Digital Training Program for Line Managers (Managing Minds at Work): Protocol for a Feasibility Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Mental health problems affect 1 in 6 workers annually and are one of the leading causes of sickness absence, with stress, anxiety, and depression being responsible for half of all working days lost in the United Kingdom. Primary interventions with a preventative focus are widely acknowledged as the priority for workplace mental health interventions. Line managers hold a primary role in preventing poor mental health within the workplace and, therefore, need to be equipped with the skills and knowledge to effectively carry out this role. However, most previous intervention studies have directly focused on increasing line managers' understanding and awareness of mental health rather than giving them the skills and competencies to take a proactive preventative approach in how they manage and design work. The Managing Minds at Work (MMW) digital training intervention was collaboratively designed to address this gap. The intervention aims to increase line managers' knowledge and confidence in preventing work-related stress and promoting mental health at work. It consists of 5 modules providing evidence-based interactive content on looking after your mental health, designing and managing work to promote mental well-being, management competencies that prevent work-related stress, developing a psychologically safe workplace, and having conversations about mental health at work. OBJECTIVE: The primary aim of this study is to pilot and feasibility test MMW, a digital training intervention for line managers. METHODS: We use a cluster randomized controlled trial design consisting of 2 arms, the intervention arm and a 3-month waitlist control, in this multicenter feasibility pilot study. Line managers in the intervention arm will complete a baseline questionnaire at screening, immediately post intervention (approximately 6 weeks after baseline), and at 3- and 6-month follow-ups. Line managers in the control arm will complete an initial baseline questionnaire, repeated after 3 months on the waitlist. They will then be granted access to the MMW intervention, following which they will complete the questionnaire post intervention. The direct reports of the line managers in both arms of the trial will also be invited to take part by completing questionnaires at baseline and follow-up. As a feasibility pilot study, a formal sample size is not required. A minimum of 8 clusters (randomized into 2 groups of 4) will be sought to inform a future trial from work organizations of different types and sectors. RESULTS: Recruitment for the study closed in January 2022. Overall, 24 organizations and 224 line managers have been recruited. Data analysis was finished in August 2023. CONCLUSIONS: The results from this feasibility study will provide insight into the usability and acceptability of the MMW intervention and its potential for improving line manager outcomes and those of their direct reports. These results will inform the development of subsequent trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154019; https://clinicaltrials.gov/study/NCT05154019. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48758.

Managing Minds at Work: Development of a Digital Line Manager Training Program.

Mental ill-health is the leading cause of sickness absence, creating a high economic burden. Workplace interventions aimed at supporting employers in the prevention of mental ill-health in the workforce are urgently required. Managing Minds at Work is a digital intervention aimed at supporting line managers in promoting better mental health at work through a preventative approach. This intervention was developed as part of the Mental Health and Productivity Pilot, a wider initiative aimed at supporting employers across the Midlands region of the United Kingdom to improve the future of workplace mental health and wellbeing. The aim of the study is to describe the design and development of the Managing Minds at Work digital training program, prior to feasibility testing. We adopted a collaborative participatory design involving co-design (users as partners) and principles of user-centred design (pilot and usability testing). An agile methodology was used to co-create intervention content with a stakeholder virtual community of practice. Development processes were mapped to core elements of the Medical Research Council (MRC) framework for developing and evaluating complex interventions. The program covers five broad areas: (i) promoting self-care techniques among line managers; (ii) designing work to prevent work-related stress; (iii) management competencies to prevent and reduce stress; (iv) having conversations with employees about mental health; (v) building a psychologically safe work environment. It was considered by stakeholders to be appropriate for any type of organization, irrespective of their size or resources. Pilot and usability testing (n = 37 surveys) aligned with the Technology Acceptance Model (TAM) demonstrated that the program was perceived to be useful, relevant, and easy to use by managers across sectors, organization types, and sizes. We identified positive impacts on manager attitudes and behavioral intentions related to preventing mental ill-health and promoting good mental wellbeing at work. The next step is to explore the feasibility and acceptability of Managing Minds at Work with line managers in diverse employment settings.

Mathematical Model for Computer-Assisted Modification of Medication Dosing Rules.

OBJECTIVE: Medication dosing in pediatrics is complex and prone to errors that may lead to patient harm. To improve computer-assisted dosing, a mathematical model and algorithm were developed to optimize clinical decision support dosing rules and reduce spurious alerts. The objective was to evaluate the feasibility of using this algorithm to adjust dosing rules. MATERIALS AND METHODS: Incorporating historical ordering data, a mathematical model and algorithm were developed to automatically determine optimal dosing rule parameters. The algorithm optimizes the dosing rules by balancing the number of alerts generated for a medication with a minimal length dose interval. In all, 5 candidate medications were tested. An analysis was performed to compare the number of alerts generated by the new model with the current dosing rules. RESULTS: For the 5 medications, the algorithm generated multiple clinically relevant rule possibilities and the rules returned performed as well as current dosing rule or matched historical prescriber behavior. The rules were comparable to or better than the existing system rules in reducing the total alert burden. DISCUSSION: The mathematical model and algorithm are an accurate and scalable solution to adjusting medication dosing rules. They can be implemented to change suboptimal rules more quickly than current manual methods and can be used to help identify and correct poor quality rules. CONCLUSIONS: Mathematical modeling using historic prescribing data can generate clinically appropriate electronic dosing rule parameters. This approach represents an automatable and scalable solution that could help reduce alert fatigue and decrease medication dosing errors.

In vitro comparison of liposomal drug delivery systems targeting the oxytocin receptor: a potential novel treatment for obstetric complications.

INTRODUCTION: Targeted intervention to the uterus has great potential for the treatment of obstetric complications (eg, preterm birth, dysfunctional labor, and postpartum hemorrhage) by improving the effectiveness and safety of therapeutic compounds. In particular, targeting the oxytocin receptor (OTR) is a novel approach for drug delivery to the uterus. The aim of this study was to report the complete data set for the pharmaceutical synthesis and in vitro characterization of PEGylated liposomes conjugated with anti-OTR monoclonal antibodies (OTR-Lipo) or atosiban (ATO-Lipo, OTR antagonist). METHODS: OTR-targeted liposomal platforms composed of 1,2-distearoyl-sn-glycero-2-phosphocholine and cholesterol were prepared according to the method of dried lipid film hydration. Ligands were conjugated with the surface of liposomes using optimized methods to maximize conjugation efficiency. The liposomes were characterized for particle size, ligand conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. RESULTS: Both OTR-Lipo and ATO-Lipo showed significant and specific binding to OTRs in a concentration-dependent manner compared to all control groups. There was no significant difference in binding values between OTR-Lipo and ATO-Lipo across all concentrations evaluated. In addition, OTR-Lipo (81.61%±7.84%) and ATO-Lipo (85.59%±8.28%) demonstrated significantly increased cellular internalization in comparison with rabbit IgG immunoliposomes (9.14%±1.71%) and conventional liposomes (4.09%±0.78%) at 2.02 mM phospholipid concentration. Cellular association following liposome incubation at 4.05 mM resulted in similar findings. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of both liposomal platforms on cell viability. CONCLUSION: This study further supports OTRs as a novel pharmaceutical target for drug delivery. OTR-targeted liposomal platforms may provide an effective way to deliver existing therapies directly to myometrial tissue and avoid adverse effects by circumventing non-target tissues.

Catalytic Synthesis of "Super" Linear Alkenyl Arenes Using an Easily Prepared Rh(I) Catalyst.

Linear alkyl benzenes (LAB) are global chemicals that are produced by acid-catalyzed reactions that involve the formation of carbocationic intermediates. One outcome of the acid-based catalysis is that 1-phenylalkanes cannot be produced. Herein, it is reported that [Rh(µ-OAc)(η2-C2H4)2]2 catalyzes production of 1-phenyl substituted alkene products via oxidative arene vinylation. Since C═C bonds can be used for many chemical transformations, the formation of unsaturated products provides a potential advantage over current processes that produce saturated alkyl arenes. Conditions that provide up to a 10:1 linear:branched ratio have been achieved, and catalytic turnovers >1470 have been demonstrated. In addition, electron-deficient and electron-rich substituted benzenes are successfully alkylated. The Rh catalysis provides ortho:meta:para selectivity that is opposite to traditional acid-based catalysis.

Mechanistic Studies of Single-Step Styrene Production Using a Rhodium(I) Catalyst.

The direct and single-step conversion of benzene, ethylene, and a Cu(II) oxidant to styrene using the Rh(I) catalyst (FlDAB)Rh(TFA)(η2-C2H4) [FlDAB = N,N'-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA = trifluoroacetate] has been reported to give quantitative yields (with Cu(II) as the limiting reagent) and selectivity combined with turnover numbers >800. This report details mechanistic studies of this catalytic process using a combined experimental and computational approach. Examining catalysis with the complex (FlDAB)Rh(OAc)(η2-C2H4) shows that the reaction rate has a dependence on catalyst concentration between first- and half-order that varies with both temperature and ethylene concentration, a first-order dependence on ethylene concentration with saturation at higher concentrations of ethylene, and a zero-order dependence on the concentration of Cu(II) oxidant. The kinetic isotope effect was found to vary linearly with the order in (FlDAB)Rh(OAc)(η2-C2H4), exhibiting no KIE when [Rh] was in the half-order regime, and a kH/kD value of 6.7(6) when [Rh] was in the first-order regime. From these combined experimental and computational studies, competing pathways, which involve all monomeric Rh intermediates and a binuclear Rh intermediate in the other case, are proposed.

Organic chemistry. A rhodium catalyst for single-step styrene production from benzene and ethylene.

Rising global demand for fossil resources has prompted a renewed interest in catalyst technologies that increase the efficiency of conversion of hydrocarbons from petroleum and natural gas to higher-value materials. Styrene is currently produced from benzene and ethylene through the intermediacy of ethylbenzene, which must be dehydrogenated in a separate step. The direct oxidative conversion of benzene and ethylene to styrene could provide a more efficient route, but achieving high selectivity and yield for this reaction has been challenging. Here, we report that the Rh catalyst ((Fl)DAB)Rh(TFA)(η(2)-C2H4) [(Fl)DAB is N,N'-bis(pentafluorophenyl)-2,3-dimethyl-1,4-diaza-1,3-butadiene; TFA is trifluoroacetate] converts benzene, ethylene, and Cu(II) acetate to styrene, Cu(I) acetate, and acetic acid with 100% selectivity and yields ≥95%. Turnover numbers >800 have been demonstrated, with catalyst stability up to 96 hours.

Trapping of embolic particles in a vessel phantom by cavitation-enhanced acoustic streaming.

Cavitation clouds generated by short, high-amplitude, focused ultrasound pulses were previously observed to attract, trap, and erode thrombus fragments in a vessel phantom. This phenomenon may offer a noninvasive method to capture and eliminate embolic fragments flowing through the bloodstream during a cardiovascular intervention. In this article, the mechanism of embolus trapping was explored by particle image velocimetry (PIV). PIV was used to examine the fluid streaming patterns generated by ultrasound in a vessel phantom with and without crossflow of blood-mimicking fluid. Cavitation enhanced streaming, which generated fluid vortices adjacent to the focus. The focal streaming velocity, uf, was as high as 120 cm/s, while mean crossflow velocities, uc, were imposed up to 14 cm/s. When a solid particle 3-4 mm diameter was introduced into crossflow, it was trapped near the focus. Increasing uf promoted particle trapping while increasing uc promoted particle escape. The maximum crossflow Reynolds number at which particles could be trapped, Rec, was approximately linear with focal streaming number, Ref, i.e. Rec = 0.25Ref + 67.44 (R(2) = 0.76) corresponding to dimensional velocities uc = 0.084uf + 3.122 for 20 < uf < 120 cm/s. The fluidic pressure map was estimated from PIV and indicated a negative pressure gradient towards the focus, trapping the embolus near this location.

A poroelastic model describing nutrient transport and cell stresses within a cyclically strained collagen hydrogel.

In the creation of engineered tissue constructs, the successful transport of nutrients and oxygen to the contained cells is a significant challenge. In highly porous scaffolds subject to cyclic strain, the mechanical deformations can induce substantial fluid pressure gradients, which affect the transport of solutes. In this article, we describe a poroelastic model to predict the solid and fluid mechanics of a highly porous hydrogel subject to cyclic strain. The model was validated by matching the predicted penetration of a bead into the hydrogel from the model with experimental observations and provides insight into nutrient transport. Additionally, the model provides estimates of the wall-shear stresses experienced by the cells embedded within the scaffold. These results provide insight into the mechanics of and convective nutrient transport within a cyclically strained hydrogel, which could lead to the improved design of engineered tissues.

Parallel EPI artifact correction (PEAC) for N/2 ghost suppression in neuroimaging applications.

Echo Planar Imaging (EPI) is a neuroimaging tool for clinical practice and research investigation. Due to odd-even echo phase inconsistencies, however, EPI suffers from Nyquist N/2 ghost artifacts. In standard neuroimaging protocols, EPI artifacts are suppressed using phase correction techniques that require reference data collected from a reference scan. Because reference-scan based techniques are sensitive to subject motion, EPI performance is sub-optimal in neuroimaging applications. In this technical note, we present a novel EPI data processing technique which we call Parallel EPI Artifact Correction (PEAC). By introducing an implicit data constraint associated with multi-coil sensitivity in parallel imaging, PEAC converts phase correction into a constrained problem that can be resolved using an iterative algorithm. This enables "reference-less" EPI that can improve neuroimaging performance. In the presented work, PEAC is investigated using a standard functional magnetic resonance imaging (fMRI) protocol with multi-slice 2D EPI. It is demonstrated that PEAC can suppress ghost artifacts as effectively as the standard reference-scan based phase correction technique used on a clinical MRI system. We also found that PEAC can achieve dynamic phase correction when motion occurs.

A mechanochemical model of striae distensae.

Striae distensae, otherwise known as stretch marks, are common skin lesions found in a variety of clinical settings. They occur frequently during adolescence or pregnancy where there is rapid tissue expansion and in clinical situations associated with corticosteroid excess. Heralding their onset is the appearance of parallel inflammatory streaks aligned perpendicular to the direction of skin tension. Despite a considerable amount of investigative research, the pathogenesis of striae remains obscure. The interpretation of histologic samples - the major investigative tool - demonstrates an association between dermal lymphocytic inflammation, elastolysis, and a scarring response. Yet the primary causal factor in their aetiology is mechanical; either skin stretching due to underlying tissue expansion or, less frequently, a compromised dermis affected by normal loads. In this paper, we investigate the pathogenesis of striae by addressing the coupling between mechanical forces and dermal pathology. We develop a mathematical model that incorporates the mechanical properties of cutaneous fibroblasts and dermal extracellular matrix. By using linear stability analysis and numerical simulations of our governing nonlinear equations, we show that this quantitative approach may provide a realistic framework that may account for the initiating events.

Bis(4-methyl-N-{(2Z,4E)-4-[(4-methyl-phen-yl)imino]-pent-2-en-2-yl}anilinido)zinc.

The title compound, [Zn(C(19)H(21)N(2))(2)], appears to be the first example of a zinc complex supported by two ß-diketiminate (nacnac) ligands. This complex crystallizes with a distorted tetra-hedrally coordinated Zn(II) atom that diposes the two nacnac ligands approximately orthogonally to one another [angle between the two N-Zn-N mean planes is 89.91 (10)°], with average Zn-N bond lengths of 1.992 (4) Å.

Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.

Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings.

The influence of fluid flow on modeling quorum sensing in bacterial biofilms.

In this paper, we study quorum sensing in Pseudomonas aeruginosa biofilms. Quorum sensing is a process where bacteria monitor their population density through the release of extra-cellular signalling molecules. The presence of these molecules affects gene modulation leading to changes in behaviour such as the release of virulence factors. Here, we use numerical methods to approximate a 2-D model of quorum sensing. It is observed that the shape of the biofilm can have a profound effect on the onset of quorum sensing. This has serious repercussions for experimental observations since biofilms of the same biomass but different shapes can produce quite different results.

Modeling the skin pattern of fishes.

Complicated patterns showing various spatial scales have been obtained in the past by coupling Turing systems in such a way that the scales of the independent systems resonate. This produces superimposed patterns with different length scales. Here we propose a model consisting of two identical reaction-diffusion systems coupled together in such a way that one of them produces a simple Turing pattern of spots or stripes, and the other traveling wave fronts that eventually become stationary. The basic idea is to assume that one of the systems becomes fixed after some time and serves as a source of morphogens for the other system. This mechanism produces patterns very similar to the pigmentation patterns observed in different species of stingrays and other fishes. The biological mechanisms that support the realization of this model are discussed.

Influence of the hydrodynamic environment on quorum sensing in Pseudomonas aeruginosa biofilms.

We provide experimental and modeling evidence that the hydrodynamic environment can impact quorum sensing (QS) in a Pseudomonas aeruginosa biofilm. The amount of biofilm biomass required for full QS induction of the population increased as the flow rate increased.