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Granular flows occur in a wide range of situations of practical interest to industry, in our natural environment and in our everyday lives. This paper focuses on granular flow in the so-called inertial regime, when the rheology is independent of the very large particle stiffness. Such flows have been modelled with the
-rheology, which postulates that the bulk friction coefficient
(i.e. the ratio of the shear stress to the pressure) and the solids volume fraction
are functions of the inertial number
only. Although the
-rheology has been validated in steady state against both experiments and discrete particle simulations in several different geometries, it has recently been shown that this theory is mathematically ill-posed in time-dependent problems. As a direct result, computations using this rheology may blow up exponentially, with a growth rate that tends to infinity as the discretization length tends to zero, as explicitly demonstrated in this paper for the first time. Such catastrophic instability due to ill-posedness is a common issue when developing new mathematical models and implies that either some important physics is missing or the model has not been properly formulated. In this paper an alternative to the
-rheology that does not suffer from such defects is proposed. In the framework of compressible
-dependent rheology (CIDR), new constitutive laws for the inertial regime are introduced; these match the well-established
relations in the steady-state limit and at the same time are well-posed for all deformations and all packing densities. Time-dependent numerical solutions of the resultant equations are performed to demonstrate that the new inertial CIDR model leads to numerical convergence towards physically realistic solutions that are supported by discrete element method simulations.
Evidence supporting the Developmental Origins of Health and Disease (DOHaD) hypothesis indicates that improving early life environments can reduce non-communicable disease risks and improve health over the lifecourse. A widespread understanding of this evidence may help to reshape structures, guidelines and individual behaviors to better the developmental conditions for the next generations. Yet, few efforts have yet been made to translate the DOHaD concept beyond the research community. To understand why, and to identify priorities for DOHaD Knowledge Translation (KT) programs, we review here a portion of published descriptions of DOHaD KT efforts and critiques thereof. We focus on KT targeting people equipped to apply DOHaD knowledge to their everyday home or work lives. We identified 17 reports of direct-to-public DOHaD KT that met our inclusion criteria. Relevant KT programs have been or are being initiated in nine countries, most focusing on secondary school students or care-workers-in-training; few target parents-to-be. Early indicators suggest that such programs can empower participants. Main critiques of DOHaD KT suggest it may overburden mothers with responsibility for children’s health and health environments, minimizing the roles of other people and institutions. Simultaneously, though, many mothers-to-be seek reliable guidance on prenatal health and nutrition, and would likely benefit from engagement with DOHaD KT. We thus recommend emphasizing solidarity, and bringing together people likely to one day become parents (youth), people planning pregnancies, expecting couples, care workers and policymakers into empowering conversation about DOHaD and about the importance and complexity of early life environments.
Carinthia's nationality struggle has raged more or less unabated since 1848. Until roughly two decades ago there was a relative dearth of secondary materials that one might regard as scholarly in any sense of the word. Polemics—admittedly of some value as a special kind of source material—predominated. Indeed emotional overtones still creep into serious studies. On balance, however, recent work in both Yugoslavia and Austria may be characterized as objective, solid, and methodologically innovative. While articles and books published in the former country are no less significant than those emanating from the latter, only titles that have appeared in German can be reviewed here.
In 785 mother–child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7–15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7–15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.
Emerging research in epigenetics has shown that there is variability in how environmental exposures “get under the skin” through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously associated with impairments in social–cognitive processes that may underlie a wide range of childhood psychopathology. Participants were 91 youth exposed to pre- and postnatal adversity with established conduct problem trajectories drawn from the Avon Longitudinal Study of Parents and Children. Consistent with our hypothesis, OXTR DNA methylation was predictive of resilience in the conduct problems domain in middle childhood. DNA methylation profiles did not predict resilience in domains of emotional, hyperactivity, and global symptomatology, suggesting a potential role for OXTR in the development of conduct problems in particular. However, individuals who were resilient to conduct problems were also broadly resilient across multiple domains. Therefore, future research should elucidate the biological pathways between OXTR DNA methylation and gene expression and its relation to impairments in social behavior.
Dietary polyunsaturated fatty acids (PUFA) are known to influence the fatty acid composition of immune and inflammatory cell membranes (Yaqoob et al, 1995). Changing the fatty acid composition and the n-6/n-3 PUFA ratio of cell membranes has been reported to have profound effects on immune cell functionality (Blok et al, 1996). Immune responses to Cooperia onchophara, a nematode parasite that infects calves, are usually slow to develop and inappropriate. The aim of this experiment was to establish the extent to which supplementation of pre-ruminant calves with an n-6 or n-3 PUFA source may influence ex-vivo lymphocyte response to an L3 C onchophara antigen.
In recent years considerable progress has been made in the continuum modelling of granular flows, in particular the
-rheology, which links the local viscosity in a flow to the strain rate and pressure through the non-dimensional inertial number
. This formulation greatly benefits from its similarity to the incompressible Navier–Stokes equations as it allows many existing numerical methods to be used. Unfortunately, this system of equations is ill posed when the inertial number is too high or too low. The consequence of ill posedness is that the growth rate of small perturbations tends to infinity in the high wavenumber limit. Due to this, numerical solutions are grid dependent and cannot be taken as being physically realistic. In this paper changes to the functional form of the
curve are considered, in order to maximise the range of well-posed inertial numbers, while preserving the overall structure of the equations. It is found that when the inertial number is low there exist curves for which the equations are guaranteed to be well posed. However when the inertial number is very large the equations are found to be ill posed regardless of the functional dependence of
. A new
curve, which is inspired by the analysis of the governing equations and by experimental data, is proposed here. In order to test this regularised rheology, transient granular flows on inclined planes are studied. It is found that simulations of flows, which show signs of ill posedness with unregularised models, are numerically stable and match key experimental observations when the regularised model is used. This paper details two-dimensional transient computations of decelerating flows where the inertial number tends to zero, high-speed flows that have large inertial numbers, and flows which develop into granular rollwaves. This is the first time that granular rollwaves have been simulated in two dimensions, which represents a major step towards the simulation of other complex granular flows.
Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.
The prevalence of colonization with toxigenic Clostridium difficile among patients with hematological malignancies and/or bone marrow transplant at admission to a 566-bed academic medical care center was 9.3%, and 13.3% of colonized patients developed symptomatic disease during hospitalization. This population may benefit from targeted C. difficile infection control interventions.
Last Supper Cave, located in northwestern Nevada, was excavated in the 1960s and 1970s. It contained a rich record of human occupation spanning the Holocene, but many artifacts from the site, including a large basketry collection, remain unstudied. We report the results of our technological analysis and radiocarbon dating of 14 fiber sandals from Last Supper Cave, which include examples of Fort Rock, Multiple Warp, and Spiral Weft types found at other sites in the northwestern Great Basin. Radiocarbon dates on the sandals correspond well with previous dates from Last Supper Cave and suggest that it was visited episodically for over 10 millennia; however, when considered together with the growing list of dates from the site, the sandal dates suggest that Last Supper Cave saw a prolonged hiatus in occupation during the Middle Holocene—a pattern common at other sandal-bearing sites in the northwestern Great Basin.
Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea, and its prevention is an urgent public health priority. However, reduction of CDI is challenging because of its complex pathogenesis, large reservoirs of colonized patients, and the persistence of infectious spores. The literature lacks high-quality evidence for evaluating interventions, and many hospitals have implemented bundled interventions to reduce CDI with variable results. Thus, we conducted a systematic review to examine the components of CDI bundles, their implementation processes, and their impact on CDI rates.
We conducted a comprehensive literature search of multiple computerized databases from their date of inception through April 30, 2016. The protocol was registered in PROSPERO, an international prospective register of systematic reviews. Bundle effectiveness, adherence, and study quality were assessed for each study meeting our criteria for inclusion.
In the 26 studies that met the inclusion criteria for this review, implementation and adherence factors to interventions were variably and incompletely reported, making study reproducibility and replicability challenging. Despite contextual differences and the variety of bundle components utilized, all 26 studies reported an improvement in CDI rates. However, given the lack of randomized controlled trials in the literature, assessing a causal relationship between bundled interventions and CDI rates is currently impossible.
Cluster randomized trials that include a rigorous assessment of the implementation of bundled interventions are urgently needed to causally test the effect of intervention bundles on CDI rates.
Rapid weight gain in infancy and low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) at birth are associated with increased adiposity later in life. The association between placental LCPUFA delivery and weight gain in infancy is poorly understood. We sought to determine the relationships between maternal phenotype, placental fatty acid transporter expression and offspring growth patterns over the first 6 months. Placental tissue and cord blood were collected at term delivery from women with uncomplicated pregnancies. Offspring body composition measurements were recorded 1 day and 6 months after birth. Body mass index (BMI) z-scores were determined using World Health Organization 2006 reference data. Body phenotype patterns were compared among offspring who had an increase in BMI z-score and those who had a decrease. High skinfold thickness at birth and positive change in BMI z-scores during infancy were associated with low neonatal n-3 LCPUFA plasma levels (r=−0.46, P=0.046) and high saturated fatty acids levels (r=0.49, P=0.034). Growth of skinfolds over 6 months of age was associated with placental fatty acid transporter gene expression. Change in BMI z-score in the first 6 months of life correlated with arm muscle area growth, a measure of lean mass (r=0.62, P=0.003), but not with growth in skinfold thickness. Early infancy weight gain was associated with poor plasma LCPUFA status at birth, and fat deposition in infancy was related to changes in placental lipid handling. Thus, neonatal fatty acid profiles may influence the trajectory of infant growth and fat and lean mass deposition.
Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses.
We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks.
Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus.
This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.
A few studies have evaluated the impact of clinical trial results on practice in paediatric cardiology. The Infant Single Ventricle (ISV) Trial results published in 2010 did not support routine use of the angiotensin-converting enzyme inhibitor enalapril in infants with single-ventricle physiology. We sought to assess the influence of these findings on clinical practice.
A web-based survey was distributed via e-mail to over 2000 paediatric cardiologists, intensivists, cardiothoracic surgeons, and cardiac advance practice nurses during three distribution periods. The results were analysed using McNemar’s test for paired data and Fisher’s exact test.
The response rate was 31.5% (69% cardiologists and 65% with >10 years of experience). Among respondents familiar with trial results, 74% reported current practice consistent with trial findings versus 48% before trial publication (p<0.001); 19% used angiotensin-converting enzyme inhibitor in this population “almost always” versus 36% in the past (p<0.001), and 72% reported a change in management or improved confidence in treatment decisions involving this therapy based on the trial results. Respondents familiar with trial results (78%) were marginally more likely to practise consistent with the trial results than those unfamiliar (74 versus 67%, p=0.16). Among all respondents, 28% reported less frequent use of angiotensin-converting enzyme inhibitor over the last 3 years.
Within 5 years of publication, the majority of respondents was familiar with the Infant Single Ventricle Trial results and reported less frequent use of angiotensin-converting enzyme inhibitor in single-ventricle infants; however, 28% reported not adjusting their clinical decisions based on the trial’s findings.
We present calculations showing how stable nonaxisymmetric magnetic fields may be excited in an alpha-quenched mean field dynamo in a deep spherical shell. The large scale velocity fields (differential rotation, meridional circulation) are determined by solving the axisymmetric Navier-Stokes equation, neglecting the Lorentz force but including a term parameterizing the turbulent Reynolds stresses.
Although the Great Basin of North America has produced some of the most robust and ancient fiber artifact assemblages in the world, many were recovered with poor chronological controls. Consequently, this class of artifacts has seldom been effectively incorporated into general discussions of early chronological and cultural patterns. In recent years, the Great Basin Textile Dating Project has accumulated direct AMS dates on textiles (bags, sandals, mats, cordage, and basketry) from dry caves in the Great Basin, particularly in the northern and western areas. We focus here on the terminal Pleistocene/early Holocene, to identify chronological patterns in this class of artifacts and to evaluate Adovasio’s characterization of the region’s earliest basketry as simple and undecorated. New AMS dates now suggest that the region’s earliest people had sophisticated textile traditions that incorporated numerous decorative elaborations. Some distinctive structures, including Fort Rock sandals and weft-faced plaited textiles, have limited early temporal ranges and may serve as diagnostic indicators for terminal Pleistocene/early Holocene times. Other basketry forms and structures that appear by about 9000 cal B.P. persist into the historic period, suggesting a stronger thread of continuity (especially in the north) from this time than is apparent in lithic traditions
Recently, large-scale trials of behavioural interventions have failed to show improvements in pregnancy outcomes. They have, however, shown that lifestyle support improves maternal diet and physical activity during pregnancy, and can reduce weight gain. This suggests that pregnancy, and possibly the whole periconceptional period, represents a ‘teachable moment’ for changes in diet and lifestyle, an idea that was made much of in the recent report of the Chief Medical Officer for England. The greatest challenge with all trials of diet and lifestyle interventions is to engage people and to sustain this engagement. With this in mind, we propose a design of intervention that aims simultaneously to engage women through motivational conversations and to offer access to a digital platform that provides structured support for diet and lifestyle change. This intervention design therefore makes best use of learning from the trials described above and from recent advances in digital intervention design.
“To reveal one's own emotional state to someone outside of the family, such as a social worker, or psychiatrist, is foreign to the usual repertoire of responses of Asians when in need of psychological support.” This assertion, made by two Asian-American mental health workers, is supported by the authors, based upon their social work experience with Indo-Chinese refugees in Queensland.