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Mathematical models of polyelectrolyte gels are often simplified by assuming the gel is electrically neutral. The rationale behind this assumption is that the thickness of the electric double layer (EDL) at the free surface of the gel is small compared to the size of the gel. Hence, the thin-EDL limit is taken, in which the thickness of the EDL is set to zero. Despite the widespread use of the thin-EDL limit, the solutions in the EDL are rarely computed and shown to match to the solutions for the electrically neutral bulk. The aims of this paper are to study the structure of the EDL and establish the validity of the thin-EDL limit. The model for the gel accounts for phase separation, which gives rise to diffuse interfaces with a thickness described by the Kuhn length. We show that the solutions in the EDL can only be asymptotically matched to the solutions for an electrically neutral bulk, in general, when the Debye length is much smaller than the Kuhn length. If the Debye length is similar to or larger than the Kuhn length, then phase separation can be initiated in the EDL. This phase separation spreads into the bulk of the gel and gives rise to electrically charged layers with different degrees of swelling. Thus, the thin-EDL limit and the assumption of electroneutrality only generally apply when the Debye length is much smaller than the Kuhn length.
Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.
We present a software package for single-dish data processing of spacecraft signals observed with VLBI-equipped radio telescopes. The Spacecraft Doppler tracking (SDtracker) software allows one to obtain topocentric frequency detections with a sub-Hz precision and reconstructed and residual phases of the carrier signal of any spacecraft or landing vehicle at any location in the Solar System. These data products are estimated using the ground-based telescope’s highly stable oscillator as a reference, without requiring an a priori model of the spacecraft dynamics nor the downlink transmission carrier frequency. The software has been extensively validated in multiple observing campaigns of various deep space missions and is compatible with the raw sample data acquired by any standard VLBI radio telescope worldwide. In this paper, we report the numerical methodology of SDtracker, the technical operations for deployment and usage, and a summary of use cases and scientific results produced since its initial release.
Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors.
Method
Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used.
Results
All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN).
Conclusions
Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden.
The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment.
Methods
The current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals. Participants were assessed at four time points over 1 year.
Results
Approximately 53% of the sample was diagnosed with PTSD at initial assessment, with declining rates of diagnostic status over time to 16%. Latent difference score (LDS) modeling revealed nonlinear declines in both clinician-assessed and self-reported PTSD symptom severity, with faster declines in earlier periods. Likewise, LDS models revealed nonlinear declines in negative (conflict) aspects of interpersonal relationship functioning, but linear declines in positive (support, depth) aspects. The relationship between PTSD and relationship functioning differed for clinician- and self-reported PTSD. Bivariate LDS modeling revealed significant cross-lagged effects from relationship conflict to clinician-assessed PTSD, and significant cross-lagged effects from self-reported PTSD to relationship conflict over time.
Conclusions
These results highlight that the variability in prior results may be related to the method of assessing PTSD symptomatology and different relational constructs. Implications for theory and early intervention are discussed.
Firefighting service is known to involve high rates of exposure to potentially traumatic situations, and research on mental health in firefighting populations is of critical importance in understanding the impact of occupational exposure. To date, the literature concerning prevalence of trauma-related mental disorders such as posttraumatic stress disorder (PTSD) has not distinguished between symptomology associated routine duty-related exposure and exposure to large-scale disaster. The present systematic review synthesizes a heterogeneous cross-national literature on large-scale disaster exposure in firefighters and provides support for the hypothesis that the prevalence of PTSD, major depressive disorder, and anxiety disorders are elevated in firefighters compared with rates observed in the general population. In addition, we conducted narrative synthesis concerning several commonly assessed predictive factors for disorder and found that sociodemographic factors appear to bear a weak relationship to mental disorder, while incident-related factors, such as severity and duration of disaster exposure, bear a stronger and more consistent relationship to the development of PTSD and depression in cross-national samples. Future work should expand on these preliminary findings to better understand the impact of disaster exposure in firefighting personnel.
To assess the differences in comorbid lifetime substance use (tobacco, alcohol and drug use) between eating disorder (ED) patients and healthy controls.
Method:
Participants were a consecutive series of 779 ED cases, who had been referred to specialised ED units in five European countries. The ED cases were compared to a balanced control group of 785 healthy individuals. Assessment: Participants completed the Substance Use Subscale of the Cross Cultural Questionnaire (CCQ), a measure of lifetime tobacco, alcohol and drug use. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used.
Results:
ED patients had higher lifetime consumption of tobacco and drugs (p <0.01). The only insignificant result was obtained for alcohol (OR= 1.29; δ =0.157; N.S.) and cannabis use (OR= 1.21; δ = 0.037, N.S.). Significant differences across ED sub diagnoses also emerged for all of the assessed variables (p<0.01), with the BN and AN-BP patients generally presenting the highest prevalence rates. The only exception was detected for alcohol consumption where EDNOS patients demonstrated the highest values (p=0.008). Only a few cultural differences between countries emerged (p<0.05).
Conclusions:
Lifetime tobacco and drug use but not alcohol consumption are more prevalent in ED patients than healthy controls. While alcohol appears to be more common in EDNOS, smoking and drug use are more frequent in patients with bulimic symptomatology. The differential risk observed in patients with bulimic features might be related to differences in temperament or might be the result of increased sensitivity to reward.
To examine whether there is an association between individual and family eating patterns during childhood and early adolescence and the likelihood of developing an eating disorder (ED) later in life.
Method:
Participants were a consecutive series of 879 ED cases from five different European countries. The ED cases were compared to a control group of 785 healthy individuals. Assessment: Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire (CCQ), a retrospective measure, which has been developed to detect dimensions associated with EDs in different countries. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used.
Results:
Five individual CatPCA procedures revealed five predetermined dimensions which were labeled: 1.) food as individualization; 2.) control and rules about food; 3.) food as social glue; 4.) healthy eating and 5.) food neglect. Logistic regression analyses indicated that the domains with the strongest effects were: food used as individualization (p=0.001; OR=1.76) and control and rules about food (p=0.001; OR=1.76). Conversely, healthy eating was negatively related to a later ED (p=0.001; OR=0.629). The pattern of associated ED factors was found to very between countries. There was very little difference in early eating behavior on the subtypes of the ED.
Conclusions:
The fragmentation of meals within the family and control and rules about food appears to be linked to the development of a subsequent ED. On the other hand mantaining a structured and balanced diet during infancy seems to protect from a later ED.
Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and β-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3′-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.
There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders.
Methods
The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models.
Results
Current combined MDD [β = 0.29, 95% confidence interval (CI) 0.03–0.55] and current atypical MDD (β = 0.32, 95% CI 0.10–0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up.
Conclusions
The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.
We derive a time-averaged ‘hydrostatic wave equation’ from the hydrostatic Boussinesq equations that describes the propagation of inertia–gravity internal waves through quasi-geostrophic flow. The derivation uses a multiple-scale asymptotic method to isolate wave field evolution over intervals much longer than a wave period, assumes the wave field has a well-defined non-inertial frequency such as that of the mid-latitude semi-diurnal lunar tide, assumes that the wave field and quasi-geostrophic flow have comparable spatial scales and neglects nonlinear wave–wave dynamics. As a result the hydrostatic wave equation is a reduced model applicable to the propagation of large-scale internal tides through the inhomogeneous and moving ocean. A numerical comparison with the linearized and hydrostatic Boussinesq equations demonstrates the validity of the hydrostatic wave equation model and illustrates how the model fails when the quasi-geostrophic flow is too strong and the wave frequency is too close to inertial. The hydrostatic wave equation provides a first step toward a coupled model for energy transfer between oceanic internal tides and quasi-geostrophic eddies and currents.
Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2–8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.
The stellar occultation technique is a powerful tool to study distant small solar system bodies. Currently, around 2 500 trans-neptunian objects (TNOs) and Centaurs are known. With the astrometry from Gaia and large surveys like the Large Synoptic Survey Telescope (LSST), accurate predictions of occultation events will be available to tens of thousands of TNOs and Centaurs and boost the knowledge of the outer solar system.
We compared the relevance of ibuprofen, vitamins C and E to control oxidative/nitrosative stress and heart disease in mice infected by Trypanosoma cruzi. Swiss mice were randomized into five groups: control, uninfected; infected without treatment; and infected treated with vitamins C, E or ibuprofen. Animals were inoculated with 2000 trypomastigote forms of T. cruzi. After 20 days, infected mice presented reduced vitamin C and E tissue levels, high cytokines (interferon gamma, tumour necrosis factor-α, interleukin 10 and chemokine ligand 2), prostaglandin F2α (PGF2α) and nitric oxide (NO) cardiac production, intense myocarditis and reactive tissue damage, which was directly correlated with the intensity of the inflammatory infiltrate and the degree of pathological cardiac remodelling. Vitamins C and E supplementation were irrelevant to counteract reactive tissue damage and myocarditis in infected animals. Conversely, ibuprofen reduced tissue levels of cytokines, PGF2α and NO, as well as lipid and protein oxidation, antioxidant enzyme activity and the cardiac damage, without interfering with heart parasitism. Our results do not support the applicability of vitamin C and E supplementation in the management of acute Chagas cardiomyopathy. By controlling the inflammatory infiltrate, anti-inflammatory-based therapy proved to be a more rational strategy than a direct antioxidant therapy in attenuating oxidative/nitrosative stress and cardiac damage.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
We derive an asymptotic model that describes the nonlinear coupled evolution of (i) near-inertial waves (NIWs), (ii) balanced quasi-geostrophic flow and (iii) near-inertial second harmonic waves with frequency near $2f_{0}$, where $f_{0}$ is the local inertial frequency. This ‘three-component’ model extends the two-component model derived by Xie & Vanneste (J. Fluid Mech., vol. 774, 2015, pp. 143–169) to include interactions between near-inertial and $2f_{0}$ waves. Both models possess two conservation laws which together imply that oceanic NIWs forced by winds, tides or flow over bathymetry can extract energy from quasi-geostrophic flows. A second and separate implication of the three-component model is that quasi-geostrophic flow catalyses a loss of NIW energy to freely propagating waves with near-$2f_{0}$ frequency that propagate rapidly to depth and transfer energy back to the NIW field at very small vertical scales. The upshot of near-$2f_{0}$ generation is a two-step mechanism whereby quasi-geostrophic flow catalyses a nonlinear transfer of near-inertial energy to the small scales of wave breaking and diapycnal mixing. A comparison of numerical solutions with both Boussinesq and three-component models for a two-dimensional initial value problem reveals strengths and weaknesses of the model while demonstrating the extraction of quasi-geostrophic energy and production of small vertical scales.
We derive a wave-averaged potential vorticity equation describing the evolution of strongly stratified, rapidly rotating quasi-geostrophic (QG) flow in a field of inertia-gravity internal waves. The derivation relies on a multiple-time-scale asymptotic expansion of the Eulerian Boussinesq equations. Our result confirms and extends the theory of Bühler & McIntyre (J. Fluid Mech., vol. 354, 1998, pp. 609–646) to non-uniform stratification with buoyancy frequency $N(z)$ and therefore non-uniform background potential vorticity $f_{0}N^{2}(z)$, and does not require spatial-scale separation between waves and balanced flow. Our interest in non-uniform background potential vorticity motivates the introduction of a new quantity: ‘available potential vorticity’ (APV). Like Ertel potential vorticity, APV is exactly conserved on fluid particles. But unlike Ertel potential vorticity, linear internal waves have no signature in the Eulerian APV field, and the standard QG potential vorticity is a simple truncation of APV for low Rossby number. The definition of APV exactly eliminates the Ertel potential vorticity signal associated with advection of a non-uniform background state, thereby isolating the part of Ertel potential vorticity available for balanced-flow evolution. The effect of internal waves on QG flow is expressed concisely in a wave-averaged contribution to the materially conserved QG potential vorticity. We apply the theory by computing the wave-induced QG flow for a vertically propagating wave packet and a mode-one wave field, both in vertically bounded domains.
The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6 % (+2 mm) and basal blood flow volume by 22 %. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.
Supersonic turbulence plays an important role in a number of extreme astrophysical and terrestrial environments, yet its understanding remains rudimentary. We use data from a three-dimensional simulation of supersonic isothermal turbulence to reconstruct an exact fourth-order relation derived analytically from the Navier–Stokes equations (Galtier & Banerjee, Phys. Rev. Lett., vol. 107, 2011, p. 134501). Our analysis supports a Kolmogorov-like inertial energy cascade in supersonic turbulence previously discussed on a phenomenological level. We show that two compressible analogues of the four-fifths law exist describing fifth- and fourth-order correlations, but only the fourth-order relation remains ‘universal’ in a wide range of Mach numbers from incompressible to highly compressible regimes. A new approximate relation valid in the strongly supersonic regime is derived and verified. We also briefly discuss the origin of bottleneck bumps in simulations of compressible turbulence.