Test development for the investigation of soil disaggregation during slurry tunnelling

Slurry tunnelling uses a water based slurry to aid in tunnel face support and transportation of the excavated material. Unlike other tunnelling methods this requires expensive surface separation plant to remove the excavated ground from the slurry. Incorrect specification of this plant can lead to significant delays and added cost to a tunnel drive. Due to the tight budgets and space constraints this can cause contracts to become unprofitable, in particular where small diameter slurry tunnels are excavated by pipe jacking. For this reason accurate prediction of the size distribution of the soil particles and lumps in the disaggregating slurry is required. This research concerns the development of test procedures and methods of soil classification that will enable improved predictions of the degree to which soils/weak rocks will disaggregate during the slurry tunnelling process

Effects of polymer and bentonite support fluids on concrete-sand interface shear strength

Support fluids are widely used for the construction of deep bored piles and diaphragm walls. Specifications for the use of these fluids vary, and a thorough understanding of their effect on pile shaft resistance has not yet been developed. This paper presents the results of a set of concrete–sand interface shear tests carried out using both polymer and bentonite support fluids, with water as a reference fluid. It was found that polymer fluids had little effect on the interface shear strength when compared with water. Furthermore, in contrast to the results of earlier studies, concrete curing time was found to have little effect on the results. However, when bentonite slurry was used, the interface shear strength was found to decrease approximately linearly with the square root of the filtration time, until the strength of the pure filter cake was reached. This was due to the development of a bentonite filter cake at the interface so that only aggregate protruding through the filter cake made contact with the sand. It was found that the full concrete–sand shearing resistance could be mobilised when the concrete–sand contact area was greater than about 50% of the total area. </jats:p

A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Cotinine-assessed second-hand smoke exposure and risk of cardiovascular disease in older adults

Objectives: To examine whether second-hand smoke (SHS) exposure measured by serum cotinine is associated with increased coronary heart disease (CHD) and stroke risk among contemporary older British adults. Design: Prospective population-based study with self-reported medical history and health behaviours. Fasting blood samples were analysed for serum cotinine and cardiovascular disease (CVD) risk markers. Setting: Primary care centres in 25 British towns in 1998–2001. Patients: 8512 60–79-year-old men and women selected from primary care registers. Main outcome measures: Fatal and non-fatal myocardial infarction (MI; n=445) and stroke (n=386) during median 7.8-year follow-up. Main exposure: Observational study of serum cotinine assayed from fasting blood sample using liquid chromatography tandem mass spectrometry method, and self-reported smoking history. Results: Among 5374 non-smokers without pre-existing CVD, geometric mean cotinine was 0.15 ng/ml (IQR 0.05–0.30). Compared with non-smokers with cotinine ≤0.05 ng/ml, higher cotinine levels (0.06–0.19, 0.2–0.7 and 0.71–15.0 ng/ml) showed little association with MI; adjusted HRs were 0.92 (95% CI 0.63 to 1.35), 1.07 (0.73 to 1.55) and 1.09 (0.69 to 1.72), p(trend)=0.69. Equivalent HRs for stroke were 0.82 (0.55 to 1.23), 0.74 (0.48 to 1.13) and 0.69 (0.41 to 1.17), p(trend)=0.065. The adjustment for sociodemographic, behavioural and CVD risk factors had little effect on the results. The HR of MI for smokers (1–9 cigarettes/day) compared with non-smokers with cotinine ≤0.05 ng/ml was 2.14 (1.39 to 3.52) and 1.03 (0.52 to 2.04) for stroke. Conclusions: In contemporary older men and women, SHS exposure (predominantly at low levels) was not related to CHD or stroke risks, but we cannot rule out the possibility of modest effects at higher exposure levels

Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study.

BACKGROUND: Physical activity (PA) levels in older adults decline with age. The prevalence and correlates of adherence to current UK PA guidelines in older adults has not been studied using objectively measured PA, which can examine precisely whether PA is carried out in bouts of specified length and intensity. METHODS: Free living men and women aged 70-93 years from 25 towns in the United Kingdom, participating in parallel on-going population based cohort studies were invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010-12. Adherence to UK PA guidelines was defined as ≥150 minutes/week of moderate or vigorous PA (MVPA) in bouts of ≥10 minutes; the effect of different intensities and durations were examined. RESULTS: 1593 men and 857 women participated (responses 51% and 29% respectively). 15% men and 10% women achieved ≥150 minutes/week of MVPA (defined as >1040 cpm) in bouts lasting ≥10 minutes. With MVPA defined as >1952 cpm, prevalences were 7% and 3% respectively. Those adhering to guidelines were younger, had fewer chronic health conditions, less depression, less severe mobility limitations, but higher exercise self-efficacy and exercise outcomes expectations. They rated their local environment more highly for social activities and leisure facilities, having somewhere nice to go for a walk and feeling safe after dark, They left the house on more days per week, were more likely to use active transport (cycle or walk) and to walk a dog regularly. CONCLUSIONS: Few older adults attain current PA guidelines. Health promotion to extend the duration of moderate-intensity activity episodes to 10 minutes or more could yield important health gains among older adults. However future studies will need to clarify whether attaining guideline amounts of PA in spells lasting 10 minutes or more is critical for reducing chronic disease risks as well as improving cardiometabolic risk factors

Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index

Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers

Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure

Background: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure. / Methods: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided. / Results: Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42). / Conclusions: Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure

Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

Objectively measured physical activity and sedentary behaviour and ankle brachial index: Cross-sectional and longitudinal associations in older men

AbstractBackgroundAssociations between bouts of physical activity (PA), sedentary behaviour (SB) and cardiovascular disease, and their mutual independence are not well defined. A low ankle brachial index (ABI ≤0.9) indicates peripheral arterial disease (PAD) and is predictive of cardiovascular events and functional impairment. We investigated the independence of PA and SB and the importance of bout duration in relation to ABI using objective measures.Methods945 men from the British Regional Heart Study, mean age 78.4 y, had concurrent measurements of ABI (Vicorder) and physical activity (Actigraph GT3X accelerometer); 427 men also had accelerometer measurements one year previously and contributed data to longitudinal analyses.Results and conclusionIn cross-sectional analyses, after adjusting for covariates each extra 10 min of moderate and vigorous PA per day was associated with an OR of 0.81 (95% CI 0.72, 0.91) for a low ABI, a stronger association than for light PA (OR 0.85, 95% CI 0.75, 0.98). Each extra 30 min of SB was associated with an OR of 1.19 (95% CI 1.07, 1.33) for a low ABI. Associations between moderate and vigorous PA and ABI persisted after adjustment for light PA or SB. Bout lengths for PA and SB were not associated with a low ABI. One year changes in PA or SB were not associated with low ABI.All physical activity and lower levels of SB, regardless of bout duration were inversely associated with ABI; more intense PA showed a stronger association. No associations between changes in PA and ABI were observed, but power may have been limited