An experimental evaluation of prediction models for the mechanical behavior of unreinforced, lime-mortar masonry under compression

This paper contributes to the understanding of lime-mortar masonry strength and deformation (which determine durability and allowable stresses/stiffness in design codes) by measuring the mechanical properties of brick bound with lime and lime-cement mortars. Based on the regression analysis of experimental results, models to estimate lime-mortar masonry compressive strength are proposed (less accurate for hydrated lime (CL90s) masonry due to the disparity between mortar and brick strengths). Also, three relationships between masonry elastic modulus and its compressive strength are proposed for cement-lime; hydraulic lime (NHL3.5 and 5); and hydrated/feebly hydraulic lime masonries respectively.

Disagreement between the experimental results and former mathematical prediction models (proposed primarily for cement masonry) is caused by a lack of provision for the significant deformation of lime masonry and the relative changes in strength and stiffness between mortar and brick over time (at 6 months and 1 year, the NHL 3.5 and 5 mortars are often stronger than the brick). Eurocode 6 provided the best predictions for the compressive strength of lime and cement-lime masonry based on the strength of their components. All models vastly overestimated the strength of CL90s masonry at 28 days however, Eurocode 6 became an accurate predictor after 6 months, when the mortar had acquired most of its final strength and stiffness.

The experimental results agreed with former stress-strain curves. It was evidenced that mortar strongly impacts masonry deformation, and that the masonry stress/strain relationship becomes increasingly non-linear as mortar strength lowers. It was also noted that, the influence of masonry stiffness on its compressive strength becomes smaller as the mortar hydraulicity increases.

Investigation of thermal resistance and bridging in examples of contemporary and vernacular solid wall architecture

Contemporary architecture has tended to increase envelope insulation levels in an unceasing effort to reduce U-values. Traditional masonry architecture in contrast was devoid of insulation, except for the inherent insulative nature of vernacular materials. Also the consistency of the outer membrane of the building skin diminished any impact due to bridging. In contemporary highly insulated walls bridges are numerous due to the necessity to bind inner and outer structural skins through insulation layers. This paper examines thermal bridging in an example of contemporary façade design and compares it with an example of traditional vernacular architecture currently being researched which is characterized by a lack of bridging elements. Focus is given to heavy weight materials of high thermal mass, which appropriately for passive architecture help moderate fluctuations in internal temperature. In an extensive experimental study samples of highly insulated precast concrete sandwich panels and lime rendered masonry walls are tested in a guarded hot-box. The building construction methods are compared for static and dynamic thermal transmittance, via heat flux and surface temperature differential measurements. Focus is given to the differential heat loss due to the thermal bridging in the sandwich panels and its associated impact on overall heat loss relative to traditional masonry construction.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase.

Life history of turbot in Icelandic waters: Intra- and inter-population genetic diversity and otolith tracking of environmental temperatures

The stock structure of turbot was investigated between samples from S-Norway, the Irish Sea and the Kattegat, using 12 microsatellite loci and compared to the turbot caught in Icelandic waters. Highly significant genetic differentiation was observed between samples from Kattegat and other areas. Significant genetic differentiation was also observed between the Irish Sea sample on one hand and Iceland and S-Norway on the other hand. No significant genetic differentiation was observed between Iceland and S-Norway. Otoliths of 25 turbot, age ranging from 3 to 19 years, were subjected to nearly 300 mass spectrometry determinations of stable oxygen and carbon isotopes. Oxygen isotope composition (δ¹⁸O) in the otolith samples was used to estimate ambient temperature at time of otolith accretion, and yielded estimated temperatures experienced by the turbot ranging from 3 to 15°C. Overall, the genetic analysis indicates panmixia between turbot in Icelandic and Norwegian waters. While the extensive migration of larvae between Norway and Iceland is unlikely, passive drift of turbot larva from other areas (e.g. Ireland) cannot be ruled out. 

Historical Dialogue and Memory in Policing Change: the Case of the Police in Northern Ireland

This paper explores the complex relationship between organisational change and historical dialogue in transitional societies. Using the policing reform process in Northern Ireland as an example, the paper does three things: the first is to explore the ways in which policing changes were understood within the policing organisation and ‘community’ itself. The second is to make use of a processual approach, privileging the interactions of context, process and time within the analysis. Thirdly, it considers this perspective through the relatively new lens of ‘historical dialogue’: understood here as a conversation and an oscillation between the past, present and future through reflections on individual and collective memory. Through this analysis, we consider how members’ understandings of a difficult past (and their roles in it) facilitated and/or impeded the organisations change process. Drawing on a range of interviews with previous and current members of the organisation, this paper sheds new light on how institutions deal with and understand the past as they experience organisational change within the a wider societal transition from conflict to non-violence.

The common vaginal commensal bacterium Ureaplasma parvum is associated with chorioamnionitis in extreme preterm labour

OBJECTIVE: To assess the association of vaginal commensal and low grade pathogenic bacteria including Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, Group B Streptococcus (GBS), and Gardnerella vaginalis, in women who delivered preterm at less than 37 weeks gestation in the presence or absence of inflammation of the chorioamnionitic membranes.

METHODS: A case control study involving women who delivered before 37 weeks gestation with and without inflammation of chorioamnionitic membranes. A total of 57 placental samples were histologically examined for polymorphonuclear leukocyte infiltration of placental tissue for evidence of chorioamnionitis, and by type-specific nucleic acid amplification for evidence of infection with one or more of the target bacteria. Demographic data was collected for each mother.

RESULTS: Amongst the 57 placental samples, 42.1% had chorioamnionitis and 24.6% delivered in the second trimester of pregnancy; U. parvum, U. urealyticum, G. vaginalis and GBS were all detected in the study with respective prevalence of 19.3%, 3.5%, 17.5% and 15.8%; M.genitalium and M. hominis were not detected. U. parvum was significantly associated with chorioamnionitis (p value = 0.02; OR 5.0; (95% CI 1.2-21.5) and was more common in women who delivered in the second (35.7%) compared to the third trimester of pregnancy (13.9%). None of the other bacteria were associated with chorioamnionitis or earlier delivery and all G.vaginalis positive women delivered in the third trimester of pregnancy (p value 0.04).

CONCLUSIONS: The detection of U. parvum in placental tissue was significantly associated with acute chorioamnionitis in women presenting in extreme preterm labour.

Biomarkers reveal the effects of hydrography on the sources and fate of marine and terrestrial organic matter in the western Irish Sea

A suite of lipid biomarkers were investigated from surface sediments and particulate matter across hydrographically distinct zones associated with the western Irish Sea gyre and the seasonal bloom. The aim was to assess the variation of organic matter (OM) composition, production, distribution and fate associated with coastal and southern mixed regions and also the summer stratified region. Based on the distribution of a suite of diagnostic biomarkers, including phospholipid fatty acids, source-specific sterols, wax esters and C₂₅ highly branched isoprenoids, diatoms, dinoflagellates and green algae were identified as major contributors of marine organic matter (MOM) in this setting. The distribution of cholesterol, wax esters and C₂₀ and C₂₂ polyunsaturated fatty acids indicate that copepod grazing represents an important process for mineralising this primary production. Net tow data from 2010 revealed much greater phytoplankton and zooplankton biomass in well-mixed waters compared to stratified waters. This appears to be largely reflected in MOM input to surface sediments. Terrestrial organic matter (TOM), derived from higher plants, was identified as a major source of OM regionally, but was concentrated in proximity to major riverine input at the Boyne Estuary and Dundalk Bay. Near-bottom residual circulation and the seasonal gyre also likely play a role in the fate of TOM in the western Irish Sea.

Nerve Growth Factor Sensitisation of TRPA1 on Sensory Neurones

Background: Sensory neurones from the trigeminal nerve innervate the oro-facial region and teeth. Transient receptor potential channels (TRPs) expressed by these neurones are responsible for relaying sensory information such as changes in ambient temperature, mechanical sensations and pain. Study of TRP channel expression and regulation in human sensory neurones therefore merits investigation to improve our understanding of allodynia and hyperalgesia. Objective: The objective of this study was to differentiate human dental pulp stem cells (hDPSCs) towards a neuronal phenotype (peripheral neuronal equivalents; PNEs) and employ this model to study TRP channel sensitisation. Method: hDPSCs were enriched by preferential adhesion to fibronectin, plated on coverslips (thickness 0) coated with poly-l-ornithine and laminin and then differentiated for 7 days in neurobasal A medium with additional supplementation. A whole cell patch clamp technique was used to investigate whether TRP channels on PNE membranes were modulated in the presence of nerve growth factor (NGF). PNEs were treated with NGF for 20 minutes immediately before experimentation and then stimulated for TRPA1 activity using cinnamaldehyde. Peak currents were read at 80 mV and -80 mV and compared to peak currents recorded in untreated PNEs. Data were analysed and plotted using Clampfit9 software (Molecular Devices, Sunnyvale, California, USA). Result: Results showed for the first time that pre-treatment of PNEs by NGF produced significantly larger inward and outward currents demonstrating that TRPA1 channels on PNE membranes were capable of becoming sensitised following treatment with NGF. Conclusion: Sensitisation of TRPA1 by NGF provides evidence of a mechanism for rapid neuronal sensitisation that is independent of TRPA1 gene expression

An in vitro model of nociceptors in human trigeminal nerves

Background: The oro-facial region is densely innervated by the trigeminal nerve, which when stimulated can induce noxious pain sensation and contribute to neurogenic inflammation in local tissues. Recent research on the expression of specialised ion channels on the trigeminal nerve has highlighted the need to undertake more extensive studies on ion channel expression/functionality with the aim of elucidating their role in pain sensations. A major family of such ion channels is the transient receptor potential (TRP) channels which are activated by a wide variety of thermal, mechanical or chemical stimuli and merit investigation as possible druggable targets for future analgesics.
Objective: Study of TRP channel expression and regulation in oro-facial tissues is hindered by the fact that the cell bodies of neurons innervating these tissues are located in the trigeminal ganglion. Using dental pulp stem cells differentiated towards peripheral neuronal equivalents (PNEs), we sought to determine TRP channel expression, functionality and potential modulation by cytokines in this novel model.
Method: Dental pulp stem cells (DPSCs) were grown on substrate-coated tissue culture plates and differentiated towards a neuronal phenotype using neuronal induction media. Quantitative polymerase chain reaction (qPCR) was performed on PNEs +/-cytokine treatment. Ion channel functionality was investigated using whole cell patch clamping.
Result: qPCR analysis showed that PNEs expressed the TRP channels TRPA1, TRPV1, TRPV4 and TRPM8. TRPA1 was the most abundantly expressed TRP channel studied whereas TRPM8 was lowly expressed. TRP channel expression was shown to be regulated by treatment with inflammatory cytokines. Patch clamp studies using specific agonists and antagonists for TRPA1 and TRPV1 showed these channels were functional.
Conclusion: PNEs differentiated from DPSCs provide a suitable model for TRP channel expression, regulation, and sensistisation in oro-facial tissues. This human neuronal model has potential for use in pre-clinical studies of novel analgesics.

Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism

Metabolic networks are highly connected and complex, but a single enzyme, O-GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179). Metabolic profiling revealed decreased glucose consumption and lactate production after OGT inhibition. This decreased glycolytic activity specifically sensitized prostate cancer cells, but not cells representing normal prostate epithelium, to inhibitors of oxidative phosphorylation (rotenone and metformin). Intra-cellular alanine was depleted upon OGT inhibitor treatment. OGT inhibitor increased the expression and activity of alanine aminotransferase (GPT2), an enzyme that can be targeted with a clinically approved drug, cycloserine. Simultaneous inhibition of OGT and GPT2 inhibited cell viability and growth rate, and additionally activated a cell death response. These combinatorial effects were predominantly seen in prostate cancer cells, but not in a cell-line derived from normal prostate epithelium. Combinatorial treatments were confirmed with two inhibitors against both OGT and GPT2. Taken together, here we report the reprogramming of energy metabolism upon inhibition of OGT activity, and identify synergistically lethal combinations that are prostate cancer cell specific.

Distant activity of 67P/Churyumov-Gerasimenko in 2014: Ground-based results during the Rosetta pre-landing phase

As the ESA Rosetta mission approached, orbited, and sent a lander to comet 67P/Churyumov-Gerasimenko in 2014, a large campaign of ground-based observations also followed the comet. We constrain the total activity level of the comet by photometry and spectroscopy to place Rosetta results in context and to understand the large-scale structure of the comet's coma pre-perihelion. We performed observations using a number of telescopes, but concentrate on results from the 8m VLT and Gemini South telescopes in Chile. We use R-band imaging to measure the dust coma contribution to the comet's brightness and UV-visible spectroscopy to search for gas emissions, primarily using VLT/FORS. In addition we imaged the comet in near-infrared wavelengths (JHK) in late 2014 with Gemini-S/Flamingos 2. We find that the comet was already active in early 2014 at heliocentric distances beyond 4 au. The evolution of the total activity (measured by dust) followed previous predictions. No gas emissions were detected despite sensitive searches. The comet maintains a similar level of activity from orbit to orbit, and is in that sense predictable, meaning that Rosetta results correspond to typical behaviour for this comet. The gas production (for CN at least) is highly asymmetric with respect to perihelion, as our upper limits are below the measured production rates for similar distances post-perihelion in previous orbits.