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Liquid-phase transmission electron microscopy is a technique for simultaneous imaging of the structure and dynamics of specimens in a liquid environment. The conventional sample geometry consists of a liquid layer tightly sandwiched between two Si3N4 windows with a nominal spacing on the order of 0.5 μm. We describe a variation of the conventional approach, wherein the Si3N4 windows are separated by a 10-μm-thick spacer, thus providing room for gas flow inside the liquid specimen enclosure. Adjusting the pressure and flow speed of humid air inside this environmental liquid cell (ELC) creates a stable liquid layer of controllable thickness on the bottom window, thus facilitating high-resolution observations of low mass-thickness contrast objects at low electron doses. We demonstrate controllable liquid thicknesses in the range 160 ± 34 to 340 ± 71 nm resulting in corresponding edge resolutions of 0.8 ± 0.06 to 1.7 ± 0.8 nm as measured for immersed gold nanoparticles. Liquid layer thickness 40 ± 8 nm allowed imaging of low-contrast polystyrene particles. Hydration effects in the ELC have been studied using poly-N-isopropylacrylamide nanogels with a silica core. Therefore, ELC can be a suitable tool for in situ investigations of liquid specimens.
Depressive and anxiety disorders are highly comorbid, which has been theorized to be due to an underlying internalizing vulnerability. We aimed to identify groups of participants with differing vulnerabilities by examining the course of internalizing psychopathology up to age 45.
We used data from 24158 participants (aged 45+) in 23 population-based cross-sectional World Mental Health Surveys. Internalizing disorders were assessed with the Composite International Diagnostic Interview (CIDI). We applied latent class growth analysis (LCGA) and investigated the characteristics of identified classes using logistic or linear regression.
The best-fitting LCGA solution identified eight classes: a healthy class (81.9%), three childhood-onset classes with mild (3.7%), moderate (2.0%), or severe (1.1%) internalizing comorbidity, two puberty-onset classes with mild (4.0%) or moderate (1.4%) comorbidity, and two adult-onset classes with mild comorbidity (2.7% and 3.2%). The childhood-onset severe class had particularly unfavorable sociodemographic outcomes compared to the healthy class, with increased risks of being never or previously married (OR = 2.2 and 2.0, p < 0.001), not being employed (OR = 3.5, p < 0.001), and having a low/low-average income (OR = 2.2, p < 0.001). Moderate or severe (v. mild) comorbidity was associated with 12-month internalizing disorders (OR = 1.9 and 4.8, p < 0.001), disability (B = 1.1–2.3, p < 0.001), and suicidal ideation (OR = 4.2, p < 0.001 for severe comorbidity only). Adult (v. childhood) onset was associated with lower rates of 12-month internalizing disorders (OR = 0.2, p < 0.001).
We identified eight transdiagnostic trajectories of internalizing psychopathology. Unfavorable outcomes were concentrated in the 1% of participants with childhood onset and severe comorbidity. Early identification of this group may offer opportunities for preventive interventions.
The current study aimed to explore the interplay between food insecurity, fast-food outlet exposure, and dietary quality in disadvantaged neighbourhoods.
In this cross-sectional study, main associations between fast-food outlet density and proximity, food insecurity status and dietary quality were assessed using Generalized Estimating Equation analyses. We assessed potential moderation by fast-food outlet exposure in the association between food insecurity status and dietary quality by testing for effect modification between food insecurity status and fast-food outlet density and proximity.
A deprived urban area in the Netherlands.
We included 226 adult participants with at least one child below the age of 18 years living at home.
Fast-food outlet exposure was not associated with experiencing food insecurity (fast-food outlet density: b=-0.026, 95%CI=-0.076; 0.024; fast-food outlet proximity: b=-0.003, 95%CI=-0.033; 0.026). Experiencing food insecurity was associated with lower dietary quality (b=-0.48 per unit increase, 95%CI=-0.94; -0.012). This association was moderated by fast-food outlet proximity (p-interaction=0.008), and stratified results revealed that the adverse effect of food insecurity on dietary quality was more pronounced for those with the nearest fast-food outlet located closer to the home.
Food insecurity but not fast-food outlet density is associated with dietary quality. However, the association between food insecurity and dietary quality may be modified by the food environment. These findings could inform policy-makers to promote a healthier food environment including less fast-food outlets, with particular emphasis on areas with high percentages of food insecure households.
Imaging of cellular layers in a gut-on-a-chip system has been confined to two-dimensional (2D)-imaging through conventional light microscopy and confocal laser scanning microscopy (CLSM) yielding three-dimensional- and 2D-cross-sectional reconstructions. However, CLSM requires staining and is unsuitable for longitudinal visualization. Here, we compare merits of optical coherence tomography (OCT) with those of CLSM and light microscopy for visualization of intestinal epithelial layers during protection by a probiotic Bifidobacterium breve strain and a simultaneous pathogen challenge by an Escherichia coli strain. OCT cross-sectional images yielded film thicknesses that coincided with end-point thicknesses derived from cross-sectional CLSM images. Light microscopy on histological sections of epithelial layers at the end-point yielded smaller layer thicknesses than OCT and CLSM. Protective effects of B. breve adhering to an epithelial layer against an E. coli challenge included the preservation of layer thickness and membrane surface coverage by epithelial cells. OCT does not require staining or sectioning, making OCT suitable for longitudinal visualization of biological films, but as a drawback, OCT does not allow an epithelial layer to be distinguished from bacterial biofilms adhering to it. Thus, OCT is ideal to longitudinally evaluate epithelial layers under probiotic protection and pathogen challenges, but proper image interpretation requires the application of a second method at the end-point to distinguish bacterial and epithelial films.
There is a substantial proportion of patients who drop out of treatment before they receive minimally adequate care. They tend to have worse health outcomes than those who complete treatment. Our main goal is to describe the frequency and determinants of dropout from treatment for mental disorders in low-, middle-, and high-income countries.
Respondents from 13 low- or middle-income countries (N = 60 224) and 15 in high-income countries (N = 77 303) were screened for mental and substance use disorders. Cross-tabulations were used to examine the distribution of treatment and dropout rates for those who screened positive. The timing of dropout was examined using Kaplan–Meier curves. Predictors of dropout were examined with survival analysis using a logistic link function.
Dropout rates are high, both in high-income (30%) and low/middle-income (45%) countries. Dropout mostly occurs during the first two visits. It is higher in general medical rather than in specialist settings (nearly 60% v. 20% in lower income settings). It is also higher for mild and moderate than for severe presentations. The lack of financial protection for mental health services is associated with overall increased dropout from care.
Extending financial protection and coverage for mental disorders may reduce dropout. Efficiency can be improved by managing the milder clinical presentations at the entry point to the mental health system, providing adequate training, support and specialist supervision for non-specialists, and streamlining referral to psychiatrists for more severe cases.
In the Netherlands, the Depression Initiative has been launched in 2006 as a nationwide attempt to implement the Multidisciplinary Guideline for Depression and to evaluate its cost effectiveness. Evaluation of a collaborative stepped care model in several health care settings is one of the objectives of the Depression Initiative. Currently a stepped collaborative care project is being evaluated in the primary care setting, evaluating stepped collaborative care for depressive disorder provided by the primary care practitioner, a nurse-care-manager, and a consultant psychiatrist, in a Randomised Controlled Trial. 150 Patients with depressive disorder are offered a treatment plan. They can choose from two options: Problem Solving Treatment with or without antidepressant treatment. The medication is prescribed by the PCP, PST and monitoring is provided by the care manager, and the psychiatrist can be consulted every 6 weeks in order to see if the intervention is sufficient to improve the symptoms of the patient. The PHQ is used for monitoring. A two step approach is aimed at; if the patient does not achieve remission after 18 weeks, the patient is referred to mental health care. This stepwise approach is supported by a training and supervision program and by a web-based tracking system in which the care-manager and the patient can monitor progress and consult the psychiatrist. This approach is compared with Care As Usual in the primary care setting. In the presentation, preliminary results will be presented.
Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment.
IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment.
The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults.
The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.
Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.
The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.
Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.
Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.
New cryogenic characterization techniques for exploring the nanoscale structure and chemistry of intact solid–liquid interfaces have recently been developed. These techniques provide high-resolution information about buried interfaces from large samples or devices that cannot be obtained by other means. These advancements were enabled by the development of instrumentation for cryogenic focused ion beam liftout, which allows intact solid–liquid interfaces to be extracted from large samples and thinned to electron-transparent thicknesses for characterization by cryogenic scanning transmission electron microscopy or atom probe tomography. Future implementation of these techniques will complement current strides in imaging of materials in fluid environments by in situ liquid-phase electron microscopy, providing a more complete understanding of the morphology, surface chemistry, and dynamic processes that occur at solid–liquid interfaces.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Hendra virus (HeV) continues to cause fatal infection in horses and threaten infection in close-contact humans in eastern Australia. Species of Pteropus bats (flying-foxes) are the natural reservoir of the virus. We caught and sampled flying-foxes from a multispecies roost in southeast Queensland, Australia on eight occasions between June 2013 and June 2014. The effects of sample date, species, sex, age class, body condition score (BCS), pregnancy and lactation on HeV antibody prevalence, log-transformed median fluorescent intensity (lnMFI) values and HeV RNA status were assessed using unbalanced generalised linear models. A total of 1968 flying-foxes were sampled, comprising 1012 Pteropus alecto, 742 P. poliocephalus and 214 P. scapulatus. Sample date, species and age class were each statistically associated with HeV RNA status, antibody status and lnMFI values; BCS was statistically associated with HeV RNA status and antibody status. The findings support immunologically naïve sub-adult P. alecto playing an important role in maintaining HeV infection at a population level. The biological significance of the association between BCS and HeV RNA status, and BCS and HeV antibody status, is less clear and warrants further investigation. Contrary to previous studies, we found no direct association between HeV infection and pregnancy or lactation. The findings in P. poliocephalus suggest that HeV exposure in this species may not result in systemic infection and virus excretion, or alternatively, may reflect assay cross-reactivity with another (unidentified) henipavirus.
The Greek rhetorician and historian Dionysius of Halicarnassus was active in Rome at the end of the first century BC.2 His extant works include a history of early Rome, critical letters, and rhetorical treatises with a focus on style: On Composition, On Imitation, On Thucydides, and On the Ancient Orators, including separate essays on Lysias, Isocrates, Isaeus, and Demosthenes. Engaged as he was in the oratory, history, and poetry of the classical Greek past, Dionysius himself lived in the Golden Age of Latin Literature. Born before 55 BC, he was a contemporary of Virgil and Horace. When Dionysius arrived in Rome in 30 BC, Marcus Tullius Cicero (106–43 BC) had been dead for more than a decade, but Marcus Terentius Varro (116–27 BC) was still alive.
The mechanisms underlying both depressive and anxiety disorders remain poorly understood. One of the reasons for this is the lack of a valid, evidence-based system to classify persons into specific subtypes based on their depressive and/or anxiety symptomatology. In order to do this without a priori assumptions, non-parametric statistical methods seem the optimal choice. Moreover, to define subtypes according to their symptom profiles and inter-relations between symptoms, network models may be very useful. This study aimed to evaluate the potential usefulness of this approach.
A large community sample from the Canadian general population (N = 254 443) was divided into data-driven clusters using non-parametric k-means clustering. Participants were clustered according to their (co)variation around the grand mean on each item of the Kessler Psychological Distress Scale (K10). Next, to evaluate cluster differences, semi-parametric network models were fitted in each cluster and node centrality indices and network density measures were compared.
A five-cluster model was obtained from the cluster analyses. Network density varied across clusters, and was highest for the cluster of people with the lowest K10 severity ratings. In three cluster networks, depressive symptoms (e.g. feeling depressed, restless, hopeless) had the highest centrality. In the remaining two clusters, symptom networks were characterised by a higher prominence of somatic symptoms (e.g. restlessness, nervousness).
Finding data-driven subtypes based on psychological distress using non-parametric methods can be a fruitful approach, yielding clusters of persons that differ in illness severity as well as in the structure and strengths of inter-symptom relationships.
The aim of this study was to explore lameness and the associations between lameness and health/production measures of animal welfare in commercial broiler production, using the Welfare Quality® protocol for broilers. A total of 50 flocks were included in the sample and farm visits were conducted for lameness scoring at a mean age of 28.9 days. The percentage of animals (n=7500) in the six different gait score (GS) categories were GS0: 2.53%, GS1: 44.19%, GS2: 33.84%, GS3: 16.32%, GS4: 2.36% and GS5: 0.53%. Production and other welfare data were collected for each flock after slaughter. Higher gait scores were associated with increased hock burn score (P<0.02), increased footpad dermatitis score (P<0.01), reduced bird cleanliness score (P<0.01) and peat litter (P<0.01). Although not statistically significant, there was a tendency for increased flock gait score being associated with wet litter (P=0.07). In addition, condemnations at postmortem inspection were associated with increasing gait scores (P<0.05), indicating that at least a portion of the lameness cases display pathological changes on the carcasses. In conclusion, 19%of the birds showed moderate-to-severe lameness, which was associated with several production or health and welfare observations including feather cleanliness and condemnations as unfit for human consumption at slaughter. Although stocking density and growth rate are already known key factors for lameness, associations of lameness with hock burns, footpad dermatitis and cleanliness of the birds suggest that a suboptimal physical environment (e.g. litter- and air quality) may be detrimental to leg health. Further studies are needed to explore these associations in more detail.
The role of diet on breast cancer risk is not well elucidated but animal food sources may play a role through, for example, the pathway of the insulin-like growth factor 1 system or cholesterol metabolism. The aim of this study was to evaluate the association between animal foods and the risk of postmenopausal breast cancer. This study was embedded in the Rotterdam Study, a population-based prospective cohort study of subjects aged 55 years and over (61 % female). Dietary intake of different animal foods was assessed at baseline using a validated FFQ and adjusted for energy intake using the residual method. We performed Cox proportional hazards modelling to analyse the association between the intake of the different food sources and breast cancer risk after adjustment for socio-demographic, lifestyle and metabolic factors. During a median follow-up of 17 years, we identified 199 cases of breast cancer (6·2 %) among 3209 women. After adjustment for multiple confounders, no consistent association was found between the intake of red meat intake, poultry, fish or dairy products and breast cancer risk. However, we found that egg intake was significantly associated with a higher risk of breast cancer (hazard ratioQ4 v. Q1: 1·83; 95 % CI 1·20, 2·79; Ptrend=0·01). In conclusion, this study found that dietary egg intake but no other animal foods was associated with a higher risk of postmenopausal breast cancer. Further research on the potential mechanisms underlying this association is warranted.
We study the resistive evolution of a localized self-organizing magnetohydrodynamic equilibrium. In this configuration the magnetic forces are balanced by a pressure force caused by a toroidal depression in the pressure. Equilibrium is attained when this low-pressure region prevents further expansion into the higher-pressure external plasma. We find that, for the parameters investigated, the resistive evolution of the structures follows a universal pattern when rescaled to resistive time. The finite resistivity causes both a decrease in the magnetic field strength and a finite slip of the plasma fluid against the static equilibrium. This slip is caused by a Pfirsch–Schlüter-type diffusion, similar to what is seen in tokamak equilibria. The net effect is that the configuration remains in magnetostatic equilibrium whilst it slowly grows in size. The rotational transform of the structure becomes nearly constant throughout the entire structure, and decreases according to a power law. In simulations this equilibrium is observed when highly tangled field lines relax in a high-pressure (relative to the magnetic field strength) environment, a situation that occurs when the twisted field of a coronal loop is ejected into the interplanetary solar wind. In this paper we relate this localized magnetohydrodynamic equilibrium to magnetic clouds in the solar wind.
Sufficient protein intake has been suggested to be important for preventing physical frailty, but studies show conflicting results which may be explained because not all studies address protein source and intake of other macronutrients and total energy. Therefore, we studied 2504 subjects with data on diet and physical frailty, participating in a large population-based prospective cohort among subjects aged 45+ years (the Rotterdam Study). Dietary intake was assessed with a FFQ. Frailty was defined according to the frailty phenotype as the presence of at least three out of the following five symptoms: weight loss, low physical activity, weakness, slowness and fatigue. We used multinomial logistic regression models to evaluate the independent association between protein intake and frailty using two methods: nutrient residual models and energy decomposition models. With every increase in 10 g total, plant or animal protein per d, the odds to be frail were 1·06 (95 % CI 0·98, 1·15), 0·87 (95 % CI 0·71, 1·07) and 1·07 (95 % CI 0·99, 1·15), respectively, using the nutrient residual method. Using the energy partition model, we observed that the odds to be frail were lower with higher vegetable protein intake (OR per 418·4 kJ (100 kcal): 0·61, 95 % CI 0·39, 0·97), however, results disappeared when adjusting for physical activity. For energy intake from any source we observed that with every 418·4 kJ (100 kcal) increase, the odds to be frail were 5 % lower (OR: 0·95, 95 % CI 0·93, 0·97). Our results suggest that energy intake, but not protein specifically, is associated with less frailty. Considering other macronutrients, physical activity and diet quality seems to be essential for future studies on protein and frailty.
Dionysius of Halicarnassus was a rhetorician, critic and historiographer in Augustan Rome. This volume seeks to understand Dionysius as a writer positioned between Greece and Rome and between rhetoric and historiography. The introduction discusses the complex relationship between Dionysius’ history of early Rome and his rhetorical and critical works, and it presents Dionysius as both thoroughly Greek and very Roman. Dionysius’ works are interpreted as part of the Greek literature of the Augustan Age and as responding to the political, cultural and intellectual climate of Rome under Augustus. The following chapters are presented in three parts: (1) Dionysius and Augustan Rhetoric and Literary Criticism, (2) Dionysius and Augustan Historiography, and (3) Dionysius and Augustan Rome. The introduction concludes with a consideration of Dionysius’ intended audience.