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.

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.

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.

3-M syndrome: a growth disorder associated with IGF2 silencing.

3-M syndrome is an autosomal recessive disorder characterised by pre- and post-natal growth restriction, facial dysmorphism, normal intelligence and radiological features (slender long bones and tall vertebral bodies). It is known to be caused by mutations in the genes encoding cullin 7, obscurin-like 1 and coiled-coil domain containing 8. The mechanisms through which mutations in these genes impair growth are unclear. The aim of this study was to identify novel pathways involved in the growth impairment in 3-M syndrome. RNA was extracted from fibroblast cell lines derived from four 3-M syndrome patients and three control subjects, hybridised to Affymetrix HU 133 plus 2.0 arrays with quantitative real-time PCR used to confirm changes found on microarray. IGF-II protein levels in conditioned cell culture media were measured by ELISA. Of the top 10 downregulated probesets, three represented IGF2 while H19 was identified as the 23rd most upregulated probeset. QRT-PCR confirmed upregulation of H19 (P<0.001) and downregulation of IGF2 (P<0.001). Levels of IGF-II secreted into conditioned cell culture medium were higher for control fibroblasts than those for 3-M fibroblasts (10.2±2.9 vs 0.6±0.9 ng/ml, P<0.01). 3-M syndrome is associated with a gene expression profile of reduced IGF2 expression and increased H19 expression similar to that found in Silver-Russell syndrome. Loss of autocrine IGF-II in the growth plate may be associated with the short stature seen in children with 3-M syndrome.

Exploring the effects of immunity and life history on the dynamics of an endogenous retrovirus.

Mammalian DNA is littered with the signatures of past retroviral infections. For example, at least 8% of the human genome can be attributed to endogenous retroviruses (ERVs). We take a single-locus approach to develop a simple susceptible-infected-recovered model to investigate the circumstances under which a disease-causing retrovirus can become incorporated into the host genome and spread through the host population if it were to confer an immunological advantage. In the absence of any fitness benefit provided by the long terminal repeat (LTR), we conclude that signatures of ERVs are likely to go to fixation within a population when the probability of evolving cellular/humoral immunity to a related exogenous version of the virus is extremely small. We extend this model to examine whether changing the speed of the host life history influences the likelihood that an exogenous retrovirus will incorporate and spread to fixation. Our results reveal the parameter space under which incorporation of exogenous retroviruses into a host genome may be beneficial to the host. In our final model, we find that the likelihood of an LTR reaching fixation in a host population is not strongly affected by host life history.

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.

Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling.

3-M syndrome is a primordial growth disorder caused by mutations in CUL7, OBSL1 or CCDC8. 3-M patients typically have a modest response to GH treatment, but the mechanism is unknown. Our aim was to screen 13 clinically identified 3-M families for mutations, define the status of the GH-IGF axis in 3-M children and using fibroblast cell lines assess signalling responses to GH or IGF1. Eleven CUL7, three OBSL1 and one CCDC8 mutations in nine, three and one families respectively were identified, those with CUL7 mutations being significantly shorter than those with OBSL1 or CCDC8 mutations. The majority of 3-M patients tested had normal peak serum GH and normal/low IGF1. While the generation of IGF binding proteins by 3-M cells was dysregulated, activation of STAT5b and MAPK in response to GH was normal in CUL7(-/-) cells but reduced in OBSL1(-/-) and CCDC8(-/-) cells compared with controls. Activation of AKT to IGF1 was reduced in CUL7(-/-) and OBSL1(-/-) cells at 5 min post-stimulation but normal in CCDC8(-/-) cells. The prevalence of 3-M mutations was 69% CUL7, 23% OBSL1 and 8% CCDC8. The GH-IGF axis evaluation could reflect a degree of GH resistance and/or IGF1 resistance. This is consistent with the signalling data in which the CUL7(-/-) cells showed impaired IGF1 signalling, CCDC8(-/-) cells showed impaired GH signalling and the OBSL1(-/-) cells showed impairment in both pathways. Dysregulation of the GH-IGF-IGF binding protein axis is a feature of 3-M syndrome.

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.

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.

Age-related shapes of the cost of reproduction in vertebrates.

The shape of the association between age and the cost of reproduction varies across species. However, it is unclear whether there are any general patterns in the way the cost of reproduction varies with life history, taxon or ecological function. Using a simple theoretical method, we identified three characteristic patterns to describe the age-related survival cost of reproduction. The most frequent pattern is an approximately exponential decay (ED) with increasing age. Two additional u-shaped patterns were identified, where the cost of reproduction was higher for young and old individuals compared with intermediate-aged individuals. The majority of these u-shaped curves suggested higher costs of reproduction at older ages (RQ), with the rest suggesting a higher cost at young ages (LQ). While predators were most likely to exhibit ED-shaped cost curves, herbivores were equally likely to exhibit ED and RQ curves; birds were likely to exhibit ED-shaped curves and mammals were split equally between ED and RQ curves. These findings suggest that there may be predictable differences in the age-related shape of the cost of reproduction between species, but further research is required to identify the mechanisms generating such differences.

Evolutionary responses to harvesting in ungulates.

1. We investigate the evolutionary responses to harvesting in ungulates using a state-dependent, stochastic, density-dependent individual-based model of red deer Cervus elaphus (L.) females subject to different harvesting regimes. 2. The population's mean weight at first reproduction shifts towards light weights as harvesting increases, and its distribution changes from a single peak distribution under very low or high harvest rates, to a bimodal distribution under intermediate harvest rates. 3. These results suggest that, consistent with previous studies on aquatic species, harvesting-induced mortality may drive adaptive responses in ungulates by reducing the fitness benefits from adult survival and growth in favour of early and lightweight reproduction. 4. Selective harvesting for heavy animals has no additional effect on the evolutionarily stable strategy, suggesting that harvest rate is more important than the degree of selectivity in driving adaptive responses. However, selective harvesting of light females is positively associated with maturation weights even higher than those of a nonharvested population, probably due to the reduction in the fitness value of the offspring. 5. The average number of weight at maturation strategies in the population declines but the total number of strategies across all simulations increases with harvest rate, suggesting that harvesting-induced selection on weight at maturity overcomes the increase in strategy diversity expected from density-dependent release. 6. Yield initially increases with harvesting due to enhanced productivity of light females experiencing density-dependent release. However, it crashes under intense harvesting resulting in a population skewed to light, young and, therefore, less reproductive animals.

The contributions of age and sex to variation in common tern population growth rate.

1. The decomposition of population growth rate into contributions from different demographic rates has many applications, ranging from evolutionary biology to conservation and management. Demographic rates with low variance may be pivotal for population persistence, but variable rates can have a dramatic influence on population growth rate. 2. In this study, the mean and variance in population growth rate (lambda) is decomposed into contributions from different ages and demographic rates using prospective and retrospective matrix analyses for male and female components of an increasing common tern (Sterna hirundo) population. 3. Three main results emerged: (1) subadult return was highly influential in prospective and retrospective analyses; (2) different age-classes made different contributions to variation in lambda: older age classes consistently produced offspring whereas young adults performed well only in high quality years; and (3) demographic rate covariation explained a significant proportion of variation in both sexes. A large contribution to lambda did not imply a large contribution to its variation. 4. This decomposition strengthens the argument that the relationship between variation in demographic rates and variation in lambda is complex. Understanding this relationship and its consequences for population persistence and evolutionary change demands closer examination of the lives, and deaths, of the individuals within populations within species.