Layer-by-layer coating of alginate matrices with chitosan–alginate for the improved survival and targeted delivery of probiotic bacteria after oral administration

The oral administration of probiotic bacteria has shown potential in clinical trials for the alleviation of specific disorders of the gastrointestinal tract. However, cells must be alive in order to exert these benefits. The low pH of the stomach can greatly reduce the number of viable microorganisms that reach the intestine, thereby reducing the efficacy of the administration. Herein, a model probiotic, Bifidobacterium breve, has been encapsulated into an alginate matrix before coating in multilayers of alternating alginate and chitosan. The intention of this formulation was to improve the survival of B. breve during exposure to low pH and to target the delivery of the cells to the intestine. The material properties were first characterized before in vitro testing. Biacore™ experiments allowed for the polymer interactions to be confirmed; additionally, the stability of these multilayers to buffers simulating the pH of the gastrointestinal tract was demonstrated. Texture analysis was used to monitor changes in the gel strength during preparation, showing a weakening of the matrices during coating as a result of calcium ion sequestration. The build-up of multilayers was confirmed by confocal laser-scanning microscopy, which also showed the increase in the thickness of coat over time. During exposure to in vitro gastric conditions, an increase in viability from <3 log(CFU) per mL, seen in free cells, up to a maximum of 8.84 ± 0.17 log(CFU) per mL was noted in a 3-layer coated matrix. Multilayer-coated alginate matrices also showed a targeting of delivery to the intestine, with a gradual release of their loads over 240 min.

Rhythmic behavior of social insects from single to multibody

Revealing the evolution of well-organized social behavior requires understanding a mechanism by which collective behavior is produced. A well-organized group may be produced by two possible mechanisms, namely, a central control and a distributed control. In the second case, local interactions between interchangeable components function at the bottom of the collective behavior. We focused on a simple behavior of an individual ant and analyzed the interactions between a pair of ants. In an experimental set-up, we placed the workers in a hemisphere without a nest, food, and a queen, and recorded their trajectories. The temporal pattern of velocity of each ant was obtained. From this bottom-up approach, we found the characteristic behavior of a single worker and a pair of workers as follows: (1) Activity of each individual has a rhythmic component. (2) Interactions between a pair of individuals result in two types of coupling, namely the anti-phase and the in-phase coupling. The direct physical contacts between the pair of workers might cause a phase shift of the rhythmic components in individual ants. We also build up a simple model based on the coupled oscillators toward the understanding of the whole colony behavior.

Proposal of redundant drive wire mechanism for producing motions with high acceleration and high precision

A new wire mechanism called Redundant Drive Wire Mechanism (RDWM) is proposed. The purpose of this paper is to build up the theory of a RDWM with fast motion and fine motion. First, the basic concepts of the proposed mechanism is presented. Second, the vector closure condition for the proposed mechanism is developed. Next, we present the basic equations, propose the basic structure of RDWM with the Internal DOF module, Double Actuation Modules and Precision Modules together with the properties of the mechanism. Finally, we conduct the simulation to show the validity of the RDWM.

Understanding advances in the simulation of intraseasonal variability in the ECMWF model. Part II: the application of process-based diagnostics

In Part I of this study it was shown that moving from a moisture-convergent- to a relative-humidity-dependent organized entrainment rate in the formulation for deep convection was responsible for significant advances in the simulation of the Madden – Julian Oscillation (MJO) in the ECMWF model. However, the application of traditional MJO diagnostics were not adequate to understand why changing the control on convection had such a pronounced impact on the representation of the MJO. In this study a set of process-based diagnostics are applied to the hindcast experiments described in Part I to identify the physical mechanisms responsible for the advances in MJO simulation. Increasing the sensitivity of the deep convection scheme to environmental moisture is shown to modify the relationship between precipitation and moisture in the model. Through dry-air entrainment, convective plumes ascending in low-humidity environments terminate lower in the atmosphere. As a result, there is an increase in the occurrence of cumulus congestus, which acts to moisten the mid troposphere. Due to the modified precipitation – moisture relationship more moisture is able to build up, which effectively preconditions the tropical atmosphere for the t ransition t o d eep convection. R esults from this study suggest that a tropospheric moisture control on convection is key to simulating the interaction between the convective heating and the large-scale wave forcing associated with the MJO.

Does managerial turnover affect football club share prices?

This paper analyses the 53 managerial sackings and resignations from 16 stock exchange listed English football clubs during the nine seasons between 2000/01 and 2008/09. The results demonstrate that, on average, a managerial sacking results in a post-announcement day market-adjusted share price rise of 0.3%, whilst a resignation leads to a drop in share price of 1% that continues for a trading month thereafter, cumulating in a negative abnormal return of over 8% from a trading day before the event. These findings are intuitive, and suggest that sacking a poorly performing manager may be welcomed by the markets as a possible route to better future match performance, while losing a capable manager through resignation, who typically progresses to a superior job, will result in a drop in a club’s share price. The paper also reveals that while the impact of managerial departures on stock price volatilities is less clear-cut, speculation in the newspapers is rife in the build-up to such an event.

Response of the Atlantic meridional overturning circulation to a reversal of greenhouse gas increases

The reversibility of the Atlantic meridional overturning circulation (AMOC) is investigated in multi-model experiments using global climate models (GCMs) where CO2 concentrations are increased by 1 or 2 % per annum to 2× or 4× preindustrial conditions. After a period of stabilisation the CO2 is decreased back to preindustrial conditions. In most experiments when the CO2 decreases, the AMOC recovers before becoming anomalously strong. This "overshoot" is up to an extra 18.2Sv or 104 % of its preindustrial strength, and the period with an anomalously strong AMOC can last for several hundred years. The magnitude of this overshoot is shown to be related to the build up of salinity in the subtropical Atlantic during the previous period of high CO2 levels. The magnitude of this build up is partly related to anthropogenic changes in the hydrological cycle. The mechanisms linking the subtropical salinity increase to the subsequent overshoot are analysed, supporting the relationship found. This understanding is used to explain differences seen in some models and scenarios. In one experiment there is no overshoot because there is little salinity build up, partly as a result of model differences in the hydrological cycle response to increased CO2 levels and partly because of a less aggressive scenario. Another experiment has a delayed overshoot, possibly as a result of a very weak AMOC in that GCM when CO2 is high. This study identifies aspects of overshoot behaviour that are robust across a multi-model and multi-scenario ensemble, and those that differ between experiments. These results could inform an assessment of the real-world AMOC response to decreasing CO2.

Microbial community dynamics in the forefield of glaciers

Retreating ice fronts (as a result of a warming climate) expose large expanses of deglaciated forefield, which become colonized by microbes and plants. There has been increasing interest in characterizing the biogeochemical development of these ecosystems using a chronosequence approach. Prior to the establishment of plants, microbes use autochthonously produced and allochthonously delivered nutrients for growth. The microbial community composition is largely made up of heterotrophic microbes (both bacteria and fungi), autotrophic microbes and nitrogen-fixing diazotrophs. Microbial activity is thought to be responsible for the initial build-up of labile nutrient pools, facilitating the growth of higher order plant life in developed soils. However, it is unclear to what extent these ecosystems rely on external sources of nutrients such as ancient carbon pools and periodic nitrogen deposition. Furthermore, the seasonal variation of chronosequence dynamics and the effect of winter are largely unexplored. Modelling this ecosystem will provide a quantitative evaluation of the key processes and could guide the focus of future research. Year-round datasets combined with novel metagenomic techniques will help answer some of the pressing questions in this relatively new but rapidly expanding field, which is of growing interest in the context of future large-scale ice retreat.

The current status of anticoagulant resistance in rats and mice in the UK

Introduction: Resistance to anticoagulants in Norway rats (Rattus norvegicus) and house mice (Mus domesticus) has been studied in the UK since the early 1960s. In no other country in the world is our understanding of resistance phenomena so extensive and profound. Almost every aspect of resistance in the key rodent target species has been examined in laboratory and field trials and results obtained by independent researchers have been published. It is the principal purpose of this document to present a short synopsis of this information. More recently, however, the development of genetical techniques has provided a definitive means of detection of resistant genotypes among pest rodent populations. Preliminary information from a number of such surveys will also be presented. Resistance in Norway rats: A total of nine different anticoagulant resistance mutations (single nucleotide polymorphisms or SNPs) are found among Norway rats in the UK. In no other country worldwide are present so many different forms of Norway rat resistance. Among these nine SNPs, five are known to confer on rats that carry them a significant degree of resistance to anticoagulant rodenticides. These mutations are: L128Q, Y139S, L120Q, Y139C and Y139F. The latter three mutations confer, to varying degrees, practical resistance to bromadiolone and difenacoum, the two second-generation anticoagulants in predominant use in the UK. It is the recommendation of RRAG that bromadiolone and difenacoum should not be used against rats carrying the L120Q, Y139C and Y139F mutations because this will promote the spread of resistance and jeopardise the long-term efficacy of anticoagulants. Brodifacoum, flocoumafen and difethialone are effective against these three genotypes but cannot presently be used because of the regulatory restriction that they can only be applied against rats that are living and feeding predominantly indoors. Our understanding of the geographical distribution of Norway rat resistance in incomplete but is rapidly increasing. In particular, the mapping of the focus of L120Q Norway rat resistance in central-southern England by DNA sequencing is well advanced. We now know that rats carrying this resistance mutation are present across a large part of the counties of Hampshire, Berkshire and Wiltshire, and the resistance spreads into Avon, Oxfordshire and Surrey. It is also found, perhaps as outlier foci, in south-west Scotland and East Sussex. L120Q is currently the most severe form of anticoagulant resistance found in Norway rats and is prevalent over a considerable part of central-southern England. A second form of advanced Norway rat resistance is conferred by the Y139C mutation. This is noteworthy because it occurs in at least four different foci that are widely geographically dispersed, namely in Dumfries and Galloway, Gloucestershire, Yorkshire and Norfolk. Once again, bromadiolone and difenacoum are not recommended for use against rats carrying this genotype and a concern of RRAG is that continued applications of resisted active substances may result in Y139C becoming more or less ubiquitous across much of the UK. Another type of advanced resistance, the Y139F mutation, is present in Kent and Sussex. This means that Norway rats, carrying some degree of resistance to bromadiolone and difenacoum, are now found from the south coast of Kent, west into the city of Bristol, to Yorkshire in the north-east and to the south-west of Scotland. This difficult situation can only deteriorate further where these three genotypes exist and resisted anticoagulants are predominantly used against them. Resistance in house mice: House mouse is not so well understood but the presence in the UK of two resistant genotypes, L128S and Y139C, is confirmed. House mice are naturally tolerant to anticoagulants and such is the nature of this tolerance, and the presence of genetical resistance, that house mice resistant to the first-generation anticoagulants are considered to be widespread in the UK. Consequently, baits containing warfarin, sodium warfarin, chlorophacinone and coumatetralyl are not approved for use against mice. This regulatory position is endorsed by RRAG. Baits containing brodifacoum, flocoumafen and difethialone are effective against house mice and may be applied in practice because house mouse infestations are predominantly indoors. There are some reports of resistance among mice in some areas to the second-generation anticoagulant bromadiolone, while difenacoum remains largely efficacious. Alternatives to anticoagulants: The use of habitat manipulation, that is the removal of harbourage, denial of the availability of food and the prevention of ingress to structures, is an essential component of sustainable rodent pest management. All are of importance in the management of resistant rodents and have the advantage of not selecting for resistant genotypes. The use of these techniques may be particularly valuable in preventing the build-up of rat infestations. However, none can be used to remove any sizeable extant rat infestation and for practical reasons their use against house mice is problematic. Few alternative chemical interventions are available in the European Union because of the removal from the market of zinc phosphide, calciferol and bromethalin. Our virtual complete reliance on the use of anticoagulants for the chemical control of rodents in the UK, and more widely in the EU, calls for improved schemes for resistance management. Of course, these might involve the use of alternatives to anticoagulant rodenticides. Also important is an increasing knowledge of the distribution of resistance mutations in rats and mice and the use of only fully effective anticoagulants against them.

Childhood trauma: methods for the identification of physeal fractures in non-adult skeletal remains

Objectives Today, fractures at the growth plate (or physis) are common injuries in children, but provide challenges of identification in skeletonized remains. Clinical studies provide detailed information on the mechanisms, locations, age of occurrence, and complications associated with physeal fractures, enabling the development of new criteria for identifying this injury in non-adults. To test these criteria, skeletal remains from five rural and urban medieval cemeteries were examined. Methods The sample consisted of 961 skeletons (0-17 years) with open epiphyses. Macroscopic observation looked for any irregularities of the metaphysis or epiphysis which was consistent with the clinical appearance of physeal fractures or resulting complications. Radiographic examination was applied to identify fracture lines or early growth arrest. Results This study revealed 12 cases of physeal trauma (1.2%). Physeal fractures occurred predominantly at the distal end (75%), and while they were identified in all age categories, they were most frequent in those aged 12-17 years (0.2% TPR). The humerus was the most commonly affected location (3/12 or 25%). Conclusions This study highlights the potential for recognizing physeal fractures in children of all ages, enhancing our understanding of non-adult trauma, and enabling us to assign a more precise age of the injury to build up a picture of their activities in the past.

SHIMMER (1.0): a novel mathematical model for microbial and biogeochemical dynamics in glacier forefield ecosystems

SHIMMER (Soil biogeocHemIcal Model for Microbial Ecosystem Response) is a new numerical modelling framework designed to simulate microbial dynamics and biogeochemical cycling during initial ecosystem development in glacier forefield soils. However, it is also transferable to other extreme ecosystem types (such as desert soils or the surface of glaciers). The rationale for model development arises from decades of empirical observations in glacier forefields, and enables a quantitative and process focussed approach. Here, we provide a detailed description of SHIMMER, test its performance in two case study forefields: the Damma Glacier (Switzerland) and the Athabasca Glacier (Canada) and analyse sensitivity to identify the most sensitive and unconstrained model parameters. Results show that the accumulation of microbial biomass is highly dependent on variation in microbial growth and death rate constants, Q10 values, the active fraction of microbial biomass and the reactivity of organic matter. The model correctly predicts the rapid accumulation of microbial biomass observed during the initial stages of succession in the forefields of both the case study systems. Primary production is responsible for the initial build-up of labile substrate that subsequently supports heterotrophic growth. However, allochthonous contributions of organic matter, and nitrogen fixation, are important in sustaining this productivity. The development and application of SHIMMER also highlights aspects of these systems that require further empirical research: quantifying nutrient budgets and biogeochemical rates, exploring seasonality and microbial growth and cell death. This will lead to increased understanding of how glacier forefields contribute to global biogeochemical cycling and climate under future ice retreat.

Understanding advances in the simulation of the Madden-Julian Oscillation in a numerical weather prediction model.

The Madden-Julian Oscillation (MJO) is the dominant mode of intraseasonal variability in the Trop- ics. It can be characterised as a planetary-scale coupling between the atmospheric circulation and organised deep convection that propagates east through the equatorial Indo-Pacific region. The MJO interacts with weather and climate systems on a near-global scale and is a crucial source of predictability for weather forecasts on medium to seasonal timescales. Despite its global signifi- cance, accurately representing the MJO in numerical weather prediction (NWP) and climate models remains a challenge. This thesis focuses on the representation of the MJO in the Integrated Forecasting System (IFS) at the European Centre for Medium-Range Weather Forecasting (ECMWF), a state-of-the-art NWP model. Recent modifications to the model physics in Cycle 32r3 (Cy32r3) of the IFS led to ad- vances in the simulation of the MJO; for the first time the observed amplitude of the MJO was maintained throughout the integration period. A set of hindcast experiments, which differ only in their formulation of convection, have been performed between May 2008 and April 2009 to asses the sensitivity of MJO simulation in the IFS to the Cy32r3 convective parameterization. Unique to this thesis is the attribution of the advances in MJO simulation in Cy32r3 to the mod- ified convective parameterization, specifically, the relative-humidity-dependent formulation for or- ganised deep entrainment. Increasing the sensitivity of the deep convection scheme to environmen- tal moisture is shown to modify the relationship between precipitation and moisture in the model. Through dry-air entrainment, convective plumes ascending in low-humidity environments terminate lower in the atmosphere. As a result, there is an increase in the occurrence of cumulus congestus, which acts to moisten the mid-troposphere. Due to the modified precipitation-moisture relationship more moisture is able to build up which effectively preconditions the tropical atmosphere for the transition to deep convection. Results from this thesis suggest that a tropospheric moisture control on convection is key to simulating the interaction between the physics and large-scale circulation associated with the MJO.

Indoor microclimate in a South Africa School: impact of indoor environmental factors

Demand for good indoor air quality is increasing as people recorgnise the risks to their health and productivity from indoor pollutants. There is a tendency to reduce ventilation rates to ensure energy conservation in buildings; in this instance schools. However, evidence reviewed shows that this can be detrimental to health and wellbeing in schools because of the learner density within a small area (1.8 - 2.4m2/person); eventually indicating that carbon dioxide (CO2) levels can rise to very high levels in classroom occupancy periods. A preliminary study to investigate the impact of indoor environmental parameters has been performed in a secondary school classroom in Pretoria, South Africa. Factors monitored include temperature, relative humidity, lighting, air velocities and CO2 concentrations. From the results low air velocities are recorded (i.e. 0.1-0.3m/s) impacting on the retention of CO2 build-up in the classroom. Results presented in this paper are the initial findings of ongoing research.

Detecting defects in the UK new-build housing sector: a learning perspective

Rapid growth in the production of new homes in the UK is putting build quality under pressure as evidenced by an increase in the number of defects. Housing associations (HAs) contribute approximately 20% of the UK’s new housing supply. HAs are currently experiencing central government funding cuts and rental revenue reductions. As part of HAs’ quest to ramp up supply despite tight budget conditions, they are reviewing how they learn from defects. Learning from defects is argued as a means of reducing the persistent defect problem within the UK housebuilding industry, yet how HAs learn from defects is under-researched. The aim of this research is to better understand how HAs, in practice, learn from past defects to reduce the prevalence of defects in future new homes. The theoretical lens for this research is organizational learning. The results drawn from 12 HA case studies indicate that effective organizational learning has the potential to reduce defects within the housing sector. The results further identify that HAs are restricting their learning to focus primarily on reducing defects through product and system adaptations. Focusing on product and system adaptations alone suppresses HAs’ abilities to reduce defects in the future.