Confidence intervals and P-valves for meta analysis with publication bias

We study publication bias in meta analysis by supposing there is a population (y, σ) of studies which give treatment effect estimates y ~ N(θ, σ2). A selection function describes the probability that each study is selected for review. The overall estimate of θ depends on the studies selected, and hence on the (unknown) selection function. Our previous paper, Copas and Jackson (2004, A bound for publication bias based on the fraction of unpublished studies, Biometrics 60, 146-153), studied the maximum bias over all possible selection functions which satisfy the weak condition that large studies (small σ) are as likely, or more likely, to be selected than small studies (large σ). This led to a worstcase sensitivity analysis, controlling for the overall fraction of studies selected. However, no account was taken of the effect of selection on the uncertainty in estimation. This paper extends the previous work by finding corresponding confidence intervals and P-values, and hence a new sensitivity analysis for publication bias. Two examples are discussed

Spatio-temporal dynamics and aetiology of proliferative leg skin lesions in wild British finches

Proliferative leg skin lesions have been described in wild finches in Europe although there have been no large-scale studies of their aetiology or epizootiology to date. Firstly, disease surveillance, utilising public reporting of observations of live wild finches was conducted in Great Britain (GB) and showed proliferative leg skin lesions in chaffinches (Fringilla coelebs) to be widespread. Seasonal variation was observed, with a peak during the winter months. Secondly, pathological investigations were performed on a sample of 39 chaffinches, four bullfinches (Pyrrhula pyrrhula), one greenfinch (Chloris chloris) and one goldfinch (Carduelis carduelis) with proliferative leg skin lesions and detected Cnemidocoptes sp. mites in 91% (41/45) of affected finches and from all species examined. Fringilla coelebs papillomavirus (FcPV1) PCR was positive in 74% (23/31) of birds tested: a 394 base pair sequence was derived from 20 of these birds, from all examined species, with 100% identity to reference genomes. Both mites and FcPV1 DNA were detected in 71% (20/28) of birds tested for both pathogens. Histopathological examination of lesions did not discriminate the relative importance of mite or FcPV1 infection as their cause. Development of techniques to localise FcPV1 within lesions is required to elucidate the pathological significance of FcPV1 DNA detection.We thank the members of the public and BTO Garden BirdWatch participants who reported garden bird morbidity and mortality incidents and our colleagues, Katie Beckmann, Shaheed Macgregor, Ricardo Castro Cesar de Sa, Lydia Franklinos and Tim Hopkins from the Zoological Society of London; Kirsi Peck from the Royal Society for the Protection of Birds; BTO staff members in the Garden BirdWatch team; the staff at Abbey Veterinary Services and the Animal & Plant Health Agency (Daniel Hicks, Richard Irvine, Alejandro Núñez and Scott Reid) for their assistance with this investigation. This work was financially supported by the following organisations; Birdcare Standards Association, British Trust for Ornithology, British Veterinary Association Animal Welfare Foundation, CJ Wildbird Foods, Cranswick Pet Products, UK Department for the Environment Food & Rural Affairs and Welsh Government through the Animal & Plant Health Agency’s Diseases of Wildlife Scheme Scanning Surveillance Programme (Project ED1600), Esmée Fairbairn Foundation, Gardman Ltd, Institute of Zoology, Royal Society for the Protection of Birds and the Universities Federation for Animal Welfare. RAJW was supported by the Moncloa of Excellence PICATA programme and Crafoord Foundation Sweden (grant number 20160971). Molecular and sequencing costs were funded by the Spanish Ministry of Science and Innovation, (Ref: CGL2013-41642-P/BOS)

The genomic epidemiology of Escherichia albertii

Escherichia albertii is a recently identified gastrointestinal bacterial pathogen of humans and animals which is typically misidentified and generally only detected during genomic surveillance of other Enterobacteriaceae. The incidence of E. albertii is likely underestimated and its epidemiology and clinical relevance are poorly characterised. Here, we whole genome sequenced E. albertii isolates from humans (n = 83) and birds (n = 79) in Great Britain and analysed a broader public dataset (n = 475) to address these gaps. We found human and avian isolates typically (90%; 148/164) belonged to host-associated monophyletic groups with distinct virulence and antimicrobial resistance profiles. Overlaid patient epidemiological data suggested that human infection was likely related to travel and possibly foodborne transmission. The Shiga toxin encoding stx2f gene was associated with clinical disease (OR = 10.27, 95% CI = 2.98–35.45 p = 0.0002) in finches. Our results suggest that improved future surveillance will further elucidate disease ecology and public and animal health risks associated with E. albertii

Epidemiological evidence that garden birds are a source of human salmonellosis in England and Wales

The importance of wild bird populations as a reservoir of zoonotic pathogens is well established. Salmonellosis is a frequently diagnosed infectious cause of mortality of garden birds in England and Wales, predominantly caused by Salmonella enterica subspecies enterica serovar Typhimurium definitive phage types 40, 56(v) and 160. In Britain, these phage types are considered highly host-adapted with a high degree of genetic similarity amongst isolates, and in some instances are clonal. Pulsed field gel electrophoresis, however, demonstrated minimal variation amongst matched DT40 and DT56(v) isolates derived from passerine and human incidents of salmonellosis across England in 2000-2007. Also, during the period 1993-2012, similar temporal and spatial trends of infection with these S. Typhimurium phage types occurred in both the British garden bird and human populations; 1.6% of all S. Typhimurium (0.2% of all Salmonella) isolates from humans in England and Wales over the period 2000-2010. These findings support the hypothesis that garden birds act as the primary reservoir of infection for these zoonotic bacteria. Most passerine salmonellosis outbreaks identified occurred at and around feeding stations, which are likely sites of public exposure to sick or dead garden birds and their faeces. We, therefore, advise the public to practise routine personal hygiene measures when feeding wild birds and especially when handling sick wild birds

Emerging Infectious Disease leads to Rapid Population Decline of Common British Birds

Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period

Combining host and vector data informs emergence and potential impact of an Usutu virus outbreak in UK wild birds

Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak. Although the Eurasian blackbird (Turdus merula) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events

Multi-locus analysis resolves the epidemic finch strain of Trichomonas gallinae and suggests introgression from divergent trichomonads

In Europe, Trichomonas gallinae recently emerged as a cause of epidemic disease in songbirds. A highly virulent and clonal strain of the parasite, first found in the UK, has become the predominant strain there and spread to continental Europe. Discriminating this epidemic strain of T. gallinae from other strains necessitated development of multi-locus sequence typing (MLST). Development of the MLST was facilitated by the assembly and annotation of a 54.7 Mb draft genome of a cloned stabilate of the A1 European finch epidemic strain (isolated from Greenfinch, Carduelis chloris, XT-1081/07 in 2007) containing 21,924 protein coding genes. This enabled construction of a robust 19 locus MLST based on existing typing loci for Trichomonas vaginalis and T. gallinae. Our MLST has the sensitivity to discriminate strains within existing genotypes confidently, and resolves the American finch A1 genotype from the epidemic European finch A1 genotype. Interestingly, one isolate we obtained from a captive black-naped fruit dove Ptilinopsus melanospilus, was not truly T. ¬¬¬gallinae but a hybrid of T. gallinae with a distant trichomonad lineage. Phylogenetic analysis of the individual loci in this fruit dove provides evidence of gene flow between distant trichomonad lineages at two of the 19 loci examined and may provide precedence for the emergence of other hybrid trichomonad genomes including T. vaginalis

Characterization of the DIMS system based on astronomical meteor techniques for macroscopic dark matter search

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