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During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
Adult schistosomes live in the blood vessels and cannot easily be sampled from humans, so archived miracidia larvae hatched from eggs expelled in feces or urine are commonly used for population genetic studies. Large collections of archived miracidia on FTA cards are now available through the Schistosomiasis Collection at the Natural History Museum (SCAN). Here we describe protocols for whole genome amplification of Schistosoma mansoni and Schistosome haematobium miracidia from these cards, as well as real time PCR quantification of amplified schistosome DNA. We used microgram quantities of DNA obtained for exome capture and sequencing of single miracidia, generating dense polymorphism data across the exome. These methods will facilitate the transition from population genetics, using limited numbers of markers to population genomics using genome-wide marker information, maximising the value of collections such as SCAN.
When a rigid body collides with a liquid surface with sufficient velocity, it creates a splash curtain above the surface and entrains air behind the sphere, creating a cavity below the surface. While cavity dynamics has been studied for over a century, this work focuses on the water entry characteristics of deformable elastomeric spheres, which has not been studied. Upon free surface impact, an elastomeric sphere deforms significantly, giving rise to large-scale material oscillations within the sphere resulting in unique nested cavities. We study these phenomena experimentally with high-speed imaging and image processing techniques. The water entry behaviour of deformable spheres differs from rigid spheres because of the pronounced deformation caused at impact as well as the subsequent material vibration. Our results show that this deformation and vibration can be predicted from material properties and impact conditions. Additionally, by accounting for the sphere deformation in an effective diameter term, we recover previously reported characteristics for time to cavity pinch off and hydrodynamic force coefficients for rigid spheres. Our results also show that velocity change over the first oscillation period scales with the dimensionless ratio of material shear modulus to impact hydrodynamic pressure. Therefore, we are able to describe the water entry characteristics of deformable spheres in terms of material properties and impact conditions.
Background: Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing condition for which there are several evidence-based psychotherapies. However, a significant proportion of patients fail to complete a ‘sufficient dose’ of psychotherapy, potentially limiting treatment gains. Aims: The present study investigated predictors of premature treatment discontinuation during a trial of prolonged exposure (PE) therapy for PTSD. Method: Combat veterans with PTSD were recruited to participate in a randomized clinical trial of PE delivered in person or via telehealth technologies. Of the 150 initial participants, 61 participants discontinued the trial before the completion of eight sessions (of an 8‒12 session protocol). Treatment condition (telehealth or in person) and factors identified by prior research (age, combat theatre, social support, PTSD symptoms) were tested as predictors of treatment discontinuation. Results: A Cox proportional hazards model (a subtype of survival analysis) was used to evaluate predictors of treatment discontinuation. Disability status and treatment condition were identified as significant predictors of discontinuation, with a noted disability and use of telehealth demonstrating higher risk. Conclusions: The present findings highlight the influence of telehealth and disability status on treatment discontinuation, while minimizing the role of the previously identified variables from studies with less sensitive analyses.
Avian malaria is a vector transmitted disease caused by Plasmodium and recent studies suggest that variation in its prevalence across avian hosts is correlated with a variety of ecological traits. Here we examine the relationship between prevalence and diversity of Plasmodium lineages in southeastern Amazonia and: (1) host ecological traits (nest location, nest type, flocking behaviour and diet); (2) density and diversity of avian hosts; (3) abundance and diversity of mosquitoes; and (4) season. We used molecular methods to detect Plasmodium in blood samples from 675 individual birds of 120 species. Based on cytochrome b sequences, we recovered 89 lineages of Plasmodium from 136 infected individuals sampled across seven localities. Plasmodium prevalence was homogeneous over time (dry season and flooding season) and space, but heterogeneous among 51 avian host species. Variation in prevalence among bird species was not explained by avian ecological traits, density of avian hosts, or mosquito abundance. However, Plasmodium lineage diversity was positively correlated with mosquito abundance. Interestingly, our results suggest that avian host traits are less important determinants of Plasmodium prevalence and diversity in southeastern Amazonia than in other regions in which they have been investigated.
A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.
The origin of magnetic cycles in the Sun and other cool stars is one of the great theoretical challenge in stellar astrophysics that still resists our understanding. Ab-initio numerical simulations are today required to explore the extreme turbulent regime in which stars operate and sustain their large-scale, cyclic magnetic field. We report in this work on recent progresses made with high performance numerical simulations of global turbulent convective envelopes. We rapidly review previous prominent results from numerical simulations, and present for the first time a series of turbulent, global simulations producing regular magnetic cycles whose period varies systematically with the convective envelope parameters (rotation rate, convective luminosity). We find that the fundamentally non-linear character of the dynamo simulated in this work leads the magnetic cycle period to be inversely proportional to the Rossby number. These results promote an original interpretation of stellar magnetic cycles, and could help reconcile the cyclic behaviour of the Sun and other solar-type stars.
During the PMS, structure and rotation rate of stars evolve significantly. We wish to assess the consequences of these drastic changes on stellar dynamo, internal magnetic field topology and activity level by mean of HPC simulations with the ASH code. To answer this question, we develop 3D MHD simulations that represent specific stages of stellar evolution along the PMS. We choose five different models characterized by the radius of their radiative zone following an evolutionary track, from 1 Myr to 50 Myr, computed by a 1D stellar evolution code. We introduce a seed magnetic field in the youngest model and then we spread it through all simulations. First of all, we study the consequences that the increase of rotation rate and the change of geometry of the convective zone have on the dynamo field that exists in the convective envelop. The magnetic energy increases, the topology of the magnetic field becomes more complex and the axisymmetric magnetic field becomes less predominant as the star ages. The computation of the fully convective MHD model shows that a strong dynamo develops with a ratio of magnetic to kinetic energy reaching equipartition and even super-equipartition states in the faster rotating cases. Magnetic fields resulting from our MHD simulations possess a mixed poloidal-toroidal topology with no obvious dominant component. We also study the relaxation of the vestige dynamo magnetic field within the radiative core and found that it satisfies stability criteria. Hence it does not experience a global reconfiguration and instead slowly relaxes by retaining its mixed poloidal-toroidal topology.
Little is known about whether siblings have similar or different eating behaviours or whether parents tailor their feeding practices to different siblings. The main objectives of the present study were to examine similarities and differences in child eating behaviours and parental feeding practices with siblings and to determine whether child eating behaviours and parental feeding practices differ depending on sibling concordant (i.e. both siblings overweight or healthy weight) or discordant (i.e. one sibling overweight and one sibling healthy weight) weight status.
Cross-sectional, mixed-methods study.
In-home visits were conducted by research staff. Surveys were conducted with parents and anthropometry was collected on parents and siblings.
Children (n 88) aged 6–12 years (mean age 9 (sd 2) years), their parents (mean age 34 (sd 7) years) and near-age siblings (mean age 9 (sd 4) years) from diverse racial/ethnic and low-income households participated.
Results indicated that siblings with higher BMI engaged in higher levels of emotional eating compared with siblings with lower BMI. Additionally, results indicated that when families had sibling dyads discordant on weight status, the sibling who was overweight had higher food enjoyment and lower levels of food satiety. Additionally, within siblings with discordant weight status, parents were more likely to use restrictive feeding practices with the overweight sibling and pressure-to-eat and encouragement-to-eat feeding practices with the healthy-weight sibling.
Family-based childhood obesity interventions may need to assess for sibling weight status when researching the home environment and intervene with parents to avoid using restriction or pressure-to-eat feeding practices when siblings are discordant on weight status.
The management of patients with a glioma is challenging and best achieved by a team approach encompassing a combination of chemotherapy, radiotherapy, immunotherapy, and surgical excision in a specialist Cancer Center - the balance of treatment depending on the site and grade of tumor. Survival rates are improving and care of patients with or recovering from gliomas is increasingly handled in the community under the care of local physicians. This book provides an authoritative, multi-disciplinary summary of glioma biology, genetics, management and social issues, based on the world-leading program at the Duke University Preston Robert Tisch Brain Tumor Center, one of the world's largest and most successful Centers to offer brain cancer treatment and translational research. The text is written by specialists from this Center, giving it a consistent approach and style. This is an important educational resource for neurologists, neurosurgeons, oncologists, psychiatrists, neurohospitalists and ancillary members of neuro-oncology teams.
Chloroplast division is driven by a macromolecular complex that assembles at the midplastid. The FtsZ ring (Z ring) is the central structure in this complex, and is composed of the functionally distinct cytoskeletal proteins FtsZ1 and FtsZ2. Recent studies in the heterologous Schizosaccharomyces pombe system showed that Arabidopsis FtsZ1 and FtsZ2 filaments have distinct assembly and turnover characteristics. To further analyze these FtsZs, we employed this system to compare the assembly and dynamic properties of FtsZ1 and FtsZ2 lacking their N- and/or C-termini with those of their full-length counterparts. Our data provide evidence that the N-terminus of FtsZ2 is critical for its structural dominance over FtsZ1, and that the N- and C-termini promote polymer bundling and turnover of both FtsZs and contribute to their distinct behaviors. We also assessed how ARC6 affects FtsZ2 filament dynamics, and found that it interacts with and stabilizes FtsZ2 filaments in S. pombe independent of its presumed Z-ring tethering function in planta. Finally, we generated FtsZ1-FtsZ2 coexpression constructs to facilitate reconstitution of more complex interaction networks. Our experiments yield new insight into factors influencing FtsZ behavior and highlight the utility of S. pombe for analyzing chloroplast FtsZs and their assembly regulators.
We show that as equilibrium is approached in deep gravity wells, such as those of galactic halos, gravitational quantum theory predicts that radial particle densities ρ(r) tend toward 1/r2 profiles, and photon-baryon scattering cross sections are significantly reduced.
The assembly of matter in the universe proliferates a wide variety of halo structures, often with enigmatic consequences. Giant spiral galaxies, for example, contain both dark matter and hot gas, while dwarf spheroidal galaxies, with weaker gravity, contain much larger fractions of dark matter, but little gas. Globular clusters, superficially resembling these dwarf spheroidals, have little or no dark matter. Halo temperatures are also puzzling: hot cluster halos contain cooler galaxy halos; dwarf galaxies have no hot gas at all despite their similar internal processes. Another mystery is the origin of the gas that galaxies require to maintain their measured star formation rates (SFRs). We outline how gravitational quantum theory solves these problems, and enables baryons to function as weakly-interacting-massive-particles (WIMPs) in Lambda Cold Dark Matter (LCDM) theory. Significantly, these dark-baryon ensembles may also be consistent with primordial nucleosynthesis (BBN) and cosmic microwave background (CMB) anisotropies.