Effect of in-water administration of quorum system inhibitors in broilers' productive performance and intestinal microbiome in a mild necrotic enteritis challenge.

The poultry industry has been facing the impact of necrotic enteritis (NE), a disease caused by the bacterium Clostridium perfringens producing the haemolytic toxin NetB. NE severity may vary from mild clinical to prominent enteric signs causing reduced growth rates and affecting feed conversion ratio. NetB production is controlled by the Agr-like quorum-sensing (QS) system, which coordinates virulence gene expression in response to bacterial cell density. In this study, the peptide-containing cell-free spent media (CFSM) from Enterococcus faecium was tested in NE challenged broilers in two battery cage and one floor pen studies. Results showed a significant reduction of NE mortality. Metagenomic sequencing of the jejunum microbiome revealed no impact of the CFSM on the microbial community, and growth of C. perfringens was unaffected by CFSM in vitro. The expression of QS-controlled virulence genes netB, plc and pfoA was found to be significantly repressed by CFSM during the mid-logarithmic stage of C. perfringens growth and this corresponded with a significant decrease in haemolytic activity. Purified fractions of CFSM containing bioactive peptides were found to cause reduced haemolysis. These results showed that bioactive peptides reduce NE mortality in broilers by interfering with the QS system of C. perfringens and reducing bacterial virulence. Furthermore, the microbiome of C. perfringens-challenged broilers is not affected by quorum sensing inhibitor containing CFSM.

A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery.

Acute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double-blind, randomised feasibility trial comparing peri-operative angiotensin-2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin-2 or noradrenaline infusion intra-operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70-80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin-2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160-270 [30-315]) vs. 185 (135-301 [0-480]) min (p = 0.78) min intra-operatively, and 5 (0-16 [0-48]) vs. 14.5 (4.8-29 [0-48]) hours (p = 0.075) postoperatively for angiotensin-2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin-2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin-2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin-2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin-2 in cardiac surgery.

Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery.

BACKGROUND: The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. METHODS: This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). RESULTS: Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73-83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28-1.49) for ≤43 yr, 1.15 (1.09-1.20) for 44-63 yr, 1.05 (1.00-1.09) for 64-72 yr, and 1.03 (0.94-1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). CONCLUSIONS: We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

The association between peri-operative acute risk change (ARC) and long-term survival after cardiac surgery.

Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. 'Rising risk' represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.

Acute risk change (ARC) identifies outlier institutions in perioperative cardiac surgical care when the standardized mortality ratio cannot.

BACKGROUND: With improvements in short-term mortality after cardiac surgery, the sensitivity of the standardized mortality ratio (SMR) as a performance-monitoring tool has declined. We assessed acute risk change (ARC) as a new and potentially more sensitive metric to differentiate overall cardiac surgical unit performance. METHODS: Retrospective analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian and New Zealand Intensive Care Society Adult Patient Database was performed. The 16 656 patients who underwent coronary artery bypass grafting or cardiac valve procedures during a 4 yr period were included. The ARC was generated using the change between preoperative and postoperative probability of death. Outlier institutions were those with higher (outside 99.8% confidence intervals) ARC or SMR on annual and 4 yr funnel plots. Outliers were grouped and compared with non-outliers for baseline characteristics, intraoperative events, and postoperative morbidity. RESULTS: No outliers were identified using SMR. Two outliers were identified using ARC. Outliers had higher rates of new renal failure (5.7 vs 4.5%, P=0.017), stroke (1.6 vs 0.9%, P=0.001), reoperation (9 vs 6.0%, P<0.001), and prolonged ventilation (15.3 vs 9.5%, P<0.001). Outliers transfused more blood products (P<0.001) and had longer cardiopulmonary bypass times (P<0.001) and less senior surgeons operating (P<0.001). CONCLUSIONS: Acute risk change was able to discriminate between units where SMR could not. Outliers had more adverse events. Acute risk change can be calculated before mortality outcome and identifies outliers with lower patient numbers. This may allow early recognition and investigation of outlier units.

Python farming as a flexible and efficient form of agricultural food security.

Diminishing natural resources and increasing climatic volatility are impacting agri-food systems, prompting the need for sustainable and resilient alternatives. Python farming is well established in Asia but has received little attention from mainstream agricultural scientists. We measured growth rates in two species of large pythons (Malayopython reticulatus and Python bivittatus) in farms in Thailand and Vietnam and conducted feeding experiments to examine production efficiencies. Pythons grew rapidly over a 12-month period, and females grew faster than males. Food intake and growth rates early in life were strong predictors of total lifetime growth, with daily mass increments ranging from 0.24 to 19.7 g/day for M. reticulatus and 0.24 to 42.6 g/day for P. bivittatus, depending on food intake. Pythons that fasted for up to 4.2 months lost an average of 0.004% of their body mass per day, and resumed rapid growth as soon as feeding recommenced. Mean food conversion rate for dressed carcasses was 4.1%, with useable products (dressed carcass, skin, fat, gall bladder) comprising 82% of the mass of live animals. In terms of food and protein conversion ratios, pythons outperform all mainstream agricultural species studied to date. The ability of fasting pythons to regulate metabolic processes and maintain body condition enhances food security in volatile environments, suggesting that python farming may offer a flexible and efficient response to global food insecurity.

Social structure mediates environmental effects on group size in an obligate cooperative breeder, Suricata suricatta.

Population dynamics in group-living species can be strongly affected both by features of sociality per se and by resultant population structure. To develop a mechanistic understanding of population dynamics in highly social species we need to investigate how processes within groups, processes linking groups, and external drivers act and interact to produce observed patterns. We model social group dynamics in cooperatively breeding meerkats, Suricata suricatta, paying attention to local demographic as well as dispersal processes. We use generalized additive models to describe the influence of group size, population density, and environmental conditions on demographic rates for each sex and stage, and we combine these models into predictive and individual-based simulation models of group dynamics. Short-term predictions of expected group size and simulated group trajectories over the longer term agree well with observations. Group dynamics are characterized by slow increases during the breeding season and relatively sharp declines during the pre-breeding season, particularly after dry years. We examine the demographic mechanisms responsible for environmental dependence. While individuals appear more prone to emigrate after dry years, seasons of low rainfall also cause reductions in reproductive output that produce adult-biased age distributions in the following dispersal season. Adult subordinates are much more likely to disperse or be evicted than immature individuals, and demographic structure thus contributes to crashes in group size. Our results demonstrate the role of social structure in characterizing a population's response to environmental variation. We discuss the implications of our findings for the population dynamics of cooperative breeders and population dynamics generally.

Predicting trait values and measuring selection in complex life histories: reproductive allocation decisions in Soay sheep.

Accurate prediction of life history phenomena and characterisation of selection in free-living animal populations are fundamental goals in evolutionary ecology. In density regulated, structured populations, where individual state influences fate, simple and widely used approaches based on individual lifetime measures of fitness are difficult to justify. We combine recently developed structured population modelling tools with ideas from modern evolutionary game theory (adaptive dynamics) to understand selection on allocation of female reproductive effort to singletons or twins in a size-structured population of feral sheep. In marked contrast to the classical selection analyses, our model-based approach predicts that the female allocation strategy is under negligible directional selection. These differences arise because classical selection analysis ignores components of offspring fitness and fails to consider selection over the complete life cycle.

Overexpression of hns in the plant growth-promoting bacterium Enterobacter cloacae UW5 increases root colonization.

AIMS: Plant growth-promoting rhizobacteria (PGPR) introduced into soil often do not compete effectively with indigenous micro-organisms for plant colonization. The aim of this study was to identify novel genes that are important for root colonization by the PGPR Enterobacter cloacae UW5. METHODS AND RESULTS: A library of transposon mutants of Ent. cloacae UW5 was screened for mutants with altered ability to colonize canola roots using a thermal asymmetric interlaced (TAIL)-PCR-based approach. A PCR fragment from one mutant was reproducibly amplified at greater levels from genomic DNA extracted from mutant pools recovered from seedling roots 6 days after seed inoculation compared to that from the cognate inoculum cultures. Competition assays confirmed that the purified mutant designated Ent. cloacae J28 outcompetes the wild-type strain on roots but not in liquid cultures. In Ent. cloacae J28, the transposon is inserted upstream of the hns gene. Quantitative RT-PCR showed that transposon insertion increased expression of hns on roots. CONCLUSIONS: These results indicate that increased expression of hns in Ent. cloacae enhances competitive colonization of roots. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of the genes involved in plant colonization will contribute to the development of PGPR that can compete more effectively in agricultural soils.

Red deer stocks in the Highlands of Scotland.

Grazing by hill sheep and red deer prevents the regeneration of woodland in many parts of the Scottish Highlands and has also led to extensive loss of heather cover. Conservation bodies claim that there has been a rapid rise in Highland deer numbers caused by inadequate management and that these need to be drastically reduced. Here we show that the recent increase in red deer stocks has probably been overestimated and suggest that the gradual rise in numbers since 1970 may be a consequence of a reduction in sheep stocks and of changes in winter weather, rather than of a reduction in culling rate. Although there would be environmental benefits in reducing deer numbers, there is an equal need to reduce the numbers of hill sheep in many parts of the Highlands.

Why large-scale climate indices seem to predict ecological processes better than local weather.

Large-scale climatic indices such as the North Atlantic Oscillation are associated with population dynamics, variation in demographic rates and values of phenotypic traits in many species. Paradoxically, these large-scale indices can seem to be better predictors of ecological processes than local climate. Using detailed data from a population of Soay sheep, we show that high rainfall, high winds or low temperatures at any time during a 3-month period can cause mortality either immediately or lagged by a few days. Most measures of local climate used by ecologists fail to capture such complex associations between weather and ecological process, and this may help to explain why large-scale, seasonal indices of climate spanning several months can outperform local climatic factors. Furthermore, we show why an understanding of the mechanism by which climate influences population ecology is important. Through simulation we demonstrate that the timing of bad weather within a period of mortality can have an important modifying influence on intraspecific competition for food, revealing an interaction between climate and density dependence that the use of large-scale climatic indices or inappropriate local weather variables might obscure.

Sex determination in malaria parasites.

A century ago, W. G. MacCallum identified distinct male and female forms in malaria parasites of both birds and humans. Since then, scientists have been puzzled by the high female-to-male ratios of parasites in Plasmodium infections and by the mechanism of sex determination. The sex ratio of malaria parasites was shown to become progressively more male as conditions that allow motility and subsequent fertilization by the male parasites become adverse. This resulted from an increased immune response against male gametes, which coincides with intense host erythropoietic activity. Natural and artificial induction of erythropoiesis in vertebrate hosts provoked a shift toward male parasite production. This change in parasite sex ratio led to reduced reproductive success in the parasite, which suggests that sex determination is adaptive and is regulated by the hematologic state of the host.

Age, sex, density, winter weather, and population crashes in Soay sheep.

Quantifying the impact of density, extrinsic climatic fluctuations, and demography on population fluctuations is a persistent challenge in ecology. We analyzed the effect of these processes on the irregular pattern of population crashes of Soay sheep on the St. Kilda archipelago, United Kingdom. Because the age and sex structure of the population fluctuates independently of population size, and because animals of different age and sex respond in different ways to density and weather, identical weather conditions can result in different dynamics in populations of equal size. In addition, the strength of density-dependent processes is a function of the distribution of weather events. Incorporating demographic heterogeneities into population models can influence dynamics and their response to climate change.

Estimating the functional form for the density dependence from life history data.

Two contrasting approaches to the analysis of population dynamics are currently popular: demographic approaches where the associations between demographic rates and statistics summarizing the population dynamics are identified; and time series approaches where the associations between population dynamics, population density, and environmental covariates are investigated. In this paper, we develop an approach to combine these methods and apply it to detailed data from Soay sheep (Ovis aries). We examine how density dependence and climate contribute to fluctuations in population size via age- and sex-specific demographic rates, and how fluctuations in demographic structure influence population dynamics. Density dependence contributes most, followed by climatic variation, age structure fluctuations and interactions between density and climate. We then simplify the density-dependent, stochastic, age-structured demographic model and derive a new phenomenological time series which captures the dynamics better than previously selected functions. The simple method we develop has potential to provide substantial insight into the relative contributions of population and individual-level processes to the dynamics of populations in stochastic environments.

Analyzing complex capture-recapture data in the presence of individual and temporal covariates and model uncertainty.

SUMMARY: We consider the issue of analyzing complex ecological data in the presence of covariate information and model uncertainty. Several issues can arise when analyzing such data, not least the need to take into account where there are missing covariate values. This is most acutely observed in the presence of time-varying covariates. We consider mark-recapture-recovery data, where the corresponding recapture probabilities are less than unity, so that individuals are not always observed at each capture event. This often leads to a large amount of missing time-varying individual covariate information, because the covariate cannot usually be recorded if an individual is not observed. In addition, we address the problem of model selection over these covariates with missing data. We consider a Bayesian approach, where we are able to deal with large amounts of missing data, by essentially treating the missing values as auxiliary variables. This approach also allows a quantitative comparison of different models via posterior model probabilities, obtained via the reversible jump Markov chain Monte Carlo algorithm. To demonstrate this approach we analyze data relating to Soay sheep, which pose several statistical challenges in fully describing the intricacies of the system.

Estimating individual contributions to population growth: evolutionary fitness in ecological time.

Ecological and evolutionary change is generated by variation in individual performance. Biologists have consequently long been interested in decomposing change measured at the population level into contributions from individuals, the traits they express and the alleles they carry. We present a novel method of estimating individual contributions to population growth and changes in distributions of quantitative traits and alleles. An individual's contribution to population growth is an individual's realized annual fitness. We demonstrate how the quantities we develop can be used to address a range of empirical questions, and provide an application to a detailed dataset of Soay sheep. The approach provides results that are consistent with those obtained using lifetime estimates of individual performance, yet is substantially more powerful as it allows lifetime performance to be decomposed into annual survival and fecundity contributions.

Perioperative management of patients treated with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a quality improvement audit.

Previous studies have shown that patients continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers on the day of surgery are more likely to have significant intraoperative hypotension, higher rates of postoperative acute kidney injury, and lower incidences of postoperative atrial fibrillation. However, many of these studies were prone to bias and confounding, and questions remain over the validity of these outcomes. This observational, before-and-after quality improvement audit aimed to assess the effect of withholding these medications on the morning of surgery. We recruited 323 participants, with 83 (26%) having their preoperative angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) withheld on the day of surgery. There were only very small Spearman rank-order correlations between time since last dose of these medications (rho -0.12, P=0.057) and intraoperative and recovery room intravenous fluid administration (rho -0.11, P=0.042). There was no statistically significant difference between the continued or withheld groups in vasopressor (metaraminol use 3.5 [1.5-8.3] mg versus 3.5 [1.5-8.5] mg, P=0.67) or intravenous fluid administration (1000 ml [800-1500] ml versus 1000 [800-1500] ml, P=0.096), nor rates of postoperative acute kidney injury (13% vs 18%, P=0.25) or atrial fibrillation (15% versus 18%, P=0.71). This audit found no significant differences in measured outcomes between the continued or withheld ACEi/ARB groups. This finding should be interpreted with caution due to the possibility of confounding and an insufficient sample size. However, as the finding is in contrast to many previous studies, future prospective randomised clinical trials are required to answer this important question.

Estimating selection on neonatal traits in red deer using elasticity path analysis.

Van Tienderen recently published a method that links selection gradients between a phenotypic trait and multiple fitness components with the effects of these fitness components on the population growth rate (mean absolute fitness). The method allows selection to be simultaneously estimated across multiple fitness components in a population dynamic framework. In this paper we apply the method to a population of red deer living in the North Block of the Isle of Rum, Scotland. We show that (1) selection on birth date and birth weight can operate through multiple fitness components simultaneously; (2) our estimates of the response to selection are consistent with the observed change in trait values that we cannot explain with environmental and phenotypic covariates; (3) selection on both traits has fluctuated over the course of the study; (4) selection operates through different fitness components in different years; and (5) no environmental covariates correlate with selection because different fitness components respond to density and climatic variation in contrasting ways.