Farm-level risk factors for fluoroquinolone resistance in E-coli and thermophilic Campylobacter spp. on finisher pig farms

Logistic regression, supported by other statistical analyses was used to explore the possible association of risk factors with the fluoroquinolone (FQ)-resistance status of 108 pig finisher farms in Great Britain. The farms were classified as 'affected' or 'not affected' by FQ-resistant E. coli or Campylobacter spp. on the basis of isolation of organisms from faecal samples on media containing 1 mg/l FQ. The use of FQ was the most important factor associated with finding resistant E. coli and/or Campylobacter, which were found on 79% (FQ-resistant E. coli) and 86% (FQ-resistant Campylobacter) of farms with a history of FQ use. However, resistant bacteria were also found on 19% (FQ-resistant E. coli) and 54% (FQ-resistant Campylobacter) of farms with no history of FQ use. For FQ-resistant E. coli, biosecurity measures may be protective and there was strong seasonal variation, with more farms found affected when sampled in the summer. For FQ-resistant Campylobacter, the buying-in of grower stock may increase risk and good on-farm hygiene may be protective. The findings suggest that resistant organisms, particularly Campylobacter, may spread between pig farms.

Enhancing and diminishing gene function in human embryonic stem cells

It is widely recognized that gain- and loss-of-function approaches are essential for understanding the functions of specific genes, and such approaches would be particularly valuable in studies involving human embryonic stem (hES) cells. We describe a simple and efficient approach using lipofection to transfect hES cells, which enabled us to generate hES cell lines expressing naturally fluorescent green or red proteins without affecting cell pluripotency. We used these cell lines to establish a means of diminishing gene function using small interfering (si)RNAs, which were effective at knocking down gene expression in hES cells. We then demonstrated that stable expression of siRNA could knock down the expression of endogenous genes. Application of these gain- and loss-of-function approaches should have widespread use, not only in revealing the developmental roles of specific human genes, but also for their utility in modulating differentiation.

How contractors price risk in bids: theory and practice

Formal and analytical models that contractors can use to assess and price project risk at the tender stage have proliferated in recent years. However, they are rarely used in practice. Introducing more models would, therefore, not necessarily help. A better understanding is needed of how contractors arrive at a bid price in practice, and how, and in what circumstances, risk apportionment actually influences pricing levels. More than 60 proposed risk models for contractors that are published in journals were examined and classified. Then exploratory interviews with five UK contractors and documentary analyses on how contractors price work generally and risk specifically were carried out to help in comparing the propositions from the literature to what contractors actually do. No comprehensive literature on the real bidding processes used in practice was found, and there is no evidence that pricing is systematic. Hence, systematic risk and pricing models for contractors may have no justifiable basis. Contractors process their bids through certain tendering gateways. They acknowledge the risk that they should price. However, the final settlement depends on a set of complex, micro-economic factors. Hence, risk accountability may be smaller than its true cost to the contractor. Risk apportionment occurs at three stages of the whole bid-pricing process. However, analytical approaches tend not to incorporate this, although they could.

Interpreting information about medication side effects: differences in risk perception and intention to comply when medicines are prescribed for adults or young children

This study investigates whether, and how, people's perception of risk and intended health behaviours are affected by whether a medicine is prescribed for themselves or for a young child. The question is relevant to the issue of whether it is beneficial to produce medicines information that is tailored to particular subgroups of the population, such as parents of young children. In the experiment, participants read scenarios which referred either to themselves or their (imagined) 1-year-old child, and were required to make a number of risk judgements. The results showed that both parents and non-parents were less satisfied, perceived side effects to be more severe and more likely to occur, risk to health to be higher, and said that they would be less likely to take (or give) the medicine when the recipient was the child. On the basis of the findings, it is suggested that it may well be beneficial to tailor materials to broader classes of patient type.

Risk pricing practices in finance, insurance and construction

A review of current risk pricing practices in the financial, insurance and construction sectors is conducted through a comprehensive literature review. The purpose was to inform a study on risk and price in the tendering processes of contractors: specifically, how contractors take account of risk when they are calculating their bids for construction work. The reference to mainstream literature was in view of construction management research as a field of application rather than a fundamental academic discipline. Analytical models are used for risk pricing in the financial sector. Certain mathematical laws and principles of insurance are used to price risk in the insurance sector. construction contractors and practitioners are described to traditionally price allowances for project risk using mechanisms such as intuition and experience. Project risk analysis models have proliferated in recent years. However, they are rarely used because of problems practitioners face when confronted with them. A discussion of practices across the three sectors shows that the construction industry does not approach risk according to the sophisticated mechanisms of the two other sectors. This is not a poor situation in itself. However, knowledge transfer from finance and insurance can help construction practitioners. But also, formal risk models for contractors should be informed by the commercial exigencies and unique characteristics of the construction sector.

Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults.

The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05–2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28–4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18–3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92–2.94) and insulin resistance (OR 3.40–3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.

Cyclic loss of open solar flux since 1868: the link to heliospheric current sheet tilt and implications for the Maunder Minimum

Open solar flux (OSF) variations can be described by the imbalance between source and loss terms. We use spacecraft and geomagnetic observations of OSF from 1868 to present and assume the OSF source, S, varies with the observed sunspot number, R. Computing the required fractional OSF loss, χ, reveals a clear solar cycle variation, in approximate phase with R. While peak R varies significantly from cycle to cycle, χ is surprisingly constant in both amplitude and waveform. Comparisons of χ with measures of heliospheric current sheet (HCS) orientation reveal a strong correlation. The cyclic nature of χ is exploited to reconstruct OSF back to the start of sunspot records in 1610. This agrees well with the available spacecraft, geomagnetic, and cosmogenic isotope observations. Assuming S is proportional to R yields near-zero OSF throughout the Maunder Minimum. However, χ becomes negative during periods of low R, particularly the most recent solar minimum, meaning OSF production is underestimated. This is related to continued coronal mass ejection (CME) activity, and therefore OSF production, throughout solar minimum, despite R falling to zero. Correcting S for this produces a better match to the recent solar minimum OSF observations. It also results in a cycling, nonzero OSF during the Maunder Minimum, in agreement with cosmogenic isotope observations. These results suggest that during the Maunder Minimum, HCS tilt cycled as over recent solar cycles, and the CME rate was roughly constant at the levels measured during the most recent two solar minima.

Prebiotics and the health benefits of fiber: current regulatory status, future research, and goals.

First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.

Identification of components of the Sigma B Regulon in Listeria monocytogenes that contribute to acid and salt tolerance

Sigma B (σB) is an alternative sigma factor that controls the transcriptional response to stress in Listeria monocytogenes and is also known to play a role in the virulence of this human pathogen. In the present study we investigated the impact of a sigB deletion on the proteome of L. monocytogenes grown in a chemically defined medium both in the presence and in the absence of osmotic stress (0.5 M NaCl). Two new phenotypes associated with the sigB deletion were identified using this medium. (i) Unexpectedly, the strain with the ΔsigB deletion was found to grow faster than the parent strain in the growth medium, but only when 0.5 M NaCl was present. This phenomenon was independent of the carbon source provided in the medium. (ii) The ΔsigB mutant was found to have unusual Gram staining properties compared to the parent, suggesting that σB contributes to the maintenance of an intact cell wall. A proteomic analysis was performed by two-dimensional gel electrophoresis, using cells growing in the exponential and stationary phases. Overall, 11 proteins were found to be differentially expressed in the wild type and the ΔsigB mutant; 10 of these proteins were expressed at lower levels in the mutant, and 1 was overexpressed in the mutant. All 11 proteins were identified by tandem mass spectrometry, and putative functions were assigned based on homology to proteins from other bacteria. Five proteins had putative functions related to carbon utilization (Lmo0539, Lmo0783, Lmo0913, Lmo1830, and Lmo2696), while three proteins were similar to proteins whose functions are unknown but that are known to be stress inducible (Lmo0796, Lmo2391, and Lmo2748). To gain further insight into the role of σB in L. monocytogenes, we deleted the genes encoding four of the proteins, lmo0796, lmo0913, lmo2391, and lmo2748. Phenotypic characterization of the mutants revealed that Lmo2748 plays a role in osmotolerance, while Lmo0796, Lmo0913, and Lmo2391 were all implicated in acid stress tolerance to various degrees. Invasion assays performed with Caco-2 cells indicated that none of the four genes was required for mammalian cell invasion. Microscopic analysis suggested that loss of Lmo2748 might contribute to the cell wall defect observed in the ΔsigB mutant. Overall, this study highlighted two new phenotypes associated with the loss of σB. It also demonstrated clear roles for σB in both osmotic and low-pH stress tolerance and identified specific components of the σB regulon that contribute to the responses observed.

Farmers’ attitudes to disease risk management in England: a comparative analysis of sheep and pig farmers

The UK Department for Environment, Food and Rural Affairs (Defra) identified practices to reduce the risk of animal disease outbreaks. We report on the response of sheep and pig farmers in England to promotion of these practices. A conceptual framework was established from research on factors influencing adoption of animal health practices, linking knowledge, attitudes, social influences and perceived constraints to the implementation of specific practices. Qualitative data were collected from nine sheep and six pig enterprises in 2011. Thematic analysis explored attitudes and responses to the proposed practices, and factors influencing the likelihood of implementation. Most feel they are doing all they can reasonably do to minimise disease risk and that practices not being implemented are either not relevant or ineffective. There is little awareness and concern about risk from unseen threats. Pig farmers place more emphasis than sheep farmers on controlling wildlife, staff and visitor management and staff training. The main factors that influence livestock farmers’ decision on whether or not to implement a specific disease risk measure are: attitudes to, and perceptions of, disease risk; attitudes towards the specific measure and its efficacy; characteristics of the enterprise which they perceive as making a measure impractical; previous experience of a disease or of the measure; and the credibility of information and advice. Great importance is placed on access to authoritative information with most seeing vets as the prime source to interpret generic advice from national bodies in the local context. Uptake of disease risk measures could be increased by: improved risk communication through the farming press and vets to encourage farmers to recognise hidden threats; dissemination of credible early warning information to sharpen farmers’ assessment of risk; and targeted information through training events, farming press, vets and other advisers, and farmer groups, tailored to the different categories of livestock farmer.

Forecasting economic and financial time series with non-linear models

In this paper we discuss the current state-of-the-art in estimating, evaluating, and selecting among non-linear forecasting models for economic and financial time series. We review theoretical and empirical issues, including predictive density, interval and point evaluation and model selection, loss functions, data-mining, and aggregation. In addition, we argue that although the evidence in favor of constructing forecasts using non-linear models is rather sparse, there is reason to be optimistic. However, much remains to be done. Finally, we outline a variety of topics for future research, and discuss a number of areas which have received considerable attention in the recent literature, but where many questions remain.

Calculating the application criticality and business risk from technology obsolescence

The problem of technology obsolescence in information intensive businesses (software and hardware no longer being supported and replaced by improved and different solutions) and a cost constrained market can severely increase costs and operational, and ultimately reputation risk. Although many businesses recognise technological obsolescence, the pervasive nature of technology often means they have little information to identify the risk and location of pending obsolescence and little money to apply to the solution. This paper presents a low cost structured method to identify obsolete software and the risk of their obsolescence where the structure of a business and its supporting IT resources can be captured, modelled, analysed and the risk to the business of technology obsolescence identified to enable remedial action using qualified obsolescence information. The technique is based on a structured modelling approach using enterprise architecture models and a heatmap algorithm to highlight high risk obsolescent elements. The method has been tested and applied in practice in three consulting studies carried out by Capgemini involving four UK police forces. However the generic technique could be applied to any industry based on plans to improve it using ontology framework methods. This paper contains details of enterprise architecture meta-models and related modelling.

Science for Humanitarian Emergencies and Resilience (SHEAR) scoping study: Annex 3 - Early warning system and risk assessment case studies

This report provides case studies of Early Warning Systems (EWSs) and risk assessments encompassing three main hazard types: drought; flood and cyclone. The case studies are taken from ten countries across three continents (focusing on Africa, South Asia and the Caribbean). The case studies have been developed to assist the UK Department for International Development (DFID) to prioritise areas for Early Warning System (EWS) related research under their ‘Science for Humanitarian Emergencies and Resilience’ (SHEAR) programme. The aim of these case studies is to ensure that DFID SHEAR research is informed by the views of Non-Governmental Organisations (NGOs) and communities engaged with Early Warning Systems and risk assessments (including community-based Early Warning Systems). The case studies highlight a number of challenges facing Early Warning Systems (EWSs). These challenges relate to financing; integration; responsibilities; community interpretation; politics; dissemination; accuracy; capacity and focus. The case studies summarise a number of priority areas for EWS related research: • Priority 1: Contextualising and localising early warning information • Priority 2: Climate proofing current EWSs • Priority 3: How best to sustain effective EWSs between hazard events? • Priority 4: Optimising the dissemination of risk and warning information • Priority 5: Governance and financing of EWSs • Priority 6: How to support EWSs under challenging circumstances • Priority 7: Improving EWSs through monitoring and evaluating the impact and effectiveness of those systems

Responsibility effects in decision making under risk

We systematically explore decision situations in which a decision maker bears responsibility for somebody else's outcomes as well as for her own in situations of payoff equality. In the gain domain we confirm the intuition that being responsible for somebody else's payoffs increases risk aversion. This is however not attributable to a 'cautious shift' as often thought. Indeed, looking at risk attitudes in the loss domain, we find an increase in risk seeking under responsibility. This raises issues about the nature of various decision biases under risk, and to what extent changed behavior under responsibility may depend on a social norm of caution in situations of responsibility versus naive corrections from perceived biases. To further explore this issue, we designed a second experiment to explore risk-taking behavior for gain prospects offering very small or very large probabilities of winning. For large probabilities, we find increased risk aversion, thus confirming our earlier finding. For small probabilities however, we find an increase of risk seeking under conditions of responsibility. The latter finding thus discredits hypotheses of a social rule dictating caution under responsibility, and can be explained through flexible self-correction models predicting an accentuation of the fourfold pattern of risk attitudes predicted by prospect theory. An additional accountability mechanism does not change risk behavior, except for mixed prospects, in which it reduces loss aversion. This indicates that loss aversion is of a fundamentally different nature than probability weighting or utility curvature. Implications for debiasing are discussed.

Climatic risks and impacts in South Asia: extremes of water scarcity and excess

This paper reviews the current knowledge of climatic risks and impacts in South Asia associated with anthropogenic warming levels of 1.5°C to 4°C above pre-industrial values in the 21st century. It is based on the World Bank Report “Turn Down the Heat, Climate Extremes, Regional Impacts and the Case for Resilience” (2013). Many of the climate change impacts in the region, which appear quite severe even with relatively modest warming of 1.5–2°C, pose significant hazards to development. For example, increased monsoon variability and loss or glacial meltwater will likely confront populations with ongoing and multiple challenges. The result is a significant risk to stable and reliable water resources for the region, with increases in peak flows potentially causing floods and dry season flow reductions threatening agriculture. Irrespective of the anticipated economic development and growth, climate projections indicate that large parts of South Asia’s growing population and especially the poor are likely to remain highly vulnerable to climate change.