Time series modelling: applications for groundwater control in urban tunnelling

Water ingress to tunnels may result in pore pressure drawdown and consolidation settlements in areas above tunnels founded on soft soil deposits, potentially causing damage to buildings and infrastructure. To limit pore pressure drawdown, requirements are set on water ingress to bedrock tunnels. To meet these requirements, pre-excavation grouting is often performed to reduce the hydraulic conductivity of the rock mass surrounding the tunnel. Real-time pore pressure monitoring may be used to document pore pressure drawdown during construction. However, the effect of tunnel water ingress can be difficult to distinguish from natural pore pressure fluctuations. This paper presents a tunnel case in Oslo, Norway, where time series modelling was applied to local pore pressure data using the transfer function model framework. The input to the models was daily meteorological data considering precipitation and evapotranspiration, and the output was simulated pore pressure levels with impulse response functions. The models were optimised with data from before tunnel excavation, and simulations were run during the tunnel excavation period. Simulated pore pressure levels were compared with observed pore pressure levels to assess tunnelling-induced drawdown. Model uncertainty ranges were used to produce upper, lower, and best estimates of the drawdown. The findings show that time series modelling with transfer function models may be used in tunnel projects to continuously assess the impact on the local groundwater environment, for better evaluation of the pre-grouting performance, and for quantifying both the temporary and long-term drawdown with increased accuracy.Time series modelling: applications for groundwater control in urban tunnellingpublishedVersio

Numerical hydrogeological modelling of drainage to an excavation

The report regards the conceptual and numerical modelling of drainage scenarios to a planned excavation in a deep clay deposit in Oslo, Norway. The modelling was performed in SEEP/W 2D. Ground investigations indicate that the clay lies directly on top of the bedrock, without a layer of moraine between them. The upper metres of the bedrock is assumed to be weathered and serve as a draining layer. The drainage of groundwater to the excavation along steel core piles, and the mitigating effect of cut-off walls of various lengths, were modelled. There were made several versions of the numerical model, with a variation of conductivity and upstream boundary conditions. The simulation results were compared with empirical pore pressure data presented by the R&D project BegrensSkade I (2012-2015). The simulation results deviated notably from the empirical data, leading to the conclusion that the model itself is unreliable. Although there were found weaknesses with the model that could have been improved and resulted in better compliance, some major uncertainties are considered to remain and to affect the results to a significant degree. The uncertainties are in particular related to the modelling of the (weathered) bedrock conductivity, i.e. how the groundwater flows horizontally, vertically and across large distances within the bedrock joints. The discussion of these uncertainties is only introductory, and there is first of all a need to study the literature in greater detail to find out whether these issues are as important as argued here, and whether researchers already have studied them sufficiently. If the literature study comes to the conclusion that more research is needed, two modelling tasks are proposed with the aim to get a better understanding of how the groundwater flow could have been modelled more realistically in a continuum two-dimensional model.Norges Forskningsråd Research Council of Norwa

Analysis of water ingress, grouting effort, and pore pressure reduction caused by hard rock tunnels in the Oslo region

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Assessing potential building damage caused by leakage to urban tunnels

Building damage is a major risk for urban tunnelling. In areas with soft soil conditions, water ingress to bedrock tunnels can cause significant pore pressure reduction, consolidation settle-ments and damage to nearby buildings and infrastructure. In Norway, guidelines to determine leakage limits are based on a national database, containing data on water ingress, pore pressure reduction and influence zone. To support future projects, the database has been implemented into an ArcGIS-tool and merged with the Ground Impact and Building Vulnerability (GIBV) method to assess potential building damage at early project stages. This paper presents the adopted methodology and shows its application for a new subway tunnel in Oslo, Norway.Assessing potential building damage caused by leakage to urban tunnelsacceptedVersio

Work Package 3 – Hydrogeological methods, drainage and grouting

Ground works such as deep excavations and foundation works performed in soft clay can cause damage to neighbouring buildings and structures. Drainage causes pore pressure lowering, followed by consolidation settlements. The costs related to settlement damage can be substantial and there is a considerable potential for reducing these costs. The risk of settlement damage caused by drainage and pore pressure reduction can be reduced during the early design phase of a project by undertaking the correct type of investigations and understanding the hydrogeological conditions. Furthermore, one may select construction methods, which reduce risk of drainage. In case the selected construction solution yields an unacceptable risk for settlement damage to surrounding buildings and infrastructure, remedial measures may be designed to mitigate the effects, followed by implementation and monitoring during the construction phase. This report provides State-of-the-Art related to hydrogeological investigation methods, hydrogeological modelling and numerous measures to mitigate the effects of drainage to excavations. In addition, governing Norwegian rules and regulations are discussed, as well as the causes of drainage to excavations in Norwegian ground conditions.Norges forskningsråd / The Research Council of Norwa

Bolaamphiphile Analogues of 12-bis-THA Cl2 Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens

12-Bis-THA Cl2 [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications. IMPORTANCE While we face an acute threat from antibiotic resistant bacteria and a lack of new classes of antibiotic, there are many effective antimicrobials which have limited application due to concerns regarding their toxicity and which could be more useful if such risks are reduced or eliminated. We modified a bolalipid antiseptic used in throat lozenges to see if it could be made more effective against some of the highest-priority bacteria and less toxic. We found that structural modifications that rendered the lipid more toxic against human cells made it less toxic in infection models and we could effectively treat caterpillars infected with either Mycobacterium tuberculosis, methicillin resistant Staphylococcus aureus, or Acinetobacter baumannii. The study provides a rationale for further adaptation toward diversifying the range of indications in which this class of antimicrobial may be used

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Trial baseline characteristics of a cluster randomised controlled trial of a school-located obesity prevention programme; the Healthy Lifestyles Programme (HeLP) trial

This is the final version of the article. Available from BioMed Central via the DOI in this record.Background We have developed a healthy lifestyles programme (HeLP) for primary school aged children (9–10 years), currently being evaluated in a definitive cluster randomised controlled trial. This paper descriptively presents the baseline characteristics of trial children (BMI, waist circumference, % body fat, diet and physical activity) by gender, cluster level socio-economic status, school size and time of recruitment into the trial. Methods Schools were recruited from across the South West of England and allocated 1:1 to either intervention (HeLP) or control (usual practice) stratified by the proportion of children eligible for free school meals (FSM, 1 Year 5 class). The primary outcome is change in body mass index standard deviation score (BMI sds) at 24 months post-randomisation. Secondary outcomes are BMI sds at 18 months, waist circumference and percentage body fat sds at 18 and 24 months, proportion of children classified as underweight, overweight and obese at 18 and 24 months, physical activity (for a sub-sample) and food intake at 18 months. Results At baseline 11.4% and 13.6% of children were categorised as overweight or obese respectively. A higher percentage of girls than boys (25.3% vs 24.8%) and children from schools in FSM category 2 (28.2% vs 23.2%) were overweight or obese. Children were consuming a mean (range) of 4.15 (0–13) energy dense snacks (EDS) and 3.23 (0–9) healthy snacks (HS) per day with children from schools in FSM category 2 consuming more EDS and negative food markers and less HS and positive food markers. Children spent an average 53.6 min per day (11.9 to 124.8) in MVPA and thirteen hours (779.3 min) per day (11 h to 15 h) doing less than ‘light’ intensity activity. Less than 5% of children achieved the Departments of Health’s recommendation of 60 min of MVPA every day. Conclusion We have excellent completeness of baseline data for all measures and have achieved compliance to accelerometry not seen before in other large scale studies. Our anthropometric baseline data is representative of local and national data for children this age and reflects the gender and socio-economic variations expected of children this age in relation to physical activity and weight status.The definitive trial of HeLP is funded by the UK National Institute for Health Research (NIHR) Public Health Research Programme (10/3010/01) and a full report will be published on the NIHR website. Intervention materials and delivery was funded by the Peninsula College of Medicine and Dentistry. PenCLAHRC provided methodological support during the transition from the exploratory trial to the definitive evaluation

Bolaamphiphile analogues of 12-bis-THA Cl2 are potent antimicrobial therapeutics with distinct mechanisms of action against bacterial, mycobacterial, and fungal pathogens

12-Bis-THA Cl2 [12,12′-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl2 and its analogues accumulate within bacteria and fungi. More hydrophobic analogues with larger headgroups show reduced potential for DNA binding but increased and broader spectrum antibacterial activity. In contrast, analogues with less bulky headgroups and stronger DNA binding affinity were more active against Candida spp. Shortening the interconnecting chain, from the most lipophilic twelve-carbon chain to six, improved the selectivity index against Mycobacterium tuberculosis in vitro, but only the longer chain analogue was therapeutic in a Galleria mellonella infection model, with the shorter chain analogue exacerbating the infection. In vivo therapy of Escherichia coli ATCC 25922 and epidemic methicillin-resistant Staphylococcus aureus 15 (EMRSA-15) infections in Galleria mellonella was also achieved with longer-chain analogues, as was therapy for an A. baumannii 17978 burn wound infection with a synergistic combination of bolaamphiphile and gentamicin. The present study shows how this class of bolalipids may be adapted further to enable a wider range of potential applications