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Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.
We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.
This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.
A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = −0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.
Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.
The dynamics of a stably and thermally stratified fluid-filled cavity harmonically forced in the vertical direction, resulting in a periodic gravity modulation, is studied numerically. Prior simulations in a two-dimensional cavity showed a myriad of complex dynamic behaviours near the onset of instabilities, and here we address the extent to which these persist in three dimensions. Focusing on a parameter regime where the primary subharmonic mode is resonantly driven, we demonstrate comprehensive qualitative agreement between the dynamics in two and three dimensions; the quantitative difference is due to the larger forcing amplitudes needed in three dimensions to overcome the additional viscous damping from the spanwise walls. Using a small detuning of the forcing frequency, together with a relatively large forcing amplitude, leads to a wave-breaking regime where the qualitative agreement between two and three dimensions breaks down.
Previous studies attest that early bilinguals can modify their perceptual identification according to the fine-grained phonetic detail of the language they believe they are hearing. Following Gonzales et al. (2019), we replicate the double phonemic boundary effect in late learners (LBs) using conceptual-based cueing. We administered a forced choice identification task to 169 native English adult learners of Spanish in two sessions. In both sessions, participants identified the same /b/-/p/ voicing continuum, but language context was cued conceptually using the instructions. The data were analyzed using Bayesian multilevel regression. Learners categorized the continuum in a similar manner when they believed they were hearing English. However, when they believed they were hearing Spanish, “voiceless” responses increased as a function of L2 proficiency. This research demonstrates the double phonemic boundary effect can be conceptually cued in LBs and supports accounts positing selective activation of independent perception grammars in L2 learning.
The response to librational forcing of a cube in rapid rotation about a diagonal axis is explored. In this orientation, the faces of the cube are all oblique to the rotation axis. The system supports inertial waves, which predominantly comprise beams emitted from the edges and vertices of the cube. Which ones emit and the resulting complicated pattern of three-dimensional reflections and subsequent focusing depend on the libration frequency. Direct numerical simulations of the Navier–Stokes flows with no-slip boundary conditions at low Ekman number (
) and small libration amplitude (
) exhibit complicated spatio-temporal structure that is remarkably well described by considerations of the inviscid reflections of wavebeams over the whole range of libration frequencies from zero to twice the mean rotation rate of the cube.
A clinical case is presented. The reason for admission was for behavioral disturbances and agitation piscomotriz episode in the street: she had gone to a library to “denounce” the police for entering the subway without paying several times. The patient was very distraught because she was heavily guarded (someone had tapped her phone, entered her house, changed objects place, she was chased down the street…). In the psychopathological examination revealed the sphere of language, her speech was fluid, with pressured speech, full of details, with loss of thread and highlighted the presence of neologisms and grammatical errors (changes of subject and predicate…) and changes some letters by others in the same word. She often used sayings incorrectly and, when you are exploring about this fact, objectively presenting alteration in abstract thinking. In addition, it presents self-references on television. The diagnostic impression was chronic psychotic process of years of evolution. In this case, it was decided to administer intramuscular antipsychotic treatment because she was not aware of the disease but presenting good tolerability profile because, otherwise, leave the track and also a good social functioning was sought. Currently, she continues in mental health, she has not reported new crisis and a progressive scan objective improvement in the organization of thought and speech, leaving the psychotic symptoms.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In a recent experiment on the flow between two concentric cylinders with the inner cylinder rotating and the fluid being stably stratified, Flór et al. (Phys. Fluids, vol. 30, 2018, 084103) found helical wave structures confined to the inner cylinder in an annulus with small inner-to-outer radius ratio (very large gap) in regimes where the Froude number (ratio of cylinder rotation frequency to buoyancy frequency) is less than one. These helical waves were reported to originate at the corners where the inner cylinder meets the top and bottom boundaries, and were found to be asymmetric with the lower helical wave being more intense. These observations are in marked contrast with other stratified Taylor–Couette experiments that employed much larger inner-to-outer radius ratios and much larger annulus height-to-gap ratios. Here, we present direct numerical simulations of the Navier–Stokes equations, with a Boussinesq approximation that accounts for centrifugal buoyancy effects which are normally neglected. Fixing the stratification and increasing the rotation rate of the inner cylinder (quantified by a Reynolds number), we find a sequence of bifurcations, each one introducing a new frequency, from the steady base state to a three-torus state. The instabilities are generated at the corners where the inner cylinder meets the endwalls, and the first instability is localized at the lower corner as a consequence of centrifugal buoyancy effects. We have also conducted simulations without centrifugal buoyancy and find that centrifugal buoyancy plays a crucial role in breaking the up–down reflection symmetry of the problem, capturing the most salient features of the experimental observations.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Numerical simulations of the response flow in a fluid-filled rotating cube that is subjected to precessional forcing are examined over a wide range of rotation, precession and forcing frequencies. The responses are shown to correspond to resonantly excited inertial modes of the rotating cube that have the same spatio-temporal symmetry as the precessional forcing and, under certain conditions, the response flow loses stability via symmetry breaking that is intricately associated with a triadic resonance between the forced flow and two free inertial modes whose spatio-temporal symmetries do not coincide with that of the precessional forcing.
Introduced species can have strong ecological, social and economic effects on their non-native environment. Introductions of megafaunal species are rare and may contribute to rewilding efforts, but they may also have pronounced socio-ecological effects because of their scale of influence. A recent introduction of the hippopotamus Hippopotamus amphibius into Colombia is a novel introduction of a megaherbivore onto a new continent, and raises questions about the future dynamics of the socio-ecological system into which it has been introduced. Here we synthesize current knowledge about the Colombian hippopotamus population, review the literature on the species to predict potential ecological and socio-economic effects of this introduction, and make recommendations for future study. Hippopotamuses can have high population growth rates (7–11%) and, on the current trajectory, we predict there could be 400–800 individuals in Colombia by 2050. The hippopotamus is an ecosystem engineer that can have profound effects on terrestrial and aquatic environments and could therefore affect the native biodiversity of the Magdalena River basin. Hippopotamuses are also aggressive and may pose a threat to the many inhabitants of the region who rely upon the Magdalena River for their livelihoods, although the species could provide economic benefits through tourism. Further research is needed to quantify the current and future size and distribution of this hippopotamus population and to predict the likely ecological, social and economic effects. This knowledge must be balanced with consideration of social and cultural concerns to develop appropriate management strategies for this novel introduction.
The dynamics of a fluid flow in a differentially heated square container is investigated numerically. Two opposite conducting walls are maintained at constant temperatures, one hot and the other cold, and the other two walls are insulated. When the conducting walls are horizontal with the lower one cold, the static linearly stratified state is stable. When the container is tilted, the static equilibrium ceases to exist and the fluid flows due to the baroclinic torque arising from the bending of isotherms near the tilted insulated walls. This flow is found to be steady for tilt angles less than
, regardless of the relative balance between buoyancy and viscous effects (quantified by a buoyancy number
). For tilt angles above
, the flow becomes unsteady above a critical
with localized boundary layer undulations at the conducting walls, at the heights of the horizontally opposite corners. From these corners emanate horizontal shear layers, which become thinner and more intense with increasing
. As the tilt angle approaches
, the nature of the instability changes, corresponding to that of the well-studied laterally heated cavity flow.
The dynamics of a fluid-filled square cavity with stable thermal stratification subjected to harmonic vertical oscillations is investigated numerically. The nonlinear responses to this parametric excitation are studied over a comprehensive range of forcing frequencies up to two and a half times the buoyancy frequency. The nonlinear results are in general agreement with the Floquet analysis, indicating the presence of nested resonance tongues corresponding to the intrinsic
eigenmodes of the stratified cavity. For the lowest-order subharmonic
tongue, the responses are analysed in great detail, with complex dynamics identified near onset, most of which involves interactions with unstable saddle states of a homoclinic or heteroclinic nature.
The dynamic response to shear of a fluid-filled square cavity with stable temperature stratification is investigated numerically. The shear is imposed by the constant translation of the top lid, and is quantified by the associated Reynolds number. The stratification, quantified by a Richardson number, is imposed by maintaining the temperature of the top lid at a higher constant temperature than that of the bottom, and the side walls are insulating. The Navier–Stokes equations under the Boussinesq approximation are solved, using a pseudospectral approximation, over a wide range of Reynolds and Richardson numbers. Particular attention is paid to the dynamical mechanisms associated with the onset of instability of steady state solutions, and to the complex and rich dynamics occurring beyond.
The linear stability of a stably stratified fluid-filled cavity subject to vertical oscillations is determined via Floquet analysis. Retaining the viscous and diffusion terms in the Navier–Stokes–Boussinesq equations, with no-slip velocity boundary conditions, no-flux temperature conditions on the sidewalls and constant temperatures on the top and bottom walls, we find that the instabilities are primarily subharmonic (as is typical in many parametrically forced systems), except for in a few low-forcing-frequency ranges where the instabilities are synchronous. When the viscosity is small, the Floquet modes resemble the inviscid eigenmodes of the unforced problem, except in boundary layers. We establish scaling laws quantifying how viscosity regularizes the degeneracy associated with the inviscid idealization, and how it scales the thickness and intensity of the boundary layers. The product of boundary layer thickness and intensity remains constant with decreasing viscosity, leading to a delta distribution of vorticity on the walls in the limit of zero viscosity. This is in contrast to the zero wall vorticity in the inviscid case.
The flow response of a rapidly rotating fluid-filled cube to low-amplitude librational forcing is investigated numerically. Librational forcing is the harmonic modulation of the mean rotation rate. The rotating cube supports inertial waves which may be excited by libration frequencies less than twice the rotation frequency. The response is comprised of two main components: resonant excitation of the inviscid inertial eigenmodes of the cube, and internal shear layers whose orientation is governed by the inviscid dispersion relation. The internal shear layers are driven by the fluxes in the forced boundary layers on walls orthogonal to the rotation axis and originate at the edges where these walls meet the walls parallel to the rotation axis, and are hence called edge beams. The relative contributions to the response from these components is obscured if the mean rotation period is not small enough compared to the viscous dissipation time, i.e. if the Ekman number is too large. We conduct simulations of the Navier–Stokes equations with no-slip boundary conditions using parameter values corresponding to a recent set of laboratory experiments, and reproduce the experimental observations and measurements. Then, we reduce the Ekman number by one and a half orders of magnitude, allowing for a better identification and quantification of the contributions to the response from the eigenmodes and the edge beams.
The bryozoan genus Aspidostoma Hincks, 1881 has been regarded as the only representative of the Aspidostomatidae Jullien, 1888 in Argentina to date. Its type species, Aspidostoma giganteum (Busk, 1854), is presently distributed in the Magellanic Region (Argentina and Chile) and has been recorded in Oligocene and Miocene fossil deposits of Santa Cruz and Chubut, respectively. New material from San Julián (late Oligocene), Monte León (early Miocene), Chenque (early to middle Miocene), and Puerto Madryn (late Miocene) formations suggests, however, that A. giganteum is not represented in the fossil record. Material from Puerto Madryn Formation previously regarded as A. giganteum is here recognized as Aspidostoma roveretoi new species. Aspidostoma ortmanni Canu, 1904 is revalidated for the species from the San Julián Formation. Aspidostoma armatum new species and Aspidostoma tehuelche new species are introduced for material from the Monte León and Chenque formations, respectively. Aspidostoma incrustans Canu, 1908, from the early Miocene, is redescribed. Melychocella Gordon and Taylor, 1999, which differs from Aspidostoma in having vicarious avicularia and lacking a median ridge and a quadrangular process proximal to the opesia-orifice, is so far represented by three Paleogene species from the Chatham Islands (Southwest Pacific). The material from Monte León allowed us to transfer Aspidostoma flammulum Canu, 1908 to Melychocella, resulting in the new combination Melychocella flammula (Canu, 1908). Melychocella biperforata new species is described from the lower Miocene Monte León and Chenque formations. The presence of Melychocella in the Neogene of Patagonia extends its geographic distribution and its temporal range.
Contained rotating flows subject to precessional forcing are well known to exhibit rapid and energetic transitions to disorder. Triadic resonance of inertial modes has been previously proposed as an instability mechanism in such flows, and that idea was developed into a successful model for predicting instability in a cylindrical container when departures from solid-body rotation are sufficiently small. Using direct numerical simulation and dynamic mode decomposition, we analyse instabilities of precessing cylinder flows whose three-dimensional basic states, steady in the gimbal frame of reference, may depart substantially from solid-body rotation. In the gimbal frame, the instability can be interpreted as resulting from a supercritical Hopf bifurcation that results in a limit-cycle flow. In the cylinder frame of reference, the basic state is a rotating wave with azimuthal wavenumber
, and the instability satisfies triadic-resonance conditions with the instability mode maintaining a fixed orientation with respect to the basic state. Thus, we are able to demonstrate the existence of two alternative but congruent explanations for the instability. Additionally, we show that basic states may depart substantially from solid-body rotation even with modest cylinder tilt angles, and growth rates for instabilities may be sufficiently large that nonlinear saturation to disordered states can occur within approximately ten cylinder revolutions, in agreement with experimental observations.
Rapidly rotating cylinder flows subjected to low-amplitude precessional forcing are studied numerically over a range of cylinder and precessional rotation rates. For sufficiently small rotation rates, viscous effects lead to a forced overturning flow that is steady in the precession (table) frame of reference. Increasing the rotation rates, this forced flow loses stability in a Hopf bifurcation, which can be either supercritical or subcritical, and may preserve or break the symmetry of the system, depending on the parameter regime studied. Regardless of these details of the Hopf bifurcation, it is found that the Hopf instability is associated with a slightly detuned triadic resonance between the forced overturning flow and two free Kelvin modes (inviscid eigenmodes of the rotating cylinder). Further increases in rotation rates lead to a sequence of secondary instabilities which also follow a generic pattern irrespective of the parameter regime investigated. The relationship between this sequence of instabilities and the resultant nonlinear dynamics with the experimentally observed phenomenon of resonant collapse is discussed.
Stereo-electroencephalography (SEEG) has been shown to be a valuable tool for the anatomo-electroclinic definition of the epileptogenic zone (EZ) in some patients with medically refractory epilepsy considered for surgery. In Spain, many of those patients are not offered this diagnostic procedure. The objective of our health technology assessment (HTA) report was to evaluate the effectiveness, safety and cost-effectiveness of SEEG to define the EZ in patients with refractory epilepsy considered for surgery compared to no SEEG intervention (i.e. remaining with further antiepileptic drugs).
We undertook a systematic review with meta-analyses on the effectiveness and safety of SEEG. A cost-effectiveness analysis was conducted using a Markov model which simulates the costs and health outcomes of individuals for a lifetime horizon from the perspective of the Spanish National Health Service (NHS). The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.
The EZ was found in 92 percent of patients who underwent SEEG, 72 percent were eligible for epilepsy surgery and 33 percent were free of seizures after surgery (47 percent of those who received surgery). Any complications related to insertion and monitoring of SEEG and the subsequent intervention occurred in 1.3 percent of patients. In the base case analysis, SEEG led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio of EUR 10,368 (USD 12,217) per QALY. The sensitivity analyses showed that the results of the study were robust.
SEEG is a cost-effective technology in patients with refractory epilepsy considered for surgery when compared to no SEEG intervention.
Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings.
An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology.
Palivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1–2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions.
Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.
The origins of the large Classic and Postclassic urban centres of Central Mexico remain poorly understood. Archaeological investigations at the Formative site of Tlalancaleca in Puebla (Mexico) provide the first detailed study of a large-scale urban centre of that period. Preliminary results suggest that the growth and development of this particular site may have influenced the subsequent growth of Teotihuacan itself. This study explores how urbanisation can be identified archaeologically by tracing the expansion of population and the emergence of monumental architecture.