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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence from randomized controlled trials have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan soluble fiber. However, oats contain an array of phenolic acids, including ferulic acid and also structurally related avenanthramides, which may also contribute to the cardiovascular health benefits of oat intake. We investigated whether 4 weeks, daily consumption of oat phenolics leads to improvement in markers of CVD risk men and women.In a 3 arm crossover single-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (-containing 48.9 mg of phenolic acids and 19.2 mg of avenanthramides); 2) oatbran concentrate + rice porridge/wheat cracker intervention (-containing 38.4 mg of phenolic acids and 0.5 mg of avenanthramides) or 3) rice porridge/wheat cracker intervention (containing 13.8 mg of phenolic acids). All treatments were matched in soluble fiber (4.8g) and energy (500kcal). The primary endpoint was FMD and other cardiovascular endpoints were blood pressure, LDI, LDL/HDL cholesterol, platelets and endothelial cell-derived extracellular vesicles (EVs). All measures were taken at baseline and after three, 4 week long intervention periods and two washout periods.Our data indicates an increase by 1.09 % ± 0.41 %(Mean ± SEM) in FMD response following high phenolic oat intake with a significant difference (P = 0.007) between baseline and post-intervention. Consumption of high phenolic oats also led to a significant improvement in 24-hour SBP, day time SBP and night time SBP (P < 0.01, P < 0.01 and P < 0.05) and day time and night time DBP (p < 0.05). There was also a significant decrease with total and LDL cholesterol after the consumption of moderate and high phenolic oat interventions (P < 0.05) and a small improvement in LDI (both Ach and SNP) but not significant. The number of resting endothelial EVs were also found to be increasing after the consumption of high phenolic oats.The findings of this study may provide evidence about the role of oat phenolic acids and avenanthramides in cardiovascular health and contribute to more effective public health advice about the consumption of oats and healthy cardiovascular aging.
Oceanic internal waves can be decomposed into an infinite set of modes, and the dominant internal mode 1 waves have been extensively investigated. Although mode 2 waves have been observed, they have not received comparable attention, especially the generation mechanisms. In this work, we examine the generation of mode 2 internal waves by the interaction of mode 1 waves with topography. We use a coupled linear long-wave theory with mode coupling through topography, combined with evolution using a Korteweg–de Vries model, to predict the mode 2 wave amplitude, in an ideal three-layer fluid model, in a smooth density stratification and in two realistic oceanic settings. We find that the mode 2 wave amplitude is usually much smaller than the incident mode 1 wave amplitude and is quite sensitive to the pycnocline thickness, topographic slope and background stratification.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Shallow granular avalanches on slopes close to repose exhibit hysteretic behaviour. For instance, when a steady-uniform granular flow is brought to rest it leaves a deposit of thickness
on a rough slope inclined at an angle
to the horizontal. However, this layer will not spontaneously start to flow again until it is inclined to a higher angle
, or the thickness is increased to
. This simple phenomenology leads to a rich variety of flows with co-existing regions of solid-like and fluid-like granular behaviour that evolve in space and time. In particular, frictional hysteresis is directly responsible for the spontaneous formation of self-channelized flows with static levees, retrogressive failures as well as erosion–deposition waves that travel through the material. This paper is motivated by the experimental observation that a travelling-wave develops, when a steady uniform flow of carborundum particles on a bed of larger glass beads, runs out to leave a deposit that is approximately equal to
. Numerical simulations using the friction law originally proposed by Edwards et al. (J. Fluid Mech., vol. 823, 2017, pp. 278–315) and modified here, demonstrate that there are in fact two travelling waves. One that marks the trailing edge of the steady-uniform flow and another that rapidly deposits the particles, directly connecting the point of minimum dynamic friction (at thickness
) with the deposited layer. The first wave moves slightly faster than the second wave, and so there is a slowly expanding region between them in which the flow thins and the particles slow down. An exact inviscid solution for the second travelling wave is derived and it is shown that for a steady-uniform flow of thickness
it produces a deposit close to
for all inclination angles. Numerical simulations show that the two-wave structure deposits layers that are approximately equal to
for all initial thicknesses. This insensitivity to the initial conditions implies that
is a universal quantity, at least for carborundum particles on a bed of larger glass beads. Numerical simulations are therefore able to capture the complete experimental staircase procedure, which is commonly used to determine the
curves by progressively increasing the inclination of the chute. In general, however, the deposit thickness may depend on the depth of the flowing layer that generated it, so the most robust way to determine
is to measure the deposit thickness from a flow that was moving at the minimum steady-uniform velocity. Finally, some of the pathologies in earlier non-monotonic friction laws are discussed and it is explicitly shown that with these models either steadily travelling deposition waves do not form or they do not leave the correct deposit depth
When a layer of static grains on a sufficiently steep slope is disturbed, an upslope-propagating erosion wave, or retrogressive failure, may form that separates the initially static material from a downslope region of flowing grains. This paper shows that a relatively simple depth-averaged avalanche model with frictional hysteresis is sufficient to capture a planar retrogressive failure that is independent of the cross-slope coordinate. The hysteresis is modelled with a non-monotonic effective basal friction law that has static, intermediate (velocity decreasing) and dynamic (velocity increasing) regimes. Both experiments and time-dependent numerical simulations show that steadily travelling retrogressive waves rapidly form in this system and a travelling wave ansatz is therefore used to derive a one-dimensional depth-averaged exact solution. The speed of the wave is determined by a critical point in the ordinary differential equation for the thickness. The critical point lies in the intermediate frictional regime, at the point where the friction exactly balances the downslope component of gravity. The retrogressive wave is therefore a sensitive test of the functional form of the friction law in this regime, where steady uniform flows are unstable and so cannot be used to determine the friction law directly. Upper and lower bounds for the existence of retrogressive waves in terms of the initial layer depth and the slope inclination are found and shown to be in good agreement with the experimentally determined phase diagram. For the friction law proposed by Edwards et al. (J. Fluid. Mech., vol. 823, 2017, pp. 278–315, J. Fluid. Mech., 2019, (submitted)) the magnitude of the wave speed is slightly under-predicted, but, for a given initial layer thickness, the exact solution accurately predicts an increase in the wave speed with higher inclinations. The model also captures the finite wave speed at the onset of retrogressive failure observed in experiments.
Crisis resolution teams (CRTs) offer brief, intensive home treatment for people experiencing mental health crisis. CRT implementation is highly variable; positive trial outcomes have not been reproduced in scaled-up CRT care.
To evaluate a 1-year programme to improve CRTs’ model fidelity in a non-masked, cluster-randomised trial (part of the Crisis team Optimisation and RElapse prevention (CORE) research programme, trial registration number: ISRCTN47185233).
Fifteen CRTs in England received an intervention, informed by the US Implementing Evidence-Based Practice project, involving support from a CRT facilitator, online implementation resources and regular team fidelity reviews. Ten control CRTs received no additional support. The primary outcome was patient satisfaction, measured by the Client Satisfaction Questionnaire (CSQ-8), completed by 15 patients per team at CRT discharge (n = 375). Secondary outcomes: CRT model fidelity, continuity of care, staff well-being, in-patient admissions and bed use and CRT readmissions were also evaluated.
All CRTs were retained in the trial. Median follow-up CSQ-8 score was 28 in each group: the adjusted average in the intervention group was higher than in the control group by 0.97 (95% CI −1.02 to 2.97) but this was not significant (P = 0.34). There were fewer in-patient admissions, lower in-patient bed use and better staff psychological health in intervention teams. Model fidelity rose in most intervention teams and was significantly higher than in control teams at follow-up. There were no significant effects for other outcomes.
The CRT service improvement programme did not achieve its primary aim of improving patient satisfaction. It showed some promise in improving CRT model fidelity and reducing acute in-patient admissions.
The continued development of the aquaculture industry is contributing to the proliferation of artificial structures in the marine environment. Observations of seaweed farms (infrastructure and biomass) suggest they act as a habitat for associated species. Seaweed farms differ from other forms of artificial infrastructure as the material deployed already has marine organisms (i.e. culture species) growing on it. This ‘priming’ of ropes with juvenile sporophytes may affect future development of communities by facilitating colonizing species or suppressing competitors. We call this process ‘ecological priming’: the provision of a biological platform that influences the successional development of specific communities. The communities that developed on ropes primed with Alaria esculenta individuals were compared with unprimed ropes to assess the ecological priming effect, at a commercial kelp farm in south-west Ireland. Species richness increased over two cultivation seasons and species composition was consistent between years, with distinct communities developing on primed and unprimed treatments. Timing of species occurrence on primed ropes was predictable with no predictable pattern occurring on unprimed ropes. Multivariate tests indicated distinct communities between treatments, with suppression of other algal species and potential facilitation of some species that have a particular association with A. esculenta on primed ropes. Communities from primed holdfasts contained a lower diversity of algal species compared with unprimed communities. Cultivated kelp holdfasts represent a habitat for distinct assemblages that reflect ecological priming of the substratum.
This study explored the combined impact of depression and inflammation on memory functioning among Mexican-American adults and elders.
Data were analyzed from 381 participants of the Health and Aging Brain study among Latino Elders (HABLE). Fasting serum samples were collected and assayed in duplicate using electrochemiluminesce on the SECTOR Imager 2400A from Meso Scale Discovery. Positive DepE (depression endophenotype) was codified as any score >1 on a five-point scale based on the GDS-30. Inflammation was determined by TNFα levels and categorized by tertiles (1st, 2nd, 3rd). WMS-III LMI and LMII as well as CERAD were utilized as measures of memory. ANOVAs examined group differences between positive DepE and inflammation tertiles with neuropsychological scale scores as outcome variables. Logistic regressions were used to examine level of inflammation and DepE positive status on the risk for MCI.
Positive DepE as well as higher inflammation were both independently found to be associated with lower memory scores. Among DepE positive, those who were high in inflammation (3rd tertile) were found to perform significantly worse on WMS-III LM I (F = 4.75, p = 0.003), WMS-III LM II (F = 8.18, p < 0.001), and CERAD List Learning (F = 17.37, p < 0.001) when compared to those low on inflammation (1st tertile). The combination of DepE positive and highest tertile of inflammation was associated with increased risk for MCI diagnosis (OR = 6.06; 95% CI = 3.9–11.2, p < 0.001).
Presence of elevated inflammation and positive DepE scores increased risk for worse memory among Mexican-American older adults. Additionally, the combination of DepE and high inflammation was associated with increased risk for MCI diagnosis. This work suggests that depression and inflammation are independently associated with worse memory among Mexican-American adults and elders; however, the combination of both increases risk for poorer memory beyond either alone.
Population-based registries report 95% 5-year survival for children undergoing surgery for CHD. This study investigated paediatric cardiac surgical outcomes in the Australian indigenous population.
All children who underwent cardiac surgery between May, 2008 and August, 2014 were studied. Demographic information including socio-economic status, diagnoses and co-morbidities, and treatment and outcome data were collected at time of surgery and at last follow-up.
A total of 1528 children with a mean age 3.4±4.6 years were studied. Among them, 123 (8.1%) children were identified as indigenous, and 52.7% (62) of indigenous patients were in the lowest third of the socio-economic index compared with 28.2% (456) of non-indigenous patients (p⩽0.001). The indigenous sample had a significantly higher Comprehensive Aristotle Complexity score (indigenous 9.4±4.2 versus non-indigenous 8.7±3.9, p=0.04). The probability of having long-term follow-up did not differ between groups (indigenous 93.8% versus non-indigenous 95.6%, p=0.17). No difference was noted in 30-day mortality (indigenous 3.2% versus non-indigenous 1.4%, p=0.13). The 6-year survival for the entire cohort was 95.9%. The Cox survival analysis demonstrated higher 6-year mortality in the indigenous group – indigenous 8.1% versus non-indigenous 5.0%; hazard ratio (HR)=2.1; 95% confidence intervals (CI): 1.1, 4.2; p=0.03. Freedom from surgical re-intervention was 79%, and was not significantly associated with the indigenous status (HR=1.4; 95% CI: 0.9, 1.9; p=0.11). When long-term survival was adjusted for the Comprehensive Aristotle Complexity score, no difference in outcomes between the populations was demonstrated (HR=1.6; 95% CI: 0.8, 3.2; p=0.19).
The indigenous population experienced higher late mortality. This apparent relationship is explained by increased patient complexity, which may reflect negative social and environmental factors.
Geophysical granular flows, such as avalanches, debris flows, lahars and pyroclastic flows, are always strongly influenced by the basal topography that they flow over. In particular, localised bumps or obstacles can generate rapid changes in the flow thickness and velocity, or shock waves, which dissipate significant amounts of energy. Understanding how a granular material is affected by the underlying topography is therefore crucial for hazard mitigation purposes, for example to improve the design of deflecting or catching dams for snow avalanches. Moreover, the interactions with solid boundaries can also have important applications in industrial processes. In this paper, small-scale experiments are performed to investigate the flow of a granular avalanche over a two-dimensional smooth symmetrical bump. The experiments show that, depending on the initial conditions, two different steady-state regimes can be observed: either the formation of a detached jet downstream of the bump, or a shock upstream of it. The transition between the two cases can be controlled by adding varying amounts of erodible particles in front of the obstacle. A depth-averaged terrain-following avalanche theory that is formulated in curvilinear coordinates is used to model the system. The results show good agreement with the experiments for both regimes. For the case of a shock, time-dependent numerical simulations of the full system show the evolution to the equilibrium state, as well as the deposition of particles upstream of the bump when the inflow ceases. The terrain-following theory is compared to a standard depth-averaged avalanche model in an aligned Cartesian coordinate system. For this very sensitive problem, it is shown that the steady-shock regime is captured significantly better by the terrain-following avalanche model, and that the standard theory is unable to predict the take-off point of the jet. To retain the practical simplicity of using Cartesian coordinates, but have the improved predictive power of the terrain-following model, a coordinate mapping is used to transform the terrain-following equations from curvilinear to Cartesian coordinates. The terrain-following model, in Cartesian coordinates, makes identical predictions to the original curvilinear formulation, but is much simpler to implement.
This chapter is about the tension between two ideal type modes of learning and innovation. One mode is based on the production and use of codified scientific and technical knowledge namely Science, Technology and Innovation (STI) mode, while the other one is an experience-based mode of learning through Doing, Using and Interacting (DUI-mode). At the level of the firm, this tension may be seen in the need to reconcile knowledge management strategies prescribing the use of Information and Communication Technologies (ICT) as tools for codifying and sharing knowledge with strategies emphasizing the role played by informal communication and communities of practice in mobilizing tacit knowledge for problem solving and learning.
The tension between the STI-and DUI-modes corresponds to two different approaches to national innovation systems: One perspective focusing on the role of formal processes of R&D that produce explicit and codified knowledge and another perspective focusing on the learning from informal interaction within and between organizations resulting in competence building often with tacit elements.
There is, of course, an important body of empirical and historical work showing that both these modes of learning and innovation play a role in most sectors, the role being different depending on the sector characteristics as well as the strategy of the firm (von Hippel 1976; Rothwell 1977; Rosenberg 1982; Pavitt 1984). Recent models of innovation emphasize that innovation is an interactive process in which firms interact both with customers and suppliers and with knowledge institutions (Freeman 1986; Kline and Rosenberg 1986; Lundvall 1988; Vinding 2002).
Despite the broad acceptance of this literature, there remains a bias among scholars and policymakers to consider innovation processes largely as aspects connected to formal processes of R&D, especially in the science-based industries. At the policy level, this can be seen in the emphasis on benchmarking variables related to STI and in the focus on instruments such as tax subsidies to R&D, the training of scientists in high-tech fields such as ICT, bio and nanotechnology and strengthening the linkages between firms and universities in these specific fields. At the level of scholarly research, there is a tendency to expect that the increasing reliance on science and technology in the ‘knowledge-based economy’ will enhance the role played by formal processes of R&D requiring personnel with formal science and technology qualifications.
The dynamic nature of sand dunes over relatively short spatial and temporal scales makes them an ideal phenomenon from which to obtain a better understanding of the interactions between the geosciences and biological sciences. Most early studies of sand dunes focused on classification of dune forms, plant species composition on various dune types, plant succession, and the morphological adaptation of plants to sand burial, salt spray, and xeric conditions. In this chapter, the interaction of ecology and geomorphology in the development of coastal sand dunes will be discussed, from the origin of ecology in the 1800s through to the present. Underlying this history is a struggle by both disciplines to move from a mainly descriptive approach toward an understanding of how sand dunes and plants influence each other. The difficulty has always been how to couple the physical processes of sand transport with the influence of plants and, in turn, how to connect plants with different life histories to sand transport. This undertaking is still in its infancy.
Physiography and Physiographic Ecology
At the end of the 1800s, both physiography (as geomorphology was called at the time) and biology adopted a neo-Lamarckian evolutionary viewpoint (Johnson, 1979; Inkpen and Collier, 2007). Evolution, at this time, incorporated ideas of directional development that could take place at scales above the individual or population (today this idea is called group selection and is mostly rejected as having no valid mechanism (Williams, 1966)). Stages in this directional development were believed to facilitate further evolution. The result was a belief that many forms in biology developed in a progressive, integrated manner with an end-stage that would be in equilibrium. Herbert Spencer, a prolific but now largely forgotten philosopher, was a popular exponent of these ideas, combining both “evolutionary” and “quasi-thermodynamic” ideas in Principles of Biology (1864). He is best remembered for the teleological term “survival of the fittest.”
These evolutionary viewpoints can be found in numerous scientific studies, such as the landscape cycles of Davis (1889; 1899) and in the ecology of communities and succession of Cowles (1899), Clements (1916), and Cooper (1926).