Identifying acne treatment uncertainties via a James Lind Alliance Priority Setting Partnership

Objectives: The Acne Priority Setting Partnership (PSP) was set up to identify and rank treatment uncertainties by bringing together people with acne, and professionals providing care within and beyond the National Health Service (NHS). Setting: The UK with international participation. Participants: Teenagers and adults with acne, parents, partners, nurses, clinicians, pharmacists, private practitioners. Methods: Treatment uncertainties were collected via separate online harvesting surveys, embedded within the PSP website, for patients and professionals. A wide variety of approaches were used to promote the surveys to stakeholder groups with a particular emphasis on teenagers and young adults. Survey submissions were collated using keywords and verified as uncertainties by appraising existing evidence. The 30 most popular themes were ranked via weighted scores from an online vote. At a priority setting workshop, patients and professionals discussed the 18 highest-scoring questions from the vote, and reached consensus on the top 10. Results: In the harvesting survey, 2310 people, including 652 professionals and 1456 patients (58% aged 24 y or younger), made submissions containing at least one research question. After checking for relevance and rephrasing, a total of 6255 questions were collated into themes. Valid votes ranking the 30 most common themes were obtained from 2807 participants. The top 10 uncertainties prioritised at the workshop were largely focused on management strategies, optimum use of common prescription medications and the role of nondrug based interventions. More female than male patients took part in the harvesting surveys and vote. A wider range of uncertainties were provided by patients compared to professionals. Conclusions: Engaging teenagers and young adults in priority setting is achievable using a variety of promotional methods. The top 10 uncertainties reveal an extensive knowledge gap about widely used interventions and the relative merits of drug versus non-drug based treatments in acne management

Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in situ in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications

Comparison of a Novel Insulin Bolus-Patch with Pen/Syringe Injection to Deliver Mealtime Insulin for Efficacy, Preference, and Quality of Life in Adults with Diabetes: A Randomized, Crossover, Multicenter Study

Objective: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. Research Design and Methods: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). Results: Using bolus-patch, MDBG (mean•SE) was equivalent to that using pen/syringe (8.61+/-0.28 vs. 9.02+/-0.26-mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18+/-0.18 vs. 3.63+/-0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2+/-1.7 vs. 40.3+/-1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). Conclusions: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90477/1/dia-2E2011-2E0047.pd

Evaluation of an internet-based animated preparatory video for children undergoing non-sedated MRI

OBJECTIVES: We evaluate the value of an internet-based educational animated video designed to prepare children for MRI scans, and whether this video reduces scan-related anxiety in children with a neurological disorder, and healthy controls. METHODS: Participants completed a pre- and post-scan questionnaire evaluating participant online viewing behaviour, understanding of the MRI procedure, anxiety regarding the MRI, impact of animation in preparing the child and whether the child's expectation of the MRI scan matched their experience. RESULTS: 21 children were recruited (12 healthy controls) ranging in age from 6.5 to 11.5 years. The animation was successfully accessed by participants on a range of digital devices and had high levels of approval. Children who viewed the animation had a good understanding of the MRI procedure and low anxiety levels prior to the scan, and reported that their expectations broadly matched the real-life MRI experience. Children reported that the animation positively impacted on their preparation with similar ratings before and after the scan, and the impact on preparation was rated greater by younger children. There were no group differences between healthy children and those with the neurological disorder for ratings of anxiety, impact on preparation and expectation of the experience. CONCLUSION: This evaluation demonstrates accessibility, acceptability and relevance of internet-based educational animation for typically developing children, and children with a neurodisability aged 6 to 11 years, with positive impact on preparation for MRI. Advances in knowledge: The internet-based educational animation provides a widely accessible tool to support preparation of children for non-sedated MRI

Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance

The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy, however the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is not well understood. Here, we determined the myocardial tolerance of the chronically hypoxic heart to subsequent acute injury, and hypothesised that activation of a key regulator of myocardial metabolism, the pyruvate dehydrogenase complex (PDC), could improve hypoxic tolerance. Mouse hearts, perfused in Langendorff mode, were exposed to 30min of hypoxia, and lost 80% of prehypoxic function (p=0.001), with only 27% recovery of pre-hypoxic function with 30min of re-oxygenation (p=0.046). Activation of the PDC with infusion of 1mM dicholorocacetate (DCA) during hypoxia and re-oxygenation did not alter function. Acute hypoxic tolerance was assessed in hearts of mice housed in hypoxia for 3wks. Chronic hypoxia reduced cardiac tolerance to subsequent acute hypoxia, with recovery of function 22% of pre-acute hypoxic levels, vs 39% in normoxic control hearts (p=0.012). DCA feeding in chronic hypoxia (per os, 70mg/kg/day) doubled cardiac acetylcarnitine content, and this fell following acute hypoxia. This acetylcarnitine use maintained cardiac ATP and glycogen content during acute hypoxia, with hypoxic tolerance normalised. In summary, chronic hypoxia renders the heart more susceptible to acute hypoxic injury, which can be improved by activation of the PDC and pooling of acetylcarnitine. This is the first study showing functional improvement of the chronically hypoxic heart with activation of the PDC, and offers therapeutic potential in cardiac disease with a hypoxic component

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of theESSCAnetwork, 2015-2018

BACKGROUND Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen

Language lateralization of hearing native signers: A functional transcranial Doppler sonography (fTCD) study of speech and sign production

Neuroimaging studies suggest greater involvement of the left parietal lobe in sign language compared to speech production. This stronger activation might be linked to the specific demands of sign encoding and proprioceptive monitoring. In Experiment 1 we investigate hemispheric lateralization during sign and speech generation in hearing native users of English and British Sign Language (BSL). Participants exhibited stronger lateralization during BSL than English production. In Experiment 2 we investigated whether this increased lateralization index could be due exclusively to the higher motoric demands of sign production. Sign naïve participants performed a phonological fluency task in English and a non-sign repetition task. Participants were left lateralized in the phonological fluency task but there was no consistent pattern of lateralization for the non-sign repetition in these hearing non-signers. The current data demonstrate stronger left hemisphere lateralization for producing signs than speech, which was not primarily driven by motoric articulatory demands

An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is "fragile". Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no "gold-standard" to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test--a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI)

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure