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The use of trait-based approaches to understand ecological communities has increased in the past two decades because of their promise to preserve more information about community structure than taxonomic methods and their potential to connect community responses to subsequent effects of ecosystem functioning. Though trait-based approaches are a powerful tool for describing ecological communities, many important properties of commonly-used trait metrics remain unexamined. Previous work with simulated communities and trait distributions shows sensitivity of functional diversity measures to the number and correlation of traits used to calculate them, but these relationships have yet to be studied in actual plant communities with a realistic distribution of trait values, ecologically meaningful covariation of traits, and a realistic number of traits available for analysis. To address this gap, we used data from six grassland plant communities in Minnesota and New Mexico, USA to test how the number of traits and the correlation between traits used in the calculation of eight functional diversity indices impact the magnitude of functional diversity metrics in real plant communities. We found that most metrics were sensitive to the number of traits used to calculate them, but functional dispersion (FDis), kernel density estimation dispersion (KDE dispersion), and Raos quadratic entropy (Raos Q) maintained consistent rankings of communities across the range of trait numbers. Despite sensitivity of metrics to trait correlation, there was no consistent pattern between communities as to how metrics were affected by the correlation of traits used to calculate them. We recommend that future use of evenness metrics include sensitivity analyses to ensure results are robust to the number of traits used to calculate them. In addition, we recommend use of FDis, KDE dispersion, and Raos Q when ecologically applicable due to their ability to produce consistent rankings among communities across a range of the numbers of traits used to calculate them.

Abstract Objectives This article describes and tests a novel multi-method approach to examine decision-making: Virtual Reality-Based Retrospective Think-Aloud (VR-RTA). The VR-RTA method taps into the offender perspective and aims to enhance memory recall and information elicitation. Methods We applied VR-RTA among a sample of incarcerated burglars (N = 200) who scouted virtual neighborhoods to explore opportunities for burglary in immersive VR equipped with integrated eye tracking. Subsequently, they viewed a screen recording of their scouting process and simultaneously “thought aloud” about their assessment of the environment and decision-making strategies. Emerging themes were then further examined in an interview and linked to survey data. Recorded eye tracking data were used to examine burglars’ attention towards environmental features to identify deterrent and attracting cues, and were triangulated with the survey and interview data. Results Rich and detailed insights into participants’ interpretation of the environment and their decision-making strategies were obtained. VR-RTA assisted in verbalizing automated cognitive processes and increased participant engagement by building rapport. Conclusions As a multi-method approach able to capture in-the-moment considerations underlying decision-making during crime commission, VR-RTA offers potential to develop into an important tool for crime research. It is able to both overcome limitations of studies using retrospective methods, such as interviews and surveys, and contribute to the nascent field of criminological research using immersive technologies.

This study examines the contribution of university educators toward prefiguratively creating tomorrow today in the higher education classroom. Educators often teach for peace and social justice through a variety of normative pedagogical frameworks. Yet, this linkage of pedagogy and prefigurative politics in university classrooms is frequently under-examined. Moreover, such research has not yet been conducted within the context of Korea. Hence, this paper investigates -- through a qualitative case study methodology -- the varied approaches to pedagogy for social change in Korean universities today, including but not limited to: (a) democratic pedagogy, (b) critical pedagogy, (c) peace and social justice pedagogy, and (d) decolonial pedagogy. The paper examines these intersectional pedagogies through the lens of prefigurative politics, which is understood as a form of praxis that attempts to (re)construct through education a more just society. Findings indicate challenges and opportunities that Korean university educators face today in teaching for social change in higher education classrooms.

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.

Abstract Communication by rare, binary spikes is a key factor for the energy efficiency of biological brains. However, it is harder to train biologically-inspired spiking neural networks than artificial neural networks. This is puzzling given that theoretical results provide exact mapping algorithms from artificial to spiking neural networks with time-to-first-spike coding. In this paper we analyze in theory and simulation the learning dynamics of time-to-first-spike-networks and identify a specific instance of the vanishing-or-exploding gradient problem. While two choices of spiking neural network mappings solve this problem at initialization, only the one with a constant slope of the neuron membrane potential at threshold guarantees the equivalence of the training trajectory between spiking and artificial neural networks with rectified linear units. For specific image classification architectures comprising feed-forward dense or convolutional layers, we demonstrate that deep spiking neural network models can be effectively trained from scratch on MNIST and Fashion-MNIST datasets, or fine-tuned on large-scale datasets, such as CIFAR10, CIFAR100 and PLACES365, to achieve the exact same performance as that of artificial neural networks, surpassing previous spiking neural networks. Our approach accomplishes high-performance classification with less than 0.3 spikes per neuron, lending itself for an energy-efficient implementation. We also show that fine-tuning spiking neural networks with our robust gradient descent algorithm enables their optimization for hardware implementations with low latency and resilience to noise and quantization.

BACKGROUND: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy. METHODS: Eligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data. RESULTS: Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events. CONCLUSIONS: In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).

Objectives The aim of this study was to combine deep T cell phenotyping with assessment of citrulline-reactive CD4+T cells in the pre-rheumatoid arthritis (RA) phase.Methods 20 anti-CCP2 positive individuals (HLA-DRB1*04:01) presenting musculoskeletal complaints without clinical or ultrasound signs of synovitis; 10 arthritis progressors and 10 matched non-arthritis progressors were included. Longitudinal samples (1–3 time points) of peripheral blood mononuclear cells were assessed using HLA-class II tetramers with 12 different citrullinated candidate autoantigens combined in a >20-colour spectral flow cytometry panel.Results The baseline CD4+T cell phenotype was similar between individuals who progressed to arthritis (ie, in the pre-RA phase) and the non-progressors, when studying markers associated with Th1, Th17, T-peripheral and T-regulatory cells as well as with T-cell activation. Citrulline-reactive CD4+T cells were present in both groups but at significantly lower frequency in the progressor group. CD4+T cells specific for citrullinated tenascin-C were the most frequently observed among the progressors, and their frequencies diminished during follow-up that is, closer to arthritis onset. Notably, PD-1 and CD95 expression on the memory cit-tenascin-C-specific T cells in this group indicated repeated antigen exposure.Conclusions Our data lend support to citrullinated tenascin-C as an interesting T cell antigen in RA. Moreover, lower frequency of circulating citrulline-specific cells in arthritis progressing individuals suggest an initiated homing of these cells to the joints and/or their associated lymph nodes in the pre-RA phase and a possible window of opportunity for therapeutic preventive interventions.

BackgroundDigitalization in disaster medicine holds significant potential to accelerate rescue operations and ultimately save lives. Mass casualty incidents demand rapid and accurate information management to coordinate effective responses. Currently, first responders manually record triage results on patient cards, and brief information is communicated to the command post via radio communication. Although this process is widely used in practice, it involves several time-consuming and error-prone tasks. To address these issues, we designed, implemented, and evaluated an app-based mobile triage system. This system allows users to document responder details, triage categories, injury patterns, GPS locations, and other important information, which can then be transmitted automatically to the incident commanders. ObjectiveThis study aims to design and evaluate an app-based mobile system as a triage and coordination tool for emergency and disaster medicine, comparing its effectiveness with the conventional paper-based system. MethodsA total of 38 emergency medicine personnel participated in a within-subject experimental study, completing 2 triage sessions with 30 patient cards each: one session using the app-based mobile system and the other using the paper-based tool. The accuracy of the triages and the time taken for each session were measured. Additionally, we implemented the User Experience Questionnaire along with other items to assess participants’ subjective ratings of the 2 triage tools. ResultsOur 2 (triage tool) × 2 (tool order) mixed multivariate analysis of variance revealed a significant main effect for the triage tool (P

The experience of meaning has been found to be mapped onto spatial proximity whereby coherent—in contrast to incoherent—elements in a set are mentally represented as closer together in physical space. In a series of four experiments, we show that spatial representation of coherence is malleable and can employ other meaningful concrete dimensions of space that are made salient. When given task instructions cueing verticality, participants represented coherence in the upper vertical location when making judgements about the logical validity of realistic (Experiments 1 and 4) and unrealistic syllogistic scenarios (Experiment 3). When the task instruction made the spatial proximity between the stimuli materials and the participant salient (subjective proximity), participants represented coherence as spatially close to themselves (Experiment 2). We also found that being accurate in judging the validity of syllogisms was associated with representing coherence in the upper visual field or close to oneself. Overall, our findings show that identifying semantic links between an abstract concept and a given spatial dimension involves using that dimension to create spatial metaphoric mappings of the concept.

Maurice Pialat (1925–2003) in his Libération article “Éloge de Poussin” (1987) tells us that cinema has made no progress since the Lumière brothers’ first projected images. Provocatively, he informs his readers that only painting has progressed and, as such, remains the far more innovative art form. For all the pointed remarks directed with some force towards French film critics and filmmakers, Pialat’s short notes in Libé offer us something more. It is one of the few opportunities to consider the auteur’s critical and aesthetic approaches to filmmaking. While Pialat emphasises the failure of critics and filmmakers to elevate cinema to the level of art, the article more saliently invites us to analyse Pialat’s understanding of cinematic practice as an intricate enfolding of painterly and cinematic concepts. In this article I contend that, through a reading of the theoretical dimensions Pialat introduces in his “elegy” to the Classicist painter Nicolas Poussin (1594–1665), along with an analysis of a selection of the director’s films, we not only discover Pialat’s film-philosophy; moreover, we discover new ways to study Pialat’s acute rendering of fraught manhood. Significantly, I argue, Pialat’s wrestling with masculinity (fatherhood, sexual desire, boyhood, and so on) reveals itself through a key element critical to Poussin’s aesthetic palette: the colour blue.

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.

Abstract The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma–C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.

Abstract Background While the impacts of atopic dermatitis (AD) on maternal and child sleep outcomes have been previously explored, less is known about the associations between infantile AD and sleep quality and quantity. Objective To describe the perceived causes of AD-associated maternal sleep disturbances and the association between AD severity and infant sleep outcomes. Methods Mothers with infants aged

Imaging response assessment is a cornerstone of patient care and drug development in oncology. Clinicians/clinical researchers rely on tumor imaging to estimate the impact of new treatments and guide decision making for patients and candidate therapies. This is important in brain cancer, where associations between tumor size/growth and emerging neurological deficits are strong. Accurately measuring the impact of a new therapy on tumor growth early in clinical development, where patient numbers are small, would be valuable for decision making regarding late-stage development activation. Current attempts to measure the impact of a new therapy have limited influence on clinical development, as determination of progression, stability or response does not currently account for individual tumor growth kinetics prior to the initiation of experimental therapies. Therefore, we posit that imaging-based response assessment, often used as a tool for estimating clinical effect, is incomplete as it does not adequately account for growth trajectories or biological characteristics of tumors prior to the introduction of an investigational agent. Here, we propose modifications to the existing framework for evaluating imaging assessment in primary brain tumors that will provide a more reliable understanding of treatment effects. Measuring tumor growth trajectories prior to a given intervention may allow us to more confidently conclude whether there is an anti-tumor effect. This updated approach to imaging-based tumor response assessment is intended to improve our ability to select candidate therapies for later-stage development, including those that may not meet currently sought thresholds for "response" and ultimately lead to identification of effective treatments.

Behavioral problems are commonly observed in primary school children, yet the educational contexts in which children's behaviors occur vary across regions of the world. Thus, culturally adapted and context-specific behavioral assessments are needed to successfully identify and support children at risk for severe behavior problems. This study examines behavior problems in a nationally representative sample (N = 700) of primary school students in Trinidad and Tobago using the Adjustment Scales for Children and Adolescents, a contextually-based assessment that has been adapted and standardized for use with this population. We applied latent profile analysis, a person-centered approach, to identify distinct patterns of behavior problems and contexts in which behaviors occurred. The resultant 6-profile model consisted of two profiles of adjusted children making up 60% of the sample and four profiles of at-risk children with elevated underactive and/or overactive behavior problems associated with different classroom contexts. Profiles were differentially associated with classroom learning behaviors and reading ability. The most vulnerable subgroup of primary school students showed high levels of under- and overactive behaviors in peer, learning, and teacher contexts, deficits in reading fluency, problem-solving, and motivation.