To date, few studies have examined the implementation of asset-based integrated care in the UK. This paper aims to address this gap in knowledge through examining the implementation of one model of asset-based integrated care, Local Area Coordination (LAC), within two localities in England.This paper draws upon data collected from two local authorities (site A and site B), which had both implemented LAC. Using a case study approach, qualitative data was collected from interviews with relevant stakeholders both internal and external to the local authorities. Data was analysed thematically.The findings demonstrate the marked differences between the two sites’ approaches to LAC, especially in relation to: the implementation process; impact; and their collaboration with other agencies and communities.The evidence presented in this paper demonstrates that the implementation of LAC, as with most complex service innovations, is dependent on the interplay of organisational and people-based components. In particular, successful implementation depends on maintaining a common vision of what an intervention will achieve and how it will work in practice, continual engagement with the political and organisational leaders of influence, positively addressing the anxieties of existing services and professions, and working with community groups. The importance of integrated care encompassing not only ‘clinical pathways’ between professionals but also partnership working between health care and broader community agencies has long been recognised in holistic models 2. This r3Integrated care policies in England have not only sought to improve the relationship between the delivery of formal health and social care services , but als16In common with the implementation and sustainability of most complex service innovations, components that determine success of integrated care programmes are “multifactorial in nature and are characterized by a complex interplay” . ImplemeThis paper aims to address this gap in knowledge through reflecting on the implementation of one model of asset-based integrated care, Local Area Coordination (LAC), within two localities in England.Originating in Western Australia during the 1980s, LAC originally emerged to support individuals with learning disabilities living in rural areas, offering people direct family support and access to services . Over tiTable 1). Coordinators are place-based, defined by a geographical area and work flexibly to build positive and trusting relationships with individuals, families and communities.LAC aims to help people and their communities to be self-supporting by transforming systems and strengthening relationships between people, communities and services 31. The mThere has been a recent increase in the adoption of LAC in the UK, with 11 regions implementing LAC and 90 coordinators working across England and Wales , and a g35363730This paper draws upon data collected as part of a larger research study funded by the Department of Health and Social Care to explore how prevention has progressed following the Care Act 2014 . In EnglThe research study comprised an online national survey and a case study methodology to investigate seven local authorities who were undertaking innovative work in prevention. Within the case study sites between 2017- 2018, we undertook interviews with stakeholders, service users and carers and collected data about service-user outcomes via Quality of Life (ICECAP-A) questionnaires . The resTable 2). These two local authorities were selected for discussion in this paper as they were the only two sites that had implemented LAC. Both sites are largely urban areas on the outskirts of major cities, with deprived and increasingly diverse populations, though Site B has areas of higher affluence. In both cases, LAC was part of a strategy to move towards a more community orientated model based on encouragement to access informal networks and voluntary support before resorting to formal health and care services. However, their approach to implementation of LAC showed marked differences, as discussed in the findings section below.This paper draws upon data collected from two local authorities (site A and site B – see The findings discussed here are based on the following data collected in Sites A and B: 32 interviews and 4 focus groups (approximately 10 people in each focus group) with relevant stakeholders both internal and external to the local authorities . The findings in this paper are primarily based on this data, but also on the observations and experiences gained from the wider project of the LAC services including people with lived experience. All interviews were audio recorded, transcribed and analysed using NVivo coding and thematic analysis .We present key findings under three themes: implementation process; impact and collaboration with other agencies and communities. These themes were developed through the data analysis of the interviews and focus groups.Both sites aspired to introduce the same model of integrated community-based support with much similarity regarding core elements of their implementation process. LAC was framed within a wider vision to achieve more preventative care based on principles of co-production and partnership. Both drew on advice from the national LAC network and gained peer support and insights from other areas. The two sites decided to employ their coordinators within the public sector rather than commission the service from the private or voluntary sectors. Communities were involved in the recruitment of coordinators and they were selected on the basis of values, ability to engage and local knowledge rather than a professional qualification. Coordinators were expected to locate themselves predominantly within community bases and spend time developing relationships with public and voluntary organisations. Implementation began in both within a limited number of localities with the aspiration that it would in time be introduced across the local authority, although it was only Site A that was able to achieve this aspiration.Despite these similarities, the implementation in Site A was undoubtedly more successful. Unlike Site B, LAC became available to the whole population as a core element of local provision, not only by social services but also by other sectors including health, housing, and community-based organisations. There was a conviction from the outset from key decision makers in Site A that LAC should become mainstream activity. The initial limited introduction was due to not all the necessary funding being secured at the beginning, rather than any question about whether this should happen, and the first areas were seen as generating insights for wider implementation. In Site B, five areas were selected to test out LAC. It was quickly emphasised that long-term funding and wider adoption of the model were dependent on a demonstration of financial efficiency. Whereas in Site A, LAC was assumed to be effective and the issue was how best to implement it, in Site B LAC had to prove its case in a challenging, if not unrealistic, timescale. This was reflected in the type of funding that was deployed – in Site A much of the funding came from mainstream budgets, whereas in Site B the pilot was supported through a time-limited innovation grant from central government. This meant that within Site B there was an anxiety about long-term sustainability, which was heightened when funding for a similar local service (care navigation) was withdrawn. Site A also saw the importance of understanding impact and sharing this with local stakeholders but this was from a position of much greater confidence and security.Leadership also played a major role in shaping these different assumptions of the value of LAC. In Site B, LAC was introduced by the most senior social services director who left during the period of the pilot with their successor not favouring the approach. There was also turnover at this level within Site A, but influential operational managers who championed LAC from the outset remained within the local authority. They secured support from new senior directors and worked to promote its effectiveness with local politicians. Engagement in national networks and good practice events helped to consolidate its local standing alongside sharing learning with other areas. Beyond such stakeholder diplomacy, the leaders of LAC within Site A also sought to embed a culture in which the coordinators (and their service manager) had considerable autonomy to respond creatively to local needs. They felt positively about what was being achieved and were keen to promote this. In Site B, there was considerable criticism of the operational management style and a perceived lack of support for the coordinators from senior leaders. These contrasting experiences are illustrated here:“We have always somehow found the time to kind of be a sort of modern day evangelist. So we’ve gone around a lot, we’ve worked with a lot of other local authorities, we shared our learning, we’ve always responded positively to any introduction to come and tell people about what we’re doing. … if you get some people who have respect and a reputation on board and they start to say good things about you, it makes life easier.” (Site A: LA Manager)“I was telling people within the Council about them (coordinators) that didn’t even know that they existed, … that should be the role of the manager in my opinion … I get the feeling … they were just left to their own devices … I think it’s been really disappointing because I think the people at the top haven’t led it at all.” (Site B: Community Member)The Sites also differed in their success in, and perhaps commitment to, engaging with local citizens in the development and management of LAC. In Site A, there were efforts to develop and maintain a stakeholder group of people who had accessed LAC to provide challenge and support to the running of the service. Although this presented some logistical difficulties in practice, an informal network of people with direct experience was established and there were plans to involve the user network in more strategic discussions in the future. In contrast, there was criticism from some community groups in Site B about the perceived minimal and tokenistic attempts to involve people with lived experience in the planning and operation of LAC:“It would have been nicer to be involved in the actual coproduction of the solution in the first place. The community weren’t involved in that. It was, ‘We’re going to have this scheme. Now we want you involved’. It was that kind of process, rather than saying, ‘What’s the best scheme to work in this area and how do we work through that appropriately?’ and ‘How do we make sure that the community remain engaged in it?”. The two local authorities had different expectations of LAC. Whereas Site A was anticipating that it would deliver increased value from the same service costs, Site B was expecting it to demonstrate cost savings. Both sites found it problematic to demonstrate the impact of LAC in terms of increased value (Site A) and reduced costs (Site B). Neither site had a structured process for gathering and monitoring outcomes for the LAC service. This was in part due to the challenges of measuring preventative impacts and being able to attribute beneficial outcomes to LAC.Both sites approached monitoring and evaluation activities differently. In Site A, early intervention reports played an influential role in making the case for LAC. Initially there was considerable scepticism within the wider LA and partners around the potential benefits of LAC. However, as feedback and evidence of its benefited emerged, LAC became increasingly valued by strategic leaders:“I absolutely feel we’ve proved the point now, so the fact we’ve been able to sustain it and build it – at the beginning there was real scepticism about LAC. It was something that could’ve been dropped easily, it was nice to do, but not essential. Everywhere in the council I go now people talk about LAC … so the reward is huge.” Early intervention reports drew on a range of outcome data by combining quantitative data alongside people’s individual stories about the benefits of the service. These reports became an important part of the sustainability of the programme in the longer term, with senior leaders fully aware of the importance of demonstrating beneficial outcomes.The methodological difficulties in evaluating the service and demonstrating cost-effectiveness were widely acknowledged in Site B. There was a preference for collecting quantitative data (evidence of cost savings), which ultimately failed to capture the impact LAC had on people’s lives. The lack of interest in individual ‘success’ stories and demand for numerical data were seen as instrumental in the project’s demise:“I think it’s really difficult to measure it in terms of saving and I think … big managers focused on savings and want the numbers. Whereas something like this I think you can only measure with the stories, I think that’s where as I said the frustration comes in because … a lot of resource was invested in it and a lot of time and then literally to pull something within two years when it’s not that it’s because it’s been a flop, I don’t believe that. If it had been like a flop it’s different isn’t it? You could say ‘Oh the pilot’s not worked’, but I don’t believe that that’s been the case.” Similar to Site A, stakeholders in Site B understood the significance of demonstrating impact in order to secure future sustainability, but LAC coordinators continued to struggle with how to demonstrate its positive impact in the way that seemed to be required by decision-makers. Coordinators deemed the lack of guidance they had received about how this could be done as a significant barrier:“I’ve just found out recently that the care navigators have been decommissioned because they haven’t evidenced their cost effectiveness ….We can give fantastic examples of where we’ve connected people and where people’s lives have changed but people want hard figures, don’t they?” Unrealistic time-scales set for gathering meaningful evidence was identified as another barrier to collecting outcome data in Site B. The pressure to demonstrate cost-savings was evident at the time of the first stakeholder interviews, when LAC had only been in operation for around nine months. The coordinators in Site B felt that the time-scale for being expected to generate evidence of progress and cost-effectiveness was too short, especially as the first three months of their employment were devoted to getting to know their communities.“So although LAC was clearly established as long term, something that would start slowly and take time, I feel that we’re being challenged to show that we’re making immediate cashable savings and I don’t think that’s the bases on which we were set up.” In Site B, LAC was unable to demonstrate cost savings in such a short period of time and without this evidence the LA would not commit to it financially. Ultimately, LAC was seen by senior managers as ‘not giving a good return on investment’. With hindsight, several stakeholders commented that insufficient thought had been given to the need for partnership and commitment at a strategic level to plan service provision, maximise co-operation, avoid duplication and ensure that LAC  would be sustainable.Despite the difficulties each site experienced in producing ‘hard’ outcomes data, stakeholders, community members and the coordinators themselves were able to provide many examples of how their work had improved the lives of individuals and their families. This was mostly achieved through enabling individuals and communities to ‘help themselves’. Key outcomes identified included: the development of personal skills, such as in managing finances and self-care; building of social networks which reduced isolation and increased community capacity; and increasing individual and community morale. These successes were attributed to the continuity of relationships, building trust, and engaging with people in personal and meaningful ways:“It’s on a much more personal level. You’re talking about people and valuing people. That is absolutely the core of what LAC is, other professionals focus on paperwork, doing the assessments, care and support plans.” Local Area Coordinators in both sites were faithful to the LAC model in terms of rooting themselves firmly in their local communities. This was seen as an important enabler of engaging key community ‘actors’ and resources to develop community capacity. For example, a Local Area Coordinator in Site A identified people who struggled with healthy eating and lacked opportunities to eat socially. The local authority worked with a local organisation willing to offer a venue and established a cook-eat group. In Site B, the support of local organisations was enlisted to provide resources to help set up a Junk Food project and a community café in one of the more deprived areas of the Borough. The projects in both Sites were instigated by the ideas and needs of local people. They were sustainable in the longer-term by the securing of local funding and through staffing by volunteers who gained skills and qualifications in necessary areas such as food hygiene and first aid.The sites also shared some similar tensions in their relationships with other organisations and services. LAC was being implemented at a time of austerity and service cut-backs. Coordinators in both sites commented on the complexity of the difficulties faced by the people they worked with, particularly in relation to adverse social circumstances and mental health. Coordinators felt they were having to ‘fill the gap’ left by the withdrawal of other services and that this risked undermining their unique and distinctive role.“They bat it back to us to pick it up and it’s not really a role for us, but no-one else is going to pick it up.” The most problematic relationship with other agencies in both sites seemed to be with social work teams. In both boroughs, Local Area Coordinators were paid the same salary grade as entry level social workers and this generated some resentment amongst social workers who saw the coordinators as unqualified and having a less challenging role. There was also uncertainty in both sites about the boundaries of their respective roles and responsibilities. In Site A, coordinators feared that a reorganisation of social work services to community teams might duplicate and undermine their roles and threaten their long-term sustainability. Senior managers were deliberating whether to amalgamate LAC with community social work, which risked diluting it, or retain LAC as a distinct role, which then raised questions about the interface between the LAC and community social work roles. In Site B, a decision was made to discontinue LAC as a distinct service but to embed elements of its principles and practices in new community development teams.Despite some similarities, there were significant differences between the two sites in their relationships with their local communities and other organisations. Much of this stemmed from the historical context of these relationships. In Site A, a history of strong collaboration between agencies and sectors was described as the ‘bedrock’ of the implementation of LAC and this carried through into day-to-day management and practice. A multi-agency steering group with wide representation from agencies including health, the voluntary sector, housing, HealthWatch, public health, fire and rescue services and the police, generated knowledge, interest and commitment on the part of these services towards LAC.“The fact that we kind of built for years on a strong partnership so we’ve been very lucky in having the same personnel in place across health, social care, voluntary community sector for a number of years now, I think that, and all seemingly thinking in the same direction. I think that’s really, really made a big difference.” Local Area Coordinators developed collaborative relationships with other local agencies, who understood their role and could refer people to them. Site B lacked this strong foundation of multi-agency collaboration and the coordinators struggled to convey a clear sense of their role to others, including both community members and other professionals and organisations. The restriction of the implementation of LAC to only five out of seventeen wards made it difficult for practitioners and organisations whose remit was Borough-wide to know whether LAC was operating in a particular area. Although more could have been done to promote the service, there was reluctance to do this when it seemed increasingly unlikely that LAC would continue.Site A worked hard with the voluntary and community sector to ensure that LAC was seen as a complement to their activities rather than a duplication and threat. This helped with practical implementation on the ground but also provided another important set of allies to support continuation of funding. In Site B, LAC appeared more marginal to other stakeholders and activities, was seen to duplicate with other initiatives. It was particularly seen as overlapping with care navigation funded through health. Coordinators had to spend considerable time understanding and explaining the differences and connections between the two supports. Although there was a similar issue in Site A where the clinical commissioning group had introduced social prescribing, the coordinators were able to forge a more distinct ‘doing’ role, beyond the signposting undertaken by the social prescribers:“I think we understand that signposting is not going to be achievable, so we try to walk alongside them so that they do access, they do get from A to B. And that’s where we get a lot of our positive outcomes, the real complex people that are just not able to do things independently at that time.” In Site B, inter-agency collaboration was undermined by the sense of competition that was fuelled by service cutbacks and threats to funding. Some local organisations who had faced reduction or withdrawal of funding for their own service commented that their organisation either provided or could have offered the same service delivered through LAC. Examples were given of over-lapping roles and duplication and, sometimes, a view that the coordinators lacked the expertise for some of the work they were undertaking.One of the main motivations for pursuing integrated care is to overcome service fragmentation and the associated consequences of service users falling between the cracks of care 43. The eResearch has highlighted that successful implementation depends on an agreed vision of the role of the coordinators and associated support for this vision from their employing organisations and the wider system . For exaOrganisational issues were determining factors in the overall outcome of LAC within the sites 48. SucceAlongside organisational issues, this study reinforces the role of people and culture to implementation 51. Leade54This study suggests that LAC can be an effective means to enabling asset-based integrated care. Beyond consideration of the adoption of this model per se, the main learning for other systems is that community based integration should not only seek to connect people with existing community assets but also have the capacity and skills to facilitate the development of new resources to respond to identified needs.The experiences of these two sites reflect the common complexity of implementation and the many factors that can lead to a promising intervention not being well received in a local context . The finUnlike many such studies, it also confirms that implementation challenges can be overcome if there is sufficient attention to both organisational and people-based issues. These include: maintenance of a common vision of what an intervention will achieve and how it will work in practice; continual engagement with the political and organisational leaders of influence; positively addressing the anxieties of existing services and professions; and working with community groups. This also includes learning about the importance of stakeholder relationships within a wider system that will influence the deployment of an intervention, and how these can be engaged with proactively to increase successful implementation.Finally, it highlights that further work must be done to address the methodological difficulties of evaluating outcomes within such initiatives. For example, understanding what outcomes are likely to be realised by such interventions and when by, and the methodologies that will provide an appropriate assessment of the success of the interventions.Without robust and timely evidence, the potential contribution of such community-based approaches may not be recognised by funders and policy makers.


Histological diagnoses within the spectrum from moderately dysplastic nevi to thin melanomas are neither accurate nor reproducible, emphasizing the need for more objective supplemental immunohistochemical markers. PRAME immunohistochemistry aids in differentiating unequivocal melanomas from unequivocal nevi. The aim of our study was to determine whether PRAME IHC also allows differentiation of severely dysplastic nevi from thin melanomas and whether PRAME is of prognostic significance in thin melanomas. We studied 70 thin melanomas, of which 35 metastasized and 35 did not metastasize and 35 severely dysplastic nevi. We found that diffuse PRAME expression was highly specific but only moderately sensitive for thin melanomas. Melanomas and severely dysplastic nevi with PRAME immunoreactivity had different staining patterns. Most Melanomas demonstrated diffuse PRAME staining of intraepidermal and dermal melanocytes while most severely dysplastic nevi showed a decreasing gradient with depth. PRAME did not allow for the differentiation of metastasizing and non-metastasizing melanomas.p = 0.81). A superficial atypical melanocytic proliferation of uncertain significance, in which the final diagnostic interpretation favored a SDN was the only nevus with diffuse PRAME expression (1/45). Melanomas and SDN with PRAME immunoreactivity exhibited different staining patterns. Most melanomas (67.6%) showed uniform PRAME expression in the in situ and invasive component, whereas most SDN (81.0%) showed a decreasing gradient with depth. Conclusion: Diffuse intraepidermal and dermal PRAME staining is highly specific for melanomas in the distinction from SDN. PRAME expression is not a prognostic biomarker in melanomas ≤1.0 mm.Background: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is increasingly used as diagnostic adjunct in the evaluation of melanocytic tumors. The expression and prognostic significance of PRAME in melanomas ≤1.0 mm and its diagnostic utility in the distinction from severely dysplastic compound nevi (SDN) have not been studied. Methods: We investigated and compared the immunohistochemical PRAME expression in 70 matched thin metastasizing and non-metastasizing melanomas and 45 nevi from patients with long-term follow-up . Results: Diffuse PRAME staining in >75% of lesional epidermal and dermal melanocytes identified 58.6% of thin melanomas but did not distinguish metastasizing from non-metastasizing melanomas ( PReferentially expressed Antigen in MElanoma (PRAME) belongs to the group of cancer testis antigens (CTA) and its eponymous expression in melanomas may provide an immunohistochemical aid in the diagnosis of melanocytic lesions . LezcanoThin melanomas (≤1.0 mm) represent by far the largest subgroup of all melanomas  and are In this study, we investigated the expression and prognostic significance of PRAME expression in thin melanomas and assessed its diagnostic utility in the distinction from SDN.A total of 70 melanomas and 45 melanocytic nevi with follow-up were retrieved from the archives of the Department of Dermatology, University Hospital Tübingen. Patients with thin melanomas (≤1.0 mm Breslow thickness) and initial diagnosis between 2005 and 2020 were searched in the German Central Malignant Melanoma Registry and 35 patients with metastasizing melanomas (MM) and available paraffin-embedded material were identified. Patients with thicker second primary melanomas were excluded. The group with MM was compared with an equally sized control group with non-metastasizing melanomas (NMM). The patients in this group were matched for Breslow thickness (within a 0.1 mm range), sex, age (within a 10-year range), and site . These two groups were further compared with a third group of 35 patients with SDN. The diagnosis of SDN was based on the presence of certain cytologic and architectural criteria according to the World Health Organization classification of skin tumors . These cImmunohistochemistry (IHC) was performed with antibodies to Ki-67  and PRAME/Melan-A double staining with antibodies to Melan-A  and PRAME  on an automated immunostainer  using a brown chromogen (DAB) for PRAME and a red chromogen (FastRed) for Melan-A for a more accurate PRAME quantification and enhanced identification of dermal melanocytes. The percentage of PRAME immunoreactive cells was scored as previously described [p-values < 0.05 were considered as statistically significant. Interrater concordance regarding diffuse vs. non-diffuse PRAME staining was calculated using Cohen’s kappa (κ). Survival rates were estimated according to Kaplan–Meier and compared with the log-rank test.Statistical calculations were performed with IBM SPSS version 26 and p = 0.81). Mean follow-up was 65 months (range 5–139) for patients with MM and was 99 months (range 31–153) for patients with NMM. The clinicopathologic features of the analyzed melanomas and SDN are summarized in Seventy primary cutaneous melanomas ≤1.0 mm, of which 35 metastasized and 35 did not metastasize, were compared in a case-control study. Patient age ranged from 30 to 91 years with a mean of 62 years. The male to female ratio was 1.5 to 1. Lesions were predominantly localized on the trunk (40.0%), followed by the head and neck (28.6%), lower extremities (20.0%) and upper extremities (11.4%). Cases included 48 superficial spreading melanomas, 16 lentigo maligna melanomas, 3 acral lentiginous melanomas, 2 nevoid melanomas, and 1 spitzoid melanoma. The mean Breslow thickness was 0.7 mm (range 0.3–1.0) and did not differ significantly between melanomas with and without regression  with locoregional metastasis in their further course and one nevus-associated NMM (patient #11). Of these, only the NMM showed diffuse PRAME staining .The epidermal PRAME expression of unequivocally benign compound nevi ranged from 1+ to 2+ and the dermal PRAME expression from 0 to 1+. PRAME immunoreactive melanocytes were distributed very heterogeneously and were present predominantly at the lateral margins of the nevi .The mean age of the 35 patients with SDN was 45 years and ranged from 20 to 70 years. The male to female ratio was 1.3 to 1 and 13/35 patients (37.1%) had one or more invasive cutaneous melanomas. None of the patients developed metastases after a mean follow-up of 92 months (range 31–141). PRAME expression in the epidermal and dermal portions of the 70 matched melanomas and 45 nevi is summarized in (I)The mean Breslow thickness of the studied invasive melanomas was 3.3 mm (median 1.7 mm), which represents a clear selection towards thicker melanomas than in reality, in which the median tumor thickness ranges around 0.58 mm and melanomas ≤1.0 mm account for approximately 70% of all cases ,23.(II)The utility of PRAME IHC for the distinction of thin melanomas from SDN, the most common dilemma in the diagnosis of melanocytic lesions, was not studied.(III)PRAME expression was not compared between metastasizing and non-metastasizing melanomas and the prognostic significance of PRAME in cutaneous melanomas remains to be clarified.In recent years, the CTA PRAME has received much attention in the diagnosis of melanocytic tumors following the description by Lezcano et al. that diffuse PRAME expression is highly specific and sensitive for non-spindle cell melanomas ,5,21. LeThe aim of our study was to answer these unresolved questions by investigating PRAME expression in thin melanomas (≤1.00 mm) and SDN including ambiguous melanocytic tumors with long-term follow-up in a real-world setting.Here, we show that diffuse PRAME expression in superficial atypical melanocytic proliferations is highly specific for melanomas. The previously reported high sensitivity of diffuse PRAME staining for thick melanomas cannot be confirmed for thin melanomas and was only 58.6% in our study . The facNon-diffuse PRAME expression by no means excludes a thin melanoma, as this staining pattern was observed in almost half of our studied melanomas. The finding that even fatal thin melanomas often demonstrate intermediate PRAME staining (scores from 1+ to 3+) and may exhibit low or even no PRAME expression in the invasive component is important, as this could lead to the misinterpretation of a nevus-associated melanoma in situ (MIS) or SDN by the unaware. Our findings recapitulate the experiences by Lohman et al., who noticed in clinical practice that “PRAME does tend to highlight MIS more diffusely than early invasive dermal components” and “more advanced melanomas tend to be equally diffusely positive as the MIS component” . These sOur work, together with other studies on PRAME expression in melanocytic tumors, raises the question which PRAME threshold supports a melanoma diagnosis. Lezcano et al. reported that diffuse PRAME expression in >75% of lesional melanocytes was found in around 90% of conventional melanomas  but only in 0.7% of nevi . HoweverLowering the threshold to more than 50% PRAME positive epidermal and dermal melanocytes in our study would have resulted in a slightly better sensitivity for melanomas (67.1% vs. 58.6%) with unchanged specificity. However, a lower cut-off carries a higher risk that SDN with borderline PRAME expression will be misclassified as melanomas. This is especially true for nevi with inhomogeneous and weak PRAME expression, in which interpretation of the staining result may vary interindividually. It is also worth noting that 3+ PRAME staining was not described by Lezcano et al. in any of the investigated unequivocally benign nevi, but in diagnostically problematic benign melanocytic tumors . These aPRAME promotes the colony formation of melanoma cells in vitro  and tumoPRAME was originally described in melanoma cell lines as a tumor antigen recognized by autologous cytotoxic T cells . Its preWith regard to histological subtype, it is striking that thin melanomas with high cumulative sun damage  demonstrated more often diffuse PRAME staining than melanomas with low cumulative sun damage . Lezcano et al. reported scattered PRAME positive melanocytes in non-lesional portions of lentigo maligna reexcisions and solar lentigines, indicating that in sun-damaged skin the frequency of PRAME positive melanocytes is intrinsically higher .The high incidence of melanomas in our cohort with SDN (37.1%) confirms the observation that patients with dysplastic nevi are more likely to develop melanomas. Melanoma risk correlates with the severity of dysplasia and was 5.7% in patients with mild dysplastic, 8.1% with moderate, and 19.7% with severe dysplastic nevi in one study .The comparability of our data with previous studies is limited by the use of a different PRAME clone QR005). Clone QR005 yielded the best staining results in our laboratory and shows strong cytoplasmic labeling of sebaceous glands as described for clone EPR20330. Given that our staining results closely reflect the experiences and findings of other authors, however, we believe that clone QR005 has a comparable sensitivity and specificity ,5,6.. Clone QIn summary, we demonstrate that PRAME IHC is a useful adjunct in the distinction of thin melanomas from SDN. This study highlights that PRAME expression in thin melanomas is lower and more heterogeneous than has been demonstrated for in situ and thicker melanomas. The utility of diffuse PRAME staining in the group of superficial atypical melanocytic proliferations lies particularly in its high specificity for melanomas. The comparison of PRAME expression between MM and NMM showed that PRAME IHC is not a prognostic biomarker in thin melanomas.


Employees rated champions’ training delivery “very good” to “excellent”, on average; both champions and employees were, on average, “satisfied” to “extremely satisfied” with the curriculum and training received. There was an increase over baseline in trainings delivered during follow-up, and trainings increased in length and topic coverage. Ultimately, the train-the-trainer program achieved the intended goals, although not all changes were statistically significant, likely at least partially attributable to small sample sizes. Overall, these results suggest that TTTF’s train-the-trainer program was successful in its delivery and intention to build capacity for the provision of in-house tobacco education trainings to behavioral health employees/providers. However, further evaluation in additional settings, with more champions, et cetera, is necessary to validate these findings, ensure their replicability, link program implementation with reduced patient tobacco use rates, and assess long-term sustainability.Despite prior successful implementation of Taking Texas Tobacco Free (TTTF), an evidence-based tobacco-free workplace program, in local mental health authorities (LMHAs), post-implementation employee attrition necessitated continuing education on tobacco-free policies and tobacco treatment practices. Here, we report on the outcomes of a train-the-trainer program which trained “champions” to deliver tobacco cessation education at their LMHAs. Three LMHAs participated in program implementation via 10 champions, iteratively trained and coached by TTTF. Measures administered evaluated four goals: (1) increase champions’ self-efficacy in delivering trainings, (2) achieve program fidelity via TTTF staff evaluation of trainer effectiveness and knowledge increases among attending employees, (3) achieve stakeholder program acceptability, and (4) achieve program adoption via an increase in follow-up trainings. Champions’ self-efficacy increased throughout TTTF training. TTTF staff ratings of champion-led trainings met the targeted range for trainer effectiveness; employees had a 28.71% knowledge increase over baseline post-training ( Tobacco use remains the number one cause of preventable death and disability within the United States . AlthougDespite this alarming evidence, according to the most comprehensive national evaluation conducted to date, only 48.9% of behavioral health treatment centers screened for tobacco use in 2016, and only 25.2% of centers offered nicotine replacement therapy . FurtherTaking Texas Tobacco Free (TTTF) is an evidence-based, multi-component tobacco control program designed to build healthcare agencies’ organizational capacity to address tobacco use with evidence-based policies and practices. The current study focuses on the education components of the TTTF program that include provision of tobacco education and training for both non-clinical staff and clinical providers . To addrTTTF worked closely with “champions”, who were employees appointed by center leadership to oversee and ensure the success of program implementation as part of their workplace responsibilities. Champions were supported to attend Certified Tobacco Treatment Specialist training and were tasked with being a long-term (post-funding) internal resource to their colleagues about treating tobacco use disorder, to include leading subsequent internal employee trainings on the topic  . UnfortuThe current study describes the implementation and outcomes associated with TTTF’s “train-the-trainer program”, which can serve as a model for wider dissemination and implementation in behavioral health treatment settings.Recruitment for the current study was accomplished via an email invitation addressed to each LMHA Chief Executive Officer (CEO) who provided a letter of support to accompany the grant application to conduct this work. Of the 5 LMHAs providing letters of support (in 2019), each of which had participated previously in the overall TTTF comprehensive tobacco-free workplace implementation , 3 ultimWritten consent for participation was obtained from participating LMHA leadership prior to study participation via a memorandum of understanding. Program implementation spanned the fall of 2020 through the spring of 2021 with start and end dates varying by participating LMHA based on their preferences and progress. All procedures were approved by the Institutional Review Board of the University of Houston (STUDY00002164 beginning 8 April 2020).The LMHA CEO and/or their designee selected the treatment providers who would participate in this project as part of their workplace responsibilities. The team encouraged, to the extent possible, that the champions for the larger/prior comprehensive workplace program administration ,14,16,17The train-the-trainer program was implemented in a series of steps see , TTTF prThe goals and objectives of the program were as follows:  increase champions’ self-efficacy for delivering tobacco education throughout our training program;  evaluate program fidelity by achieving (a) team observer ratings of “very good” to “excellent” in the delivery of the education to the employees by the trained champions, and (b) achieve ≥20% knowledge increase among employee attendees from the delivered trainings;  evaluate program acceptability by achieving (a) employee attendees’ ratings of “very good” or “excellent” for the effectiveness of the trainer and ratings of “satisfied” or “extremely satisfied” with the training provided by the champion, and (b) champion ratings of “satisfied” or “extremely satisfied” with the curriculum and their training to implement it; and  evaluate program adoption via an increase over baseline in the number of education sessions delivered to employees by the champions post-program implementation.Champions completed a 10-item face-valid, investigator-generated survey administered online to assess changes in their training self-efficacy over time; this was completed (1) prior to undergoing TTTF-led training; (2) post-training but prior to the champion-led delivery of the training to employee attendees; and (3) post the champion-led employee trainings. See TTTF staff used a 17-item face-valid, investigator-generated survey to rate the champions’ delivery of the training during “practice” presentations and two “actual” employee trainings. An example item was, “The trainer appeared confident and comfortable with the material,” with ratings from 1 = strongly disagree through 5 = strongly agree. These items were meant to provide feedback to the champion about areas for improvement. The 2 final items were intended to summarize performance and read: “Overall, how would you rate the delivery of the training curriculum by the trainer to setting stakeholders?” and “Overall, how would you rate the effectiveness of the trainer as a teacher?” on a 5-point response scale where 1 = poor through 5 = excellent. Champions had to achieve ratings of “very good” (4) or “excellent” (5) by each observing TTTF staff member in practice presentations to progress on to train employees; thus, Goal 2a for fidelity was measured with each of the final 2 items as rated by TTTF staff for the presentations the champions gave to actual employee trainees. The goal was that TTTF staff would rate the delivery of these actual trainings, on average, as falling between “very good” and “excellent”.Knowledge gain from the champion-delivered training was collected before and after training using a 10-item face valid, investigator-generated knowledge test with items directly reflecting training content. In each case, a champion emailed the knowledge test link to employees who signed up for the training to complete within the week prior to the training, and then emailed a link to the post-training knowledge test immediately following training, with a request to complete it as soon as possible, preferably within the same day but at most within 7 days. Employees were instructed to complete the tests without reference to training slides, the internet, etc. Items on both the pre- and post-training knowledge tests were the same; however, no feedback on pre-test accuracy was presented to the test taker, in an attempt not to bias responses to the post-training knowledge test. An example item was, “Which of the following is NOT one of the “5As” or tobacco cessation brief intervention?” with answer options (a) ask; (b) arrange; (c) assess; and (d) allow. This measure has been used in our prior work ,22,23,24Employee attendees rated the champion on the delivered trainings using a 16-item face-valid, investigator-generated survey administered online. The first 14 items assessed different aspects of the trainer and the presentation, with items such as: “The training was engaging”, “The trainer’s articulation and voice level were clear”, and “The trainer seemed well-prepared for the training”, that were rated on a 5-point scale where 1 = strongly disagree and 5 = strongly agree. These items were meant to provide feedback to the champion about areas of strength as well as areas for improvement. The other 2 items were: (1) “Overall, how would you rate the effectiveness of the trainer as a teacher?” (1 = poor through 5 = excellent); and (2) “Overall, please rate how satisfied you were with this training”, (1 = extremely dissatisfied through 5 = extremely satisfied). These 2 final items measured program acceptability from the employee attendees’ perspective . The goal was for employee attendees, on average, to rate the trainer effectiveness as falling between “very good” and “excellent” and that, on average, they were between “satisfied” and “extremely satisfied” with the training content. No personally identifying information about the employee attendee was collected on this survey.Champions were asked 2 questions about the materials and instruction the train-the-trainer program provided them: (1) “Overall, please rate your satisfaction with curriculum provided to you by the TTTF team”, and (2) “Overall, please rate your satisfaction with the training you received to implement the curriculum provided to you by the TTTF team”, with response options ranging from 1 = extremely dissatisfied and 5 = extremely satisfied. These items measured program acceptability from the champions’ perspective .Champions provided TTTF with the number and duration of trainings delivered following successful completion of the train-the-trainer program, which is how Goal 4 (adoption) was assessed. This information was gathered quarterly for each LMHA post-program completion on a form via email. LMHA 1 provided 2 quarters (6 months), LMHA 2 provided 3 quarters (9 months), and LMHA 3 provided 2 quarters (6 months) of post-implementation training information. The different follow-up periods were based on when each LMHA finished the program and the consequent time remaining in the grant follow-up data collection period.Goal 1 (increase champions’ self-efficacy over time) was assessed using Wilcoxon signed-rank tests to test the changes over time within each champion. This test was used because there were few observations. Goal 2, Objective 2a  was assessed with descriptive statistics, and Objective 2b (assess fidelity by employee knowledge gain) was assessed by calculating the percent increase in knowledge within training session, with an analysis of covariance using employee as the analysis unit (controlling for champion) assessing statistical significance of the change. The formula for the percent increase in knowledge is as follows:Goal 3, Objective 3a (acceptability of champion-led training as reported by attending employees), and 3b (acceptability of TTTF training and curriculum) were assessed with descriptive statistics. Finally, Goal 4 (adoption) was calculated numerically by LMHA. Because the number of trainings occurring pre-implementation was assessed over a 12-month period, and the number of trainings conducted post-implementation was assessed over varying numbers of quarters, the assessment of this goal was achieved by dividing the number of trainings by the number of months assessed. The percent increase in trainings offered from before to after program implementation was calculated with equation 1.Alpha, for goals that used statistical comparisons of change over time , was set at 0.05. All analyses were conducted using SAS 9.4 .S = 7.5, p = 0.0625) or by LMHA .n = 8 champions completed 1 practice training; n = 2 champions completed 3 practice trainings). All champions successfully received ratings of 4 “very good” or 5 “excellent” on their delivery of the training curriculum and on their effectiveness as a trainer.Overall, champions received between 1 and 3 “practice” trainings with TTTF staff observers  and by LMHA . While overall knowledge gain exceeded the program goal of ≥20% and was statistically significant at each LMHA, it is worthy of note that LMHA 2′s knowledge gain was <20%.TTTF records indicated that LMHA 1 conducted 6 trainings for 30 employees across 2 follow-up quarters, LMHA 2 conducted 16 trainings for 135 employees across 3 follow-up quarters, and LMHA 3 conducted 7 trainings for 57 employees across 2 follow-up quarters. Relative to baseline, this represents a 35.02% increase in the number of education sessions delivered to employees by the champions post-training. Education sessions typically lasted 90 min and were administered to new and old employees alike, a stark contrast to the pre-champion training sessions which mostly lasted 10 min and were only given to new employees.This study described the implementation and outcomes of a train-the-trainer program aimed at building capacity for in-house tobacco education provision to employees by designated champions at behavioral health treatment centers 4–6 years following their participation in a comprehensive tobacco-free workplace program. Each program goal for this train-the-trainer program was met. Overall, these results suggest that TTTF’s train-the-trainer program was successful in its delivery and intention to build capacity for the provision of in-house tobacco education trainings to behavioral health employees/providers. Future work will need to assess the impacts of this program on the sustainment of all evidence-based tobacco use policies and practices as associated with a comprehensive tobacco-free workplace program , which was beyond the scope and timeline of the underlying grant. However, results speak to the potential upkeep of one major component of the TTTF comprehensive tobacco-free workplace program: the provision of employee education about addressing tobacco use amongst their behavioral health patients, which has previously been associated with increased screening and treatment of tobacco use ,22,23,24Programs such as this, which create opportunities for cascade training within an organization and that empower employee stakeholders to be the “experts” in tobacco use cessation continuing education, are vital for implementation in behavioral health settings given that a lack of education on these issues has been cited by providers as a major impediment to providing tobacco cessation care ,12,13. TThe processes and evaluation of TTTF’s train-the-trainer program were aligned with other train-the-trainer programs and included the measurement of champion self-efficacy for training , the assessment of program fidelity through employee knowledge gain , and the acceptability of the program’s curriculum by the champions  ,33,34,35Another potentially unique aspect of the current work relative to the literature was the sustainment follow-up, albeit for a limited time, which was only evident in three of the eight train-the-trainer programs identified in the literature ,31,35, od = 1.1 implying a large effect size  to an outcome approaching “very good” (3.90), these improvements were not statistically significant. This inability to detect a significant finding was likely a function of the study being underpowered (N = 10). A sample size of 35 would be needed to achieve an adequate power of 80%, with practical significance of ize  and training duration (90 min versus 10–60 min), which likely also increased the depth or breadth of relevant topics covered. The TTTF curriculum included information on the prevalence of smoking amongst behavioral health patients, the benefits of quitting on their mental health and quality of life, how to screen for and intervene on tobacco use with recommended pharmacotherapies and dosages, and the reasons for the tobacco-free workplace policy and how to address violators. Thus, it was fairly comprehensive in its coverage of multi-level, empirically-supported tobacco control strategies that had been part of the comprehensive tobacco-free workplace program previously implemented years before. It is possible that more comprehensive trainings are associated with greater long-term compliance with tobacco-free policies and cessation treatment provision; however, this needs to be assessed in future work.n = 3) and champions (n = 10); however, program participants were commensurate with the underlying funding mechanism and funder-approved recruitment goals. Furthermore, certain assessments  were completed by employees, for which there were larger sample sizes (N = 197–265). Despite this, future research should replicate this program using a greater number of participating behavioral health centers and champions to facilitate the evaluation of statistically significant changes. A second limitation is that we do not know the extent to which this program is adaptable outside of the specific behavioral health settings in which it took place. Future research should validate the impact of this program outside of the behavioral health settings as well as outside of Texas, especially given its possible utility across different treatment settings  and states. For example, different degrees and areas of staff training might be necessary in states with existing policies around tobacco use within addiction treatment settings, such as New York [Results should be considered in terms of limitations and strengths. One limitation is a low number of participating LMHAs (New York ,38. A thNew York ,22,23,24One strength of this project is that an additional project goal included developing a step-by-step implementation guide available online for broad passive dissemination , which wOne reason cited for why tobacco use is not regularly addressed in behavioral health/addiction treatment settings is a lack of clinician knowledge/training on the topic ,40,41,42


Increasing trends in global flood risk are driven by a complex web of interactions among natural, built environment, and social systems. As a result, flood resilience research is an ideal topic for an interdisciplinary approach. Core characteristics of interdisciplinary research are team collaboration and the systematic integration of disciplinary knowledge, in both problem formulation and analytical methods. Indicators of interdisciplinarity tend to focus on scholarly outcomes, but collaborative processes may be even more important for knowledge integration. In this Perspective piece, we outline and advocate a two‐pronged approach to enhance potential for integrating knowledge: using collaborative proximity to assess team readiness to conduct interdisciplinary research and employing program evaluation to assess change in proximity components over time. To do so, we draw on scholarship in economic geography, team science, and program evaluation. We then connect the findings to a case study of collaboration within our interdisciplinary team of flood researchers, program evaluators, and local stakeholders, as we navigate a multi‐institutional project on flood resilience. The overall project goal is to improve resilience to flood hazards at the watershed scale. Nine watersheds serve as IWA project sites, with programs to be implemented in each to increase resilience to future floods. The IWA objectives in each watershed are to reduce flood risk, improve water quality, increase flood resilience, engage stakeholders, improve quality of life , and develop a scalable and replicable program  and scale of analysis (watershed) that were sufficiently holistic to necessitate integration across disciplines, but also sufficiently specific to allow team members to find their own problem within it.During proposal development, proximity components heavily influenced the composition and leadership of the flood resilience team. The engineering institute selected an environmental engineer as team leader based on his experience working on interdisciplinary teams requiring community engagement, and disciplinary overlap with the engineering focus of the institute. Thus, spatial and institutional proximities between the team leader and engineering institute were high. However, the engineering institute had originally targeted a geographer as the flood resilience team leader, given his cognitive alignment with the disaster resilience focus of the proposal. But lower institutional proximity and limited schedule availability emerged as suboptimal traits for leading the team.Fig. Our main challenge early on was bridging low cognitive proximity. The team members bring knowledge of disaster resilience theory and measurement, stakeholder engagement, program evaluation, and geovisualization, but much of this expertise is mutually exclusive. We initially struggled with divergent understanding and expectations in measuring, visualizing, communicating, and improving flood resilience. For example, should disaster resilience be defined more as resistance or recovery? What degree of emphasis should be placed on constitutive physical, social, economic, and natural processes? An additional ongoing challenge has been navigating tensions between academic research and the action‐oriented and engagement goals of the IWA.On these and other matters, the inclusion of program evaluation experts as core team members has significantly improved clarity in the research process. Selecting program evaluation methods requires robust characterization of the research framework, inputs, activities, and expected outcomes. Compared to previous interdisciplinary projects in which we have participated, the program evaluation component has compelled earlier and more explicit definition of these elements, while simultaneously building consensus and facilitating communication among the team. Overall, the evaluators have provided critical, timely, and actionable feedback about the project components and how they contribute toward identified goals and outcomes. It is unlikely that the level of cognitive alignment and progress monitoring we have achieved would have been possible without substantive investment in program evaluation as part of the original grant proposal.I feel we have GOOD evaluation experts on this team. This is key. Also, I LIKE our evaluators personally. This is key as well, and a bit surprising for me. What I mean is that I assumed that evaluators would have to keep themselves at arm's length to somehow remain “independent.” If this did happen, then the van rides would be pretty stuffy and potentially awkward. I didn't know that the evaluators could/would embed themselves in the process so fully and I didn't know they would be interested in the project itself and have informed opinions about how to put it all together.However, initial misunderstanding of the evaluator role added stress to the resilience team leader. In particular, there was a misconception that program evaluation includes personnel evaluation. This highlighted that despite high spatial proximity and frequent team meetings, there was a glaring need to devote greater attention to increasing cognitive proximity. Social interaction has helped bridge this distance, for example, through discussions during meals and shared van rides during trips to and from meetings in the nine project watersheds. This development aligns with previous findings of how processes in one proximity dimension can facilitate change in another Boschma, . As voicEntering year three of the five‐year flood resilience project, we have found that proximity concepts effectively explain the collaborative successes and barriers we have experienced. Spatial and institutional proximity have been essential for team formation and communication, as they bounded the potential universe of team members Balland,  and incrHowever, a deep understanding of collaborative processes only began to emerge after two years of frequent interaction. A core characteristic of interdisciplinary research is higher time requirements (Brown, Deletic, & Wong, 5Flood disasters are inherently complex, societally relevant, and require solutions reflective of interactions among underlying natural, physical, social, institutional, economic, and decision‐making dimensions (Morss, Wilhelmi, Downton, & Gruntfest, Integrating readiness assessment into interdisciplinary hazards research increases the potential for innovative and societally relevant knowledge integration. Further embedding this approach into a program evaluation may produce even more robust pathways between interdisciplinary research objectives and outcomes, while also satisfying increasing demands from funding agencies for inclusion of program evaluation. Doing so requires research teams to be purposeful about knowledge integration as a core research outcome. Fitting a research plan into a logical structure through program evaluation can facilitate intentional discussion among team members about program goals, components, and priorities. We have come to understand that interdisciplinary team functioning and knowledge integration can be improved by devoting focus throughout the research, not only to knowledge generation and outcomes, but also to the collaborative processes affecting how they will be produced.


A refined risk assessment was conducted to evaluate the efficacy of different glove materials in reducing the potential hazards associated with using paint strippers containing N-methylpyrrolidone (NMP) under the scenarios defined by USEPA’s TSCA risk assessment. Three categories of gloves were identified based on measured permeation rates for NMP: (1) minimal protection; (2) moderate protection; and (3) maximal protection. Simulations for eight acute and chronic occupational exposure scenarios identified by USEPA as having a potential hazard  were reassessed for each glove category using PBPK modeling to predict peak (Cmax) and cumulative (AUC) internal doses of NMP. For the acute assessment, the refined MOE values were ≥30 for half of the scenarios for gloves from the moderate protection group category, and all of the scenarios for gloves from the maximal protection category. For the chronic assessment, the refined MOE values were ≥30 for all scenarios except one for gloves from the maximal protection category. The results of this assessment indicate that: (1) the degree of protection provided by gloves from NMP permeation can vary widely depending upon the glove material, NMP formulation, and internal dose measure ; and (2) NMP-containing paint strippers can be used safely when appropriate PPE are used. As such, these results can be used to support risk-reduction methods  as alternatives to banning NMP use under TSCA. The use of gloves was determined to be effective in reducing modeled estimates of exposure, as demonstrated by the higher MOEs. For chronic exposure, gloves may not provide sufficient protection in all scenarios. More importantly, not all glove types are effective in protecting against NMP exposure. USEPA did not evaluate glove efficacy, however California DOH recommends the use of gloves made of butyl rubber or laminated polyethylene/EVOH2.”“The Toxic Substances Control Act (TSCA), originally passed in 1976 and amended in 2016, provides EPA with authority to require reporting, record-keeping and testing requirements, and restrictions relating to chemical substances and/or mixtures. In March of 2015, USEPA released its final risk assessment for N-methylpyrrolidone (NMP) used in paint strippers under TSCA . These scenarios are not reassessed here. However, MOE values calculated for eight mid- and high-exposure level occupational scenarios were <30, with some calculated to be as low as 0.1. A summary of the results for the occupational scenarios (without gloves) from USEPA’s risk assessment with MOE values <30 is provided in Table Internal doses of NMP used by USEPA in their assessment include peak blood concentrations  to assess acute exposures, and area under the curve  for NMP in blood to assess chronic exposures. MOE values for all consumer, nearby occupational, and low-level occupational scenarios were calculated to be 30 or higher, where 30 is identified as an acceptable MOE value by USEPA [i.e., no concern for adverse effects of NMP if exposure  for calculating acute and chronic MOE values in Eq.  serve as the numerators (IDUSEPA’s exposure assessment included consideration of three exposure pathways: 1) inhalation exposures to NMP vapors; (2) dermal exposure to NMP vapors; and (3) dermal exposure to NMP liquid. For this assessment, the first two exposure pathways remain unchanged, while the later pathway was refined to permit a characterization of the effect of different glove materials on estimated internal doses of NMP. Acute exposures were assessed for both occupational and consumer scenarios, while chronic exposures were assessed only for occupational scenarios, since consumer scenarios are expected to be associated with short-term specific tasks. Occupational scenarios include miscellaneous stripping  and graffiti removal . Consumer scenarios include brush on  and spray on (indirect and high exposures) applications either in a workshop or bathroom. The use of PPE (respirator and/or gloves) was varied to determine how this might affect exposure in both occupational and consumer scenarios. As stated above, only a subset of these scenarios  are considered here . InternA literature search was conducted to identify key studies and datasets for evaluating the permeation of NMP through glove materials. Three studies were identified and are summarized briefly below.2/min.Zellers and Sulewski  assessed2/min).Stull et al.  conducte2/min).Crook and Simpson  tested 22 min) from these three studies are summarized in Table 2/min; Table C = NMP test concentration .NMP steady-state permeation rates as reported in the permeation studies ; (2) moderate protection ; and (3) maximal protection   minimal protection ; and  maximal net = net permeability coefficient for NMP through gloved skin ; and Kpglove = permeability coefficient for NMP through glove material , was assumed to remain constant and unchanged . The mean and range of net permeability coefficients identified for each glove category  to calculate glove protection factor (PF) values for each glove category using the equation below:no gloves = Internal dose for occupational simulations of the dermal liquid pathway without gloves ; and IDgloves = Internal dose for occupational simulations of the dermal liquid pathway with gloves .No changes were made to the PBPK model structure, parameter values , or assumptions defined by USEPA . For theMOE results for the acute exposure scenarios are provided in Fig. MOE results for the chronic exposure scenarios are provided in Fig. For both acute and chronic scenarios, by greatly reducing the contribution of the dermal liquid pathway to total internal dose, the refined MOE values for the maximal protection glove groups are driven primarily by the inhalation and dermal vapor pathways .Glove protection factors calculated from PBPK simulations  performed for the eight exposure scenarios indicate that the degree of protection to NMP permeation offered by gloves varies by several orders of magnitude, and depends on glove material, NMP formulation (NMP solution vs. neat NMP), and measure of internal dose (Cmax vs AUC) Table .A refined risk assessment was conducted to assess the efficacy of different glove materials in reducing the potential hazards associated with use of NMP-containing paint strippers. For acute exposure scenarios, gloves from the moderate protection group (polyethylene) offered sufficient protection for half of the scenarios assessed here, while gloves from the maximum protection group  offered sufficient protection for all scenarios. Gloves from the minimum protection group offer minimal protection when used on a task-specific basis . Furthermore, their use cannot be recommended due to their risk of acute failure  , a factonet values derived in this assessment reflect a relatively simple approach for incorporating the best available data for NMP glove permeation from in vitro studies. Future in vivo studies that characterize the absorbed dose of NMP in humans, both with and without gloves made from different materials, would be valuable in validating, refining, and/or replacing the approach taken in this assessment.The KpConstant concentration of NMP in liquid on skin—Consistent with the USEPA assessment, the concentration of NMP in liquid on skin or glove was assumed to be constant and infinite, rather than decrease over time due to absorption, volatilization, and transdermal flux of water [of water . This isRespirator efficacy—The range of respirator efficacies at reducing inhalation exposures to NMP was not evaluated in this assessment. Instead, USEPA’s assumption of a 90% reduction in the air concentration was maintained for this assessment. Like glove permeation rate, the efficacy of respirators is expected to vary. Bader et al. [3 (20 ppm), which suggests that the MOE values calculated here for respirator use scenarios may be underestimated for high efficacy respirators. However, a comparison of MOE values for scenarios with and without respirator show very similar results for scenarios without gloves  and repeated dermal contact with NMP. Because NMP is considered to be irritating to eyes and skin [and skin , prolongEndpoint selection—Because the endpoint selected for NMP risk assessment  are applicable to exposures to pregnant women, MOE values for male and non-pregnant female workers exposed to NMP are expected to be higher than those calculated here, since they would be based upon on a less sensitive endpoint .Human PBPK model parameterization—In developing their PBPK model for NMP, USEPA relied upon conservative parameter values for humans using only the low-concentration data from the human volunteer study of Bader et al. [r et al.  xposures –20.Intraspecies variation—An acceptable MOE value of 30 was defined by USEPA [by USEPA  for NMP,by USEPA  suggestsby USEPA . A PBPK by USEPA , This chBenchmark response rate—For the acute assessment, the use of a benchmark response rate of 1% for developmental effects is lower than has been selected for other chemicals, which typically rely upon a benchmark response rate of 5% or equivalent to one standard deviation. In this case, use of benchmark response rate of one standard deviation would results in an acute POD (IDTA) and corresponding MOE values that are ~2.5-fold higher than those calculated here. Similarly, use of a benchmark response rate of one standard deviation would result in a 1.1-fold change in chronic POD and MOE values. This change alone would result in acceptable acute MOE values for all scenarios for glove from the moderately and maximally protective categories, while chronic MOE value conclusions would remain unchanged.Exposure duration concordance—There is some degree of discordance in the exposure durations used in acute toxicity and acute exposure assessments conducted for NMP. Specifically, the point of departure for acute endpoints relies upon observations following a 15-day exposure to NMP, which covers the majority of the rat gestation period (21 days). On the other hand, the exposure duration assumed for acute exposures to workers (1 day) reflects a small fraction of the human gestation period (40 weeks). Based upon a consideration of this issue for chemicals in general [ general  and on N general , a one-dThe MOE values calculated in this assessment are higher than calculated for the no-glove scenarios in USEPA’s TSCA risk assessment . The adoRefinements to the NMP risk assessment that address combinations of these conservative assumptions using probabilistic methods would be expected to result in MOE values that are considerably higher than calculated in this assessment, by perhaps as much as an order of magnitude. Such refinements would be consistent with USEPA’s definition for Reasonable Maximum Exposure (RME) , which sThe results of this refined risk assessment indicate that NMP-containing paint strippers can be used safely, provided that appropriate PPE  are used. In this assessment, use of gloves from the maximum protection category reduced internal dose estimates of NMP following acute and chronic exposures by more than 90%, indicating that the dermal absorption of liquid NMP is the most important pathway contributing to total exposure to workers in the eight scenarios evaluated. These results can be used to support risk-reduction methods as pragmatic alternatives to banning the use of NMP paint strippers under TSCA, including better instructions  regarding the use of appropriate glove material when using NMP paint strippers.