Introduction Regenerative solutions of the skin represent a hope for burn victims with extensive skin loss and chronic wound patients. The development of xeno-free workflow is crucial for clinical application in compliance with the directives of the European Medicines Agency. This study aimed at evaluating the outcome of the xeno-free isolation workflow of keratinocytes from human skin biopsy. Methods Skin biopsies were obtained from volunteers. The epidermis was digested with TrypLE™ Select, which was deactivated by dilution or with trypsin, deactivated by media with fetal bovine serum. Freshly isolated cells were compared for total cell number, viability, activity of caspase 3, gene expression and the presence of the keratinocyte surface markers cytokeratin 14. The cells were cultured in xeno-free conditions for one week and characterized regarding the number and viability as well as the metalloproteinase secretion. Results The number of obtained cells was similar in both workflows. The cell viability was less in the TrypLE group, with slight reduction of the cell surface marker cytokeratin 14. Caspase 3 activity was comparable as well as the gene expression of the apoptotic markers BAX, BCL2 and SLUG, as well as the keratinocyte markers cytokeratin 14, stratifin and filaggrin. Upon culture, the number of keratinocytes, their viability and secretion of matrix metalloproteinases 1 and 10 were equal in both groups. Conclusion This study reports the possibility of isolating functioning and viable keratinocytes through a xeno-free workflow for clinical application.

The rules governing Medicinal Products in the European Union necessitates the production of cell-based therapy in good manufacturing practice facilities. The produced cells may need several hours in transportation to reach the application sites. In this study, we investigated four candidate solutions for transporting human keratinocytes. The solutions are (1) normal saline, (2) saline with 2.5% human serum albumin (Saline + HSA), (3) chemically defined, xeno-free keratinocyte media and (4) keratinocyte media with pituitary bovine extract (PBE-media). One million keratinocytes from three donors were suspended in each solution and kept at 4 °C for up to 24 h. Cells kept in Saline + HSA showed higher viability after 1, 3 and 24 h. Then, equal number of viable cells were seeded on collagenous matrix and cultured for 48 h. The adhesion and colonization were higher in the cells kept in PBE-media, while the keratinocyte surface marker, cytokeratin 14, was present in all studied groups. These results confirmed the suitability of Saline + HSA as a cell transportation solution for clinical use, which will be the choice for the planned clinical trial. Keratinocyte PBE-media can be an alternative for cells transported for research purpose, if the same media type is going to be used in the following experiments.

Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip(R) miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1 alpha) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1 alpha overexpression through four isomers of miR-30-5p and miR-181a-5p.

Gestational diabetes mellitus (GDM) is a common complication with negative impacts on mother and child. The primary aim of this study was to examine whether plasma glucose cutoffs for GDM diagnosis based on venous sampling can be replaced by cutoffs based on capillary sampling. A prospective cross-sectional study was performed at an antenatal care clinic including 175 pregnant women undergoing an oral glucose tolerance test (OGTT). Duplicate samples were collected by capillary and venous puncture while fasting and 1 h and 2 h after an OGTT. Both samples were analyzed on Accu-Chek Inform II. The cutoffs for a GDM diagnosis using capillary samples were corrected from 5.1 to 5.3 mmol/L for the fasting sample, from 10.0 to 11.1 mmol/L for the 1 h sample, and from 8.5 to 9.4 mmol/L for the 2-h sample using half of the dataset. Applying these cutoffs to the remaining dataset resulted in a sensitivity, specificity, and accuracy of 85.0%, 95.0%, and 90.3%, respectively, with a positive predictive value (PPV) of 83%, an negative predictive value (NPV) of 96%, and a positive negative likelihood ratio (LHR) of 16.4 using capillary sampling for the GDM diagnosis at fasting and 2-h after. Corrected cutoffs and capillary samples can be used for the diagnosis of GDM with maintained diagnostic accuracy using Accu-Chek Inform II.

IntroductionWomen with gestational diabetes mellitus (GDM) have higher rates of adverse perinatal outcomes compared with women without GDM, including an increased risk for having labor induced and for cesarean section. The findings from previous studies analyzing duration of labor in women with GDM are contradictory.The aim of the study was to evaluate the impact of GDM on time in spontaneous and induced active labor. Material and methodsThis was a population-based cohort study including 247 524 primiparous women who gave birth to a singleton fetus with cephalic presentation, >= 34(+0) (completed gestational weeks + additional days) between January 2014 and May 2020 in Sweden. Data was obtained from the Swedish Pregnancy Register. Time in active labor was compared between women with GDM and without GDM with a spontaneous labor onset or induction of labor using Kaplan Meier survival analysis and Cox regression analysis. ResultsWomen with GDM had significantly longer time in active labor, both with a spontaneous onset and induction of labor compared to women without GDM. Women with GDM had a decreased chance of vaginal delivery at a certain time-point compared to women without GDM, with adjusted hazard ratio of 0.92 (0.88-0.96) and 0.83 (0.76-0.90) for those with spontaneous onset and induction of labor, respectively. Women with GDM had increased risk for time in active labor >= 12 h both in spontaneous labor onset (adjusted odds ratio 1.14 [1.04-1.25]) and in induction of labor (adjusted odds ratio 1.55 [1.28-1.87]). ConclusionsWomen with GDM seem to spend a longer time in active labor, both in spontaneous and induced active labor compared to women without GDM. To be able to individualize care intrapartum, there is a need for more studies demonstrating the impact of hyperglycemia during pregnancy on outcomes during childbirth.

We investigate strategies for management of conflicts among autonomous unmanned aerial vehicles (UAVs) in high-density very low level (VLL) uncontrolled airspace. We consider deconfliction procedures which do not involve horizontal maneuvers, and study two types of airspace structure: single- and multi-layered airspace. We compare different deconfliction paradigms by simulating a busy day of operations over a geographical area. Our main contributions are a proposal of new deconfliction schemes for UAVs and an assessment of the single- and multi-layered airspace designs. Our work aims to provide regulators and policy-makers with a framework for choosing between resolution strategies for the airspace management.

We study separating urban unmanned aerial vehicles (UAV) traffic into altitude levels, using a PBN-inspired approach in which low-density airspace has few layers while congested areas in the city center are split into a larger number of layers. Navigating in the many-layers environment may require better vehicle equipage to support higher performance in terms of altimetry precision; our work thus follows the stakeholders encouragements to use performance-based navigation (PBN) in UAV traffic management (UTM). We present results for several traffic volume scenarios over Norrköping municipality in Sweden, demonstrating applicability of our solutions in a city setting.

We give algorithms for splitting a geographical region into ”approximately flat” rectangular zones. Each zone is assigned a feasible flight altitude, providing simple flight level guidance for future operations of unmanned aerial systems in low-level airspace. We consider a rural scenario with uneven ground level and an urban setting featuring many tall structures. In both cases, our solutions adapt to the underlying terrain or city landscape. In the rural scenario, operating on a fixed altitude within a rectangle allows the drone to stay within the upper limit of 120m while not flying too close to the ground; our objective is to minimize the complexity of the airspace. In the urban case, we aim at minimizing the volume of airspace reserved for drone operations, while allowing overflight over tall buildings in the city. Experiments with real landscape and city skyline data demonstrate output of our solutions with various input parameters.

This paper explores tradeoffs between ground impact and efficiency of drone flights in urban scenarios. We give an algorithm which produces a set of routes with different lengths and varying number of people affected by the drone. We also present an interactive online visualization tool allowing the user to modify flightpaths in order to explore routing options. Our path finder and the GUI are implemented for a metropolitan area of Norrköping municipality in Sweden. The methods studied in this paper may give UTM service provider the tools to negotiate flightplans which will be acceptable by both the regulator and the drone operator.

We extend the classical SIR epidemic spread model by introducing the "quarantined" compartment. We solve (numerically) the differential equations that govern the extended model and quantify how quarantining "flattens the curve" for the proportion of infected population over time. Furthermore, we explore the potential of using drones to deliver tests, enabling mass-testing for the infection; we give a method to estimate the drone fleet needed to deliver the tests in a metropolitan area. Application of our models to COVID-19 spread in Sweden shows how the proposed methods could substantially decrease the peak number of infected people, almost without increasing the duration of the epidemic.

It is likely that different industrial symbiosis collaborations will have different sets of winners and losers when it comes to benefits or costs. In this study we present an analytical framework intended for evaluating a wide-range of industrial symbiosis outcomes that will aid in research design. The framework provide a base for including a broader, but also, specific set of effects and outcomes (economic, environmental and social), including a diverse set of clearly defined actors. Used consistently, the framework can average out costs and benefits across actors in the whole society, so that each actor is more likely to (over time) realize net positive outcomes from a full set of industrial symbiosis applications. The analytical framework is developed by combining theory and concepts from the system of national accounts, the planetary boundaries, and the social foundation. The analytical framework is then applied in a state of the art review, analysing value and benefits in 56 industrial symbiosis research articles. Besides providing a robust model for analysing industrial symbiosis, the results show that private market-based outcomes are the dominant form of economic value and that nonmarket valuations are completely absent. Environmental outcomes mainly consist of decreased CO2 emissions, chemical pollution and water use. Social outcomes include private income and work and network effects for the companies involved in the industrial symbiosis.

Circular water management has the potential to close resource and material loops within and across value chains. In the water industry, circular municipal wastewater management through industrial urban symbiosis (IUS) is recognized as a solution to overcome water scarcity in urban environments. IUS involves collaboration between actors with different organizational backgrounds, which can lead to inherent risks of conflicting goals. This study explores how different values drive various organizations to participate in an emerging circular wastewater collaboration. The study comprises a literature review of 34 scientific articles and a case study of a potential circular wastewater system through IUS in Simrishamn, Sweden. It presents an interdisciplinary framework based on the total economic value concept and organizational archetypes for examining actor values in circular wastewater management. This framework provides a novel approach for assessing different values and how they may compete or align. It can also identify the absence of certain values, enabling the achievement of a minimum level of value coherence amongst different actors, and thereby increasing the sustainability and effectiveness of circular wastewater collaborations. Therefore, careful planning and stakeholder interaction, in accordance with economic value perspectives, can enhance the legitimacy and policy development of circular solutions.

Developing sustainable energy systems through system integration and sector coupling may involve permeating previous isolated and idiosyncratic reactions through the whole system. This study examines supply side dynamics of how uncertainty and spot prices influence electric power supply in an internationally connected electricity system. By applying quantile methods, the study reveals highly nonlinear and asymmetric responses in supplied electricity given a change in uncertainty or system spot prices. The findings show that while the total supply of electricity is largely unaffected by uncertainty and spot price, both supply level and changes in power supply for specific dispatchable power sources are influenced differently depending on the type of uncertainty (domestic or global). The findings also show that the response structure induced by uncertainty and spot price seems to be largely uniform and power source specific. This has implications for creating, amongst other things, integrated systems, and sector coupling, where there is a need for inexpensive excess power supply. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

_{This study aims to provide insights into the factors shaping electricity demand in Swedish industrial sectors using the nonlinear version of the autoregressive distributed lag model (NARDL). This approach captures the complex short- and long-run relationships between uncertainty and electric power use in Swedish industrial sectors. The results reveal sector-specific responses to uncertainties and asymmetries in electricity use patterns. By examining the entire industrial sector in Sweden, this approach uncovers underlying issues and hidden patterns, while also providing insights into the functioning and behaviour of industrial systems. The rapid electrification and new green industrialisation initiatives in Sweden, coupled with the integration of a circular economy, underscore the importance of understanding the dynamics of electricity use in the face of uncertain shocks. This knowledge is vital for ensuring, amongst other things, grid stability, mitigating the need for costly peaking capacity, and identifying potential challenges in the interconnection of energy and material circular flows}

The availability of digital tablets in preschools has increased significantly in recent years. Literature suggests that these tools can enhance students’ literacy and collaborative skills. As society becomes increasingly digitized, preschool curriculum reform also emphasises the subjects of technology and science as priority areas of learning. Teachers’ knowledge and experiences are of utmost importance in carrying out this mandate. Few studies have explored the use of digital tablets to teach preschool technology and science in Sweden, and there is an urgent need to ascertain the role of digital aids as teaching tools. This survey study seeks to determine how digital tablets are used to support preschool children’s learning in general, and with respect to technology education. Preschool educators (n = 327) across Sweden responded to an online survey consisting of 20 closed and 6 open items that probed the use of digital tablets. Survey results revealed a high degree of engagement with digital tablets in preschools, with activities directed toward various subject-related, social and generic skills. Programming, invention, construction and creation, problem-solving, and design emerged saliently as tablet activities in technology subject areas. Opportunities for providing meaningful learning tasks and digital adaptability were seen as pedagogical benefits of using tablets, but increasing expectations to integrate tablet activities with an accompanying lack of digital skills were expressed as limitations. Teachers’ recommendations for future tablet use included defining clearer curriculum guidelines for tablet implementation and adequate training for acquiring digital competence.

Modern preschool education is seen as an essential foundation for nurturing children’s digital literacy. Early childhood education environments have witnessed increased emphasis on integrating programming activities in combination with digital tablets. However, little is known about how preschool teachers implement programming as part of pedagogical strategies during practice. In Sweden, although there is a mandate to develop children’s understanding of the digital world, programming is not formally mentioned in the revised preschool curriculum. This study systematically investigates how Swedish preschool teachers implement programming activities in their teaching practice. Data was collected through a national online survey (n = 199). Findings revealed a range of apps and resources used in combination with tablets, where activity integration takes place as unplugged programming, digital programming, or as a combination of the former. Teachers markedly attributed intended learning goals around programming to tenets of computational thinking and “twenty-first century skills”. Moreover, programming was often actively linked to learning in other domains such as science, technology, mathematics, and language, approaches that show traditional Swedish preschool teaching practices being recontextualized in terms of programming. Based on the reported findings that provide insight into the implementation of programming in preschools, a logical future research avenue lies in exploring the documented programming activities from the perspective of the children.

Swedish preschool science practice is confined to a unique educational setting where upbringing, care, and education are intertwined. This allows teachers to develop innovative cross-curricular and multidimensional science teaching. At the same time, society demands the digitalization of preschool practice, which has caused concern not only about negative effects on children’s well-being but also the risk of foregrounding digital over analog tools in multidimensional and child-centered preschool practice. The aim of this study is to analyze how preschool teachers at the forefront of digitalization integrate digital and analog tools when teaching science and how this integration affects their practice. The data comprises documentation of digitalized science activities provided by ten preschool teachers and transcribed recall interviews with four of the teachers. Thematic content analysis and a framework for analyzing seven teaching dimensions of preschool science revealed the use of digital and analog tools as drivers for multidimensional science education. The findings show that the teachers primarily use digital tools to reinforce social learning, inclusion, and agency during science activities. Digital and analog tools were used to complement one another in pursuing the boundaries of multidimensional science. However, the content of this innovative and digitalized science teaching remained primarily within biology, the traditional scholarly discipline in preschool science. We conclude that the digitalization of preschool science seems to be used to strengthen and diversify teaching within the boundaries of overarching traditional preschool practice where nature encounters and children’s interests and well-being are at the forefront. 

Purpose Following the recent surge in research on carsharing, the paper synthesizes this growing literature to provide a comprehensive understanding of the current state of research and to identify directions for future work. Specifically, this study details implications for service theory and practice. Design/methodology/approach Systematic selection and analysis of 279 papers from the existing literature, published between 1996 and 2020. Findings The literature review identified four key themes: business models, drivers and barriers, customer behavior, and vehicle balancing. Practical implications For managers, the study illuminates the importance of collaboration among stakeholders within the automotive sector for purposes of widening their customer base and maximizing utilization and profits. For policy makers, their important role in supporting carsharing take-off is highlighted with emphasis on balancing support rendered to different mobility services to promote mutual success. Originality/value This is the first systematic multi-disciplinary literature review of carsharing. It integrates insights from transportation, environmental, and business studies, identifying gaps in the existing research and specifically suggesting implications for service research.

The last decade has brought the transport sector to the forefront of discussions on sustainability and digital innovations: practitioners, researchers, and regulators alike have witnessed the emergence of a wide diversity of shared mobility services. Based on a longitudinal case study of a regional Mobility-as-a-Service (MaaS) ecosystem in Sweden, constituted of a document analysis and 24 semi-structured interviews with 18 representatives from regional authorities, mobility service providers, and other stakeholders from the public and private sectors, this study examines the co-existing and competing institutional logics at play, identified as State logic, Market logic, Sustainability logic, Experimental logic, and Service logic. The analysis reveals that these institutional logics pertain to tensions in the collaboration within the ecosystem’s stakeholders in terms of: (1) finding a common vision and scope for MaaS, (2) establishing a sustainable business model, (3) triggering a behavioral change regarding car travel, (4) being able to find one’s role within the project and to consequently collaborate with other stakeholders, and (5) managing uncertainty through testing and experimenting innovative solutions, which ultimately yielded key learnings about MaaS and the shared mobility ecosystem and its stakeholders. These case study findings, based on an institutional logics framework, provide a novel perspective on emerging ecosystems, from which implications for MaaS developers and further research on shared mobility are drawn.

The Cauchy problem for general elliptic equations of second order is considered. In a previous paper (Berntsson et al. in Inverse Probl Sci Eng 26(7):1062–1078, 2018), it was suggested that the alternating iterative algorithm suggested by Kozlov and Maz’ya can be convergent, even for large wavenumbers k², in the Helmholtz equation, if the Neumann boundary conditions are replaced by Robin conditions. In this paper, we provide a proof that shows that the Dirichlet–Robin alternating algorithm is indeed convergent for general elliptic operators provided that the parameters in the Robin conditions are chosen appropriately. We also give numerical experiments intended to investigate the precise behaviour of the algorithm for different values of k² in the Helmholtz equation. In particular, we show how the speed of the convergence depends on the choice of Robin parameters.

We consider the Cauchy problem for the Helmholtz equation with a domain in with N cylindrical outlets to infinity with bounded inclusions in . Cauchy data are prescribed on the boundary of the bounded domains and the aim is to find solution on the unbounded part of the boundary. In 1989, Kozlov and Mazya proposed an alternating iterative method for solving Cauchy problems associated with elliptic, selfadjoint and positive-definite operators in bounded domains. Different variants of this method for solving Cauchy problems associated with Helmholtz-type operators exists. We consider the variant proposed by Berntsson, Kozlov, Mpinganzima and Turesson (2018) for bounded domains and derive the necessary conditions for the convergence of the procedure in unbounded domains. For the numerical implementation, a finite difference method is used to solve the problem in a simple rectangular domain in R-2 that represent a truncated infinite strip. The numerical results shows that by appropriate truncation of the domain and with appropriate choice of the Robin parameters mu(0) and mu(1), the Robin-Dirichlet alternating iterative procedure is convergent.

We consider an inverse problem for the Helmholtz equation of reconstructing a solution from measurements taken on a segment inside a semi-infinite strip. Homogeneous Neumann conditions are prescribed on both side boundaries of the strip and an unknown Dirichlet condition on the remaining part of the boundary. Additional complexity is that the radiation condition at infinity is unknown. Our aim is to find the unknown function in the Dirichlet boundary condition and the radiation condition. Such problems appear in acoustics to determine acoustical sources and surface vibrations from acoustic field measurements. The problem is split into two sub-problems, a well-posed and an ill-posed problem. We analyse the theoretical properties of both problems; in particular, we show that the radiation condition is described by a stable non-linear problem. The second problem is ill-posed, and we use the Landweber iteration method together with the discrepancy principle to regularize it. Numerical tests show that the approach works well.

In visually demanding environments like working positions in air traffic control, there is a risk of missing important information. Attention support might help to reduce this, but there is a risk that it introduces new issues in the form of distractions or increased visual load. The work presented in this paper explores the concept of Soft Visual Cues, with the aim to make the operator aware of missing information, but doing it discreetly enough only to be noticed when the operator is scanning the area where the information is present, thereby complementing the concepts of attention guidance, alarms, and subtle gaze direction. The qualitative evaluation performed aimed primarily at catching the operators (air traffic controllers) first impressions. Focus was on air traffic control, but was complemented with vessel traffic service and train control environments and operators. The results from air traffic control showed a preference for symbol property changes related to geometry rather than for colour or opacity changes as soft visual cues. The comparison to the other domains highlighted the contextual dependence, visual context and process context, of the concept.

Lack of support for handling a reduction of autonomy in a highly autonomous automation may lead to a stressful situation for a human when forced to take over. We present a design approach, the Reduced Autonomy Workspace, to address this. The starting point is that the human and the automation work together in parallel control processes, but at different levels of autonomy cognitive control, such as setting goals or implementing plans, which is different from levels of automation. When autonomy is reduced, the automation should consult the human by providing information that has been aligned to the level at which the human is working, and the timing of the provision should be adapted to suit the humans work situation. This is made possible by allowing the automation to monitor the human in a separate process. The combination of these processes, information level alignment and timing of the presentation, are the key characteristics of the Reduced Autonomy Workspace. The Reduced Autonomy Workspace consists of four phases: Identification of the need; evaluation of whether, and, if so, when, and how to present information; perception and response by the human; implementation of a solution by the automation. The timing of the information presentation should be adapted in real-time to provide flexibility, while the level of the information provided should be tuned offline and kept constant to provide predictability. Use of the Reduced Autonomy Workspace can reduce the risk for surprising, stressful hand-over situations, and the need to monitor the automation to avoid them.

Based on Swedish National Registry Data, this paper investigates the social structure of exclusion risks in late working life in Sweden by analyzing exit from working life, employment breaks, and late employment trajectories according to gender and education. Individuals born in 1950 (n = 107,830) are followed between the years 2010 and 2018. Results show that women with low education exit working life earlier and have a higher risk of employment breaks due to reduced working ability, while men with low education have a higher risk of employment breaks due to unemployment. Men in general and people with high education have a higher probability of moving to self-employment in late working life. We conclude that research and social policies require an understanding of multifarious late work trajectories to unearth the inequality of exclusion risks in the late phases of working life and the potential for interventions towards equal and inclusive prolongation.

Purpose In this paper, the authors attempt to understand how labour market attachment during the ages of 30–59 influences individuals' transition out of the labour market. Design/methodology/approach Using high-quality Swedish register data, the authors follow individuals born in 1950 and observe their labour market attachment during mid-life and their exit from the labour market. Findings The authors find evidence that labour market attachment in different stages of the career is differently related to exit from the labour market. At the age of 30, as well as between the ages 50–59, low attachment is related with earlier exit from the labour market. On the contrary, low labour market attachment during the ages 40–49 is related with later exit from the labour market. However, regardless of age, lower labour market attachment increases the risk of work-related benefit receipt in the exit year. The authors also find evidence that gender, migration status and childhood socioeconomic disadvantages may represent obstacles to longer working lives, while high education is a consistent factor in avoiding early exit from the labour market. Originality/value This study provides insights on the link between labour market attachment in different stages of the career and the exit from the labour market as well as work-related benefits dependency in the year of exit.

Microplastics (plastic particles < 5 mm) is a pollution of growing concern. Microplastic pollution is a complex issue that requires systematic attempts to provide an overview and avoid management solutions that have marginal effects or only move the pollution problem. Substance flow analysis (SFA) has been proposed as a useful tool to receive such an overview and has been put forward as valuable for substance management. However, as the research on microplastics has only emerged recently, detailed and reliable SFAs are difficult to perform. In this study, we use three SFA studies for three pollutants (cadmium, copper and pharmaceuticals) to compare flows and strategies to control the flows. This in order to seek guidance for microplastic management and evaluate potential strategies for controlling microplastics. The analysis shows that there has been rigorous control on different levels to abate pollution from cadmium, copper and pharmaceuticals, but where in the system the major control measures have been carried out differ. For microplastics, there are many potential solutions, both in terms of preventive actions and treatment depending on the type of source. When forming management plans for microplastics, the responsibility for each measure and the impact on the whole urban system should be taken into consideration as well as which receiving compartments are particularly valuable and should be avoided.

Microplastics are omnipresent in the environment, and wastewater treatment plants (WWTPs) have been highlighted as a transport pathway. The aim of this study is to contribute to increased understanding of microplastic sources in wastewater and test the possibilities of source tracking. Previous research has focused either on estimating microplastic contribution from various sources or on quantifying occurrence based on measurements. In this paper, these two approaches are compared. Microplastic types detected in the influent to a WWTP in Sweden are compared with estimations of sources in the WWTP catchment area. The total load from the identified sources was estimated to 1.9-14 tonnes/year, and the measurement-based load was 4.2 tonnes/year. In general, there was a good agreement between the two approaches; microplastic types with large shares at the inlet also had large contributions in the source estimates. An exception was cellulose acetate, which was not found at the inlet despite a large theoretical contribution. Many uncertainties remain, which lead to large intervals for the source estimates. The comparison can give an indication into which part of the intervals is most likely. Investigating more WWTPs with different characteristics and including particle morphology will further increase the understanding of sources that contribute to the presence of microplastics in wastewater.

Wastewater treatment plants (WWTPs) are not designed to handle many harmful substances that are present in the wastewater. The substances can also be transferred to the sewage sludge, which can make it unsuitable as a fertiliser. To alleviate these problems, Sweden has a practice called upstream work (uppstromsarbete) that aims to prevent harmful substances from entering the wastewater via efforts to control the pollution closer to the source. Upstream work has produced positive results in terms of reduced pollution in water and sludge and is seen as an important practice by both practicians and policymakers. In this paper, we investigate the incentives and challenges for upstream work as experienced by practitioners at municipal water utilities. The results show that there are two types of incentives: one related to practical problems and the other related to a perceived responsibility for the wastewater system and for the environment. The challenges were primarily related to an insufficient organisational structure for upstream work, manifested in unclear responsibilities, lack of prioritisation, and insufficient resources. The findings can be used to expand and initiate pollution control upstream of the WWTP as part of the urban water management, as well as decision support for policymakers.

Laughter is a mundane phenomenon that is ubiquitous in social life. This chapter examines young children’s laughter, specifically focusing on the calibration of shared laughter as it typically occurs in multiparty interactions. It discusses?children’s interactional competences in calibrating emotional stances and affiliation. The analysis takes into account the multimodal features that characterise situations of reciprocal laughter, contributing to the understanding of laughter as a fully embodied social phenomenon. It shows that laughter was interactionally accomplished in ways that established affiliation between a group or a dyad of children. The establishment of mutual gaze was important in initiating, reciprocating and sustaining shared emotional stance through the performance?of laughter. The embodied calibration of the children’s shared stance shows that laughter is used in the establishment of affiliation and rapport. Young children’s situated humor and ‘funniness’ is thus clearly a joint, shared interactional and social – dyadic or multiparty – accomplishment.

The present study addresses young childrens (three-to five-year-olds) peer interactions and explores a recurrent interactional genre, i.e. childrens affectively heightened attention-organizing practices used when initiating an exchange in preschool interactions in Sweden. The data consists of 40 h of video recordings collected in two regular pre-schools in Sweden. By using Multimodal Interaction Analysis (Goodwin, 2000) of video -recordings from everyday activities, we examine the verbal, embodied and material fea-tures of childrens interactions. The analysis shows that children exploited common access to objects or physical personal attributes within their socio-material environment and relied on them to secure the others attention, while using various methods for making the object noteworthy. By indexing their affective stance towards the referent, the children created the interpretative framework for the recipients response. However, the recipients orientation and stance alignment were not to be presumed. The peer responses comprised a continuum of their affective engagement: the children aligned with or downplayed the prior speakers stance through the affective quality of their response. In all, detailed interactional analysis reveals the young childrens interactional repertoires and the communicative challenges associated with childrens peer interactions.

BACKGROUND: The links between chronic illness, psychological well-being, and social support have previously been established. Social isolation and loneliness have shown an increased mortality risk for those with heart failure (HF). Increasingly more people with HF are living with an implantable cardioverter defibrillator (ICD), but only a few small-scale studies have focused on social support in this population.

OBJECTIVE: The aim of this study was to explore factors related to perceived social support in a large cohort of individuals with HF living with an ICD.

METHODS: All eligible adult ICD recipients in the Swedish ICD registry were invited to participate in this cross-sectional study. For this analysis, those with HF and complete data on perceived social support were included (N = 1550; age, 67.3 (SD, 9.8) years; 19.5% female).

RESULTS: Most reported a high level of social support, but 18% did not. In logistic regression, living alone was the greatest predictor of low/medium support. Lower social support for those living alone was associated with poorer perceived health status, having symptoms of depression, and experiencing low perceived control. For those living with someone, lower support was associated with female gender, symptoms of depression and anxiety, and less control. Heart failure status and perceived symptom severity were not related to the outcome.

CONCLUSION: One in five participants reported low/medium social support. Our study underlines the complex relationships between perceived social support, psychological well-being and perceived control over the heart condition. Multiple aspects need to be taken into account when developing interventions to provide psychosocial support and optimize outcomes in this patient group.

Background: Heart failure (HF) affects not only the person diagnosed with the syndrome but also family members, who often have the role of informal carers. The needs of these carers are not always met, and information and communications technology (ICT) could have the potential to support them in their everyday life. However, knowledge is lacking about how family members perceive ICT and see opportunities for this technology to support them. Objective: The aim of this study was to explore the perceptions of ICT solutions as supportive aids among family members of persons with HF. Methods: A qualitative design was applied. A total of 8 focus groups, comprising 23 family members of persons affected by HF, were conducted between March 2015 and January 2017. Participants were recruited from 1 hospital in Sweden. A purposeful sampling strategy was used to find family members of persons with symptomatic HF from diverse backgrounds. Data were analyzed using qualitative content analysis. Results: The analysis revealed 4 categories and 9 subcategories. The first category, about how ICT could provide relevant support, included descriptions of how ICT could be used for communication with health care personnel, for information and communication retrieval, plus opportunities to interact with persons in similar life situations and to share support with peers and extended family. The second category, about how ICT could provide access, entailed how ICT could offer solutions not bound by time or place and how it could be both timely and adaptable to different life situations. ICT could also provide an arena for family members to which they might not otherwise have had access. The third category concerned how ICT could be too impersonal and how it could entail limited personal interaction and individualization, which could lead to concerns about usability. It was emphasized that ICT could not replace physical meetings. The fourth category considered how ICT could be out of scope, reflecting the fact that some family members were generally uninterested in ICT and had difficulties envisioning how it could be used for support. It was also discussed as more of a solution for the future. Conclusions: Family members described multiple uses for ICT and agreed that ICT could provide access to relevant sources of information from which family members could potentially exchange support. ICT was also considered to have its limitations and was out of scope for some but with expected use in the future. Even though some family members seemed hesitant about ICT solutions in general, this might not mean they are unreceptive to suggestions about their usage in, for example, health care. Thus, a variety of factors should be considered to facilitate future implementations of ICT tools in clinical practice.

Aim To describe the co-designing process of an online support programme with and for informal carers of people with heart failure.Design A co-design process built on core concepts and ideas embedded in co-design methodology.Data sources Our co-design process included three phases involving 32 informal caregivers and 25 content creators; (1) Identification of topics and content through literature searches, focus group interviews and user group sessions; (2) Development of the online support programme and; (3) Refinement and finalization which included testing a paper prototype followed by testing the online version and testing and approval of the final version of the support programme.Outcomes The co-design process resulted in a support programme consisting of 15 different modules relevant to informal carers, delivered on a National Health Portal.Conclusion Co-design is an explorative process where researchers need to balance a range of potentially conflicting factors and to ensure that the end users are genuinely included in the process.Relevance to clinical practice Emphasizing equal involvement of end users (e.g. carers or patients) in the design and development of healthcare interventions aligns with contemporary ideas of person-centred care and provides a valuable learning opportunity for those involved. Furthermore, a co-designed online support programme has the capacity to be both accessible and meet end users information and support needs, thereby optimizing their self-care abilities. Additionally, an online support programme provides the opportunity to address current challenges regarding scarce resources and the lack of healthcare personnel.Reporting methods Consolidated criteria for reporting qualitative research (COREQ).Patient or public contribution Both informal carers and content creators were involved in developing the support programme.

Elderspeak refers to adapting ones language to a perceived language decline of an older interlocutor. Earlier studies have explored different features of elderspeak; some of these studies attribute positive outcomes to using elderspeak that facilitates communication, but other studies consider elderspeak a negative way of communicating that should be avoided. The aim of this study is to investigate a largely unexplored feature of elderspeak, namely sound prolongation in a multilingual context. There are five participants in this study: three carers and two care recipients in a residential care unit. The carers and care recipients have limited access to a shared spoken language. The data consist of video- and audio recordings of interaction between the participants. The recordings have been transcribed and analysed in accordance with Conversation Analytical methodology. The analysis shows that the carers use sound prolongation as part of their interactional repertoire in order to manage situations of distress. We conclude that in some distressful situations carers use of sound prolongation may help mitigating the care recipients emotional concerns since the source of agitations has been addressed properly. In other situations, the use of sound prolongation may lead to an escalation in distress, if the source of agitation is not addressed adequately. Our results bring to the fore that an interactional practice, such as the use of sound prolongation in the context of expressed distress must be interpreted in relation to the complexity of each and every situation participants find themselves in, their level of understanding, and the task/activity at hand.

Encountering residents living with dementia who come from diverse linguistic and cultural backgrounds is a common aspect of everyday life in residential care homes. These facilities may have systems of address that differ from those used in residents respective cultures of origin. Residents forms of address are elements of identity established in accordance with their life histories. The aim of this article is to investigate empirically the role of address forms for residents and care-providing staff in multilingual residential settings. The findings rely on observational and interactional data as well as interviews. The observational and interactional data includes 23 participants, consisting of five residents and 18 members of care-providing staff. The interviews consist of informal conversations and a corpus based on open-ended interviews with 21 staff members and five residents in two residential homes in Sweden. On the one hand, the findings indicate that addressing the residents with their first name is a prevalent address practice by the staff. They also displayed 20 additional types of address practices. On the other hand, these practices, which are chosen with the best of intentions, often seem to be inconsistent with the residents preferred address forms. These data lend support to the large body of gerontological literature arguing that sensitivity to the life histories of residents, here the established forms of address, is vital to sustaining their identity.

Physical inactivity and the onset of menopause increase the risk of cardiovascular disease amongst postmenopausal women. We aim to investigate the effect of resistance training (RT) on plasma levels of selected cytokines, adipokines, myokines, and sex hormones in postmenopausal women with vasomotor symptoms. This was a sub-study of a randomised controlled trial investigating the effects of RT on vasomotor symptoms in postmenopausal women. Women were randomised to join a 15-week RT program (n=26) or remain sedentary as control (n=29). Venous blood samples were taken at week-0 and week-15 for all participants. Enzyme-linked immunosorbent assays and multiple bead assays were used to measure cytokines, adipokines, myokines, and sex hormones in plasma. Plasma measurements of 16 of 33 analytes were within detectable limits. After adjusting for good compliance in the RT group (58% of RT participants), after 15 weeks, significantly lower plasma levels of adiponectin (p<0.001), lipocalin-2 (p<0.01) and resistin (p=0.04) were found. Comparing control and RT women, using change-over-time values, significant increases in median testosterone and sex hormone binding globulin levels were seen in RT women. RT intervention lowers the levels of adipokines, particularly adiponectin, in postmenopausal women with vasomotor symptoms. These results were secondary outcomes of a clinical trial, and further investigations in a larger cohort are essential with the additional control of diet control and body composition analyses. Nevertheless, our study shows RT may be a beneficial intervention in reducing inflammation amongst postmenopausal women.

Objective: To investigate if abdominal adipose tissue volumes and ratios change after a 15-week structured resistance training intervention in postmenopausal women with vasomotor symptoms (VMS).Study design: Sixty-five postmenopausal women with VMS and low physical activity were randomized to either three days/week supervised resistance training or unchanged physical activity for 15 weeks. Women underwent clinical anthropometric measurements and magnetic resonance imaging (MRI) at baseline and after 15 weeks. MRI was done using a Philips Ingenia 3.0 T MR scanner (Philips, Best, The Netherlands). The per protocol principle was used in the analysis of data.Main outcome measurements: The absolute change from baseline to week 15 in visceral adipose tissue (VAT) volume and the relative ratio (VAT ratio) between VAT and total abdominal adipose tissue (TAAT), i.e. the sum of abdominal subcutaneous adipose tissue (ASAT) and VAT.Results: There were no significant differences between the groups in characteristics, anthropometry or MRI measures at baseline. Women who were compliant with the intervention (i.e. participated in at least two of the three scheduled training sessions per week) had significantly different reduction over time in ASAT (p = 0.006), VAT (p = 0.002), TAAT (p = 0.003) and fat ratio (p < 0.001) compared with women in the control group.Conclusions: Implementation of a 15-week resistance training regimen in midlife may help women to counteract the abdominal fat redistribution associated with the menopausal transition. Clinical trials: gov registered ID: NCT01987778.

Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.

BackgroundHub transcription factors, regulating many target genes in gene regulatory networks (GRNs), play important roles as disease regulators and potential drug targets. However, while numerous methods have been developed to predict individual regulator-gene interactions from gene expression data, few methods focus on inferring these hubs.ResultsWe have developed ComHub, a tool to predict hubs in GRNs. ComHub makes a community prediction of hubs by averaging over predictions by a compendium of network inference methods. Benchmarking ComHub against the DREAM5 challenge data and two independent gene expression datasets showed a robust performance of ComHub over all datasets.ConclusionsIn contrast to other evaluated methods, ComHub consistently scored among the top performing methods on data from different sources. Lastly, we implemented ComHub to work with both predefined networks and to perform stand-alone network inference, which will make the method generally applicable.

Network-based disease modules have proven to be a powerful concept for extracting knowledge about disease mechanisms, predicting for example disease risk factors and side effects of treatments. Plenty of tools exist for the purpose of module inference, but less effort has been put on simultaneously utilizing knowledge about regulatory mechanisms for predicting disease module hub regulators.We developed MODalyseR, a novel software for identifying disease module regulators and reducing modules to the most disease-associated genes. This pipeline integrates and extends previously published software packages MODifieR and ComHub and hereby provides a user-friendly network medicine framework combining the concepts of disease modules and hub regulators for precise disease gene identification from transcriptomics data. To demonstrate the usability of the tool, we designed a case study for multiple sclerosis that revealed IKZF1 as a promising hub regulator, which was supported by independent ChIP-seq data.MODalyseR is available as a Docker image at https://hub.docker.com/r/ddeweerd/modalyser with user guide and installation instructions found at https://gustafsson-lab.gitlab.io/MODalyseR/.Supplementary data are available at Bioinformatics Advances online.

Significance: Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization.

Aim: With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification.

Approach: We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components’ spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS).

Results: Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520  ±  20  nm; 556  ±  18  nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2  =  0.987, RMSE  =  0.006 for μa, R2  =  0.994, RMSE  =  0.078 for μs′).

Conclusions: We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment.

Wound healing assessment is usually performed visually by a trained physician. This type of evaluation is very subjective and returns limited information about the wound progression. In contrast, optical imaging techniques are non-invasive ways to quantitatively measure biological parameters. Spatial frequency domain imaging (SFDI) is an optical technique that exploits sinusoidal patterns of light with multiple spatial frequencies to measure the tissue frequency-specific response, from which the absorption and scattering coefficient of the material can be derived. While SFDI is based on models of light transport that assume the tissue is homogeneous, skin is composed by several layer with very different optical properties. An underutilized property of SFDI, however, is that the spatial frequency of the patterns determines the penetration depth of photons in the tissue. By using multiple ranges of spatial frequencies, we are developing a means to obtain morphological data from different volumes of tissue. This data is used to reconstruct the optical properties in depth, allowing us to differentiate between different thin layers of tissue. In this study we have developed a 2-layer optical phantom model with realistic optical properties and dimensions, that mimics the physiology of wound healing. We have used this physical model to validate the accuracy of this approach in obtaining layer specific optical properties.

Sustainable development has been defined by 17 UN goals, with the third goal (SDG3) focusing on a universal healthcare system that ensures healthy lives and wellbeing. To implement these ambitions, the goal needs to fit a regional setting before it can achieve and support healthy lives and wellbeing amongst the population. This article analyses how four Swedish regions incorporate SDG target 3.4 on non-communicable diseases and mental health into their respective healthcare organisations. The comparative analysis applies the lens of normative institutional theory to policy documents and interviews. All the regions recognise SDG3.4 by acknowledging the need for health promotion. The results show a general absence of similarities in organisational practices and policy outcomes, which is explained by region-specific factors and a lack of governmental coordination. The analysis shows that local policy core values and the related logic of appropriateness predict local outcomes of implementation of general global policies.

During COVID-19, the demand for food relief exploded as vulnerable people were suddenly more numerous and visible than ever, for which statutory welfare was not ready to cope with. We examine the role of voluntary and community organizations (VCOs) in food relief in Stockholm, Sweden and Seoul, Korea. Interpretive analysis of interview materials reveals how VCOs perceive their role vis-à-vis the state and take actions against urban food insecurity during the pandemic. The limits of statutory welfare in reaching out to vulnerable individuals reserve an indispensable role for community action in food relief even with the well-developed welfare state. Despite starkly different welfare state contexts, VCOs in both cases complement statutory welfare by swiftly identifying the risk of hunger and organizing community actions to meet the emergent needs. Given that Sweden and Korea represent the least likely cases to observe welfare provision by VCOs, the findings may have implications to general understanding of VCOs as indispensable welfare provider.

OBJECTIVE: The indications for and the risk and benefit of concomitant surgical ablation for atrial fibrillation (AF) have not been fully delineated. Our aim was to survey whether the Cox-maze IV procedure is associated with postoperative heart failure (PHF) or other adverse short-term outcomes after mitral valve surgery (MVS).

DESIGN: Consecutive patients with AF undergoing MVS with (n = 50) or without (n = 66) concomitant Cox-maze IV cryoablation were analysed regarding perioperative data and one-year mortality.

RESULTS: The patients in the Maze group were younger, were in lower NYHA classes, had better right ventricular function and had lower pulmonary artery pressure. The Maze group had 30 min longer median cross-clamp time (CCT) and 50% had PHF compared with 33% in the No-maze group, p = 0.09. Two patients in the No-maze group died within one year of surgery. Congestive heart failure (OR 4.3 [CI 95%: 1.8-10], p < 0.0001) and CCT (OR 1.03 [CI 95%: 1.01-1.04], p = 0.001) were associated with PHF.

CONCLUSION: The current data cannot exclude that concomitant cryoablation increases the risk for PHF, possibly by increasing the cross clamp time.

Background: Surgical cryothermia and radiofrequency (RF) ablations for atrial fibrillation (AF) seem to result in similar sinus rhythm restoration, but the biochemical consequences of the two methods are unclear. We aimed to compare the biochemical responses to the two ablative methods in concomitant mitral valve surgery (MVS).

Methods: Sixty mitral valve surgery patients with AF were prospectively included. Forty-one patients planned for ablation were randomized to cryothermia (n = 20) or radiofrequency (n = 21) ablation and 19 served as controls. Markers for myocardial injury, inflammation, cell stress, apoptosis, and heart failure were analyzed pre- and postoperatively at different time points.

Results: Troponin T and creatine kinase isoenzyme MB (CK-MB) peak levels were significantly higher in the cryothermia group compared with the RF group (12,805 [6140–15,700] vs. 2790 [1880–4180] ng/L; P = 0.002 and 271 [217–357] vs. 79 [66–93] μg/L; P < 0.001, respectively). Both groups had significantly higher levels than the no-ablation group. There were no group differences in C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), but there were correlations between pre- and postoperative levels of both CRP (rs = 0.41, P = 0.001) and NT-proBNP (rs = 0.48, P < 0.001). Protease-activated receptor 1 (PAR-1) and heat shock protein 27 (HSP27) were significantly increased in the cryoablation group.

Conclusions: Cryoablation results in a larger myocardial injury and possibly more elevated apoptotic activity and cell stress compared with the RF technique. The type of ablation device did not have any significant influence on the postoperative inflammatory response nor on the early postoperative levels of NT-proBNP.

BackgroundAtrial linear scars in Cox-Maze IV procedures are achieved using Cryothermy (Cryo) or radiofrequency (RF) techniques. The subsequent postoperative left atrial (LA) reverse remodelling is unclear. We used 2- and 3-dimensional echocardiography (2-3DE) to compare the impact of Cryo and RF procedures on LA size and function 1 year after Cox-maze IV ablation concomitant with Mitral valve (MV) surgery. MethodsSeventy-two patients with MV disease and AF were randomized to Cryo (n = 35) or RF (n = 37) ablation. Another 33 patients were enroled without ablation (NoMaze). All patients underwent an echocardiogram the day before and 1 year after surgery. The LA function was assessed on 2D strain by speckle tracking and 3DE. ResultsForty-two ablated patients recovered sinus rhythm (SR) 1 year after surgery. They had comparable left and right systolic ventricular function, LA volume index (LAVI), and 2D reservoir strain before surgery. At follow-up, the 3DE extracted reservoir and booster function were higher after RF (37 & PLUSMN; 10% vs. 26 & PLUSMN; 6%; p &lt; 0.001) than Cryo ablation (18 & PLUSMN; 9 vs. 7 & PLUSMN; 4%; p &lt; 0.001), while passive conduit function was comparable between groups (24 & PLUSMN; 11 vs. 20 & PLUSMN; 8%; p = 0.17). The extent of LAVI reduction depended on the duration of AF preoperatively. ConclusionsSR restoration after MV surgery and maze results in LA size reduction irrespective of the energy source used. Compared to RF, the extension of ablation area produced by Cryo implies a structural LA remodelling affecting LA systolic function.

The Wnt signaling pathway is of paramount importance for development and disease. However, the tissue-specific regulation of Wnt pathway activity remains incompletely understood. Here we identify FOXB2, an uncharacterized forkhead box family transcription factor, as a potent activator of Wnt signaling in normal and cancer cells. Mechanistically, FOXB2 induces multiple Wnt ligands, including WNT7B, which increases TCF/LEF-dependent transcription without activating Wnt coreceptor LRP6 or beta-catenin. Proximity ligation and functional complementation assays identified several transcription regulators, including YY1, JUN, and DDX5, as cofactors required for FOXB2-dependent pathway activation. Although FOXB2 expression is limited in adults, it is induced in select cancers, particularly advanced prostate cancer. RNA-seq data analysis suggests that FOXB2/WNT7B expression in prostate cancer is associated with a transcriptional program that favors neuronal differentiation and decreases recurrence-free survival. Consistently, FOXB2 controls Wnt signaling and neuroendocrine differentiation of prostate cancer cell lines. Our results suggest that FOXB2 is a tissue-specific Wnt activator that promotes the malignant transformation of prostate cancer.

The forkhead box transcription factor FOXQ1 contributes to the pathogenesis of carcinomas. In colorectal cancers, FOXQ1 promotes tumour metastasis by inducing epithelial-to-mesenchymal transition (EMT) of cancer cells. FOXQ1 may exacerbate cancer by activating the oncogenic Wnt/beta-catenin signalling pathway. However, the role of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is an activator of Wnt-induced transcription and regulator of beta-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the beta-catenin nuclear complex to boost the expression of major Wnt targets. In parallel, we find that FOXQ1 controls the differential expression of various Wnt target genes in a beta-catenin-independent manner. Using RNA sequencing of colorectal cancer cell lines, we show that Wnt signalling and FOXQ1 converge on a transcriptional programme linked to EMT and cell migration. Additionally, we demonstrate that FOXQ1 occupies Wnt-responsive elements in beta-catenin target gene promoters and recruits a similar set of co-factors to the beta-catenin-associated transcription factor Tcf711. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/beta-catenin signalling, which may drive the metastasis of colorectal cancers.

Optic neuritis (ON) causes axonal loss as reflected by thinning of retinal nerve fiber layer (RNFL) and can be tracked by optical coherence tomography (OCT) about 6 months after ON onset, when swelling of optic nerve head (ONH) has vanished. Changes of macular ganglion cell layer (GCL) thickness provide another window to track the disease process in ON. GCL thinning over time in relation to RNFL change after ON remains elusive. Using OCT, we followed 4 patients with acute unilateral isolated ON for more than 9 months. A diagnosis of multiple sclerosis (MS) was established in all 4 patients. First follow-up was 2-3 weeks after ON onset, and thereafter every 2-3 months. RNFL swelling peaked during first month after acute ON, followed by rapidly reduced swelling (pseudoatrophy) during following 2 months, and thereafter successively vanished 6 months after ON onset. GCL thinning was observed 1-3 months after ON onset, i.e. already during optic disk swelling and before real RNFL thinning. The results imply that quantifying GCL thickness provides opportunities to monitor early axonal loss and ON-to-MS progression, and facilitates distinguishing real atrophy from pseudoatrophy of RNFL after acute ON.

Objective: Severity of papilledema and vision loss constitute a basis for therapeutic intervention in idiopathic intracranial hypertension (IIH), but both are often subjective and insensitive in guiding clinical management. The aim of this study was to identify reliable and sensitive measurements of optic nerve head (ONH) and macula, to provide objective guidance for prognostic evaluation and treatment in IIH. We analyzed potential of spectral domain optical coherence tomography (SD-OCT), to measure neuro-retinal rim thickness and area, optic cup-to-disc ratio (C/D) and cup volume of ONH which have not previously been reported in IIH. In parallel, thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell layer (GCL) together with inner plexiform layer (IPL) (GCL-IPL) were examined. Results: All 7 enrolled IIH patients had increased neuro-retinal rim thickness (p less than 0.01 for both eyes) and rim area (p less than 0.05), decreased C/D (p less than 0.01) and optic cup volume (p less than 0.01) when compared to findings in 18 sex- and age-matched healthy controls (HC). In a longitudinal study, two IIH patients were followed repetitively by SD-OCT before and after measurement of intracranial pressure (ICP) and removal of cerebrospinal fluid (CSF) by lumbar puncture. Rim thickness and area, C/D and optic cup volume remained altered. RNFL thickness may change with very high ICP, but not immediately after CSF removal. GCL-IPL thickness was unchanged irrespective of ICP change or CSF removal. Conclusion: SD-OCT allows detection of ONH changes even in subtle IIH without papilledema and has potential for routine use in IIH.

Background The ganglion cell layer (GCL) measurements with Optical Coherence Tomography (OCT) are important for both ophthalmologists and neurologists because of their association with many ophthalmic and neurological diseases. Different factors can affect these measurements, such as brain pathologies, ocular axial length (AL) as well as age and sex. Studies conducted to measure the GCL have overlooked many of these factors. The purpose of this study is to examine the effect of age, sex, and AL on normal retinal GCL thickness and volume in a healthy population without any neurological diseases. Methods A prospective cross-sectional study was designed to measure GCL thickness and total volume with OCT with automated segmentation and manual correction where needed. Visual acuity, AL, and autorefraction were also measured. A mixed linear model was used to determine the association of the effect of the various parameters on the GCL thickness and volume. Results One hundred and sixteen eyes of 60 subjects (12-76 years of age, 55% female) were examined of which 77% had 0 +/- 2 D of spherical equivalent, and mean axial length was 23.86 mm. About 25% of the OCT-automated GCL measurements required manual correction. GCL thickness did not differ in similar anatomic regions in right and left eyes (P &gt; 0.05). GCL volume was greater in males relative to females after adjustment for age and axial length (1.13 +/- 0.07 mm(3) for males vs 1.09 +/- 0.09 mm(3) for females; P = 0.031). GCL thickness differed between males and females in the inner retinal ring (P = 0.025) but not in the outer ring (P = 0.66). GCL volume declined with age (P = 0.031) but not after adjustment for sex and axial length (P = 0.138). GCL volume declined with longer axial length after adjustment for age and sex (P = 0.048). Conclusion Age, sex and axial length should be taken into consideration when measuring the GCL thickness and volume with OCT. Automated OCT segmentation should be reviewed for manual adjustments.

A benign form of multiple sclerosis (BMS) is not easily diagnosed, but changes of the retinal ganglion cell layer-inner plexiform layer (GCL-IPL) and retinal nerve fiber layer (RNFL) may be sensitive to the disease. The aim of this study was to use optical coherence tomography (OCT) to investigate longitudinal changes of GCL-IPL and RNFL in BMS. Eighteen patients with BMS and 22 healthy control (HC) subjects were included, with a mean follow-up period of 32.1 months in BMS and 34.3 months in HC. Mean disease duration in BMS was 23.3 years, with 14 patients left untreated. Unilateral optic neuritis (ON) was found in eight patients. Non-ON eyes showed thinner GCL-IPL layer in the BMS group relative to HC (p &lt; 0.001). The thinning rate of GCL-IPL in non-ON BMS, however, was -0.19 +/- 0.15 mu m/year vs. 0 +/- 0.11 mu m/year for HC (p = 0.573, age-adjusted). Thinning rate of RNFL in non-ON BMS was -0.2 +/- 0.27 mu m/year vs. -0.05 +/- 0.3 mu m/year for HC (p = 0.454, age adjusted). Conclusions: Thinning rate of the GCL-IPL and RNFL in BMS is similar to the healthy population but differs from the thinning rate in relapsing-remitting MS, presenting a non-invasive OCT-based criterion for assessing a benign course in multiple sclerosis.

The comorbidity between chronic pain and emotional problems has proven difficult to address with current treatment options. This study addresses the efficacy of a transdiagnostic emotion-focused exposure treatment ("hybrid") for chronic pain patients with comorbid emotional problems. Adults (n = 115) with chronic musculoskeletal pain and functional and emotional problems were included in a 2-centre, parallel randomized controlled, open-label trial comparing this treatment to an active control condition receiving a guided Internet-delivered pain management treatment based on CBT principles (iCBT). The hybrid treatment (n = 58, 10-16 sessions) integrates exposure in vivo for chronic pain based on the fear-avoidance model with an emotion-regulation approach informed by procedures in Dialectical Behavior Therapy. The iCBT (n = 57; 8 treatment modules) addresses topics such as pain education, coping strategies, relaxation, problem solving, stress, and sleep management using standard CBT techniques. Patient-reported outcomes were assessed before and after treatment as well as at a 9-month primary end point. Across conditions, 78% participants completed post-treatment and 81% follow-up assessment. Intent-to-treat analyses showed that the hybrid had a significantly better post-treatment outcome on pain catastrophizing (d = 0.39) and pain interference (d = 0.63) and significantly better follow-up outcomes on depression (d = 0.43) and pain interference (d = 0.51). There were no differences on anxiety and pain intensity. Observed proportions of clinically significant improvement favoured the hybrid on all but one comparison, but no statistically significant differences were observed. We conclude that the hybrid emotion-focused treatment may be considered an acceptable, credible, and efficacious treatment option for chronic pain patients with comorbid emotional problems.

Objectives: We recently developed a transdiagnostic exposure treatment (the hybrid treatment) for chronic pain patients with concurrent emotional difficulties. This paper investigates the hypothesized treatment processes, specifically: (1) if changes on pain-related dysregulation (catastrophizing, fear-avoidance, and nonacceptance of pain) and general emotion dysregulation (difficulties to regulate a broad spectrum of emotional responses) mediate effects on outcomes; and (2) if mediation is more pronounced for patients who score higher on these processes pretreatment. Materials and Methods: Structural equation modeling for longitudinal data using the full intention-to-treat sample was used to test whether proposed variables mediated the effect of the hybrid treatment (n=58) compared with a guided internet-delivered pain management treatment based on cognitive-behavioral principles (n=57) on pain interference and depressive symptoms at the 9-month follow-up. To make full use of the multiple process measures collected in the trial, we modeled mediators as 2 continuous latent variables: pain-related dysregulation and general emotion dysregulation. Results: Reduced pain-related dysregulation mediated the effects of treatment on both outcomes, whereas reduced general emotion dysregulation mediated the effects on depressive symptoms only. In the hybrid treatment, the mediated effect was more pronounced for participants who scored higher on pain-related dysregulation pretreatment relative to those who scored lower. Discussion: Our findings provide initial support for the transdiagnostic theoretical underpinnings of the hybrid treatment model. Using a hybrid treatment approach that centers on teaching patients emotion-regulation skills before commencing broad exposure successfully influenced both pain-related dysregulation and general emotion dysregulation, which in turn was associated with better treatment outcomes. It appears central to address these processes in pain patients with comorbid emotional problems, especially among patients scoring high on measures of catastrophizing, fear-avoidance, and nonacceptance of pain.