In this report we study the modelling of simple mechanical systems evolving on trivial principal bundles, specifically \emph{locomotion} systems with nonholonomic constraints. We show how we can ...model motion via group actions on configuration manifolds and assess the relationship between the constraints (and constrained variables) and the variables that physically induce motion on the vehicle by studying principal bundles. With knowledge of the controllability (using the Lie algebra rank condition) of this formulation of a constrained simple mechanical system, we proceed to outlining a methodology to design a universal control algorithm for constrained mechanical systems using the method of virtual surfaces (or potential functions). Lastly, we design a set of virtual surfaces to make a rolling disk (arguably the simplest practical nonholonomic system) stabilise to a point, track a path, and avoid a sequence of obstacles in the plane.
Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the ...PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.
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•Serotonergic psychedelics increase neuritogenesis, spinogenesis, and synaptogenesis•Psychedelics promote plasticity via an evolutionarily conserved mechanism•TrkB, mTOR, and 5-HT2A signaling underlie psychedelic-induced plasticity•Noribogaine, but not ibogaine, is capable of promoting structural neural plasticity
Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders.
Background
Despite robust evidence of fathers’ impact on children and mothers, engaging with fathers is one of the least well‐explored and articulated aspects of parenting interventions. It is ...therefore critical to evaluate implicit and explicit biases manifested in current approaches to research, intervention, and policy.
Methods
We conducted a systematic database and a thematic hand search of the global literature on parenting interventions. Studies were selected from Medline, Psychinfo, SSCI, and Cochrane databases, and from gray literature on parenting programs, using multiple search terms for parent, father, intervention, and evaluation. We tabulated single programs and undertook systematic quality coding to review the evidence base in terms of the scope and nature of data reporting.
Results
After screening 786 nonduplicate records, we identified 199 publications that presented evidence on father participation and impact in parenting interventions. With some notable exceptions, few interventions disaggregate ‘father’ or ‘couple’ effects in their evaluation, being mostly driven by a focus on the mother–child dyad. We identified seven key barriers to engaging fathers in parenting programs, pertaining to cultural, institutional, professional, operational, content, resource, and policy considerations in their design and delivery.
Conclusions
Barriers to engaging men as parents work against father inclusion as well as father retention, and undervalue coparenting as contrasted with mothering. Robust evaluations of father participation and father impact on child or family outcomes are stymied by the ways in which parenting interventions are currently designed, delivered, and evaluated. Three key priorities are to engage fathers and coparenting couples successfully, to disaggregate process and impact data by fathers, mothers, and coparents, and to pay greater attention to issues of reach, sustainability, cost, equity, and scale‐up. Clarity of purpose with respect to gender‐differentiated and coparenting issues in the design, delivery, and evaluation of parenting programs will constitute a game change in this field.
Read the Commentary on this article at doi: 10.1111/jcpp.12321
Immune-based cancer therapies such as checkpoint inhibitors (CPI) and vaccines have been increasingly studied across different cancer types. Response to such therapies depends on a number of factors ...such as mutational burden, neoantigen load, presence of tumor infiltrating lymphocytes, among others. Next-generation sequencing (NGS) technologies are particularly attractive to interrogate the immune response compared to traditional assays such as qRT-PCR and immunohistochemistry (IHC) because they enable the discovery of neoantigens and simultaneous profiling of immune infiltration using gene expression on a large scale. Current approaches in immune profiling utilizes whole-exome sequencing (WES) for human leukocyte allele (HLA) typing and neoantigen predictions, and RNA sequencing (RNA-seq) for filtering unexpressed neoantigens and inferring immune infiltration. They have been successfully applied to the tumor setting as there is abundant sample material to perform both experiments. However, premalignant specimens are often much smaller compared to tumors. Therefore, there is a need to explore the viability of adopting a single approach for immune, neoantigen, and mutation profiling. Here, we describe our workflow of using RNA-seq to analyze mutational burden, neoantigen load, and immune expression profile.
Extensive streamflow data sources exist beyond the largest streamflow data provider in the United States, the U.S. Geological Survey. We developed and distributed a survey to about 300 individuals ...and organizations that collect streamflow data across the Pacific Northwest (Idaho, Oregon, Washington). We received 100 responses with 56% of those sufficiently complete to include in the analysis. From these responses, there are about 2000 streamflow monitoring locations in the region beyond the USGS monitoring network. The duration of record for gages is related to the size of the streamflow gaging network, with small and large networks generally operating monitoring locations for less than 5 years and more than 10 years, respectively. Quality assurance and quality control are variable across organizations, with 41% of respondents having at least two review steps and 13% that audit their data for long‐term consistency. Results of this survey begin to establish the differing capabilities of large and small stream gaging networks and highlight how supporting the overall quality streamflow data collection and management within the water resources community will improve our ability to harmonize these datasets in the future.
Radiomic analysis has recently demonstrated versatile uses in improving diagnostic and prognostic prediction accuracy for lung cancer. However, since lung tumors are subject to substantial motion due ...to respiration, the stability of radiomic features over the respiratory cycle of the patient needs to be investigated to better evaluate the robustness of the inter-patient feature variability for clinical applications, and its impact in such applications needs to be assessed. A full panel of 841 radiomic features, including tumor intensity, shape, texture, and wavelet features, were extracted from individual phases of a four-dimensional (4D) computed tomography on 20 early-stage non-small-cell lung cancer (NSCLC) patients. The stability of each radiomic feature was assessed across different phase images of the same patient using the coefficient of variation (COV). The relationship between individual COVs and tumor motion magnitude was inspected. Population COVs, the mean COVs of all 20 patients, were used to evaluate feature motion stability and categorize the radiomic features into 4 different groups. The two extremes, the Very Small group (COV≤5%) and the Large group (COV>20%), each accounted for about a quarter of the features. Shape features were the most stable, with COV≤10% for all features. A clinical study was subsequently conducted using 140 early-stage NSCLC patients. Radiomic features were employed to predict the overall survival with a 500-round bootstrapping. Identical multiple regression model development process was applied, and the model performance was compared between models with and without a feature pre-selection step based on 4D COV to pre-exclude unstable features. Among the systematically tested cutoff values, feature pre-selection with 4D COV≤5% achieved the optimal model performance. The resulting 3-feature radiomic model significantly outperformed its counterpart with no 4D COV pre-selection, with P = 2.16x10-27 in the one-tailed t-test comparing the prediction performances of the two models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The first relatively complete landscape-scale social–ecological system (SES) model of a recreational fishery was developed and ground-truthed with independent angling effort data. Based on the ...British Columbia multistock recreational fishery for rainbow trout (Oncorynchus mykiss), the model includes hundreds of individual lake fisheries, hundreds of thousands of anglers, originating from tens of communities, connected by complex road and trail networks, all distributed over a landscape of approximately half a million square kilometres. The approach is unique in that it incorporates realistic and empirically derived behavioural interactions within and among the three key components of the SES: angler communities, fish populations, and management policies. Current management policies were characterized and alternate policies assessed by simulation. We examined spatial patterns in ecological and social properties of the SES and used simulations to investigate the impacts of alternate management policies on these patterns. Simulation outcomes strongly depended on the spatial redistribution of anglers across the landscape, existing road networks, heterogeneity in angler behaviours, and the spatial pattern of fish population productivity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Vascular injury secondary to an acute knee dislocation is a known complication. However, there exist wide discrepancies in the reported rate of vascular injury in this setting.
...Questions/purposes
Using a large private insurance database, we determined the frequency of vascular injury in knee dislocations across year of diagnosis, age, sex, and US geographic region and the proportion of these injuries requiring surgical repair.
Methods
The PearlDiver database, which contains records from 11 million orthopaedic patients, was searched using ICD-9 diagnostic codes for all knee dislocation events from 2004 to 2009. Within this subset, we identified which knee dislocations had an associated vascular injury ICD-9 code. Patients were stratified by year of diagnosis, age, sex, and US geographic region, and Current Procedural Terminology codes were used to identify the subset of patients with vascular injury requiring surgical repair. Differences in frequency across demographic groups and over time were analyzed with Poisson regression analysis.
Results
Among the 8050 limbs with knee dislocation identified over the study period, 267 had a concomitant vascular injury for an overall frequency of 3.3%. Males were found to have an increased risk of vascular injury compared to females (odds ratio = 2.59, p < 0.001). Additionally, patients aged 20 to 39 years had a higher risk of vascular injury when compared to those aged 0 to 19 years (odds ratio = 1.93, p = 0.001), 40 to 59 years (odds ratio = 1.57, p = 0.014), and 60 years or older (odds ratio = 2.81, p = 0.036). There were no differences in vascular injury frequency across US geographic regions or diagnosis year. Thirty-four of the 267 cases of vascular injury (13%) underwent surgical treatment.
Conclusions
This is the largest study, to our knowledge, that analyzes the proportion of knee dislocations that result in vascular injury. Our data suggest that there is a lower frequency of vascular injury associated with knee dislocation and a lower proportion of vascular injuries undergoing surgical treatment than previously reported. These findings may support a more selective angiography protocol to screen for vascular injury, rather than performing this invasive diagnostic test on all knee dislocations, as has been done historically. Future large-scale and prospective studies should analyze factors that may predispose to vascular injuries after knee dislocation and determine which patients should be screened for vascular injury after knee dislocation.
Level of Evidence
Level IV, prognostic study. See Instructions for Authors for a complete description of levels of evidence.
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