Building resilience in the UK water sector: a systems based approach to emergency management

The ability to achieve resilience to extreme events requires a shift away from the traditional risk management approach and a progression towards understanding resilience as a dynamic process operating within a complex socio-ecological-technical emergency management system. Taking a systems based approach this research applied quantitative and qualitative methods to explore how resilience to water supply failure is achieved within the UK emergency management system. This was supported through the application of the Safe and SuRe intervention framework. Semi-structured interviews with emergency management professionals revealed that the Civil Contingencies Act, 2004 is not aligned with current operational practices to enable effective collaboration between Category 1 and Category 2 responders. This is further constrained by a lack of government funding and a lack of understanding with regard to organisational culture and how this influences the operational delivery of multi-agency emergency response. The attitudes and perceptions of individuals to water supply failure was examined through individual householder questionnaires and the analysis of Facebook comments during the ‘Beast from the East’. Individuals expressed a high level of confidence in the ability of Water Service Provider’s to provide a reliable, continuous and safe supply of water. While the majority of individuals do not prepare for a failure of the water supply they actively respond during an incident to achieve resilience by purchasing water from the supermarkets, staying with relatives or attending water distribution stations. However, the ability to achieve resilience requires the provision of accurate, timely and consistent information from the Water Service Providers. Resilience to emergencies can also be strengthened at the local level through the development of collaborative working partnerships. The integration of community groups within the emergency management system enables resilience through the sharing and exchange of information to understand capabilities available for effective emergency response. This research demonstrates how the application of a systems based approach enables a greater understanding of the complex interdependencies between different parts of the emergency management system. These were explored and developed into recommendations identifying where resilient based strategies and interventions are required at the government, inter-organisational and community level

Dysfunction of phospholipase Cγ in immune disorders and cancer

The surge in genetic and genomic investigations over the past 5 years has resulted in many discoveries of causative variants relevant to disease pathophysiology. Although phospholipase C (PLC) enzymes have long been recognized as important components in intracellular signal transmission, it is only recently that this approach highlighted their role in disease development through gain-of-function mutations. In this review we describe the new findings that link the PLCγ family to immune disorders and cancer, and illustrate further efforts to elucidate the molecular mechanisms that underpin their dysfunction

Intermittent water supply systems and their resilience to COVID-19: IWA IWS SG survey

Data availability statement: All relevant data are included in the paper or its Supplementary Information.This is the final version. Available on open access from IWA Publishing via the DOI in this recordThere is limited information about the current state of intermittent water supply (IWS) systems at the global level. A survey was carried out by the Intermittent Water Supply Specialist Group of the International Water Association (IWA IWS SG) to better understand the current state of these systems and challenges that water companies may have faced under COVID-19 pandemic and to capture successful management strategies applied by water utilities. The survey consisted of three parts: (1) general information about IWS systems, (2) current state of IWS and (3) resilience of IWS under COVID-19 conditions, as well as some questions about potential interventions in order to improve system performance in general and under future uncertain conditions. The survey responses were evaluated based on the Safe & SuRe resilience framework, assessing measures of mitigation, adaptation, coping and learning, and exploring organisational and operational responses of IWS utilities. Infrastructure capacity and water resources availability were identified as the main causes of intermittency in most water distribution systems, while intermittent electricity was considered as the main external cause. Participants indicated that some risk assessment process was in place; however, COVID-19 has surpassed any provisions made to address the risks. Lessons learnt highlighted the importance of financial resources, e-infrastructure for efficient system operation and communication with consumers, and the critical role of international knowledge transfer and the sharing of best practice guidelines for improving resilience and transitioning towards continuous water supply.Royal Academy of Engineering (RAE)Engineering and Physical Sciences Research Council (EPSRC

Safeguarding sandalwood: A review of current and emerging tools to support sustainable and legal forestry

Societal Impact Statement: Sandalwood and other high value tree species are under significant threat from illegal harvest. Illegal logging is an increasing problem contributing to deforestation, biodiversity loss, human rights abuses and funding transnational crime. Successful prosecution of illegal logging is hindered by a lack of methods to provide evidence of the origin of timber. New analytical techniques have been developed to trace timber back to its source. These methods, together with the establishment of sustainable sources of forest resources, can help protect vulnerable species by providing evidence to prosecute illegal harvest and ensure that commercially available forest products come from sustainable sources. Summary: Sandalwood is highly valued for its fragrant oil and has a long history of cultural and economic importance in many regions of the world. Historical overharvest and poor management have depleted natural populations of sandalwood, which are slow to regenerate. The increasing establishment of plantation sandalwood creates an alternative resource for the sandalwood industry while potentially relieving harvesting pressure on natural stands. Due to the high demand for sandalwood, remaining wild populations are still under threat from illegal logging and methods to identify the source of harvested sandalwood are needed. Laws and regulations aimed at preventing illegal harvest and possession of sandalwood have been put in place but cannot be enforced without the forensic tools to independently verify claimed origin or product quality. The high value of sandalwood combined with the difficulties in enforcing illegal logging laws makes these species particularly vulnerable to poaching. There is an immediate need to develop tools that can identify illegally sourced and adulterated sandalwood products. This paper reviews the current and developing scientific tools that can help identify and control illegal activity in sandalwood supply chains and provides recommendations for future research. Topics include isotope and DNA analysis for tracing illegally harvested sandalwood, chemical profiling for quality control of sandalwood oils, network and policy development to establish a framework for future regulation of the sandalwood trade

Numerical models for ground deformation and gravity changes during volcanic unrest: simulating the hydrothermal system dynamics of an active caldera

Ground deformation and gravity changes in restless calderas during periods of unrest can signal an impending eruption and thus must be correctly interpreted for hazard evaluation. It is critical to differentiate variation of geophysical observables related to volume and pressure changes induced by magma migration from shallow hydrothermal activity associated with hot fluids of magmatic origin rising from depth. In this paper we present a numerical model to evaluate the thermo-poroelastic response of the hydrothermal system in a caldera setting by simulating pore pressure and thermal expansion associated with deep injection of hot fluids (water and carbon dioxide). Hydrothermal fluid circulation is simulated using TOUGH2, a multicomponent multiphase simulator of fluid flows in porous media. Changes in pore pressure and temperature are then evaluated and fed into a thermo-poroelastic model (one-way coupling), which is based on a finite-difference numerical method designed for axi-symmetric problems in unbounded domains. Informed by constraints available for the Campi Flegrei caldera (Italy), a series of simulations assess the influence of fluid injection rates and mechanical properties on the hydrothermal system, uplift and gravity. Heterogeneities in hydrological and mechanical properties associated with the presence of ring faults are a key determinant of the fluid flow pattern and consequently the geophysical observables. Peaks (in absolute value) of uplift and gravity change profiles computed at the ground surface are located close to injection points (namely at the centre of the model and fault areas). Temporal evolution of the ground deformation indicates that the contribution of thermal effects to the total uplift is almost negligible with respect to the pore pressure contribution during the first years of the unrest, but increases in time and becomes dominant after a long period of the simulation. After a transient increase over the first years of unrest, gravity changes become negative and decrease monotonically towards a steady-state value. Since the physics of the investigated hydrothermal system is similar to any fluid-filled reservoir, such as oil fields or CO2 reservoirs produced by sequestration, the generic formulation of the model will allow it to be employed in monitoring and interpretation of deformation and gravity data associated with other geophysical hazards that pose a risk to human activity

Ketamine Influences CLOCK:BMAL1 Function Leading to Altered Circadian Gene Expression

Major mood disorders have been linked to abnormalities in circadian rhythms, leading to disturbances in sleep, mood, temperature, and hormonal levels. We provide evidence that ketamine, a drug with rapid antidepressant effects, influences the function of the circadian molecular machinery. Ketamine modulates CLOCK:BMAL1-mediated transcriptional activation when these regulators are ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose-dependent manner and is attenuated after treatment with the GSK3β antagonist SB21673. We analyzed the effect of ketamine on circadian gene expression and observed a dose-dependent reduction in the amplitude of circadian transcription of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1 complex on circadian promoters in a time-dependent manner. Our results reveal a yet unsuspected molecular mode of action of ketamine and thereby may suggest possible pharmacological antidepressant strategies

NMR backbone assignments of the tyrosine kinase domain of human fibroblast growth factor receptor 3 in apo state and in complex with inhibitor PD173074

Fibroblast growth factors receptors (FGFR) are transmembrane protein tyrosine kinases involved in many cellular process, including growth, differentiation and angiogenesis. Dysregulation of FGFR enzymatic activity is associated with developmental disorders and cancers; therefore FGFRs have become attractive targets for drug discovery, with a number of agents in late-stage clinical trials. Here, we present the backbone resonance assignments of FGFR3 tyrosine kinase domain in the ligand-free form and in complex with the canonical FGFR kinase inhibitor PD173074. Analysis of chemical shift changes upon inhibitor binding highlights a characteristic pattern of allosteric network perturbations that is of relevance for future drug discovery activities aimed at development of conformationally-selective FGFR inhibitors

Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide

Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain

PVP2008-61762 DESIGN AND MANUFACTURE OF WELDED PLATE SPECIMENS FOR RESIDUAL STRESS EXPERIMENTS

ABSTRACT A long-term UK research programme has been established in order to improve the understanding of thermo-mechanical behaviour and residual stresses generated in pressure vessel steel welds as well as developing finite element (FE) welding simulation methods. The production of representative test specimens is an important element of this research project, since quality measurement data are needed to validate FE models. This paper describes the design, development and manufacture of welded plate specimens used for residual stress (RS) experiments. To date, research has focused mainly on developing the understanding of SA508 pressure vessel steel welds. Specimen dimensions were selected to facilitate stress measurements using a range of techniques. The philosophy adopted was to start with relatively simple 1-pass weld specimens and gradually increase the complexity to multi-pass groove welds in plates. Simple 1-pass weld specimens were generally designed to investigate the effect of welding parameters on thermomechanical behaviour, such as heat-affected zone (HAZ) microstructures and phase transformations. Later specimens are more representative of multi-pass power plant welds. They are being used to study material thermal cyclic hardening/softening behaviour. Other issues of concern are also being investigated, such as the effect of restraint during welding on RS and the effectiveness of post weld heat treatment (PWHT). Specimens were also designed to study peak stresses arising at bead stop/start positions and whether such peak stresses are annealed in overlaying additional weld metal. These investigations were performed on multi-pass groove welds in both austenitic and ferritic steel plates. Practical issues encountered during welding trials are discussed, including plate distortion and magnetisation of the ferritic steel plates. Information is also provided about welding temperature measurements and metallurgical examinations