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The human management of honey bees (Apis mellifera) has resulted in the widespread introduction of subspecies outside of their native ranges. One well known example of this is Apis mellifera mellifera, native to Northern Europe, which has now been significantly introgressed by the introduction of C lineage honey bees. Introgression has consequences for species in terms of future adaptive potential and long-term viability. However, estimating introgression in colony-living haplodiploid species is challenging. Previous studies have estimated introgression using individual workers, individual drones, multiple drones, and pooled workers. Here, we compare introgression estimates via three genetic approaches: SNP array, individual RAD-seq, and pooled colony RAD-seq. We also compare two statistical approaches: a maximum likelihood cluster program (ADMIXTURE) and an incomplete lineage sorting model (ABBA BABA). Overall, individual approaches resulted in lower introgression estimates than pooled colonies when using ADMIXTURE. However, the pooled colony ABBA BABA approach resulted in generally lower introgression estimates than all three ADMIXTURE estimates. These results highlight that sometimes one individual is not enough to assess colony-level introgression, and future studies that do use colony pools should not be solely dependent on clustering programs for introgression estimates.

PDF file 65K, Primers used in assessment of RINT1 transcripts

PDF file 199K, RINT1 c.1334-5delA, c.1334-1_1335delGTT minigene assay

PDF file 69K, Distribution of cases and controls included in the analysis, by study center and ethnic group

Purpose: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo diffuse large B-cell lymphoma (DLBCL) and the impact of TCR on survival.Experimental Design: We performed high-throughput unbiased TCRβ sequencing on a population-based cohort of 92 patients with DLBCL treated with conventional (i.e., non-checkpoint blockade) frontline “R-CHOP” therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString. The primary endpoints were 4-year overall survival (OS) and progression-free survival (PFS).Results: The TCR repertoire within DLBCL nodes was abnormally narrow relative to non-diseased nodal tissues (P < 0.0001). In DLBCL, a highly dominant single T-cell clone was associated with inferior 4-year OS rate of 60.0% [95% confidence interval (CI), 31.7%–79.6%], compared with 79.8% in patients with a low dominant clone (95% CI, 66.7%–88.5%; P = 0.005). A highly dominant clone also predicted inferior 4-year PFS rate of 46.6% (95% CI, 22.5%–76.6%) versus 72.6% (95% CI, 58.8%–82.4%, P = 0.008) for a low dominant clone. In keeping, clonal expansions were most pronounced in the EBV+ DLBCL subtype that is known to express immunogenic viral antigens and is associated with particularly poor outcome. Increased T-cell diversity was associated with significantly elevated PD-1, PD-L1, and PD-L2 immune checkpoint molecules.Conclusions: Put together, these findings suggest that the TCR repertoire is a key determinant of the TME. Highly dominant T-cell clonal expansions within the TME are associated with poor outcome in DLBCL treated with conventional frontline therapy. Clin Cancer Res; 23(7); 1820–8. ©2016 AACR.

Individual results of TCR sequencing for all DLBCL and non-diseased nodal tissues.

Recent research has shown drastic reductions in the global diversity and abundance of insects. This is a major concern given the expected cascade effects on ecosystem services, such as pollination. Understanding the patterns and drivers of changes in the distribution and abundance of species in our rapidly changing environment is therefore urgent. Cases of species showing trends that run counter to general population declines, especially when they deliver key ecosystem services, are especially interesting. The tree bumblebee (Bombus hypnorum), which belongs to a globally important group of pollinators, has substantially expanded its range in recent years in direct contrast to many other species within this group. Here we reconstructed the likely pattern of colonization of the UK based on RAD-seq population genomic data combined with Bayesian population modelling. This RAD-seq approach also enabled an analysis of genomic regions potentially under selection. We report a complex and dynamic colonization pattern that is most likely ongoing. Current evidence suggests that either a shift in its migration potential, and/or adaptive genomic changes have contributed to the recent range expansion of B. hypnorum. Genomic areas of potential adaptive significance included genes involved in regulation of transcription and gene expression, circadian rhythms and innate immunity. Our results are framed within the general context of understanding the factors driving successful population expansions.

Elizabeth Bishop’s relationship to the literal places she lived in, travelled through and sometimes made home, has long been a key concern of critics and readers. What interests me in this article is Bishop’s relationship to a country she visited on just a\ud few occasions, namely England. In so doing, I intend to focus not so much on Bishop’s experiences in England—she made short trips there in the 1930s, 1960s and 1970s—but rather on her idea of England as a poetic home and the extent to which\ud contemporary poets in Britain and Ireland have been influenced by her writing. Bishop’s England is thus at least two things here, a body of literature she herself reads and reinterprets in her poetry, and, more recently, a national poetry that has itself\ud become Bishopesque in light of her contemporary popularity.

Background. Next-generation sequencing (NGS) technology enables profiling of individual tumours and to measure the increasing number of biomarkers relevant to the management of breast cancer patients. The Australian Translational Genomics Centre (ATGC) is a collaboration between the healthcare sector (Metro South Hospital and Health Service), higher education sector (Queensland University of Technology) and a government-run pathology service (Pathology Queensland) to provide genomic profiling of breast cancer patients at the Princess Alexandra Hospital. The program was developed to integrate the ordering, processing and interpretation of large-scale NGS into clinical practice. Methods. Patients were consented for somatic testing and ordering was integrated into the hospital’s electronic ordering system. Samples were derived from fresh tissue biopsies after surgeries (47%) or from FFPE histology sections. No selection criteria were applied during the initial phase and the cohort was representative of newly presenting patients at the hospitals breast cancer clinic. Patients were sequenced using a NATA-accredited ISO15189 program using whole-exome sequencing (WES) combined with a high-coverage spike-in panel of known cancer genes. Clinical reports included the calculation of tumour purity, tumour mutational burden (TMB), the assessment of copy number events and somatic mutations down to 3% allele frequency. Standard molecular testing in Australia includes ER, PR and HER2 status, and additional testing included testing of Tier 1-2 somatic variants in the genes ABCC3, AKT1, CCND1, CCNE1, CDKN2A, ERBB2, ESR1, FGF3, FGFR1, FGFR2, MTOR, NCOA3, NF2, PIK3CA, PIK3R1, PTEN, RB1, RSF1, SF3B1, TP53. Results. Seventy-one patients were tested by WES/panel, and an average of 1.5 clinically significant Tier 1- 2 mutations were detected per patient. In 77% of cases, the molecular profiling could stratify patients to those with either PI3K/Akt/mTOR pathway activation (by PIK3CA activating mutations, AKT, MTOR mutations or PTEN loss) or CDK4/6 activation (by CCND1 expansion or CDKN2A loss). The most frequently observed mutations were PIK3CA activation (40%) and CCND1 copy number expansions (24%). A small proportion (n=3) were found to have mTOR or TCS1/2 mutations reported to have association with a durable response to mTOR inhibitors. Additionally, 11 patients (15%) had a high TMB (TMB, >6.8 mutations/megabase) with 6 having >10 mutations/Mb. Within this high-TMB cohort, 3 were found to be ER-PR-HER-, however, the majority (n=7) were ER+PR+HER2- patients. Calculation of the tumour purity indicated that, despite expert resection of the biopsies to isolate the most tumour dense regions, tumour purity was not significantly enriched. In 58% of cases, the tumour purity was less than 50%, and in 13% of samples, it was less than 25%, indicating that in clinical practice the method of sequencing must be robust, as many samples have significant amounts of contaminating stroma. Conclusion. We demonstrate that integration of WES/panel testing into clinical practice is practical and provides multiplexed testing of current and emerging biomarkers in a significant number of tested patients. While a high proportion of patients had mutations that could stratify them to targeted therapies in the event of metastatic disease, the somatic molecular profiles did not modify first line therapy decision-making. Training of clinical staff for patient consent and the dissemination of findings, the development of a dedicated molecular tumour board, and decision protocols to identify patients of metastatic risk were identified as key developments in this clinical program. The program identified previously unidentified subsets of patients including a subset of ER+ patients with high TMB for which for there are no effective treatments option in Australia. Citation Format: Kate Roberts, Paul J Leo, Jeremy Khoo, Alice Febery, Jonathan Ellis, Mhairi Clout, Lawrie Wheeler, Lisa Anderson, Matthew Brown, Ian Bennett. Establishing whole-exome sequencing for breast cancer patient care [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-07.

Aim: We compare the performance of habitat suitability models using climate data only or climate data together with water chemistry, land cover and predation pressure data to model the distribution of European grayling (Thymallus thymallus). From these models, we (a) investigate the relationship between habitat suitability and genetic diversity; (b) project the distribution of grayling under future climate change; and (c) model the effects of habitat mitigation on future distributions. Location: United Kingdom. Methods: Maxent species distribution modelling was implemented using a Simple model (only climate parameters) or a Full model (climate, water chemistry, land use and predation pressure parameters). Areas of high and low habitat suitability were designated. Associations between habitat suitability and genetic diversity for both neutral and adaptive markers were examined. Distribution under minimal and maximal future climate change scenarios was modelled for 2050, incorporating projections of future flow scenarios obtained from the Centre for Ecology and Hydrology. To examine potential mitigation effects within habitats, models were run with manipulation of orthophosphate, nitrite and copper concentrations. Results: We mapped suitable habitat for grayling in the present and the future. The Full model achieved substantially higher discriminative power than the Simple model. For low suitability habitat, higher levels of inbreeding were observed for adaptive, but not neutral, loci. Future projections predict a significant contraction of highly suitable areas. Under habitat mitigation, modelling suggests that recovery of suitable habitat of up to 10% is possible. Main conclusions: Extending the climate-only model improves estimates of habitat suitability. Significantly higher inbreeding coefficients were found at immune genes, but not neutral markers in low suitability habitat, indicating a possible impact of environmental stress on evolutionary potential. The potential for habitat mitigation to alleviate distributional changes under future climate change is demonstrated, and specific recommendations are made for habitat recovery on a regional basis.

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology., Chromosome arm-level aneuploidies (CAAs) are frequently observed in cancer. Here, the authors analyse CAA landscapes across different tumour types, relating these chromosome arm gains and losses to tumour evolution, metastasis, patient survival and response to a range of anti-cancer therapies.

On an intertextual level, Leonor de la Cueva’s only extant comedia has often been to compared to the biblical story of King David, Bathsheba and Uriah the Hittite, since her king, Filiberto, sends the beloved of Armesinda, Don Juan, to war in order to remove him as a rival. However, because of the threats of both rape and suicide as integral to the plot of Cueva’s work, La firmeza en la ausencia can also be read intertextually as incorporating elements from the story of the rape of Lucretia, widely known, represented and reinterpreted by writers and painters from the early modern period. There is ample precedence for combining themes from these biblical and classical stories in other comedias that served as models for Leonor de la Cueva. Lope de Vega did so most notably in Peribanez y el Comendador de Ocana, to mention one of several examples. Additionally, these comedias often include as part of the trial of virtue the betrayal of other female characters who attempt to persuade the protagonist to surrender herself sexually to an aggressor of superior social status. This article studies this tradition and how Leonor de la Cueva has adapted these themes to present a dramatic presentation of unwavering female virtue.

Advances in genomic technology have enabled a greater understanding of the genetics of common immune-mediated diseases such as ankylosing spondylitis (AS), inflammatory bowel disease (IBD) and psoriasis. The substantial overlap in genetically identified pathogenic pathways has been demonstrated between these diseases. However, to date, gene discovery approaches have only mapped a minority of the heritability of these common diseases, and most disease-associated variants have been found to be non-coding, suggesting mechanisms of disease-association through transcriptional regulatory effects. Epigenetics is a major interface between genetic and environmental modifiers of disease and strongly influence transcription. DNA methylation is a well-characterised epigenetic mechanism, and a highly stable epigenetic marker, that is implicated in disease pathogenesis. DNA methylation is an under-investigated area in immune-mediated diseases, and many studies in the field are affected by experimental design limitations, related to study design, technical limitations of the methylation typing methods employed, and statistical issues. This has resulted in both sparsity of investigations into disease-related changes in DNA methylation, a paucity of robust findings, and difficulties comparing studies in the same disease. In this review, we cover the basics of DNA methylation establishment and control, and the methods used to examine it. We examine the current state of DNA methylation studies in AS, IBD and psoriasis; the limitations of previous studies; and the best practices for DNA methylation studies. The purpose of this review is to assist with proper experimental design and consistency of approach in future studies to enable a better understanding of the functional role of DNA methylation in immune-mediated disease.

Pleural mesothelioma is a cancer of serosal surfaces caused by environmental exposure to asbestos. Clinical outcome remains poor and while trials of new treatments are ongoing it remains an understudied cancer. Mesothelioma cell lines can readily be grown from primary tumour and from tumour cells shed into pleural effusion with the latter representing a particularly valuable source of DNA in clinical settings, procurable without the need for additional invasive procedures. However, it is not well understood how accurately patient-derived cultured tumour cells represent the molecular characteristics of their primary tumour. We used whole-genome sequencing of primary tumour and matched cultured cells to comprehensively characterize mutations and structural alterations. Most cases had complex rearranged genomes with evidence of chromoanagenesis and rearrangements reminiscent of chromoplexy. Many of the identified driver mutations were structural, indicating that mesothelioma is often caused by structural alterations and catastrophic genomic events, rather than point mutations. Because the majority of genomic changes detected in tumours were also displayed by the genomes of cultured tumour cells, we conclude that low-passage cultured tumour cells are generally suitable for molecular characterization of mesothelioma and may be particularly useful where tissue samples with high tumour cell content are not available. However, the subclonal compositions of the cell lines did not fully recapitulate the subclonal diversity of the primary tumours. Furthermore, longitudinal acquisition of major alterations in subclonal cell populations was observed after long-term passaging. These two factors define limitations of tumour-derived cell lines as genomic substrate for clinical purposes.

As germline variants can influence cancer patient treatment decisions, outcomes and counselling, and the level of genetic predisposition for sporadic childhood acute myeloid leukemia (AML) is not clearly established, we undertook a comprehensive analysis of rare germline variants in childhood AML. As childhood AML is rare,1 to date pan-cancer childhood cohorts have included few AML cases and often the germline panels used have not included key genes relevant to myeloid malignancy. We therefore combined data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program together with an Australian childhood AML cohort (Supplemental Tables 1 and 2) to identify the rare germline variants in a large panel of cancer predisposition genes (n=216) compiled from literature review, and including genes involved in familial hematological malignancies (HM) and bone marrow failure (BMF) syndromes (Supplemental Table 3). We analyzed whole genome sequencing (WGS) and whole exome sequence (WES) data available through the TARGET program (n=48) (phs000218.v22.p8.c1) and WES data for the Australian cohort (n=24). Given that damaging and disease-causing variants are predicted to have a low population prevalence we identified extremely rare, potentially deleterious germline variants [VAF >30%; MAF (gnomAD) 10] and classified these as shown in Figure 1. All variants passing initial filtering are listed in Supplemental Table 4. The distribution of germline and somatic variants is shown in Supplemental Table 5, Supplemental Figure 1. Given the small cohort size pairwise comparisons of germline variants and clinico-pathological characteristics did not reveal significant associations after applying multiple correction (Supplemental Table 6).

Enzymes are renowned for their catalytic efficiency and selectivity, but relatively few carbon-carbon bond forming enzymes have found their way into the biocatalysis toolbox. While engineering can overcome the challenges associated with C-C bond formation for some enzyme systems, the broader synthetic potential of biocatalysis is hindered by the lack of high-quality C-C bond forming transformations. Here we show that the enzyme UstD performs a highly selective decarboxylative aldol addition with diverse aldehyde substrates to make non-standard, γ-hydroxy amino acids. We increased the activity of UstD through three rounds of classic directed evolution and an additional round of computationally-guided engineering. The enzyme that emerged, UstD2.0, is efficient in a whole-cell biocatalysis format, which circumvents the need for enzyme purification, thereby facilitating its use in traditional organic settings. This new, highly stereoselective enzyme represents a unique expansion of the biosynthetic toolbox. The products are highly desirable, functionally rich bioactive γ-hydroxy amino acids that we demonstrate can be prepared stereoselectively on gram-scale. The X-ray crystal structure of UstD2.0 at 2.25 Å reveals the active site and the molecular basis for the remarkably promiscuity of this catalyst. Taking inspiration from the versatile reactivity of enamines in organic synthesis, we hypothesize that the enamine intermediate of UstD can be engineered to react with electrophiles other than aldehydes. The advent of structural information enabled by engineering of UstD2.0 provides a foundation for probing the unique mechanism of UstD and will guide efforts to expand the reactivity of this unique enzyme.

e15034 Background: Identification of somatic variants in cancer by high-throughput sequencing has become common clinical practice largely because many of these variants may be predictive biomarkers for targeted therapies. However, there can be high sample QC failure rates for some assays (sometimes up to 40%), preventing the return of results that may affect patient treatment decisions. Pillar Biosciences has incorporated their patented SLIMamp technology into commercially available cancer NGS testing kits with the claim that these kits can successfully interrogate challenging formalin-fixed paraffin-embedded tissue (FFPET) samples with low tumor purity, poor DNA quality, and/or low input DNA, resulting in a high sample QC pass rate. The aim of this study was to substantiate that claim using Pillar’s amplicon-based oncoReveal Solid Tumor Panel. Methods: We acquired 48 tumor samples that had failed one or more pre-analytical QC sample parameters for whole exome sequencing (WES) from ATGC’s ISO15189 accredited diagnostic genomics laboratory. XING Genomic Services performed an exploratory data analysis using our pre-analytical QC assays to characterise the samples and then sequenced the samples in our ISO15189 accredited laboratory using the validated oncoReveal Solid Tumor Panel. Results: We were able to achieve high sequencing coverage (>3000X) for all 48 samples and explored the determinants of sample “success”. We were able to generate clinical reports for 45 samples (94%), of which 38 (79%) contained clinically actionable or significant variants that would not have otherwise been identified. Ten samples had a higher number of total variant calls with over-representation of C>T transitions representing stochastically-amplified, formalin-induced artefacts in samples with very low input template DNA. Of these, 7 cases had reportable variants and 3 were deemed unreportable. We demonstrated that DNA integrity is the major determinant of success even in samples with low input DNA or low tumor purity and were able to further refine pre-analytical and post-analytical QC metrics to better identify samples with poor quality DNA that can be sequenced reliably. Conclusions: In this study, we showed that the Pillar Biosciences oncoReveal Solid Tumor Panel, which uses SLIMam technology, was able to generate reliable, interpretable results for 94% of samples that failed pre-analytical QC for WES, substantiating Pillar’s claim.

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n = 594,881) and SCC (n = 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk = 45.45%, 95% confidence interval = 33.14–58.19%) and SCC (absolute risk = 44.12%, 95% confidence interval = 32.08–56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve = 0.77 vs. 0.75, P = 0.0691) and SCC (area under the curve = 0.84 vs. 0.82, P = 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R2 = 0.21 vs. 0.19, P = 3.2 × 10–3; SCC R2 = 0.30 vs. 0.27, P = 4.6 × 10–4).

Background Hospitalisation during the last weeks of life when there is no medical need or desire to be there is distressing and expensive. This study sought palliative care initiatives which may avoid or shorten hospital stay at the end of life and analysed their success in terms reducing bed days. Methods Part 1 included a search of literature in PubMed and Google Scholar between 2013 and 2018, an examination of governmental and organisational publications plus discussions with external and co-author experts regarding other sources. This initial sweep sought to identify and categorise relevant palliative care initiatives. In Part 2, we looked for publications providing data on hospital admissions and bed days for each category. Results A total of 1252 abstracts were reviewed, resulting in ten broad classes being identified. Further screening revealed 50 relevant publications describing a range of multi-component initiatives. Studies were generally small and retrospective. Most researchers claim their service delivered benefits. In descending frequency, benefits identified were support in the community, integrated care, out-of-hours telephone advice, care home education and telemedicine. Nurses and hospices were central to many initiatives. Barriers and factors underpinning success were rarely addressed. Conclusions A wide range of initiatives have been introduced to improve end-of-life experiences. Formal evidence supporting their effectiveness in reducing inappropriate/non-beneficial hospital bed days was generally limited or absent. Trial registration N/A

Hybridisation and introgression can have negative impacts on regional biodiversity through the potential erosion of locally adapted lineages. The honey bee (Apis mellifera L.) occurs in twenty-seven subspecies across Europe, is an extremely economically important insect, yet threatened by multifarious impacts. Transhumance of the most commercially appealing varieties threatens native honey bee diversity by introgression and subsequent loss of locally adapted traits, or even by complete removal of some subspecies from parts of the range. Here levels of admixture and introgression are examined in UK honey bees suspected to be from hives of the dark European honey bee (Apis mellifera mellifera). Microsatellite DNA and STRUCTURE analyses reveal that the studied populations are generally admixed, and discriminant analysis of principal components shows them to be intermediate between A. m. mellifera and Apis mellifera carnica populations. However, examining mitochondrial haplotype data (COI-COII intergenic spacer region) and nuclear DNA reveal that some hives are relatively pure (from 4 to 15 hives, depending on the Q-value threshold). Genetic diversity is relatively high in comparison with other European populations. Implications for conservation and management are discussed.

Atlantic salmon (Salmo salar L.) populations from different river origins mix in the North Atlantic during the marine life stage. To facilitate marine stock identification, we developed a genetic baseline covering the European component of the species’ range excluding the Baltic Sea, from the Russian River Megra in the north-east, the Icelandic Ellidaar in the west, and the Spanish Ulla in the south, spanning 3737 km North to South and 2717 km East to West. The baseline encompasses data for 14 microsatellites for 26 822 individual fish from 13 countries, 282 rivers, and 467 sampling sites. A hierarchy of regional genetic assignment units was defined using a combination of distance-based and Bayesian clustering. At the top level, three assignment units were identified comprising northern, southern, and Icelandic regions. A second assignment level was also defined, comprising eighteen and twenty-nine regional units for accurate individual assignment and mixed stock estimates respectively. The baseline provides the most comprehensive geographical coverage for an Atlantic salmon genetic data-set, and a unique resource for the conservation and management of the species in Europe. It is freely available to researchers to facilitate identification of the natal origin of European salmon.

Parasites are ubiquitous throughout nature and can have dramatic effects on their hosts. Although much is known about the pathology of parasites, the environmental factors influencing the distribution and abundance of parasites are poorly understood. Investigations into these factors could help predict the effect of parasites on the functioning of ecosystems. The limpet Patella vulgata is a key grazer on European rocky shores and is the first intermediate host for the trematode parasite, Echinostephilla patellae. This study investigated the spatial distribution of E. patellae in relation to P. vulgata at fourteen rocky shores around Ireland. Despite P. vulgata recruiting into rock pools, adults are more abundant on emergent rock and experience greater mortality in pools compared to emergent rock. It has been suggested that greater parasite prevalence in pools may be a factor driving this disjunct distribution pattern. Prevalence of infection was compared among rock and pool habitats. Size and sex of the host were also investigated in order to determine whether host phenotype influenced levels of infection prevalence. Results varied considerably among study sites, probably due to the heterogeneity of environmental conditions. No clear pattern emerged in relation to infection prevalence between habitats but this may be owing to the low numbers of limpets collected from pools. There was a significant positive relationship between infection prevalence and increasing host size. Individuals for which sex was indeterminate were more likely to be infected than distinct males or females, suggesting that infection may be causing castration and subsequent removal of these individuals from the breeding population. We discuss the importance of considering host-parasite dynamics in a period of rapid environmental change.

According to Cushman, rationalization occurs when a person has performed an action and then concocts beliefs and desires that would have made it rational. We argue that this isn't the paradigmatic form of rationalization. Consequently, Cushman's explanation of the function and usefulness of rationalization is less broad-reaching than he intends. Cushman's account also obscures some of rationalization's pernicious consequences.

The ability to determine the survey effort required to detect species presence is critical for the conservation of populations in order to monitor changes in distribution or abundance, a challenge for rare and elusive species. While designing an effective population survey may be of concern to scientists, it may also be a legal requirement for protected species. We analysed how spatial and temporal variation in sampling effort impacts detection probability in the hazel dormouse (Muscardinus avellanarius), a small mammal that naturally occurs at low density in forest habitat. We used presence and absence data from 144 sites in England, UK. We found that detection probability was strongly affected by survey intensity, with a 37.5% increase in detection probability when sampling effort was increased from 16 to 50 nest tubes per site. We also show that detection probability is highly temporally dependent; monitoring early in the year results in low detection probability (21%-53%; April-June), whilst detection dramatically increased later in the year (89%; September). Our results suggest that variation in detection probability can be complex and influenced by effects at temporal and spatial scales, and by sampling effort. We show that sampling effort can be minimised depending on seasonal variation in detection probability, however this is likely to be species and method dependent.

This chapter looks at the influence of Bishop’s poetry on Irish literature, specifically the work of Seamus Heaney and Colm Tóibín. In the process of doing so, it considers how different authors read Bishop and the extent to which Bishop might be said to read us at the same time. The chapter draws on Gillian White’s book, Lyric Shame, to explore these ideas, in particular her notion of entanglement.

This chapter offers an overview of Bishop Studies in the last 40 years. It analyses the posthumous publication of Bishop’s poems, prose, letters and unpublished material and identifies different phrases of criticism via influential readings of Bishop’s work. In the second half of the chapter, new trends in Bishop Studies are identified, alongside a consideration of Bishop’s presence in films, paintings and other media and her influence on contemporary writing.

Mass cytometry is a variation of conventional flow cytometry using metal tagged antibodies for cell staining instead of fluorochromes and detection in a mass cytometer, a modified mass spectrometer that allows for separation of discrete masses of these metal tags by time of flight (TOF). Currently, up to 50 different metal tags are available for cell analysis. The lack of any significant mass spectral overlap and autofluorescence background makes mass cytometry uniquely suited for complex high-dimensional phenotypic and functional analysis at the single cell level, thus accelerating biomarker discovery and drug screening. Here we describe a workflow for phenotyping of human peripheral blood mononuclear cells (PBMCs) covering cell staining, instrument setup of a Fluidigm Helios™ mass cytometer, and sample acquisition, and summarize a basic workflow of data analysis.