhanging margin. All clinical parameters had greater values at filled than at unfilled sites. The differences were statistically not significant. Even the sites with margins overhanging more than 0.8 mm (n=14) did not show significantly different parameters compared to unfilled sites. The comparison with a similar study involving recruits 11 years earlier assessed that the recruits of 1996 had less and smaller filling overhangs. This, in turn, means that, in Switzerland restorative dentistry in young males has been markedly improved during the 1980's and 1990's.link_to_subscribed_fulltex

Social personality traits in chimpanzees: temporal stability and structure of behaviourally assessed personality traits in three captive populations

Animals of many species show consistency in behaviour across time and contexts that differs from other individuals' behaviour in the same population. Such ‘personality’ affects fitness and has therefore become an increasingly relevant research topic in biology. However, consistent variation in social behaviour is understudied. In socially living species, behaviour occurs in a social environment and social interactions have a significant influence on individual fitness. This study addressed personality in social behaviour of 75 captive chimpanzees in three zoos by coding observed behaviour. Fifteen behavioural variables were significantly repeatable (range 0.21–0.93) in at least two of the three zoos. The behaviours showed considerable long-term stability across 3 years, which did not differ from the short-term repeatability. The repeatable behaviours were then analysed with factor analyses. They formed five independent factors, three of which consisted of social traits and were labelled ‘sociability’, ‘positive affect’ and ‘equitability’. The two non-social behaviour factors were labelled ‘anxiety’ and ‘activity’. The factor scores were analysed for sex and population differences. Males had higher factor scores in all traits except ‘sociability’. The factor scores differed also between the zoos, implying considerable external effects in trait expression. The results show that chimpanzees show personality in a broad range of social and non-social behaviours. The study highlights the importance of assessing personality in the social behaviour, especially in cohesive social species, as only then can we understand the consequences of personality in socially living species

Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.

Contains fulltext : 110619.pdf (publisher's version ) (Open Access)Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of "classical" antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design

A meta-analysis of correlated behaviours with implications for behavioural syndromes: Mean effect size, publication bias, phylogenetic effects and the role of mediator variables

In evolutionary and behavioural ecology, increasing attention is being paid to the fact that functionally distinct behaviours are often not independent from each other. Such phenomenon is labelled as behavioural syndrome and is usually demonstrated by phenotypic correlations between behaviours like activity, exploration, aggression and risk-taking across individuals in a population. However, published studies disagree on the strength, and even on the existence of such relationships. To make general inferences from this mixed evidence, we quantitatively reviewed the literature using modern meta-analytic approaches. Based on a large dataset, we investigated the overall relationship between behaviours that are expected to form a syndrome and tested which factors can mediate heterogeneities in study outcomes. The average strength of the phenotypic correlation between behaviours was weak; we found no effect of the phylogeny of species but did observe significant publication bias. However, even accounting for this bias, the mean effect size was positive and statistically different from zero (r = 0. 198). Effect sizes showed considerable heterogeneity within species, implying a role for population-specific adaptation to environmental factors and/or between-study differences in research design. There was a significant positive association between absolute effect size and repeatability of behaviours, suggesting that within-individual variation of behavioural traits can set up an upper limit for the strength of the detected phenotypic correlations. Moreover, spatial overlap between the contexts in which different behaviours were assayed increased the magnitude of the association. The small effect size for the focal relationship implies that a huge sample size would be required to demonstrate a correlation between behaviours with sufficient statistical power, which is fulfilled only in very few studies. This suggests that behavioural syndromes often remain undetected and unpublished. Collectively, our meta-analysis revealed a number of points that might be worth to consider in the future study of behavioural syndromes. © 2012 The Author(s).Peer Reviewe