Digital mental health and peer support: Building a Theory of Change informed by stakeholders' perspectives.

Digital Mental Health and Peer support has the potential to bridge gaps in support through its scalability and accessibility. Despite the increasing use of these platforms, there remains a lack of understanding of how they operate in real life, from initial engagement to longer-term impact. We aimed to explore the key inputs, processes, user interactions, assumptions, barriers, facilitators, outcomes, and impacts associated with the use of DMH and peer support platforms by developing a Theory of Change with stakeholders. Stakeholders (n = 77) contributed to the formulation of the Theory of Change through a series of online workshops, focus groups, interviews, and open-ended survey feedback. Workshops were structured to capture information related to aspects of the Theory of Change and to allow stakeholders to provide feedback to improve the diagram. A thematic framework approach was used to analyze transcripts to enable comparisons of factors reported by members, commissioners, and platform staff. Stakeholders identified a variety of factors contributing to initial inputs, processes, outcomes, and impact. Engagement emerged as the most significant barrier to the use of platforms. Motivations for use included filling in gaps in available support, connecting with others and upskilling. Different member types determined how users would interact with the platform which could influence the social response of others. Outcomes were largely positive including provision of a safe online space, improvement in wellbeing, and feeling connected to others. Stakeholders noted impact was harder to identify due to the preventative nature of these platforms but suggested this related to the knowledge of available support, reduction in waiting for support and in referrals, and increasing engagement and uptake of the platforms. Stakeholders identified assumptions regarding internet access as a significant barrier. The Theory of Change illustrated three distinct pathways in digital mental health and peer support. Further research is needed to improve engagement and factors influencing engagement, the member experience and how impact is measured.

Regulatory interactions between daptomycin- and bacitracin-responsive pathways coordinate the cell envelope antibiotic resistance response of Enterococcus faecalis.

Enterococcal infections frequently show high levels of antibiotic resistance, including to cell envelope-acting antibiotics like daptomycin (DAP). While we have a good understanding of the resistance mechanisms, less is known about the control of such resistance genes in enterococci. Previous work unveiled a bacitracin resistance network, comprised of the sensory ABC transporter SapAB, the two-component system (TCS) SapRS and the resistance ABC transporter RapAB. Interestingly, components of this system have recently been implicated in DAP resistance, a role usually regulated by the TCS LiaFSR. To better understand the regulation of DAP resistance and how this relates to mutations observed in DAP-resistant clinical isolates of enterococci, we here explored the interplay between these two regulatory pathways. Our results show that SapR regulates an additional resistance operon, dltXABCD, a known DAP resistance determinant, and show that LiaFSR regulates the expression of sapRS. This regulatory structure places SapRS-target genes under dual control, where expression is directly controlled by SapRS, which itself is up-regulated through LiaFSR. The network structure described here shows how Enterococcus faecalis coordinates its response to cell envelope attack and can explain why clinical DAP resistance often emerges via mutations in regulatory components.

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Collective synchronization through noise cancellation.

After decades of study, there are only two known mechanisms to induce global synchronization in a population of oscillators: Deterministic coupling and common forcing. The inclusion of independent noise in these models typically serves to drive disorder, increasing the stability of the incoherent state. Here we show that the reverse is also possible. We propose and analyze a simple general model of purely noise coupled oscillators. In the first explicit choice of noise coupling, we find the linear response around incoherence is identical to that of the paradigmatic Kuramoto model but exhibits binary phase locking instead of full coherence. We characterize the phase diagram, stationary states, and approximate low-dimensional dynamics for the model, revealing the curious behavior of this mechanism of synchronization. In the second minimal case we connect the final synchronized state to the initial conditions of the system.

Assisted percolation of slow-spreading mutants in heterogeneous environments.

Environmental heterogeneity can drive genetic heterogeneity in expanding populations; mutant strains may emerge that trade overall growth rate for an improved ability to survive in patches that are hostile to the wild type. This evolutionary dynamic is of practical importance when seeking to prevent the emergence of damaging traits. We show that a subcritical slow-spreading mutant can attain dominance even when the density of patches is below their percolation threshold and predict this transition using geometrical arguments. This work demonstrates a phenomenon of "assisted percolation", where one subcritical process assists another to achieve supercriticality.

Lane nucleation in complex active flows.

Laning is a paradigmatic example of spontaneous organization in active two-component flows that has been observed in diverse contexts, including pedestrian traffic, driven colloids, complex plasmas, and molecular transport. We introduce a kinetic theory that elucidates the physical origins of laning and quantifies the propensity for lane nucleation in a given physical system. Our theory is valid in the low-density regime, and it makes different predictions about situations in which lanes may form that are not parallel with the direction of flow. We report on experiments with human crowds that verify two notable consequences of this phenomenon: tilting lanes under broken chiral symmetry and lane nucleation along elliptic, parabolic, and hyperbolic curves in the presence of sources or sinks.

The Role of Moderators in Facilitating and Encouraging Peer-to-Peer Support in an Online Mental Health Community: A Qualitative Exploratory Study.

Online peer support platforms have gained popularity as a potential way for people struggling with mental health problems to share information and provide support to each other. While these platforms can offer an open space to discuss emotionally difficult issues, unsafe or unmoderated communities can allow potential harm to users by spreading triggering content, misinformation or hostile interactions. The purpose of this study was to explore the role of moderators in these online communities, and how moderators can facilitate peer-to-peer support, while minimizing harms to users and amplifying potential benefits. Moderators of the Togetherall peer support platform were recruited to participate in qualitative interviews. The moderators, referred to as 'Wall Guides', were asked about their day-to-day responsibilities, positive and negative experiences they have witnessed on the platform and the strategies they employ when encountering problems such as lack of engagement or posting of inappropriate content. The data were then analyzed qualitatively using thematic content analysis and consensus codes were deduced and reviewed to reach final results and representative themes. In total, 20 moderators participated in this study, and described their experiences and efforts to follow a consistent and shared protocol for responding to common scenarios in the online community. Many reported the deep connections formed by the online community, the helpful and thoughtful responses that members give each other and the satisfaction of seeing progress in members' recovery. They also reported occasional aggressive, sensitive or inconsiderate comments and posts on the platform. They respond by removing or revising the hurtful post or reaching out to the affected member to maintain the 'house rules'. Lastly, many discussed strategies they elicit to promote engagement from members within the community and ensure each member is supported through their use of the platform. This study sheds light on the critical role of moderators of online peer support communities, and their ability to contribute to the potential benefits of digital peer support while minimizing risks to users. The findings reported here accentuate the importance of having well-trained moderators on online peer support platforms and can guide future efforts to effectively train and supervise prospective peer support moderators. Moderators can become an active 'shaping force' and bring a cohesive culture of expressed empathy, sensitivity and care. The delivery of a healthy and safe community contrasts starkly with non-moderated online forums, which can become unhealthy and unsafe as a result.

Stochastic drift in discrete waves of nonlocally interacting particles.

In this paper, we investigate a generalized model of N particles undergoing second-order nonlocal interactions on a lattice. Our results have applications across many research areas, including the modeling of migration, information dynamics, and Muller's ratchet-the irreversible accumulation of deleterious mutations in an evolving population. Strikingly, numerical simulations of the model are observed to deviate significantly from its mean-field approximation even for large population sizes. We show that the disagreement between deterministic and stochastic solutions stems from finite-size effects that change the propagation speed and cause the position of the wave to fluctuate. These effects are shown to decay anomalously as (lnN)^{-2} and (lnN)^{-3}, respectively-much slower than the usual N^{-1/2} factor. Our results suggest that the accumulation of deleterious mutations in a Muller's ratchet and the loss of awareness in a population may occur much faster than predicted by the corresponding deterministic models. The general applicability of our model suggests that this unexpected scaling could be important in a wide range of real-world applications.

Aggregate fluctuations in adaptive production networks.

To counteract the adverse effects of shocks, such as the global pandemic, on the economy, governments have discussed policies to improve the resilience of supply chains by reducing dependence on foreign suppliers. In this paper, we develop and quantify an adaptive production network model to study network resilience and the consequences of reshoring of supply chains. In our model, firms exit due to exogenous shocks or the propagation of shocks through the network, while firms can replace suppliers they have lost due to exit subject to switching costs and search frictions. Applying our model to a large international firm-level production network dataset, we find that restricting buyer-supplier links via reshoring policies reduces output and increases volatility and that volatility can be amplified through network adaptivity.

Predictors of adolescent engagement and outcomes - A cross-sectional study using the togetherall (formerly Big White Wall) digital mental health platform.

BACKGROUND: Online mental health platforms can improve access to, and use of, mental health support for young people who may find it difficult to engage with face-to-face delivery. OBJECTIVE: We modelled predictors of engagement and symptom change in adolescent users of the Togetherall (formerly "Big White Wall") anonymous digital mental health peer-support platform. METHODS: We report a retrospective analysis of longitudinal user data from UK 16-18 year Togetherall users, referred from mental health services (N = 606). Baseline demographics were reported for participants who logged anxiety and depression measures. Number of log-ins, mean session duration, total usage time, number of guided support courses and self-help materials accessed were our usage metrics. Participant characteristics and symptoms were used to predict engagement. For n = 245 users with symptom measures at >1 timepoint we modelled the effect of predictors on symptom scores. RESULTS: Mean logins was 5.11 and mean usage time was 64.22 mins. Participants with one log-in represented 33.5% of the sample. Total time accessing Togetherall predicated greater usage of self-help materials and courses. Females made greater use of materials and courses than males. In a subsample, higher baseline depression and anxiety, longer total usage time and mean session duration predicted final depression scores, whereas higher baseline depression and anxiety and greater accessed self-help materials predicted lower final anxiety scores. LIMITATIONS: A naturalistic design was used and symptom modelling should be interpreted with caution. CONCLUSIONS: Findings suggest adolescents can engage with the Togetherall platform. Baseline symptoms and characteristics can inform user engagement with digital platforms.

Misinformation can prevent the suppression of epidemics.

The effectiveness of non-pharmaceutical interventions, such as mask-wearing and social distancing, as control measures for pandemic disease relies upon a conscientious and well-informed public who are aware of and prepared to follow advice. Unfortunately, public health messages can be undermined by competing misinformation and conspiracy theories, spread virally through communities that are already distrustful of expert opinion. In this article, we propose and analyse a simple model of the interaction between disease spread and awareness dynamics in a heterogeneous population composed of both trusting individuals who seek better quality information and will take precautionary measures, and distrusting individuals who reject better quality information and have overall riskier behaviour. We show that, as the density of the distrusting population increases, the model passes through a phase transition to a state in which major outbreaks cannot be suppressed. Our work highlights the urgent need for effective interventions to increase trust and inform the public.

Fluctuation spectra of large random dynamical systems reveal hidden structure in ecological networks.

Understanding the relationship between complexity and stability in large dynamical systems-such as ecosystems-remains a key open question in complexity theory which has inspired a rich body of work developed over more than fifty years. The vast majority of this theory addresses asymptotic linear stability around equilibrium points, but the idea of 'stability' in fact has other uses in the empirical ecological literature. The important notion of 'temporal stability' describes the character of fluctuations in population dynamics, driven by intrinsic or extrinsic noise. Here we apply tools from random matrix theory to the problem of temporal stability, deriving analytical predictions for the fluctuation spectra of complex ecological networks. We show that different network structures leave distinct signatures in the spectrum of fluctuations, and demonstrate the application of our theory to the analysis of ecological time-series data of plankton abundances.

Synchronized oscillations in growing cell populations are explained by demographic noise.

Understanding synchrony in growing populations is important for applications as diverse as epidemiology and cancer treatment. Recent experiments employing fluorescent reporters in melanoma cell lines have uncovered growing subpopulations exhibiting sustained oscillations, with nearby cells appearing to synchronize their cycles. In this study, we demonstrate that the behavior observed is consistent with long-lasting transient phenomenon initiated and amplified by the finite-sample effects and demographic noise. We present a novel mathematical analysis of a multistage model of cell growth, which accurately reproduces the synchronized oscillations. As part of the analysis, we elucidate the transient and asymptotic phases of the dynamics and derive an analytical formula to quantify the effect of demographic noise in the appearance of the oscillations. The implications of these findings are broad, such as providing insight into experimental protocols that are used to study the growth of asynchronous populations and, in particular, those investigations relating to anticancer drug discovery.

Sensorimotor synchronization in patients with mechanical neck disorders.

Background: There lacks knowledge of how patients with chronic persisting mechanical neck disorder (cMND) coordinate their movements. Objective: Analyze kinematic data from people with cMND by extracting vertical trajectories from 3D Qualisys data of the patients' hand. The time between metronome beat and bottle placement were cross-correlated to compare timing accuracy. Design: Cross-sectional case-series. Method: A cyclical overhead reach and grasp task involving lifting bottles from low to high shelves at a pace of 60 bpm tested muscular incoordination. Subjects from a convenience sample were classified by a modified Quebec Task Force Classification. Motion capture imaging and seven channel electromyography was recorded during each patients' trial. Outcome measures include: Neck Disability Index, subjective pain ratings measured by a numeric pain rating scale, and 3D coordinates from motion capture data. The time between metronome beat and bottle placement were cross-correlated to compare timing accuracy (mean percent values, standard deviation [SD]). Two within-subject variables ([1] side: affected vs. unaffected; and [2] posture: sitting vs. standing) were assessed. Results: Seven participants (five females/two male; age mean 46.7, SD 15.21 years) had a mean of 7.25, SD 2.3 in arm pain and 6.38, SD 2.60 in neck pain post trial. Timing accuracies were found while standing (mean 0.84, SD 0.04) but not sitting (mean 0.67 SD 0.16). Numeric pain ratings increased from pre (neck 4.21[1.88]; arm 3.40[2.72]) to post (neck 6.38[2.61], arm 7.25[2.30]) trial. Conclusion: Initial data suggest that patients with persisting cMND have reduced accuracy in timing when coordinating their movement to a paced external event.

Fitness differences suppress the number of mating types in evolving isogamous species.

Sexual reproduction is not always synonymous with the existence of two morphologically different sexes; isogamous species produce sex cells of equal size, typically falling into multiple distinct self-incompatible classes, termed mating types. A long-standing open question in evolutionary biology is: what governs the number of these mating types across species? Simple theoretical arguments imply an advantage to rare types, suggesting the number of types should grow consistently; however, empirical observations are very different. While some isogamous species exhibit thousands of mating types, such species are exceedingly rare, and most have fewer than 10. In this paper, we present a mathematical analysis to quantify the role of fitness variation-characterized by different mortality rates-in determining the number of mating types emerging in simple evolutionary models. We predict that the number of mating types decreases as the variance of mortality increases.

Predicting the Speed of Epidemics Spreading in Networks.

Global transport and communication networks enable information, ideas, and infectious diseases to now spread at speeds far beyond what has historically been possible. To effectively monitor, design, or intervene in such epidemic-like processes, there is a need to predict the speed of a particular contagion in a particular network, and to distinguish between nodes that are more likely to become infected sooner or later during an outbreak. Here, we study these quantities using a message-passing approach to derive simple and effective predictions that are validated against epidemic simulations on a variety of real-world networks with good agreement. In addition to individualized predictions for different nodes, we find an overall sudden transition from low density to almost full network saturation as the contagion progresses in time. Our theory is developed and explained in the setting of simple contagions on treelike networks, but we are also able to show how the method extends remarkably well to complex contagions and highly clustered networks.

International consensus statement on the psychosocial and policy-related approaches to mental health awareness programmes in sport.

BACKGROUND: Research focused on mental health in sport has revealed a need to develop evidence-supported mental health practices that are sensitive to sport culture, particularly for non-elite athletes. A consensus statement was produced to assist effective mental health awareness in sport and guide programme implementation in this rapidly emerging field. METHOD: The AGREE Reporting Checklist 2016 was used in two international expert consultation meetings, followed by two online surveys. Experts from 10 countries and over 30 organisations contributed. RESULTS: Six objectives were agreed: (1) to define mental health awareness and service implementation constructs for inclusion in programmes delivered in sporting environments; (2) to identify the need to develop and use valid measures that are developmentally appropriate for use in intervention studies with sporting populations, including measures of mental health that quantify symptom severity but also consider causal and mediating factors that go beyond pathology (ie, well-being and optimisation); (3) to provide guidance on the selection of appropriate models to inform intervention design, implementation and evaluation; (4) to determine minimal competencies of training for those involved in sport to support mental health, those experiencing mental illness and when to refer to mental health professionals; (5) to provide evidence-based guidance for selecting mental health awareness and implementation programmes in sport that acknowledge diversity and are quality assured; and (6) to identify the need for administrators, parents, officials, coaches, athletes and workers to establish important roles in the promotion of mental health in various sports settings. CONCLUSION: This article presents a consensus statement on recommended psychosocial and policy-related approaches to mental health awareness programmes in sport.

Global Sensitivity Analysis of Metabolic Models for Phosphorus Accumulating Organisms in Enhanced Biological Phosphorus Removal.

The aim of this study was to identify, quantify and prioritize for the first time the sources of uncertainty in a mechanistic model describing the anaerobic-aerobic metabolism of phosphorus accumulating organisms (PAO) in enhanced biological phosphorus removal (EBPR) systems. These wastewater treatment systems play an important role in preventing eutrophication and metabolic models provide an advanced tool for improving their stability via system design, monitoring and prediction. To this end, a global sensitivity analysis was conducted using standard regression coefficients and Sobol sensitivity indices, taking into account the effect of 39 input parameters on 10 output variables. Input uncertainty was characterized with data in the literature and propagated to the output using the Monte Carlo method. The low degree of linearity between input parameters and model outputs showed that model simplification by linearization can be pursued only in very well defined circumstances. Differences between first and total-order sensitivity indices showed that variance in model predictions was due to interactions between combinations of inputs, as opposed to the direct effect of individual inputs. The major sources of uncertainty affecting the prediction of liquid phase concentrations, as well as intra-cellular glycogen and poly-phosphate was due to 64% of the input parameters. In contrast, the contribution to variance in intra-cellular PHA constituents was uniformly distributed among all inputs. In addition to the intra-cellular biomass constituents, notably PHB, PH2MV and glycogen, uncertainty with respect to input parameters directly related to anaerobic propionate uptake, aerobic poly-phosphate formation, glycogen formation and temperature contributed most to the variance of all model outputs. Based on the distribution of total-order sensitivities, characterization of the influent stream and intra-cellular fractions of PHA can be expected to significantly improve model reliability. The variance of EBPR metabolic model predictions was quantified. The means to account for this variance, with respect to each quantity of interest, given knowledge of the corresponding input uncertainties, was prescribed. On this basis, possible avenues and pre-requisite requirements to simplify EBPR metabolic models for PAO, both structurally via linearization, as well as by reduction of the number of non-influential variables were outlined.

Universal hypotrochoidic law for random matrices with cyclic correlations.

The celebrated elliptic law describes the distribution of eigenvalues of random matrices with correlations between off-diagonal pairs of elements, having applications to a wide range of physical and biological systems. Here, we investigate the generalization of this law to random matrices exhibiting higher-order cyclic correlations between k tuples of matrix entries. We show that the eigenvalue spectrum in this ensemble is bounded by a hypotrochoid curve with k-fold rotational symmetry. This hypotrochoid law applies to full matrices as well as sparse ones, and thereby holds with remarkable universality. We further extend our analysis to matrices and graphs with competing cycle motifs, which are described more generally by polytrochoid spectral boundaries.

Correction: New framework for automated article selection applied to a literature review of Enhanced Biological Phosphorus Removal.

[This corrects the article DOI: 10.1371/journal.pone.0216126.].