ABSTRACT
BACKGROUND: Timely and informed public health responses to infectious diseases such as COVID-19 necessitate reliable information about infection dynamics. The case ascertainment rate (CAR), the proportion of infections that are reported as cases, is typically much less than one and varies with testing practices and behaviours, making reported cases unreliable as the sole source of data. The concentration of viral RNA in wastewater samples provides an alternate measure of infection prevalence that is not affected by clinical testing, healthcare-seeking behaviour or access to care. METHODS: We construct a state-space model with observed data of levels of SARS-CoV-2 in wastewater and reported case incidence and estimate the hidden states of the effective reproduction number, R, and CAR using sequential Monte Carlo methods. RESULTS: We analyse data from 1 January 2022 to 31 March 2023 from Aotearoa New Zealand. Our model estimates that R peaks at 2.76 (95% CrI 2.20, 3.83) around 18 February 2022 and the CAR peaks around 12 March 2022. We calculate that New Zealand's second Omicron wave in July 2022 is similar in size to the first, despite fewer reported cases. We estimate that the CAR in the BA.5 Omicron wave in July 2022 is approximately 50% lower than in the BA.1/BA.2 Omicron wave in March 2022. CONCLUSIONS: Estimating R, CAR, and cumulative number of infections provides useful information for planning public health responses and understanding the state of immunity in the population. This model is a useful disease surveillance tool, improving situational awareness of infectious disease dynamics in real-time.
To make informed public health decisions about infectious diseases, it is important to understand the number of infections in the community. Reported cases, however, underestimate the number of infections and the degree of underestimation likely changes with time. Wastewater data provides an alternative data source that does not depend on testing practices. Here, we combined wastewater observations of SARS-CoV-2 with reported cases to estimate the reproduction number (how quickly infections are increasing or decreasing) and the case ascertainment rate (the fraction of infections reported as cases). We apply the model to Aotearoa New Zealand and demonstrate that the second wave of infections in July 2022 had approximately the same number of infections as the first wave in March 2022 despite reported cases being 50% lower.
ABSTRACT
Antimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes and are therefore expected to be rapidly evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that insect AMPs tend to evolve more slowly than the genome average. Metchikowin (Mtk) is a Drosophila AMP that has a single amino acid residue that segregates as either proline (P) or arginine (R) in populations of four different species, some of which diverged more than 10 million years ago. These results suggest that there is a distinct functional importance to each allele. The most likely hypotheses are driven by two main questions: does each allele have a different efficacy against different specific pathogens (specificity hypothesis)? Or, is one allele a more potent antimicrobial, but with a host fitness cost (autoimmune hypothesis)? To assess their functional differences, we created D. melanogaster lines with the P allele, R allele, or Mtk null mutation using CRISPR/Cas9 genome editing and performed a series of life history and infection assays to assess them. In males, testing of systemic immune responses to a repertoire of bacteria and fungi demonstrated that the R allele performs as well or better than the P and null alleles with most infections. Females show some results that contrast with males, with Mtk alleles either not contributing to survival or with the P allele outperforming the R allele. In addition, measurements of life history traits demonstrate that the R allele is more costly in the absence of infection for both sexes. These results are consistent with both the specificity hypothesis (either allele can perform better against certain pathogens depending on context), and the autoimmune hypothesis (the R allele is generally the more potent antimicrobial in males, and carries a fitness cost). These results provide strong in vivo evidence that differential fitness with or without infection and sex-based functional differences in alleles may be adaptive mechanisms of maintaining immune gene polymorphisms in contrast with expectations of rapid evolution. Therefore, a complex interplay of forces including pathogen species and host sex may lead to balancing selection for immune genotypes. Strikingly, this selection may act on even a single amino acid polymorphism in an AMP.
Subject(s)
Anti-Infective Agents , Drosophila , Male , Female , Animals , Drosophila/genetics , Drosophila melanogaster/genetics , Alleles , Amino Acids/genetics , Polymorphism, GeneticABSTRACT
Antimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes and are therefore expected to be fast evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that one AMP, Metchikowin (Mtk), has a single residue that segregates as either proline (P) or arginine (R) in populations of four different Drosophila species, some of which diverged more than 10 million years ago. The recurrent finding of this polymorphism regardless of geography or host species, coupled with evidence of balancing selection in Drosophila AMPs, suggest there is a distinct functional importance to each allele. The most likely hypotheses involve alleles having specificity to different pathogens or the more potent allele conferring a cost on the host. To assess their functional differences, we created D. melanogaster lines with the P allele, R allele, or Mtk null mutation using CRISPR/Cas9 genome editing. Here, we report results from experiments assessing the two hypotheses using these lines. In males, testing of systemic immune responses to a repertoire of bacteria and fungi demonstrated that the R allele performs as well or better than the P and null alleles with most infections. With some pathogens, however, females show results in contrast with males where Mtk alleles either do not contribute to survival or where the P allele outperforms the R allele. In addition, measurements of life history traits demonstrate that the R allele is more costly in the absence of infection for both sexes. These results provide strong in vivo evidence that differential fitness with or without infection and sex-based functional differences in alleles may be adaptive mechanisms of maintaining immune gene polymorphisms in contrast with expectations of rapid evolution. Therefore, a complex interplay of forces including pathogen species and host sex may lead to balancing selection for immune genotypes. Strikingly, this selection may act on even a single amino acid polymorphism in an AMP.
ABSTRACT
To assist public health responses to COVID-19, wastewater-based epidemiology (WBE) is being utilised internationally to monitor SARS-CoV-2 infections at the community level. However, questions remain regarding the sensitivity of WBE and its use in low prevalence settings. In this study, we estimated the total number of COVID-19 cases required for detection of SARS-CoV-2 RNA in wastewater. To do this, we leveraged a unique situation where, over a 4-month period, all symptomatic and asymptomatic cases, in a population of approximately 120,000, were precisely known and mainly located in a single managed isolation and quarantine facility (MIQF) building. From 9 July to 6 November 2020, 24-hr composite wastewater samples (n = 113) were collected daily from the sewer outside the MIQF, and from the municipal wastewater treatment plant (WWTP) located 5 km downstream. New daily COVID-19 cases at the MIQF ranged from 0 to 17, and for most of the study period there were no cases outside the MIQF identified. SARS-CoV-2 RNA was detected in 54.0% (61/113) at the WWTP, compared to 95.6% (108/113) at the MIQF. We used logistic regression to estimate the shedding of SARS-CoV-2 RNA into wastewater based on four infectious shedding models. With a total of 5 and 10 COVID-19 infectious cases per 100,000 population (0.005% and 0.01% prevalence) the predicated probability of SARS-CoV-2 RNA detection at the WWTP was estimated to be 28 and 41%, respectively. When a proportional shedding model was used, this increased to 58% and 87% for 5 and 10 cases, respectively. In other words, when 10 individuals were actively shedding SARS-CoV-2 RNA in a catchment of 100,000 individuals, there was a high likelihood of detecting viral RNA in wastewater. SARS-CoV-2 RNA detections at the WWTP were associated with increasing COVID-19 cases. Our results show that WBE provides a reliable and sensitive platform for detecting infections at the community scale, even when case prevalence is low, and can be of use as an early warning system for community outbreaks.
Subject(s)
COVID-19 , RNA, Viral , Humans , Prevalence , RNA, Viral/genetics , SARS-CoV-2 , Wastewater , Wastewater-Based Epidemiological MonitoringABSTRACT
Blockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 antibody, pembrolizumab (Keytruda) on the activation of human T cells: focussing on the release of pro-inflammatory IFNγ and anti-inflammatory IL-10 to assess functionality. Firstly, we investigated the actions of pembrolizumab in an acute model of T-cell activation with either immature or mature allogeneic dendritic cells (DCs); pembrolizumab enhanced IFNγ and IL-10 release from purified CD4+ T-cells in the majority of donors with a bias towards pro-inflammatory cytokine release. Next, we modelled the impact of pembrolizumab in settings of more chronic T-cell activation. In a 7-day antigen-specific response to EBV peptides, the presence of pembrolizumab resulted in a relatively modest increase in both IFNγ and IL-10 release. Where pembrolizumab was assessed against long-term stimulated CD4+ cells that had up-regulated the exhaustion markers TIM-3 and PD-1, there was a highly effective enhancement of the otherwise exhausted response to allogeneic DCs with respect to IFNγ production. By contrast, the restoration of IL-10 production was considerably more limited. Finally, to assess a direct clinical relevance we investigated the consequence of PD-1/PD-L1 blockade in the disease setting of dissociated cells from lung and colon carcinomas responding to allogeneic DCs: here, pembrolizumab once more enhanced IFNγ production from the majority of tumour preparations whereas, again, the increase in IL-10 release was modest at best. In conclusion, we have shown that the contribution of PD-1-revealed by using a canonical blocking antibody to interrupt its interaction with PD-L1-to the production of an exemplar pro- and anti-inflammatory cytokine, respectively, depends in magnitude and ratio on the particular stimulation setting and activation status of the target T cell. We have identified a number of in vitro assays with response profiles that mimic features of dissociated cell populations from primary tumours thereby indicating these represent disease-relevant functional assays for the screening of immune checkpoint inhibitors in current and future development. Such in vitro assays may also support patient stratification of those likely to respond to immuno-oncology therapies in the wider population.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Lymphocyte Activation/drug effects , T-Lymphocytes/metabolism , Antibodies, Monoclonal, Humanized/metabolism , B7-H1 Antigen/drug effects , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cytokines/immunology , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Immune Checkpoint Inhibitors/pharmacology , Immunotherapy/methods , Lymphocyte Activation/genetics , Neoplasms/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/drug effects , Programmed Cell Death 1 Receptor/metabolism , T-Lymphocytes/drug effectsABSTRACT
Changes within the Coronary veins secondary to pacing leads have not been described, this study assessed these changes in explanted hearts. Macroscopically fibrous sheaths formed around longstanding leads, leading to slit like channels for venous return in smaller veins. Histologically changes included bland fibrosis, a foreign body response to the lead, a chronic inflammatory response and inflammatory destruction of the media. Individuals responded in different ways with no clear relationship of changes to duration of the lead.
Subject(s)
Coronary Vessels/pathology , Foreign-Body Reaction/pathology , Inflammation/pathology , Pacemaker, Artificial/adverse effects , Equipment Design , Fibrosis , Foreign-Body Reaction/etiology , Humans , Inflammation/etiologyABSTRACT
Dissecting the genetic basis of natural variation in disease response in hosts provides insights into the coevolutionary dynamics of host-pathogen interactions. Here, a genome-wide association study of Drosophila melanogaster survival after infection with the Gram-positive entomopathogenic bacterium Enterococcus faecalis is reported. There was considerable variation in defense against E. faecalis infection among inbred lines of the Drosophila Genetics Reference Panel. We identified single nucleotide polymorphisms associated with six genes with a significant (p < 10-08, corresponding to a false discovery rate of 2.4%) association with survival, none of which were canonical immune genes. To validate the role of these genes in immune defense, their expression was knocked-down using RNAi and survival of infected hosts was followed, which confirmed a role for the genes krishah and S6k in immune defense. We further identified a putative role for the Bomanin gene BomBc1 (also known as IM23), in E. faecalis infection response. This study adds to the growing set of association studies for infection in Drosophila melanogaster and suggests that the genetic causes of variation in immune defense differ for different pathogens.
Subject(s)
Drosophila melanogaster/genetics , Drosophila melanogaster/immunology , Genetic Variation/genetics , Animals , Drosophila Proteins/genetics , Drosophila Proteins/immunology , Drosophila Proteins/metabolism , Drosophila melanogaster/microbiology , Enterococcus faecalis/genetics , Enterococcus faecalis/immunology , Enterococcus faecalis/pathogenicity , Genome-Wide Association Study , Gram-Positive Bacteria/genetics , Gram-Positive Bacteria/immunology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Immunity, Innate/genetics , Selection, Genetic/geneticsABSTRACT
Benign xanthomatous pseudotumors are rare, mass forming lesions composed of lipid laden histiocytes and tumor necrosis following chemotherapy. We present a rare case of young 36 year old male with primary mediastinal Hodgkin's lymphoma who developed xanthomatous pseudotumor mimicking relapse at the site of original disease on positron emission tomography. This scenario places emphasis on histologic confirmation of suspected treatment failure or relapse.
ABSTRACT
Genes involved in immune defense against pathogens provide some of the most well-known examples of both directional and balancing selection. Antimicrobial peptides (AMPs) are innate immune effector genes, playing a key role in pathogen clearance in many species, including Drosophila. Conflicting lines of evidence have suggested that AMPs may be under directional, balancing, or purifying selection. Here, we use both a linear model and control-gene-based approach to show that balancing selection is an important force shaping AMP diversity in Drosophila. In Drosophila melanogaster, this is most clearly observed in ancestral African populations. Furthermore, the signature of balancing selection is even more striking once background selection has been accounted for. Balancing selection also acts on AMPs in Drosophila mauritiana, an isolated island endemic separated from D. melanogaster by about 4 Myr of evolution. This suggests that balancing selection may be broadly acting to maintain adaptive diversity in Drosophila AMPs, as has been found in other taxa.
Subject(s)
Antimicrobial Cationic Peptides/genetics , Drosophila Proteins/genetics , Drosophila/classification , Drosophila/genetics , Evolution, Molecular , Animals , Drosophila melanogaster/genetics , Selection, GeneticABSTRACT
This article provides data on primer sequences used to amplify the innate immune genes RIG-I and Mx and a set of normalizing reference genes in mallards (Anas platyrhynchos), and shows which reference genes are stable, per tissue, for our experimental settings. Data on the expressional changes of these two genes over a time-course of infection with low pathogenic avian influenza virus (LPAI) are provided. Individual-level data are also presented, including LPAI infection load, and per tissue gene expression of RIG-I and Mx. Gene expression in two outlier individuals is explored in more depth.
ABSTRACT
The vertebrate innate immune system provides hosts with a rapid, non-specific response to a wide range of invading pathogens. However, the speed and duration of innate responses will be influenced by the co-evolutionary dynamics of specific host-pathogen combinations. Here, we show that low pathogenic avian influenza virus (LPAI) subtype H1N1 elicits a strong but extremely transient innate immune response in its main wildlife reservoir, the mallard (Anas platyrhynchos). Using a series of experimental and methodological improvements over previous studies, we followed the expression of retinoic acid inducible gene 1 (RIG-I) and myxovirus resistance gene (Mx) in mallards semi-naturally infected with low pathogenic H1N1. One day post infection, both RIG-I and Mx were significantly upregulated in all investigated tissues. By two days post infection, the expression of both genes had generally returned to basal levels, and remained so for the remainder of the experiment. This is despite the fact that birds continued to actively shed viral particles throughout the study period. We additionally show that the spleen plays a particularly active role in the innate immune response to LPAI. Waterfowl and avian influenza viruses have a long co-evolutionary history, suggesting that the mallard innate immune response has evolved to provide a minimum effective response to LPAIs such that the viral infection is brought under control while minimising the damaging effects of a sustained immune response.
Subject(s)
Ducks , Immunity, Innate/physiology , Influenza A Virus, H1N1 Subtype/immunology , Influenza in Birds/immunology , Animals , Ducks/genetics , Ducks/immunology , Ducks/virology , Gene Expression Regulation , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Immunity, Innate/genetics , Influenza in Birds/genetics , Male , Pathogen-Associated Molecular Pattern Molecules/metabolism , Poultry Diseases/genetics , Poultry Diseases/immunology , Poultry Diseases/virology , Transcription Factors/geneticsABSTRACT
AIM AND OBJECTIVES: To describe and compare identification of delirium, length of stay and discharge locations in two patient samples of falls, before and after an organisation-wide interprofessional delirium education and practice change along with implementation of a policy. BACKGROUND: Delirium is a common and severe problem for hospitalised patients, with occurrence ranging from 14%-56%, morbidity and mortality from 25%-33%. Recent studies report that 73%-96% of patients who fell during a hospital stay had symptoms of delirium; however, the delirium went undiagnosed and untreated in 75% of the cases. DESIGN: A descriptive, retrospective observational study using a pre/postdesign. METHODS: Two chart reviews were performed on patient falls as identified in the hospital safety reporting system in 2009-2010 (98 fallers) and 2012 (108 fallers). An organisation-wide education was planned and implemented with monitoring of policy compliance. RESULTS: After the education, documentation of the "diagnosis of delirium" and "no evidence of delirium" increased from 14.3%-29.5% and from 27.6%-44.4%. The documentation of "evidence of delirium" decreased significantly from 58.2%-25.9% (p < .001). The confusion assessment method (CAM) identified the diagnosis of delirium at 76% accuracy. The length of stay decreased by 7.3 days. The fall rates in 2011 and 2012 were 3.01 and 2.82 falls per 1,000 patient days and in 2013 decreased to 2.16. CONCLUSION: The results indicate that improving delirium recognition and treatment through interprofessional education can reduce falls and length of stay. RELEVANCE TO CLINICAL PRACTICE: The results demonstrate that when staff learn to prevent, identify, manage and document delirium more accurately the fall rate decreases. The practice change, including the use of CAM, was sustained by continuous auditing including re-education, and the re-enforcement of learning along with the implementation of a policy.
Subject(s)
Accidental Falls/statistics & numerical data , Delirium/diagnosis , Delirium/therapy , Aged , Controlled Before-After Studies , Critical Care/methods , Critical Care/statistics & numerical data , Delirium/epidemiology , Delirium/etiology , Female , Humans , Inservice Training , Length of Stay/statistics & numerical data , Male , Quality Improvement , Retrospective StudiesABSTRACT
In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. ß-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five ß-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific ß-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated ß-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of ß-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian ß-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.
Subject(s)
Anseriformes/genetics , Anseriformes/immunology , beta-Defensins/genetics , Alleles , Amino Acid Sequence , Animals , Antimicrobial Cationic Peptides/genetics , Evolution, Molecular , Gene Duplication , Genetic Variation , Immunity, Innate/genetics , Multigene Family/genetics , Phylogeny , Selection, Genetic , beta-Defensins/immunologyABSTRACT
BACKGROUND: Delirium has been previously implicated as a risk factor for patient falls. This is a replication study of a 2009 investigation examining the prevalence of diagnosed and undiagnosed delirium in patients who fell during their hospital stay. OBJECTIVE: To determine the prevalence of delirium at our institution and to examine the relationship of falls with delirium, advanced age, and hospital procedures. METHOD: Using the data collection tool developed for the 2009 study, the authors performed a retrospective review of records of 99 patients who fell during their inpatient stay. Similar information was gathered on patient demographics, fall date, fall location, hospital service type, discharge disposition, diagnosis of delirium (DD), synonyms used to describe delirium, metabolic derangements, and surgeries or procedures performed. Data were collected on the day of admission, day of the fall, and 2 days before the fall. RESULTS: Falls in the general hospital were associated with delirium (73% of subjects had evidence or a DD at the time of their fall), advanced age (64.5% were older than 70 years), and specific procedures and surgeries. CONCLUSION: As identified in the previous study, improving delirium recognition and treatment may reduce the number of patient falls and promote more favorable outcomes such as reduced length of stay, fewer discharges to intermediate care facilities, and prevention of fall injuries. A comprehensive fall risk assessment that includes a delirium detection tool would improve the sensitivity and specificity of these instruments to detect those at greatest risk.
Subject(s)
Accidental Falls/statistics & numerical data , Delirium/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Delirium/diagnosis , Female , Hospitalization , Hospitals, General , Hospitals, Teaching , Hospitals, Urban , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Tertiary Care Centers , Young AdultABSTRACT
Determining which reference genes have the highest stability, and are therefore appropriate for normalising data, is a crucial step in the design of real-time quantitative PCR (qPCR) gene expression studies. This is particularly warranted in non-model and ecologically important species for which appropriate reference genes are lacking, such as the mallard--a key reservoir of many diseases with relevance for human and livestock health. Previous studies assessing gene expression changes as a consequence of infection in mallards have nearly universally used ß-actin and/or GAPDH as reference genes without confirming their suitability as normalisers. The use of reference genes at random, without regard for stability of expression across treatment groups, can result in erroneous interpretation of data. Here, eleven putative reference genes for use in gene expression studies of the mallard were evaluated, across six different tissues, using a low pathogenic avian influenza A virus infection model. Tissue type influenced the selection of reference genes, whereby different genes were stable in blood, spleen, lung, gastrointestinal tract and colon. ß-actin and GAPDH generally displayed low stability and are therefore inappropriate reference genes in many cases. The use of different algorithms (GeNorm and NormFinder) affected stability rankings, but for both algorithms it was possible to find a combination of two stable reference genes with which to normalise qPCR data in mallards. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies in ducks. The fact that nearly all previous studies of the influence of pathogen infection on mallard gene expression have used a single, non-validated reference gene is problematic. The toolkit of putative reference genes provided here offers a solid foundation for future studies of gene expression in mallards and other waterfowl.
Subject(s)
Ducks/genetics , Gene Expression Regulation , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/standards , Animals , Genetic Association Studies , Reference Standards , SoftwareABSTRACT
The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with ß-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.
Subject(s)
Gene Expression Profiling/methods , Gene Expression , Genes , Real-Time Polymerase Chain Reaction/standards , Animals , Humans , Mammals/classification , Mammals/genetics , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/methods , Reference Standards , Research Design , Specimen Handling , Statistics, Nonparametric , Transcription, GeneticABSTRACT
Understanding causes of variation in promiscuity within populations remain a major challenge. While most studies have focused on quantifying fitness costs and benefits of promiscuous behaviour, an alternative possibility--that variation in promiscuity within populations is maintained because of linkage with other traits-has received little attention. Here, we examine whether promiscuity in male and female great tits (Parus major)--quantified as extra-pair paternity (EPP) within and between nests--is associated with variation in a well-documented personality trait: exploration behaviour in a novel environment. Exploration behaviour has been shown to correlate with activity levels, risk-taking and boldness, and these are behaviours that may plausibly influence EPP. Exploration behaviour correlated positively with paternity gained outside the social pair among males in our population, but there was also a negative correlation with paternity in the social nest. Hence, while variation in male personality predicted the relative importance of paternity gain within and outside the pair bond, total paternity gained was unrelated to exploration behaviour. We found evidence that males paired with bold females were more likely to sire extra-pair young. Our data thus demonstrate a link between personality and promiscuity, with no net effects on reproductive success, suggesting personality-dependent mating tactics, in contrast with traditional adaptive explanations for promiscuity.
Subject(s)
Passeriformes/physiology , Paternity , Personality/physiology , Reproduction/physiology , Sexual Behavior, Animal/physiology , Animals , Exploratory Behavior/physiology , Female , MaleABSTRACT
A major theoretical consequence of selection at a locus is the genetic hitchhiking of linked sites (selective sweep). The extent of hitchhiking around a gene is related to the strength of selection and the rate of recombination, with its impact diminishing with distance from the selected site. At the Rop-1 locus of the sheep blowfly, Lucilia cuprina, polymorphisms at two different sites within the LcαE7 gene encode forms of the protein that confer organophosphorus insecticide resistance. To assess the impact of selection at these two sites on variation around LcαE7, we sequenced regions within six other genes along chromosome IV across isogenic (IV) strains of L. cuprina. High levels of linkage disequilibrium, characterized by low haplotype number (K) and diversity (H), and significant R(2) values were observed for two genes, LcαE1 and LcαE10, both members of the same α-esterase gene cluster as LcαE7. A significant R(2) value was also observed for a gene predicted to be the next closest to LcαE7, AL03, but not for any of the other genes, LcRpL13a, Lcdsx, or LcAce. Skews in the site frequency spectra toward high-frequency variants were significant for LcαE1 (Fay and Wu's H = -2.91), LcαE10 (H = -1.85), and Lcdsx (H = -2.00). Since the selective sweeps, two forms of likely returning variation were observed, including variation in microsatellites in an intron of LcαE10 and a recombination event between LcαE7 and LcαE10. These data suggest that two incomplete soft sweeps have occurred at LcαE7 that have significantly affected variation across, and beyond, the α-esterase gene cluster of L. cuprina. The speed and impact of these selective sweeps on surrounding genomic variation and the ability of L. cuprina to respond to future environmental challenges are discussed.
Subject(s)
Diptera/genetics , Esterases/genetics , Genes, Insect/genetics , Genetic Variation , Insecticide Resistance/genetics , Multigene Family/genetics , Animals , Base Sequence , Cluster Analysis , Diptera/enzymology , Evolution, Molecular , Haplotypes/genetics , Insecticides , Linkage Disequilibrium/genetics , Male , Microsatellite Repeats/genetics , Molecular Sequence Data , Polymorphism, Genetic , Sequence AlignmentABSTRACT
AIM: This paper reports on a study undertaken to test the sensitivity, specificity and feasibility of four fall risk assessment tools. BACKGROUND: Falls risk assessment tools have been developed based on literature and findings from empirical studies, but the instruments often lack further testing in the clinical setting. METHOD: Four falls risk assessment tools were tested simultaneously in this study. The data was collected in May-June 2006. All assessment tools were completed on a total of 1546 patients. Descriptive statistics were used for data analysis. RESULTS: The use of the instruments was moderately consistent among registered nurses, but the education provided did not entirely eliminate problems with accuracy. The sensitivity of the instruments was 57.1-100% and specificity was 24.9-69.3%. CONCLUSION: The sensitivity and specificity of the instruments are important factors to consider when choosing an instrument. However, the strategies to educate staff and to intervene appropriately are equally important for an organization undertaking a proactive stance in mitigating the risk of falls. IMPLICATIONS FOR NURSING MANAGEMENT: It is important for managers to test instruments in their own organizations and specific populations. It is also critical to carefully assess that the chosen instrument is easy and accurate in use.
Subject(s)
Accidental Falls/prevention & control , Nursing Assessment/methods , Risk Assessment/methods , Accidental Falls/statistics & numerical data , Bias , Clinical Competence , Clinical Nursing Research , Cross-Sectional Studies , Education, Nursing, Continuing , Feasibility Studies , Humans , Maine/epidemiology , Models, Nursing , Nurse Administrators , Nursing Assessment/standards , Nursing Evaluation Research , Nursing Staff, Hospital/education , Nursing Staff, Hospital/organization & administration , Pilot Projects , Practice Patterns, Nurses'/organization & administration , Risk Assessment/standards , Risk Factors , Sensitivity and SpecificityABSTRACT
AIM: To evaluate currently available paediatric falls assessments instruments and to build a predictive fall model while also evaluating injury risk as a predictor of fall likelihood within the paediatric inpatient population. BACKGROUND: There is lack of paediatric-specific fall assessment instruments and little information on the exploration of injury risk as related to falls in hospitalized children. METHOD: An ambispective, matched case-control design conducted in a sample of 100 inpatient paediatric patients. Results Two out of five instruments performed well to classify children at risk of falls. Longer length of stay, bleeding cautions/blood disorders and temperament/behaviour issues were significant predictors of fall likelihood. Cognitive impairment or neurological disease was not related to an increased likelihood of fall or injury risk for this sample. CONCLUSIONS: More research is required to institute and standardize paediatric fall and injury risk assessments for everyday use. The explicit approach of using predictive modelling is critical in creating a universal, baseline reference for the most reliable and valid measure of assessment in children. IMPLICATIONS FOR NURSING MANAGEMENT: Findings of the present study increase awareness of nursing managers and leaders as to the necessity for fall and injury risk assessment as a safety and quality measure for inpatient paediatric populations.