Background: Precision medicine for multiple sclerosis (MS) involves choosing a treatment that best balances efficacy and disadvantages such as side effects, cost, and inconvenience, based on an individual’s unique characteristics. Machine learning can be used to model the relationship between a baseline brain MRI and future new and enlarging T2 (NE-T2) lesion count to provide personalized treatment recommendations. Methods: We present a multi-head, deep neural network for making individualized treatment decisions from baseline MRI and clinical information which (a) predicts future NE-T2 lesion counts on multiple treatments and (b) estimates the conditional average treatment effect (CATE), as defined by the predicted suppression of NE-T2 lesions, between different treatment options and placebo. We validate our model on a dataset pertaining to 1817 patients from four randomized clinical trials. Results: Our model predicts favorable outcomes (< 3 NE-T2 at follow-up) with average precision 0.780-0.994 across 5 different treatment arms. It correctly identifies subgroups with different treatment effect sizes and provides treatment recommendations that improve lesion suppression while limiting the need for high efficacy treatments. Conclusions: Our framework provides accurate predictions for future NE-T2 lesion counts and personalized treatment recommendations that improve outcomes while accounting for the disadvantages of different treatment options.

Background: Only one disease modifying therapy (DMT), ocrelizumab, was found to slow disability progression in primary progressive multiple sclerosis (PPMS). Modeling the conditional average treatment effect (CATE) using deep learning could identify individuals more responsive to DMTs, allowing for predictive enrichment to increase the power of future clinical trials. Methods: Baseline clinical and MRI data were acquired as part of three placebo-controlled randomized clinical trials: ORATORIO (ocrelizumab), OLYMPUS (rituximab) and ARPEGGIO (laquinimod). Data from ORATORIO and OLYMPUS was separated into a training (70%) and testing (30%) set, while ARPEGGIO served as additional validation. An ensemble of multitask multilayer perceptrons was trained to predict the rate of disability progression on both treatment and placebo to estimate CATE. Results: The model could separate individuals based on their predicted treatment effect. The top 25% of individuals predicted to respond most have a larger effect size (HR 0.442, p=0.0497) than the entire group (HR 0.787, p=0.292). The model could also identify responders to laquinimod. A simulated study where the 50% most responsive individuals are randomized would require 6-times less participants to detect a significant effect. Conclusions: Individuals with PPMS who respond favourably to DMTs can be identified using deep learning based on their baseline clinical and imaging characteristics.

Temperature may regulate seed dormancy and germination and determine the geographical distribution of species. The present study investigated the thermal limits for seed germination of Polygonum ferrugineum (Polygonaceae), an aquatic emergent herb distributed throughout tropical and subtropical America. Seed germination responses to light and temperature were evaluated both before (control) and after stratification at 10, 15 and 20°C for 7, 14 and 28 d. Germination of control seeds was ~50% at 10 and 15°C, and they did not germinate from 20 to 30°C. The best stratification treatment was 7 d at 10°C, where seed germination was >76% in the dark for all temperatures, except at 30°C, and < 60% in light conditions. A thermal time approach was applied to the seed germination results. Base temperature (Tb) was 6.3°C for non-dormant seeds and optimal temperature (To) was 20.6°C, ceiling temperature (Tc (<50)) was 32.8°C, and thermal time requirement for 50% germination was 44.4°Cd. We concluded that a fraction of P. ferrugineum seeds is dormant, has a narrow thermal niche to germinate (10 and 15°C) and that cold stratification (10°C) alleviated dormancy and amplified the thermal range permissive for germination of the species. Consequently, P. ferrugineum is expected to occur in colder environments, for example, at high altitudes. Higher temperatures decrease the probabilities of alleviate dormancy and the ability of their seeds to germinate.

Understanding the physics of viscoelastic liquid jets is relevant to jet-based printing and deposition techniques. In this paper we study the behaviour of jets induced from viscoelastic liquid films, using the mechanical impulse provided by a laser pulse to actuate jet formation. We present direct numerical simulations of viscoelastic liquid jets solving the two-phase flow problem, accounting for the Oldroyd-B rheology. We describe how the jet extension time and length are controlled by the Deborah number (ratio of the elastic and inertia-capillary time scales), the viscous dissipation described by the Ohnesorge number (ratio of the viscous-capillary and inertia-capillary time scales), as well as the ratio of laser impulse energy to the energy required to create free surface during jet formation and propagation. Using the droplet ejection laser threshold energy of a Newtonian liquid, we investigate the influence of increasing viscoelastic effects. We show that viscoelastic effects can modify the effective drop size at the tip of the jet, while the maximum jet length increases with increasing Deborah number. Using the simulations, we identify a high-Deborah-number regime, where the time of maximum jet extension can be described as $t_{max} = c_1 De^{1/4}$, with $c_1$ depending on the Ohnesorge number and blister geometry, while the length of maximum extension reaches an asymptotic value $L_{max}^{\infty }$ for $De>100$, $L_{max}^{\infty }$ depending on the Ohnesorge number and laser energy. The observed asymptotic relationships are in good agreement with experiments performed at much higher Deborah numbers.

This multi-wave, multi-source study focuses on the benefits of work engagement for employee adaptation to organizational change. The change entailed the implementation of a flexible office design in an engineering firm, which caused radical change for employees. Building on conservation of resources (COR) theory and change transition models, we predict that work engagement trajectories during change are crucial for successful adaptation. The hypothesized process was that initial employee meaning-making will facilitate work engagement, which, in turn, predicts supervisor-rated adaptive performance (i.e. adaptive work-role performance and extra-role performance) via attitude-to-change. Attitude-to-change was modeled as reciprocally related to work engagement at different points in time. Weekly questionnaires were completed by 71 employees during the first five weeks of the change (296 observations). Latent growth trajectories using weekly engagement measures showed no overall growth, but did show significant variance around the slope of work engagement. Meaning-making and attitude-to-change at the onset were positively related to initial levels, but not to growth of work engagement. Meaning-making was indirectly related to short-term attitude-to-change via work engagement. Short-term attitude-to-change was predictive of supervisor-rated adaptive performance and long-term attitude-to-change. Finally, work engagement (slope) predicted long-term attitude-to-change and supervisor-rated extra-role performance via short-term attitude-to-change. Taken together, the study contributes to knowledge about micro-level transition processes of employee adaptation and the benefits of work engagement during change.

The aim of this study was to apply a back-calculation model to Great Britain (GB) classical scrapie surveillance data, and use this model to estimate how many more cases might be expected, and over what time frame these cases might occur. A back-calculation model was applied to scrapie surveillance data between 2005 and 2019 to estimate the annual rate of decline of classical scrapie. This rate was then extrapolated to predict the number of future cases each year going forward. The model shows that there may be yet further cases of classical scrapie in GB. These will most likely occur in the fallen stock scheme, with approximately a 25% probability of at least 1 further scrapie positive, with a very low probability (~0.2%) of having up to three additional scrapie positives. This highlights the difficulty of completely eliminating all further cases, even in the presence of very effective control measures.

This article introduces the concept of playful work design—the process through which employees proactively create conditions within work activities that foster enjoyment and challenge without changing the design of the job itself. First, we review play theory and the motives people may have to play during work. In addition, we use the literature on proactive work behavior to argue that individuals can take personal initiative to increase person-job fit. Combining these literatures, we provide a theoretical framework for playful work design. We discuss the development and validation of an instrument to assess playful work design, and review recent studies to elucidate the psychological effects of playful work design and its possible outcomes. Finally, we briefly discuss practical implications.

In this paper I shall provide a novel version of a traditional epistemic criterion for distinguishing mental entities from nonmental ones, and defend it from likely sorts of objections. By the phrase ‘criterion of the mental’ I mean a set of conditions which is necessary and sufficient for an entity's being mental (or psychological).

In Plamondon & Alimi's target article, a bell-shaped velocity profile typically observed in fast movements is used as a basis for the “kinematic theory” of motor control. In our opinion, kinematics is a necessary but insufficient ground for a theory of motor control. Relationships between different kinematic characteristics are an emergent property of the system dynamics controlled by the brain in a specific way. In particular, bell-shaped velocity profiles with or without additional waves are a trivial consequence of shifts in the equilibrium state of the system as suggested, for example, in the λ-model of motor control.

This study among 80 dual-earner couples examines the ripple effects of emotional labour – on a daily basis. Specifically, we propose that employees who engage in surface acting at work drain their energetic resources, and undermine their own relationship satisfaction. Drawing upon conservation of resources (COR) theory, we predicted that work-related exhaustion would mediate the relationship between surface acting at work and at home. In addition, we hypothesized that employees’ emotional energy in the evening would mediate the relationship between surface acting at home and (actor and partner) satisfaction with the relationship. Participants filled in a survey and a diary booklet during five consecutive working days (N = 80 couples, N = 160 participants x 5 days, N = 800 occasions). The hypotheses were tested with multilevel analyses, using the actor–partner interdependence model. Results showed that daily work-related exhaustion partially mediated the relationship between daily surface acting at work and at home. As hypothesized, daily surface acting at home influenced own and partner’s daily relationship satisfaction through reduced daily emotional energy. These findings offer support for COR theory, and have important implications for organizations that encourage emotion regulation.

The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.

A fundamental understanding of the filament thinning of viscoelastic fluids is important in practical applications such as spraying and printing of complex materials. Here, we present direct numerical simulations of the two-phase axisymmetric momentum equations using the volume-of-fluid technique for interface tracking and the log-conformation transformation to solve the viscoelastic constitutive equation. The numerical results for the filament thinning are in excellent agreement with the theoretical description developed with a slender body approximation. We show that the off-diagonal stress component of the polymeric stress tensor is important and should not be neglected when investigating the later stages of filament thinning. This demonstrates that such numerical methods can be used to study details not captured by the one-dimensional slender body approximation, and pave the way for numerical studies of viscoelastic fluid flows.

Background: We aimed to identify preoperative predictors of survival in Metastatic Epidural Spinal Cord Compression (MESCC) patients surgically treated, examine how these predictors relate to eight prognostic models, and to perform the first full external validation of these models in accordance with the TRIPOD statement. Methods: 142 surgically treated MESCC patients were enrolled in a prospective, multicenter cohort study and followed for 12 months or until death. Cox proportional hazards (PH) regressions were used. Non-collinear predictors with <10% missing data, ≥10 events per stratum and p<0.05 in univariable analysis were tested through a backward stepwise selection. For the original and revised Tokuhashi, Tomita, modified Bauer, van der Linden, Bartels, OSRI, Bartels and Bollen, we examined calibration and discrimination; survival stratified by risk groups with the Kaplan-Meier method and log-rank test. Results: Primary tumor, organ metastasis and SF-36v2 PC were associated with survival in multivariable analysis; corrected discrimination was 0.68. These three predictors were common to most current prognostic models. However, calibration was poor overall while discrimation was possibly helpful. Conclusions: Primary tumor type (breast, prostate and thyroid), absence of organ metastasis, and a lower degree of physical disability are preoperative predictors of longer survival in surgical MESCC patients. Clinicians should use these 8 prognostic models with caution.

This work presents the results of physiological studies developed to understand modifications linked to the reduction of seed dormancy provoked by domestication processes. The experiments performed compared wild and domesticated Cucurbita subspecies and their hybrids developed by reciprocal crossings. Seeds of two accessions of the wild subspecies presented dormancy, but it was largely reduced in seeds from the domesticated genotype, and partially reverted in hybrids, especially in those obtained when the domesticated genotype was used as the mother plant. In addition, naked embryos of all subspecies did not display dormancy when incubation was performed at 28°C, but embryo germination was progressively reduced only in the wild genotype under decreasing incubation temperatures (22 and 16°C). In the embryos, abscisic acid (ABA) concentrations were similar in both domesticated and wild subspecies, whereas in the seed coat, it was threefold higher in the wild subspecies. The naked embryos from the wild subspecies were far more responsive to ABA than those from the domesticated subspecies. These results indicate that dormancy in the wild subspecies is imposed by the seed coat tissues and that this effect is mediated by their high ABA content and the sensitivity of the embryos to ABA. These physiological aspects were apparently removed by domestication along with the temperature-dependent response for germination.