Researchers have studied psychological disorders extensively from a common cause perspective, in which symptoms are treated as independent indicators of an underlying disease. In contrast, the causal ...systems perspective seeks to understand the importance of individual symptoms and symptom-to-symptom relationships. In the current study, we used network analysis to examine the relationships between and among depression and anxiety symptoms from the causal systems perspective.
We utilized data from a large psychiatric sample at admission and discharge from a partial hospital program (N = 1029, mean treatment duration = 8 days). We investigated features of the depression/anxiety network including topology, network centrality, stability of the network at admission and discharge, as well as change in the network over the course of treatment.
Individual symptoms of depression and anxiety were more related to other symptoms within each disorder than to symptoms between disorders. Sad mood and worry were among the most central symptoms in the network. The network structure was stable both at admission and between admission and discharge, although the overall strength of symptom relationships increased as symptom severity decreased over the course of treatment.
Examining depression and anxiety symptoms as dynamic systems may provide novel insights into the maintenance of these mental health problems.
A long-standing goal of psychopathology research is to develop objective markers of symptomatic states, yet progress has been far slower than expected. Although prior reviews have attributed this ...state of affairs to diagnostic heterogeneity, symptom comorbidity and phenotypic complexity, little attention has been paid to the implications of intra-individual symptom dynamics and inter-relatedness for biomarker study designs. In this critical review, we consider the impact of short-term symptom fluctuations on widely used study designs that regress the 'average level' of a given symptom against biological data collected at a single time point, and summarize findings from ambulatory assessment studies suggesting that such designs may be sub-optimal to detect symptom-substrate relationships. Although such designs have a crucial role in advancing our understanding of biological substrates related to more stable, longer-term changes (for example, gray matter thinning during a depressive episode), they may be less optimal for the detection of symptoms that exhibit high frequency fluctuations, are susceptible to common reporting biases, or may be heavily influenced by the presence of other symptoms. We propose that a greater emphasis on intra-individual symptom chronometry may be useful for identifying subgroups of patients with common, proximal pathological indicators. Taken together, these three recent developments in the areas of symptom conceptualization and measurement raise important considerations for future studies attempting to identify reliable biomarkers in psychiatry.
Describe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings.
Subgroup analysis of a prospective, observational ...study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described.
Overall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (
< 0.001). The majority (96.1%) of Asian patients were rated as having improved.
In the Asian treatment setting, BoNT-A demonstrated a clinically significant effect on goal attainment for the real-life management of upper limb spasticity following stroke.
Patients with acute ischemic stroke require immediate medical treatment, and a CT to rule out hemorrhage is required before tPA. We adapted our protocol to include multimodal CT: unenhanced CT, CTA, ...and PCT. The purpose of this study was to determine whether multimodal CT imaging delays initiation of IV tPA beyond 60 minutes from hospital arrival.
All patients admitted during 3 years through the ED with a stroke alert and time from symptom onset to hospital arrival <2.5 hours were included. We examined 2 subgroups (multimodal CT versus unenhanced CT) to determine whether multimodal CT delayed tPA administration. Logistic regression was used to identify variables that predicted tPA within 60 minutes.
There were 123 patients in the analysis, including 108 patients who were examined with multimodal CT. The median time from arrival to tPA was 56 minutes and was shorter for patients examined with multimodal CT (55 versus 78 minutes, P = .02). After adjustment, variables that were associated with tPA administration within 60 minutes included prehospital stroke alert (OR = 3.47, P = .03), time to CT (OR = 0.94, P = .01), and onset-to-arrival time (OR = 1.02, P = .04). There was no statistically significant difference in the odds of receiving timely tPA for multimodal versus unenhanced CT (OR = 3.99, P = .07).
In our single-center experience, the use of multimodal imaging in patients with acute stroke did not delay IV tPA beyond 60 minutes. Further study is needed to assess the feasibility of the routine use of multimodal imaging in the acute stroke setting.
Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast ...Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals.
Biogeochemical models simulate soil nitrogen (N) turnover and are often used to assess N losses through denitrification. Though models simulate a complete N budget, often only a subset of N ...pools/fluxes (i.e., N2O, NO3− ${{\text{NO}}_{3}}^{-}$, NH3, NOx) are published since the full budget cannot be validated with measured data. Field studies rarely include full N balances, especially N2 fluxes, which are difficult to quantify. Limiting publication of modeling results based on available field data represents a missed opportunity to improve the understanding of modeled processes. We propose that the modeler community support publication of all simulated N pools and processes in future studies.
Plain Language Summary
Biogeochemical models calculate the entire N balance to describe soil N turnover. However, when findings are published, they often focus solely on environmentally harmful N losses like N2O fluxes and NO3− ${{\text{NO}}_{3}}^{-}$ leaching. We argue that it is crucial to publish and communicate the complete N cycle as calculated by the models. This practice is vital for advancing model development, ensuring quality control, facilitating model intercomparison, and generating new hypotheses for empirical field studies. We therefore encourage ecosystem modelers to report all results, even those that cannot be fully validated due to a lack of measurements. We particularly emphasize the importance of denitrification and reporting modeled N2 fluxes.
Key Points
Biogeochemical models simulate soil denitrification through multiple pools/processes, but the N budgets reported are incomplete
Missing (unpublished) model outputs are critical for model evaluation, model intercomparison, and model development
Ecosystem N modelers need to support and encourage the publication of all relevant N model outputs for denitrification modeling
We analyze the trajectories of 313 particles seen in the near‐Bennu environment between December 2018 and September 2019. Of these, 65% follow suborbital trajectories, 20% undergo more than one ...orbital revolution around the asteroid, and 15% directly escape on hyperbolic trajectories. The median lifetime of these particles is ∼6 hr. The trajectories are sensitive to Bennu's gravitational field, which allows us to reliably estimate the spherical harmonic coefficients through degree 8 and to resolve nonuniform mass distribution through degree 3. The particles are perturbed by solar radiation pressure, enabling effective area‐to‐mass ratios to be estimated. By assuming that particles are oblate ellipsoids of revolution, and incorporating photometric measurements, we find a median axis ratio of 0.27 and diameters for equivalent‐volume spheres ranging from 0.22–6.1 cm, with median 0.74 cm. Our size distribution agrees well with that predicted for fragmentation due to diurnal thermal cycling. Detailed models of known accelerations do not produce a match to the observed trajectories, so we also estimate empirical accelerations. These accelerations appear to be related to mismodeling of radiation pressure, but we cannot rule out contributions from mass loss. Most ejections take place at local solar times in the afternoon and evening (12:00–24:00), although they occur at any time of day. We independently identify ten ejection events, some of which have previously been reported. We document a case where a particle ricocheted off the surface, revealing a coefficient of restitution 0.57±0.01 and demonstrating that some apparent ejections are not related to surface processes.
Plain Language Summary
The Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer (OSIRIS‐REx) mission discovered that near‐Earth asteroid (101955) Bennu is periodically ejecting small particles from its surface, placing it in the uncommon class of “active asteroids.” We linked together individual detections of ejected particles and used numerical models of the forces acting on them to ascertain their trajectories and fates. We found that most particles have suborbital trajectories, meaning they fall back to Bennu's surface shortly after being ejected, but some orbit Bennu for days at a time, and some escape directly into space. From the particle trajectories, we are able to estimate their sizes (comparable to pebbles, from a few millimeters to a few centimeters in diameter) and shapes (probably flake like). Their trajectories also make it possible to estimate Bennu's gravity field more precisely than spacecraft measurements and help shed light on the possible causes of the ejections.
Key Points
Most of the 313 particles we study have suborbital trajectories, but some orbit Bennu and others directly escape
The particles appear to have flake‐like shapes and have effective diameters 0.22–6.1 cm with median 0.74 cm
Ejections tend to take place in the local afternoon and evening but can occur anytime
How should we define health? Huber, Machteld; Knottnerus, J André; Green, Lawrence ...
BMJ,
07/2011, Volume:
343, Issue:
7817
Journal Article
Peer reviewed
Open access
The WHO definition of health as complete wellbeing is no longer fit for purpose given the rise of chronic disease. Machteld Huber and colleagues propose changing the emphasis towards the ability to ...adapt and self manage in the face of social, physical, and emotional challenges
The myeolomonocytic cell line U937 differentiates into macrophages in response to a variety of agents. Several genes including the cyclin-dependent kinase inhibitor p21(waf1/cip1) and the homeobox ...gene transcription factor HOXA10 are induced at the onset of differentiation. Ectopic expression of either gene results in U937 differentiation. In this paper, we describe a mechanism by which p21 and HOXA10 may act in concert, where HOXA10 can bind directly to the p21 promoter and, together with its trimeric partners PBX1 and MEIS1, activate p21 transcription, resulting in cell cycle arrest and differentiation. These experiments for the first time identify p21 as a selective target for a HOX protein and link the differentiative properties of a transcription factor and a cell cycle inhibitor.
Insulin stimulated protein synthesis in gastrocnemius muscle of perfused rat hindlimb preparations by approximately twofold. The stimulation of protein synthesis was associated with a 12-fold ...increase in the amount of eukaryotic initiation factor eIF-4G bound to the mRNA cap-binding protein eIF-4E. In part, the increased binding of eIF-4G to eIF-4E was a result of release of eIF-4E bound to the translational regulator, PHAS-I, through a mechanism involving enhanced phosphorylation of PHAS-I. However, the insulin-induced association of eIF-4E and eIF-4G was not due to increased net phosphorylation of eIF-4E because insulin decreased the amount present in the phosphorylated form from 86 to 59% of total eIF-4E. Overall, the results suggest that insulin stimulates protein synthesis in gastrocnemius muscle through a mechanism involving increased binding of eIF-4G to eIF-4E, which is in part due to phosphorylation of PHAS-I, resulting in a release of eIF-4E from the inactive PHAS-I x eIF-4E complex.
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