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Skin ageing is an intricate physiological process affected by intrinsic and extrinsic factors. There is a demand to understand how the skin changes with age and photoexposure in individuals with Fitzpatrick skin types I-III due to accelerated photoageing and the risk of cutaneous malignancies. To assess the structural impact of intrinsic and extrinsic ageing, we analysed 14 skin parameters from the photoprotected buttock and photoexposed dorsal forearm of young and ageing females with Fitzpatrick skin types II-III (n = 20) using histomorphic techniques. Whilst the minimum viable epidermis (Emin) remained constant (Q > 0.05), the maximum viable epidermis (Emax) was decreased by both age and photoexposure (Q ≤ 0.05), which suggests that differences in epidermal thickness are attributed to changes in the dermal-epidermal junction (DEJ). Changes in Emax were not affected by epidermal cell proliferation. For the first time, we investigated the basal keratinocyte morphology with age and photoexposure. Basal keratinocytes had an increased cell size, cellular height and a more columnar phenotype in photoexposed sites of young and ageing individuals (Q ≤ 0.05), however no significant differences were observed with age. Some of the most striking changes were observed in the DEJ, and a decrease in the interdigitation index was observed with both age and photoexposure (Q ≤ 0.001), accompanied by a decreased height of rête ridges and dermal papilla. Interestingly, young photoexposed skin was comparable to ageing skin across many parameters, and we hypothesise that this is due to accelerated photoageing. This study highlights the importance of skin care education and photoprotection from an early age.

Human skin equivalents (HSEs) are a popular technology due to limitations in animal testing, particularly as they recapitulate aspects of structure and function of human skin. Many HSEs contain two basic cell types to model dermal and epidermal compartments, however this limits their application, particularly when investigating the effect of exogenous stressors on skin health. We describe the development of a novel platform technology that accurately replicates skin pigmentation in vitro. Through incorporation of melanocytes, specialized pigment producing cells, into the basal layer of the epidermis we are able to re-create skin pigmentation in vitro. We observe apical distribution of melanin within keratinocytes and formation of supranuclear caps (SPNCs), only when the epidermal compartment is co-cultured with a dermal compartment, leading to the conclusion that fibroblast support is essential for correct pigment organization. We also evaluate the commonly observed phenomenon that pigmentation darkens with time in vitro, which we further explore through mechanical exfoliation to remove a build-up of melanin deposits in the stratum corneum. Finally, we demonstrate the application of a pigmented HSE to investigate drug modulation of skin tone and protection from UV-induced damage, highlighting the importance of such a model in the wider context of skin biology.

Introduction Improving care coordination for people with rare conditions may help to reduce burden on patients and carers and improve the care that patients receive. We recently developed a taxonomy of different ways of coordinating care for rare conditions. It is not yet known which models of care coordination are appropriate in different situations. This study aimed to: (1) explore what types of care coordination may be appropriate in different situations, and (2) use these findings to develop hypothetical models of care coordination for rare conditions. Methods To explore appropriateness of different types of care coordination, we conducted interviews (n = 30), four focus groups (n = 22) and two workshops (n = 27) with patients, carers, healthcare professionals, commissioners, and charity representatives. Participants were asked about preferences, benefits and challenges, and the factors influencing coordination. Thematic analysis was used to develop hypothetical models of care coordination. Models were refined following feedback from workshop participants. Results Stakeholders prefer models of care that: are nationally centralised or a hybrid of national and local care, involve professionals collaborating to deliver care, have clear roles and responsibilities outlined (including administrative, coordinator, clinical and charity roles), provide access to records and offer flexible appointments (in terms of timing and mode). Many factors influenced coordination, including those relating to the patient (e.g., condition complexity, patient’s location and ability to coordinate their own care), the healthcare professional (e.g., knowledge and time), the healthcare environment (e.g., resources) and societal factors (e.g., availability of funding). We developed and refined ten illustrative hypothetical models of care coordination for rare conditions. Conclusion Findings underline that different models of care coordination may be appropriate in different situations. It is possible to develop models of care coordination which are tailored to the individual in context. Findings may be used to facilitate planning around which models of care coordination may be appropriate in different services or circumstances. Findings may also be used by key stakeholders (e.g. patient organisations, clinicians and service planners) as a decision-making tool.

BackgroundImproving care coordination is particularly important for individuals with rare conditions (who may experience multiple inputs into their care, across different providers and settings). To develop and evaluate strategies to potentially improve care coordination, it is necessary to develop a method for organising different ways of coordinating care for rare conditions. Developing a taxonomy would help to describe different ways of coordinating care and in turn facilitate development and evaluation of pre-existing and new models of care coordination for rare conditions. To the authors’ knowledge, no studies have previously developed taxonomies of care coordination for rare conditions. This research aimed to develop and refine a care coordination taxonomy for people with rare conditions.MethodsThis study had a qualitative design and was conducted in the United Kingdom. To develop a taxonomy, six stages of taxonomy development were followed. We conducted interviews (n=30 health care professionals/charity representatives/commissioners) and focus groups (n=4 focus groups, 22 patients/carers with rare/ultra-rare/undiagnosed conditions). Interviews and focus groups were audio-recorded with consent, and professionally transcribed. Findings were analysed using thematic analysis. Themes were used to develop a taxonomy, and to identify which types of coordination may work best in which situations. To refine the taxonomy, we conducted two workshops (n=12 patients and carers group; n=15 professional stakeholder group).ResultsOur taxonomy has six domains, each with different options. The six domains are: 1) Ways of organising care (local, hybrid, national), 2) Ways of organising professionals involved in care (collaboration between many or all professionals, collaboration between some professionals, a lack of collaborative approach), 3) Responsibility for coordination (administrative support, formal roles and responsibilities, supportive roles and no responsibility), 4) How often appointments and coordination take place (regular, on demand, hybrid), 5) Access to records (full or filtered access), and 6) Mode of care coordination (face-to-face, digital, telephone).ConclusionsFindings indicate that there are different ways of coordinating care across the six domains outlined in our taxonomy. This may help to facilitate the development and evaluation of existing and new models of care coordination for people living with rare conditions.

Imaging tools advance nanoscience education by enabling students to see and engage with matter that is not visible to the human eye. However, undergraduate students generally lack access to expensi...

Introduction: During pregnancy, women may be exposed to teratogenic medications resulting in a risk of complications and poor maternal-fetal outcomes. The objective of this study was to evaluate the prescription of teratogenic medications in women of childbearing age and the associated prescription of contraception in the primary care setting. Methods: The use of high-risk, potentially teratogenic, medications was retrospectively evaluated in women of childbearing age (13 to 45 years old) at 2 family medicine practices. Charts were reviewed for medication use and whether patients received a form of birth control (medication, sterilization, or postmenopausal) with the teratogenic medications. A multivariable logistic regression model was used to estimate the age-adjusted association between receiving a teratogenic medication and contraception. A subgroup analysis excluding ondansetron was also performed. Results: A total of 3,956 nonpregnant women were included with 988 (25%) prescribed at least 1 high-risk medication. The most commonly prescribed high-risk medications were ondansetron (n = 724, 73%) and lisinopril (n = 195, 20%). More than half (55%) of the women prescribed a high-risk medication were without a form of birth control. When ondansetron was excluded, 10% of the population was prescribed at least 1 high-risk medication with 62% also without a form of birth control. Women less than 25 years of age had decreased odds of receiving contraception when prescribed a teratogenic medication (adjusted odds ratio, 0.47; 95% confidence interval, 0.34–0.66). Conclusion: In a family medicine setting, 25% of women of childbearing age were prescribed a high-risk medication with over half not having evidence of contraception management. Interestingly, younger age women had lower odds of receiving contraceptive management when prescribed high-risk medications. Prescribers should be aware of and counsel on the risks of teratogenic medications and regularly evaluate reproductive plans for patients.

Background: the UK Rare Diseases Framework is the latest policy initiative that aims to improve healthcare for rare diseases in the UK, with four priorities focussed on faster diagnosis, increasing awareness among healthcare professionals, better care coordination and improved access to specialist care and treatment. A survey of over 1,000 people living with rare diseases in the UK immediately prior to the publication of the Framework captured quantitative and qualitative data about their experiences. The qualitative analysis is presented here and compared with the content of the Framework.Results: People living with a rare condition in the UK continue to have very mixed experiences of healthcare and our findings illustrate substantial continuing unmet needs that fall under each of the four priorities of the Framework. Conclusions: Comparing the findings with what is emphasised in the Framework suggests specific key changes to policy and practice which might be missed by action plans developed under the Framework. The overall provision in the UK for people living with rare conditions needs to be improved and regularly reviewed, to ensure they are not being unfairly excluded from appropriate diagnosis, treatment or support.

Background Care coordination is considered important for patients with rare conditions, yet research addressing the impact of care coordination is limited. This study aimed to explore how care coordination (or lack of) impacts on patients and carers. Semi-structured interviews were conducted with 15 patients and carers/parents in the UK, representing a range of rare conditions (including undiagnosed conditions). Transcripts were analysed thematically in an iterative process. Results Participants described a range of experiences and views in relation to care coordination. Reports of uncoordinated care emerged: appointments were uncoordinated, communication between key stakeholders was ineffective, patients and carers were required to coordinate their own care, and care was not coordinated to meet the changing needs of patients in different scenarios. As a result, participants experienced an additional burden and barriers/delays to accessing care. The impacts described by patients and carers, either attributed to or exacerbated by uncoordinated care, included: impact on physical health (including fatigue), financial impact (including loss of earnings and travel costs), and psychosocial impact (including disruption to school, work and emotional burden). Overall data highlight the importance of flexible care, which meets individual needs throughout patients’/carers’ journeys. Specifically, study participants suggested that the impacts may be addressed by: having support from a professional to coordinate care, changing the approach of clinics and appointments (where they take place, which professionals/services are available and how they are scheduled), and improving communication through the use of technology, care plans, accessible points of contact and multi-disciplinary team working. Conclusion This study provides further evidence of impacts of uncoordinated care; these may be complex and influenced by a number of factors. Approaches to coordination which improve access to care and lessen the time and burden placed on patients and carers may be particularly beneficial. Findings should influence future service developments (and the evaluation of such developments). This will be achieved, in the first instance, by informing the CONCORD Study in the UK.

More than half the world’s population lives in urban environments, and the proportion is rising. Cities provide opportunities for infectious diseases to infect large numbers of people and rapidly spread globally. Following outbreaks such as Severe Acute Respiratory Syndrome (SARS) in 2003, the Ebola outbreak in West Africa in 2014, and the Coronavirus Disease 2019 pandemic, it is evident that a whole of society approach is required to address global health threats. The role of the private sector is threefold – to safeguard its business and its stakeholders; protect and promote the wellbeing of its staff, community and clients; and support national and international public health efforts.This chapter reviews national and international guidance and the evolution of private sector preparedness and involvement in health security. Best practice principles for global health security planning and response for the private sector are provided. Several case studies are presented.

High-throughput genomic and molecular profiling of tumors is emerging as an important clinical approach. Molecular profiling is increasingly being used to guide cancer patient care, especially in advanced and incurable cancers. However, navigating the scientific literature to make evidence-based clinical decisions based on molecular profiling results is overwhelming for many oncology clinicians and researchers. The Personalized Cancer Therapy website (www.personalizedcancertherapy.org) was created to provide an online resource for clinicians and researchers to facilitate navigation of available data. Specifically, this resource can be used to help identify potential therapy options for patients harboring oncogenic genomic alterations. Herein, we describe how content on www.personalizedcancertherapy.org is generated and maintained. We end with case scenarios to illustrate the clinical utility of the website. The goal of this publicly available resource is to provide easily accessible information to a broad oncology audience, as this may help ease the information retrieval burden facing participants in the precision oncology field. Cancer Res; 77(21); e123–6. ©2017 AACR.

Australian Army equipment is rarely designed and acquired in a manner that meets the expectations of human factors specialists; early consideration of human factors to inform human centred design. This issue is in part due to the difficulty of accessing Australian soldiers to support human centred design. One strategy to mitigate the consequences of such an issue (equipment that is not fit-for-purpose) is formulation of a human systems integration process within the Army acquisition process. This study describes a process by which end-user human factors information can be collated and provided to suit relevant stakeholders. This dissemination of customised end-user information can assist designers, industry partners, and acquisition personnel to design, request, offer, and acquire fit-for-purpose and user-friendly equipment.

Background Rare disease patients and carers report significant impacts on mental health but this has not been extensively studied. We explored the experiences of UK-based individuals through an online survey, and offer recommendations for policy and practice developed with a multi-stakeholder workshop. Results In total 1,355 patients and 571 carers responded to the survey.Due to their rare condition, the majority of respondents had felt worried/anxious (95%); stressed (93%); low/depressed (90%); emotionally exhausted (88%). Thirty-six percent of patients and 19% of carers had had suicidal thoughts.Challenges that are particular to rare conditions and which negatively affect mental health included limited knowledge of the condition amongst healthcare professionals (88%), not being believed or taken seriously by healthcare professionals (80%), and lack of available information about the condition (76%). Only 23% of respondents felt healthcare professionals considered mental health as equally important as physical health. Almost half of patients (46%) and carers (48%) reported never having been asked about their mental health, or that of the person they care for, by healthcare professionals.Forty-six percent of respondents had received professional psychological support; the most common reason for not having accessed professional psychological support was that it had not been suggested (41%).Fifty-nine percent of respondents had accessed sources of additional emotional support, such as patient groups, with the majority (75%) having found this support themselves. With input from our multi-stakeholder workshop we developed recommendations for healthcare professionals to be supported to effectively and sensitively recognise and address patients’ and carers’ mental health needs; and for service level coordination of care to integrate professional psychological support with rare disease services.Conclusions Living with a rare disease substantially impacts mental health. Many of the drivers of poor mental health reflect issues specific to managing rare conditions. To meet existing UK government commitments, there should be a focus on empowering healthcare professionals who treat rare disease patients and on integration of mental health support with rare disease services.

Spiritual struggles (SSs) are distressing spiritual thoughts associated with poorer health outcomes. This study’s purpose was to test feasibility, acceptability, and fidelity of an intervention to decrease SS of parents of children with CF. Parents screening positive for SS were enrolled and were randomized to intervention or attention-control condition. Intervention focused on intra-, inter-, and divine SS. Mixed linear modeling examined between-group differences. We present analyses of N = 23, and participants all showed decreased levels of SS. Acceptability was high; feasibility was higher in the intervention arm. GuideSS_CF is acceptable and feasible and warrants development as a potentially efficacious intervention.

The Ebola outbreak in West Africa that began with a single case in December 2013 became an unprecedented event in almost every aspect. In the twenty-first century, this outbreak has challenged ever...

This project recovers and revises late nineteenth and early twentieth-century narratives of mobility which invoke female protagonists who move from stifling, patriarchal domestic settings in the rural and suburban United States to the more symbolically emancipated settings of New York City and even Europe to reveal both the limitations and possibilities for women’s lives in the United States at the turn of the twentieth century. By challenging popular American fiction’s preoccupation with urban white slavery myths and the lingering proscriptive standards for women’s behavior of the Victorian era, the Introduction argues the selected works of this dissertation mark a significant, but perhaps fleeting moment in American history when women were on the verge of profound gains toward equality. Chapter Two reads Gertrude Atherton’s late nineteenth-century interrogation of intimate and professional mobility in Patience Sparhawk as a significant precursor, if not prototype, of the recently recognized middlebrow moderns of the 1920s. Chapter Three examines Edith Wharton’s competing views of mobility and motherhood in The House of Mirth, The Custom of the Country, and Summer. Chapter Four aims to recover David Graham Phillips’ posthumously published novel, Susan Lenox: Her Fall and Rise, as a complicated engagement with unconventional views of mobility and prostitution in early twentieth-century America, and Chapter Five argues that Jessie Redmon Fauset’s oft-maligned, sentimental novel, Plum Bun, warrants more critical attention for its revolutionary efforts to imagine an alternative cultural aesthetic whereby young, aspiring African-American women can acquire intimate and professional fulfillment through an empowering transnational mobility. Recognizing how stories of fallen womanhood in American literature traditionally overemphasized and criminalized a woman’s desire for intimacy, while stories of New Womanhood often scripted characters ultimately devoid of desire and companionship, I argue Atherton, Wharton, Phillips and Fauset examine and challenge these categories of womanhood in important, often overlooked, depictions of mobility. Too often dismissed or excused for their conservativism, these authors warrant more attention from modern literary scholars for their shared, varied, and intentionally “moving” experiences for women in late nineteenth and early twentieth-century America.

A significant number of children in the United States experience major emotional or behavioral problems, including problems that meet diagnostic criteria for a mental health problem. Although estimates vary from study to study, the Surgeon General's Report (U.S. Department of Health and Human Services, 1999) reported that approximately 20% of children have, or have had, a significant mental health problem (see also )affee, Harrington, Cohen, & Moffitt, 2005; National Research Council & Institute of Medicine |NRC & loM|, 2009). Unfortunately, only a small fraction of these children actually receive services. In schools, fewer than 1% of students are school identified with an emotional disability and receive special education services under the Individuals with Disabilities Education Improvement Act of 2004 (IDEA) for emotional disturbance (ED; Merikangas et al., 2010). This rate has remained relatively stable over the past several decades (Kauffman & Landrum, 2009) and suggests a lack of progress on efforts to accurately screen, identify, and serve this student population.Over the past several decades, a number of interventions and supports have been developed for the treatment of ED in schoolaged children. However, even with these efforts, the outcomes reveal that ED continues to be identified as one of the most expensive and prevalent chronic disorders in children (Blau, Huang, & Mallery, 2010). For example, the academic functioning of students with ED reveals significant levels of academic underachievement in all content areas across age categories and educational settings (Trout, Nordness, Pierce, & Epstein, 2003). Longitudinal studies such as the National Longitudinal Transition Study-2 (NLTS-2) and the Special Education Elementary Longitudinal Study have found that when compared with students with and without disabilities, students with ED present lower grade point averages across grade levels and higher levels of absenteeism, suspensions, expulsions, and course failures (Wagner, Kutash, Duchnowski, & Epstein, 2005). Eventually, these students drop out of school at much higher rates than their peers (Wagner, Cameto, & Newman, 2003) with related negative adult outcomes including high rates of unemployment, involvement with the criminal justice system, and drug and alcohol dependency and abuse (Kauffman & Landrum, 2009; Wagner, Newman, Cameto, Garza, & Levine, 2005). These poor adult outcomes result in significant individual and family struggles and ultimately lead to a significant toll to society.When students with ED go unidentified and without services, there is a greater chance that their initial emotional and behavioral challenges will continue into adulthood and lead to further mental health problems (Costello, Mustillo, Erkanli, Keeler, & Angold, 2003; Essex et al" 2009). Conversely, researchers have found that early identification and intervention for children who present atrisk behaviors can prevent or limit the intensity of problem behaviors and improve adult outcomes (Conroy, Hendrickson, & Hester, 2004; Mrazek & Mrazek, 2005; NRC & loM, 2009). In response to the increased evidence supporting the value of early identification and intervention, there have been further calls for policy makers and researchers to develop and use psychometrically sound universal screening instruments to identify students who are at risk for ED (Kendziora, 2004). To this end, professionals have identified three key considerations of effective screening instruments: (a) appropriateness of the intended use, (b) technical adequacy, and (c) consumer usefulness and acceptability (Glover & Albers, 2007). In addition, recent federal legislation asks for schools to become more proactive in identifying students with or at risk of ED (Fairbanks, Sugai, Guardino, & Lathrop, 2007).There are a number of screening instruments available to identify students at risk for ED: Behavioral and Emotional Screening System (Kamphaus & Reynolds, 2007), Social Skills Improvement System, Performance Screening Guide (Elliot & Gresham, 2008), Student Risk Screening Scale (Drummond, 1994), and Systematic Screening for Behavior Disorders (Walker & Severson, 1992). …

Background: Cardiovascular disease is a leading cause of death worldwide and genetic risk factors play a role in nearly all such cases. In the UK, health service capacity to meet either current or future estimated needs of people affected by inherited cardiac conditions (ICCs) is inadequate. In 2008 the British Heart Foundation funded nine three-year Cardiac Genetics Nurse (CGN) posts across England and Wales to enhance ICC services. The CGNs were experienced cardiac nurses who had additional training in genetics and acted to coordinate cardiac and genetics service activities. Aim: To create and apply a framework against which progress in ICC service improvement could be measured over time following the CGN appointments. Methods: A performance grid (Maturity Matrix, MM) articulating standards in five domains against stages of ICC service development was created by stakeholders through a consensus approach. The MM was used to guide staged self-assessments by the CGNs between 2009 and 2011. A six-point scale was used to locate progress from ‘emerging’ to ‘established’, represented graphically by spider diagrams. Results: Progress in all domains was significant for new, emerging and established services. It was most notable for effective utilisation of care pathways and efficient running of clinics. Commitment to family-centred care was evident. Conclusion: The ICC-MM provided a comprehensive framework for assessing ICC services and has merit in providing guidance on development. CGNs can help integrate care across specialisms, facilitating the development of effective and sustainable ICC services at new, developing, and more established ICC service locations.

This paper describes the components of a programme designed to prevent child maltreatment which includes the promising practices of a continuous engagement process, cognitive-behavioural parent and skill teaching, and development of formal and informal supports for families. The programme was also designed to be implemented wide scale. METHODS for assessment of strengths and needs, individualization of goals and intervention strategies, and assessment of goal achievement are also described. Finally, preliminary results of a programme implementation fidelity and outcome evaluation are summarized. The authors conclude that this programme is ready for a more rigorous efficacy trial to continue to build the evidence base for this promising intervention addressing a prevalent social problem. Language: en

O1 The European Social Preferences Measurement (ESPM) study project: social cost value analysis, budget impact, commercial life cycle revenue management, and the economics of biopharmaceutical Research & Development (R&D) Michael Schlander, Soren Holm, Erik Nord, Jeff Richardson, Silvio Garattini, Peter Kolominsky-Rabas, Deborah Marshall, Ulf Persson, Maarten Postma, Steven Simoens, Oriol de Sola Morales, Keith Tolley, Mondher Toumi, Harry Telser O2 Newborn Screening: the potential and the challenges James R Bonham O3 Untreatable disease outcomes - how would we measure them? Helmut Hintner, Anja Diem, Martin Laimer O4 Taking Integrated Care Forward: Experiences from Canada to inspire service provision for people living with rare disease in Europe Rejean Hebert O5 Listening to the patient’s voice: social media listening for safety and benefits in rare diseases Nabarun Dasgupta, Carrie E. Pierce, Melissa Jordan O6 Via Opta: Mobile apps making visually impaired patients’ lives easier Barbara Bori, Mohanad Fors, Emilie Prazakova O7 A report of the IRDiRC “Small Population Clinical Trial” Task Force Simon Day O8 HAE patient identification and diagnosis: An innovative, ‘game changing’ collaboration Thomas J. Croce Jr. O9 Co-creating with the community: primary packaging & administration for people with haemophilia Jonas Fransson, Philip Wood O10 Go with Gaucher, taking forward the next generation. How to involve young people to create a new generation of patient advocates Anne-Grethe Lauridsen, Joanne Higgs, Vesna Stojmirova Aleksovska P1 ODAK – Orphan Drug for Acanthamoeba Keratitis Christina Olsen, Ritchie Head, Antonio Asero, Vincenzo Papa, Christa van Kan, Loic Favennec, Silvana Venturella, Michela Salvador, Alan Krol P5 Rare Navigators help people living with rare diseases to manage the social – and healthcare systems Stephanie J. Nielsen, Birthe B. Holm P6 The eAcademy for Tay-Sachs & Sandhoff disease app Daniel Lewi, Patricia Durao P10 The role of a patient organisation in driving the research agenda in a rare disease Heather Band, Andrea West P13 Expertise for rare diseases mapped Marinda J.A. Hammann, Marije C. Effing-Boele, Hanka K. Dekker P14 The hidden costs of rare diseases: a feasibility study Amy Hunter, Amy Simpson P15 FDA’s new natural history grant program: support to build a solid foundation for development of products for rare diseases Gumei Liu, Katherine Needleman, Debra Lewis, Gayatri Rao P17 Understanding the wider impact of adrenal insufficiency: patient organisation involvement in the TAIN project Amy Simpson, Amy Hunter, Martin J Whitaker P20 Bridging the gaps between medical and social care for people living with a rare disease Raquel Castro