Regulatory mechanisms to create healthier environments: planning appeals and hot food takeaways in England.

AIMS: To explore existing regulatory mechanisms to restrict hot food takeaway (HFT) outlets through further understanding processes at local and national levels. METHODS: The Planning Appeals Portal was utilised to identify recent HFT appeal cases across England between December 2016 and March 2020. Eight case study sites were identified using a purposive sampling technique and interviews carried out with 12 professionals involved in planning and health to explore perceptions of and including factors that may impact on the HFT appeal process. Additionally, documents applicable to each case were analysed and a survey completed by seven Local Authority (LA) health professionals. To confirm findings, interpretation meetings were conducted with participants and a wider group of planning and public health professionals, including a representative from the Planning Inspectorate. RESULTS: Eight case study sites were identified, and 12 interviews conducted. Participants perceived that LAs would be better able to work on HFT appeal cases if professionals had a good understanding of the planning process/the application of local planning policy and supplementary planning documents; adequate time and capacity to deal with appeals cases; access to accurate, robust, and up to date information; support and commitment from elected members and senior management; good lines of communication with local groups/communities interested in the appeal; information and resources that are accessible and easy to interpret across professional groups. CONCLUSIONS: Communication across professional groups appeared to be a key factor in successfully defending decisions. Understanding the impact of takeaway outlets on health and communities in the long term was also important. To create a more robust appeals case and facilitate responsiveness, professionals involved in an appeal should know where to locate current records and statistical data. The enthusiasm of staff and support from senior management/elected officials will play a significant role in driving these agendas forward.

Nature-positive goals for an organization's food consumption.

Organizations are increasingly committing to biodiversity protection targets with focus on 'nature-positive' outcomes, yet examples of how to feasibly achieve these targets are needed. Here we propose an approach to achieve nature-positive targets with respect to the embodied biodiversity impacts of an organization's food consumption. We quantify these impacts using a comprehensive database of life-cycle environmental impacts from food, and map exploratory strategies to meet defined targets structured according to a mitigation and conservation hierarchy. By considering the varying needs and values across the organization's internal community, we identify a range of targeted approaches towards mitigating impacts, which balance top-down and bottom-up actions to different degrees. Delivering ambitious nature-positive targets within current constraints will be challenging, particularly given the need to mitigate cumulative impacts. Our results evidence that however committed an organization is to being nature positive in its food provision, this is unachievable in the absence of systems change.

The impact of COVID-19 on the hot food takeaway planning regulatory environment: perspectives of local authority professionals in the North East of England.

BACKGROUND & AIMS: Planning regulations have been used to prevent the over-proliferation of hot food takeaways, minimising the impact of local obesogenic environments. To help mitigate the effects of lockdown, the UK government introduced temporary changes in March 2020 to Planning Regulations for England, allowing food retailers to open for takeaway services beyond 'ancillary' level without needing to apply for planning permission through permitted development rights (PDR). Businesses are required to notify their local authority (LA) when they implement PDRs. To better understand the impact of regulations on the policy and practice of key professional groups, Public Health England commissioned Teesside University to undertake scoping research in the North East of England. METHODS: A focus group and interviews were conducted with 15 professionals from 7 of 12 North East LAs. Professions included Planners, Public Health Leads, Environmental Health Officers and Town Centre Managers. Data were analysed using a codebook thematic analysis approach. An interpretation meeting with some participants was conducted. RESULTS: LAs were not aware of most businesses notifying them of new regulation adherence despite taking up PDRs, but were considered low-priority with many lacking formal recording procedures. There were concerns about health consequences of the changes, and consensus relating to ongoing issues with capacity across all professional groups, largely due to the continuing pandemic and absence of a strategy out of temporary measures. Concerns existed around ensuring cessation of restaurants trading as takeaways, and hygiene inspections backlog. Many (personally) saw new takeaways as a lifeline, offering broader menus and preserving local economies. CONCLUSION: Lack of information around the number of restaurants/pubs using PDR to trade as takeaway services, ongoing capacity issues of LAs and, at the time, the absence of a strategy post regulation changes, meant there were high levels of uncertainty regarding the impacts of these temporary measures.

Novel functions of S1P in chronic itchy and inflammatory skin diseases.

S1P is a pleotropic sphingolipid signalling molecule that acts through binding to five high-affinity G-protein coupled receptors. S1P-signaling affects cell fate in a multitude of ways, e.g. influencing cell differentiation, proliferation, and apoptosis, as well as playing an important role in immune cell trafficking. Though many effects of S1P-signaling in the human body have been discovered, the full range of functions is yet to be understood. For inflammatory skin diseases such as atopic dermatitis and psoriasis, evidence is emerging that dysfunction and imbalance of the S1P-axis is a contributing factor. Multiple studies investigating the efficacy of S1PR modulators in alleviating the severity and symptoms of skin conditions in various animal models and human clinical trials have shown promising results and validated the interest in the S1P-axis as a potential therapeutic target. Even though the involvement of S1P-signalling in inflammatory skin diseases still requires further clarification, the implications of the recent findings may prompt expansion of research to additional skin conditions and more S1P-axis modulatory pharmaceuticals.

Pharmacological interventions for periorificial (perioral) dermatitis in children and adults: a systematic review.

The plethora of pharmacologic treatments used for periorificial dermatitis (POD) makes clinical decision-making challenging. The objectives of this review were to assess the efficacy and safety of pharmacological interventions for POD in children and adults. The search was performed on 2 February 2021 and included seven databases and trial registries, with no date or language restrictions Study selection, data extraction and risk of bias assessments were performed independently and in duplicate by two authors, in accordance with a prespecified protocol. Meta-analyses were performed and reported in accordance with PRISMA guidelines. Where meta-analysis was not possible, a narrative synthesis was performed and reported in accordance with SWiM guidelines. The certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Eleven studies representing 733 participants were included. Oral tetracycline may improve physician-reported severity of POD from day 20 onwards (low certainty evidence). Adverse effects may include abdominal discomfort, facial dryness and pruritus. Pimecrolimus cream may improve physician-reported severity slightly after 4 weeks of treatment (MD -0.49, 95% CI -1.02 to 0.04, n = 164, low certainty evidence). Adverse effects may include erythema, herpes simplex virus infection, burning and pruritus. Azelaic acid gel may result in no change in either physician- or patient-reported severity after 6 weeks of treatment. The evidence is very uncertain about the effect of praziquantel ointment on physician-reported severity and skin-related quality of life after 4 weeks of treatment. The evidence is also very uncertain about the effect of topical clindamycin/benzoyl peroxide on physician-reported severity. The body of evidence to inform treatment of POD currently consists of low and very low certainty evidence for important outcomes. Well-designed trials are needed to further investigate treatment options. Data are required for children and from low-middle income countries to improve external validity. Future trials should also include adequate post-treatment follow-up and standardized outcome measures.

Toxicological analysis of aerosols derived from three electronic nicotine delivery systems using normal human bronchial epithelial cells.

Electronic nicotine delivery systems (ENDS) are a rapidly growing global market advertised as a safer alternative to combustible cigarettes. However, comprehensive investigations of END aerosol physicochemical and toxicological properties have not been fully explored across brands to assess relative safety. In this study, we evaluated aerosols collected from three ENDS - Juul Fruit Medley (5% nicotine), Logic Power (2.4% nicotine), and Mistic (1.8% nicotine). ENDS aerosols were generated using standard machine puffing regimen and collected with a novel fluoropolymer condensation trap. Triple quadrupole-inductively coupled plasma-mass determined the presence of heavy metals in collected aerosols. The toxicological effects of ENDS aerosols on normal human bronchial epithelial cells (NHBE) were investigated using cellular viability, reactive oxygen species, oxidative stress assays, along with DNA damage assessments using the CometChip©. Results indicated the total metal concentrations within collected ENDS aerosols were higher for Mistic and Logic compared to Juul. Logic Power aerosols elicited higher reactive oxygen species levels than Mistic and Juul in NHBE after 24-h exposure. Similar dose-dependent reductions of cellular viability and total glutathione were found for each exposure. However, Logic and Juul aerosols caused greater single stranded DNA damage compared to Mistic. Our study indicates that regardless of brand, ENDS aerosols are toxic to upper airway epithelial cells and may pose a potential respiratory hazard to occasional and frequent users.

High fat diet causes distinct aberrations in the testicular proteome.

Diet has important effects on normal physiology and the potential deleterious effects of high fat diets and obesity on male reproductive health are being increasingly described. We conducted a histological review of the effects of chronic high fat (HF) diet (using a mouse model fed a 45% fat diet for 21 weeks) with a discovery proteomic study to assess for changes in the abundance of proteins in the testis. Mice on a HF diet became obese and developed glucose intolerance. Using mass spectrometry, we identify 102 proteins affected in the testis of obese mice. These included structural proteins important for the blood testis barrier (filamin A, FLNA), proteins involved in oxidative stress responses (spermatogenesis associated 20, SPATA-20) and lipid homoeostasis (sterol regulatory element-binding protein 2, SREBP2 and apolipoprotein A1, APOA1). In addition, an important regulator protein paraspeckle component 1, PSPC-1, which interacts with the androgen receptor was significantly downregulated. Proteomic data was validated using both Western blotting and immunostaining which confirmed and localised protein expression in both mouse and human testis using biopsy specimens. This study focused mainly on the abnormalities that occurred at the protein level and as a result, we have identified several candidate proteins and conducted pathway analysis around the effects of HF diet on the testis providing novel insights not previously described. Some of the identified targets could be targeted therapeutically and future work is directed in this area.

Investigating hair zinc concentrations in children with and without atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin condition that disproportionately affects children and is associated with reduced quality of life. Zinc deficiency may contribute to the pathogenesis of AD because zinc plays a role in epidermal barrier integrity and the immune system. Systematic review evidence suggests that low zinc is associated with AD, but limitations of included studies support further investigation. OBJECTIVES: To investigate hair zinc concentrations in children with AD v. healthy controls in a low- to middle-income country setting. METHODS: One hundred and five children aged 1 - 12 yea-rs participated in a frequency-matched for age case-control study. The outcome variable, AD, was confirmed by a clinician and corroborated using the UK Working Party criteria. The primary predictor, long-term average zinc concentration, was determined by measuring hair zinc using inductively coupled mass spectrometry. Baseline demographic characteristics, anthropometry and measures of socioeconomic status were included in our logistic regression analysis. Subgroup analysis was performed where interaction terms suggested effect modification. RESULTS: Using data from the overall sample, population median hair zinc was not significantly different between children with AD and healthy controls. However, subgroup analysis suggested a clinically and statistically significant difference in median zinc between children with AD (175.35 µg/g) and healthy controls (206.4 µg/g) in the older age group (5 - 12 years) (p=0.01). In this age group, multivariable logistic regression analysis also found significantly decreased hair zinc concentrations in AD (odds ratio 0.83; 95% confidence interval 0.66 - 0.96; p=0.046). CONCLUSIONS: The inverse association between zinc status and AD in children aged 5 - 12 years in our setting is consistent with the international literature. The clinical importance of decreased zinc levels in AD is not yet known. Further investigation into relevant underlying mechanisms seems warranted given the global reach of AD, its effect on quality of life, and the low cost of potential zinc-based interventions.

Home used, patient self-managed, brain-computer interface for the management of central neuropathic pain post spinal cord injury: usability study.

BACKGROUND: Central Neuropathic Pain (CNP) is a frequent chronic condition in people with spinal cord injury (SCI). Previously, we showed that using laboratory brain-computer interface (BCI) technology for neurofeedback (NFB) training, it was possible to reduce CNP in people with SCI. In this study, we show results of patient self-managed treatment in their homes with a BCI-NFB using a consumer EEG device. METHODS: Users: People with chronic SCI (17 M, 3 F, 50.6 ± 14.1 years old), and CNP ≥4 on a Visual Numerical Scale. LOCATION: Laboratory training (up to 4 sessions) followed by home self-managed NFB. User Activity: Upregulating the EEG alpha band power by 10% above a threshold and at the same time downregulating the theta and upper beta (20-30 Hz) band power by 10% at electrode location C4. Technology: A consumer grade multichannel EEG headset (Epoch, Emotiv, USA), a tablet computer and custom made NFB software. EVALUATION: EEG analysis, before and after NFB assessment, interviews and questionnaires. RESULTS: Effectiveness: Out of 20 initially assessed participants, 15 took part in the study. Participants used the system for 6.9 ± 5.5 (median 4) weeks. Twelve participants regulated their brainwaves in a frequency specific manner and were most successful upregulating the alpha band power. However they typically upregulated power around their individual alpha peak (7.6 ± 0.8 Hz) that was lower than in people without CNP. The reduction in pain experienced was statistically significant in 12 and clinically significant (greater than 30%) in 8 participants. Efficiency: The donning was between 5 and 15 min, and approximately 10-20% of EEG data recorded in the home environment was noise. Participants were mildly stressed when self-administering NFB at home (2.4 on a scale 1-10). User satisfaction: Nine participants who completed the final assessment reported a high level of satisfaction (QUESQ, 4.5 ± 0.8), naming effectiveness, ease of use and comfort as main priorities. The main factors influencing frequency of NFB training were: health related issues, free time and pain intensity. CONCLUSION: Portable NFB is a feasible solution for home-based self-managed treatment of CNP. Compared to pharmacological treatments, NFB has less side effects and provides users with active control over pain. TRIAL REGISTRATION: GN15NE124 , Registered 9th June 2016.

Zinc and atopic dermatitis: a systematic review and meta-analysis.

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21-1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non-significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71-3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High-quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.

Allergy in the elderly: A case note review of referrals to an adult allergy clinic.

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.

Determinants of hair cortisol concentration in children: A systematic review.

BACKGROUND: Several factors are known contribute to hair cortisol concentration (HCC) in adults. However, there is less research on determinants of HCC in children and adolescents. HCC is a valuable tool for medical research pertaining to the hypothalamic-pituitary-adrenal (HPA) axis. This review aims to assess the extent to which established determinants of HCC in adults have been consistently reported in children (birth - 18 years) and to identify determinants of HCC specific to this age group. METHODS: Eligible studies were identified, selected and appraised as per PRISMA-P guidelines and as detailed in our systematic review protocol, registered on PROSPERO (registration number CRD42017056220). In view of contrasting methods and measures, a meta-analysis could not be done but a qualitative synthesis was performed. RESULTS: Thirty-six studies were included in the analysis. Higher HCC is associated with male sex and anthropometry, particularly increased body mass index and waist circumference. There is preliminary evidence to suggest that socio-economic status is inversely related to child HCC, particularly with reference to caregiver education and income. Of note, most of the studies analysing socio-economic variables were performed in relatively equal societies. Hair wash frequency and use of hair products and treatments do not affect HCC when proximal segments of hair are used. There is conflicting evidence regarding the relationship between HCC and age in children and adolescents. Further investigation is required to better delineate if and how the following are associated with HCC in children: hair colour, hair type, exposure to trauma and stressors, psychiatric illness, atopic illness, steroid use (including topical and inhaled steroids) and perinatal variables. CONCLUSIONS: Sex and anthropometry are potential confounders and should be considered for adjustment in hair cortisol research. Hair wash frequency and use of hair products and treatments are not important confounders when proximal hair segments are used. A better understanding of HCC in children in relation to exposure to trauma and stressors is required before it can be used as a biomarker, particularly in terms of vulnerable developmental stages, definition and measurement of stress, and temporal relationship to stressors. Age, SES and other correlates also warrant further investigation.

Higher concentrations of dithranol appear to induce hair growth even in severe alopecia areata.

Alopecia areata (AA) is the commonest autoimmune cause of non-scarring alopecia. Topical treatments including corticosteroids and irritants maybe beneficial. Studies report variable hair regrowth with dithranol (anthralin) but all used low concentrations (0.1-1.25%) and inconsistent measurements of AA severity. We report retrospective data (2005-2014) of 102 patients who had failed ultra-potent topical steroids and were referred to a specialist hair clinic for treatment with dithranol up to 3%. The severity of alopecia areata tool was used and participants graded as mild (<25%), moderate (>25 to 75%), and severe (>75%) hair loss. Compared with baseline any and at-least 50% hair regrowth [72%, 68%, 50% and 61.5%, 48.4%, 37.5%, in mild, moderate and severe AA respectively] occurred in all groups (median treatment duration 12 months). Twenty-nine patients (28.4%) were discharged with complete regrowth; with no difference in proportions in severity groups (33.3%, 29%, and 21.9%) but in the period to discharge [7.9, 6.3, and 29.4 months (p-values <.05)] for mild, moderate, and severe AA. Treatment trials of 12 months with dithranol at higher concentrations may be an option in patients who failed potent topical or intra-lesional steroids) regardless of AA severity. Randomized trials (of less staining formulations) of dithranol are warranted.

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy: longitudinal analysis from the TOMBOLA randomised trial.

OBJECTIVE: To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. METHODS: Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. RESULTS: On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. CONCLUSIONS: Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

c-Jun N-terminal kinase promotes stem cell phenotype in triple-negative breast cancer through upregulation of Notch1 via activation of c-Jun.

c-Jun N-terminal kinase (JNK) plays a vital role in malignant transformation of different cancers, and JNK is highly activated in basal-like triple-negative breast cancer (TNBC). However, the roles of JNK in regulating cancer stem-like cell (CSC) phenotype and tumorigenesis in TNBC are not well defined. JNK is known to mediate many cellular events via activating c-Jun. Here, we found that JNK regulated c-Jun activation in TNBC cells and that JNK activation correlated with c-Jun activation in TNBC tumors. Furthermore, the expression level of c-Jun was significantly higher in TNBC tumors than in non-TNBC tumors, and high c-Jun mRNA level was associated with shorter disease-free survival of patients with TNBC. Thus, we hypothesized that the JNK/c-Jun signaling pathway contributes to TNBC tumorigenesis. We found that knockdown of JNK1 or JNK2 or treatment with JNK-IN-8, an adenosine triphosphate-competitive irreversible pan-JNK inhibitor, significantly reduced cell proliferation, the ALDH1+ and CD44+/CD24- CSC subpopulations, and mammosphere formation, indicating that JNK promotes CSC self-renewal and maintenance in TNBC. We further demonstrated that both JNK1 and JNK2 regulated Notch1 transcription via activation of c-Jun and that the JNK/c-Jun signaling pathway promoted CSC phenotype through Notch1 signaling in TNBC. In a TNBC xenograft mouse model, JNK-IN-8 significantly suppressed tumor growth in a dose-dependent manner by inhibiting acquisition of the CSC phenotype. Taken together, our data demonstrate that JNK regulates TNBC tumorigenesis by promoting CSC phenotype through Notch1 signaling via activation of c-Jun and indicate that JNK/c-Jun/Notch1 signaling is a potential therapeutic target for TNBC.

Evaluating an anaerobic digestion (AD) feedstock derived from a novel non-source segregated municipal solid waste (MSW) product.

In many nations industrial scale AD of non-agricultural waste materials (such as MSW) has not yet reached its full potential, often constrained by the lack of secure, inexpensive, high quality AD feedstocks, and markets for the resulting digestate material. We tested the output material of a high throughput novel industrial process to define its potential as an AD feedstock (based on quality and consistency). This process, designed to circumvent the constraints of source segregation while still generating segregated waste streams, resulted in the production of a temporally homogenous fibrous material with: an average moisture content of 44.2 (±2.33)%; C:N ratio of ∼32.9:1 (±3.46:1), C:P ratio of ∼228:1 and gross calorific value of 17.4 (±0.29)MJ/kg(DM). This material provided a CH4 yield of between 201 and 297m3 CH4/tonne(DM) (271-401m3CH4/tonne(vs)) comparable to commonly used AD feedstocks. Material contaminant levels were temporally consistent (P>0.05), (average values being Cd 0.63 (±0.19), Cu 56.3 (±7.45), Crtot 51.4 (±4.41), Hg<0.3, Ni 28.9 (±5.17), Pb 79.2 (±23.71), Zn 202 (±44.5), total polyaromatic hydrocarbons (PAH) 2.2 (±0.3), and total polychlorinated biphenyls (PCB) (<0.2)mg/kg(DM)). Calculated digestate contaminant levels were below the median contaminant threshold limits for anaerobic digestates of all countries within the European Union i.e. of Cd 3.35, Cu 535, Crtot 535, Hg 8.15, Ni 185, Pb 397.5, Zn 2100mg/kg(DM). We suggest that novel high throughput processes that produce high quality AD feedstocks, may have a place in further diversion of waste from landfill.

Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells. Mechanistically, KLF4 represses the gene encoding the kinase MAP2K7. Our results showed that in murine and pediatric T-ALL, loss of KLF4 leads to aberrant activation of MAP2K7 and of the downstream effectors JNK and ATF2. As a proof-of-concept for the development of a targeted therapy, administration of JNK inhibitors reduced the expansion of leukemia cells in cell-based and patient-derived xenograft models. Collectively, these data uncover a novel function for KLF4 in regulating the MAP2K7 pathway in T-ALL cells, which can be targeted to eradicate leukemia-initiating cells in T-ALL patients.

The RUDY study platform - a novel approach to patient driven research in rare musculoskeletal diseases.

BACKGROUND: Research into rare diseases is becoming more common, with recognition of the significant diagnostic and therapeutic care gaps. Registries are considered a key research methodology to address rare diseases. This report describes the structure of the Rare UK Diseases Study (RUDY) platform that aims to improve research processes and address many of the challenges of carrying out rare musculoskeletal disease research. RUDY is an internet-based platform with online registration, initial verbal consent, online capture of patient reported outcome measures and events within a dynamic consent framework. The database structure, security and governance framework are described. RESULTS: There have been 380 participants recruited into RUDY with completed questionnaire rates in excess of 50 %. There has been one withdrawal and two participants have amended their consent options. CONCLUSIONS: The strengths of RUDY include low burden for the clinical team, low research administration costs with high participant recruitment and ease of data collection and access. This platform has the potential to be used as the model for other rare diseases globally.

"Sometimes I feel like a pharmacist": identity and medication use among adolescents with juvenile arthritis.

BACKGROUND: Taking medicines as intended is difficult for everybody, but young people going through adolescence have greater problems than adults and younger children. One of the most important things that happen during the teenage years is the development of individual identities, which might not remain constant during this time and can be affected deeply by the diagnosis of a long-term condition. The aim of this study was to examine the relationships between identity and medication use among young people with juvenile arthritis. METHODS: A prospective qualitative study was undertaken to collect private online 'blog' style data from young people (aged 11-19 years) with juvenile arthritis, and their parents, to examine their views about their condition, identity, medication and use of health services. Participants were identified from a large paediatric hospital in the UK. RESULTS: Young people (n = 21) with a median age 14 years (range 11-17 years) posted a median (range) of 8 (1-36) blogs and parents (n = 6) posted 4 (1-12) blogs. Young people gave a strong sense of both private and public identity that was intertwined with their arthritis and treatment. It was evident that young people's self-care was intrinsically linked to their attempts to maintain a sense of individually and socially constructed definitions of normality. The act of taking medication, and the consequences (positive or negative) of that act, had an impact both personally and socially. CONCLUSIONS: Young people with juvenile arthritis reflect on their medication as a factor affecting their perception of themselves. Acknowledging the roles of both personal and social identity will be important in any strategies to support optimal medication use. This includes an understanding of the identity transformations that young people can experience and how decision-making may be affected by their attempts to retain pre-diagnosis identities and/or develop new social identities.