Growth dynamics and amorphous-to-crystalline phase transformation in natural nacre.

Biominerals, such as nacreous bivalve shells, are important archives of environmental information. Most marine calcifiers form their shells from amorphous calcium carbonate, hypothesised to occur via particle attachment and stepwise crystallisation of metastable precursor phases. However, the mechanism of this transformation, including the incorporation of trace elements used for environmental reconstructions, are poorly constrained. Here, using shells of the Mediterranean mussel, we explore the formation of nacre from the meso- to the atomic scale. We use a combination of strontium pulse-chase labelling experiments in aquaculture and correlated micro- to sub-nanoscale analysis to show that nacre grows in a dynamic two-step process with extensional and space-filling growth components. Furthermore, we show that nacre crystallizes via localised dissolution and reprecipitation within nanogranules. Our findings elucidate how stepwise crystallization pathways affect trace element incorporation in natural biominerals, while preserving their intricate hierarchical ultrastructure.

Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

The psychological impact of Stevens-Johnson syndrome and toxic epidermal necrolysis on patients' lives: a Critically Appraised Topic.

CLINICAL SCENARIO: A 65-year-old man presented with a 12-h history of deteriorating rash. Two weeks previously he had completed a course of neoadjuvant chemotherapy for ductal carcinoma of the breast. On examination there were bullae, widespread atypical targetoid lesions and 15% epidermal detachment. There was no mucosal involvement on presentation, but subsequently it did evolve. Skin biopsy showed subepidermal blistering with epidermal necrosis. This confirmed our clinical diagnosis of overlap Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). On transfer to intensive care he was anxious and fearful. MANAGEMENT QUESTION: What are the psychological impacts of SJS/TEN on this man's life? BACKGROUND: SJS and TEN have devastating outcomes for those affected. OBJECTIVES: To conduct a Critically Appraised Topic to (i) analyse existing research related to the psychological impact of SJS and TEN and (ii) apply the results to the clinical scenario. METHODS: Seven electronic databases were searched for publications focusing on the psychological impact of SJS/TEN on adults over 18 years of age. RESULTS: Six studies met the inclusion criteria. Healthcare practitioners' (HCPs') lack of information around the disorder was highlighted. Patients experienced undue stress and fear. Some patients had symptoms aligned to post-traumatic stress disorder (PTSD), anxiety and depression. DISCUSSION AND RECOMMENDATION: The evidence suggests that SJS and TEN impact psychologically on patients' lives. Education of HCPs, to address their lack of awareness and information on SJS/TEN, should facilitate their capacity to provide information and support to patients, thereby reducing patient anxiety. On discharge, a follow-up appointment with relevant HCPs to reduce the possibility of PTSD occurring should be considered.

Coming of Age in Ireland: the Twilight Zone!

Aim To describe the healthcare needs of adolescent patients inhabiting the 'seventh age of childhood' in our region with a view towards future workforce and infrastructure planning. Methods This is a retrospective descriptive study of patients aged between 14 and 16 years presenting to each of the six hospitals in our hospital group over a 10 year period (01.07.2006-1.07.2016) using electronic databases. Results There were 10,992 hospital admissions, 41,456 outpatient appointments and an average of 1,847 attendances per year at our Emergency Department in this age group. Seventeen percent (n=1,873) of patients were admitted to age appropriate wards. Only 11.3% (n=1,242) of our cohort were admitted under the care of a Paediatrician. Conclusion The Irish healthcare agenda needs to be advanced to ensure the optimal health for this valuable, yet vulnerable generation. Further investment will help shape the fledgling discipline of 'adolescent health' in Ireland.

Predicting educational achievement from DNA.

This corrects the article DOI: 10.1038/mp.2016.107.

Multi-polygenic score approach to trait prediction.

A primary goal of polygenic scores, which aggregate the effects of thousands of trait-associated DNA variants discovered in genome-wide association studies (GWASs), is to estimate individual-specific genetic propensities and predict outcomes. This is typically achieved using a single polygenic score, but here we use a multi-polygenic score (MPS) approach to increase predictive power by exploiting the joint power of multiple discovery GWASs, without assumptions about the relationships among predictors. We used summary statistics of 81 well-powered GWASs of cognitive, medical and anthropometric traits to predict three core developmental outcomes in our independent target sample: educational achievement, body mass index (BMI) and general cognitive ability. We used regularized regression with repeated cross-validation to select from and estimate contributions of 81 polygenic scores in a UK representative sample of 6710 unrelated adolescents. The MPS approach predicted 10.9% variance in educational achievement, 4.8% in general cognitive ability and 5.4% in BMI in an independent test set, predicting 1.1%, 1.1%, and 1.6% more variance than the best single-score predictions. As other relevant GWA analyses are reported, they can be incorporated in MPS models to maximize phenotype prediction. The MPS approach should be useful in research with modest sample sizes to investigate developmental, multivariate and gene-environment interplay issues and, eventually, in clinical settings to predict and prevent problems using personalized interventions.

Widespread covariation of early environmental exposures and trait-associated polygenic variation.

Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R2 = 0.008; P = 5e-13), parental smacking (R2 = 0.01; P = 4e-15), household income (R2 = 0.032; P = 1e-22), watching television (R2 = 0.034; P = 5e-47), and maternal education (R2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

Rotavirus Gastroenteritis is Associated with Increased Morbidity and Mortality in Children with Inherited Metabolic Disorders.

Rotavirus is the leading cause of infantile diarrhoea worldwide in children <5 years1. Although mortality rates are low in Ireland, certain populations are more susceptible to the associated morbidity and mortality of infection. A retrospective chart review of 14 patients with confirmed IMDs who were admitted to Temple Street Children's Hospital between 2010 to 2015 with rotavirus infection were compared with 14 randomly selected age matched controls. The median length of stay was 7 days (SD25.3) in IMD patients versus 1.5 days (SD 2.1) in the controls. IV fluids were required on average for 4.5 days (range 0-17) in IMD patients versus 0.63 days (range 0-3) in controls. This report highlights the increased morbidity of rotavirus infection in patients with IMD compared to healthy children. This vulnerable population are likely to benefit from the recent introduction of the rotavirus oral vaccination in October 2016.

Predicting educational achievement from DNA.

A genome-wide polygenic score (GPS), derived from a 2013 genome-wide association study (N=127,000), explained 2% of the variance in total years of education (EduYears). In a follow-up study (N=329,000), a new EduYears GPS explains up to 4%. Here, we tested the association between this latest EduYears GPS and educational achievement scores at ages 7, 12 and 16 in an independent sample of 5825 UK individuals. We found that EduYears GPS explained greater amounts of variance in educational achievement over time, up to 9% at age 16, accounting for 15% of the heritable variance. This is the strongest GPS prediction to date for quantitative behavioral traits. Individuals in the highest and lowest GPS septiles differed by a whole school grade at age 16. Furthermore, EduYears GPS was associated with general cognitive ability (~3.5%) and family socioeconomic status (~7%). There was no evidence of an interaction between EduYears GPS and family socioeconomic status on educational achievement or on general cognitive ability. These results are a harbinger of future widespread use of GPS to predict genetic risk and resilience in the social and behavioral sciences.

A Prospective Analysis of the Relationship between Chronic Diseases and Adiposity in older adults: Findings from the Lifeways Cross-Generation Cohort Study of a Thousand Families 2001-2014.

This study assesses the relationship between body mass index (BMI) and adult chronic diseases (diabetes mellitus type 2 [DM2], cardiovascular diseases [CVD] and cancers), in grandparents in the Lifeways Cross-Generation Cohort Study. BMI was either measured or reported, at baseline or 10-year follow-up, in 1,244 grandparents. Cumulative morbidity data were recorded at baseline, 3 and 10-year follow-up through questionnaires, General Practice note search, or both. Just over 42% of grandparents were overweight and 32.1% obese. In the multivariate analysis BMI showed a strong linear association with both DM2 (ptrend <0.001) and CVD (ptrend <0.001). There were no significant associations with cancers, but case numbers were small. Results were similar for waist circumference. This prospective study presents novel Irish data and confirms other recent Irish cross-sectional reports on adiposity and adult chronic disease, highlighting the need for effective health promotion interventions in older adults.

Neuromas as the cause of pain in the residual limbs of amputees. An ultrasound study.

AIM: To explore the morphology of neuromas and to determine the differences, if any, between asymptomatic and symptomatic neuromas using ultrasound. MATERIALS AND METHODS: Eighty patients with symptomatic neuromas were included in this retrospective review. High-resolution ultrasound examination was performed. Transducer pressure allowed real-time analysis of both symptomatic and asymptomatic neuromas. Quantifiable assessment of pain by the patient assigned a pain score of 0, 1, 2, or 3, to each neuroma. RESULTS: One hundred and fifty-nine neuromas were identified in total. Fifty-three neuromas were asymptomatic (pain score=0), very severe pain was recorded in 54 (pain score=3), 16 neuromas were mildly painful (pain score=1) and 36 were moderately painful (pain score=2). The average number of neuromas per patient was 1.98, and the average number of symptomatic neuromas per patient was 1.3. There was no correlation between pain score and patient age, neuroma volume, amputation type, and time since amputation. CONCLUSIONS: High-resolution ultrasound can distinguish between asymptomatic and symptomatic neuromas. Patient age, time since amputation, the type of amputation, and the neuroma volume were not related to the presence of pain.

Phenome-wide analysis of genome-wide polygenic scores.

Genome-wide polygenic scores (GPS), which aggregate the effects of thousands of DNA variants from genome-wide association studies (GWAS), have the potential to make genetic predictions for individuals. We conducted a systematic investigation of associations between GPS and many behavioral traits, the behavioral phenome. For 3152 unrelated 16-year-old individuals representative of the United Kingdom, we created 13 GPS from the largest GWAS for psychiatric disorders (for example, schizophrenia, depression and dementia) and cognitive traits (for example, intelligence, educational attainment and intracranial volume). The behavioral phenome included 50 traits from the domains of psychopathology, personality, cognitive abilities and educational achievement. We examined phenome-wide profiles of associations for the entire distribution of each GPS and for the extremes of the GPS distributions. The cognitive GPS yielded stronger predictive power than the psychiatric GPS in our UK-representative sample of adolescents. For example, education GPS explained variation in adolescents' behavior problems (~0.6%) and in educational achievement (~2%) but psychiatric GPS were associated with neither. Despite the modest effect sizes of current GPS, quantile analyses illustrate the ability to stratify individuals by GPS and opportunities for research. For example, the highest and lowest septiles for the education GPS yielded a 0.5 s.d. difference in mean math grade and a 0.25 s.d. difference in mean behavior problems. We discuss the usefulness and limitations of GPS based on adult GWAS to predict genetic propensities earlier in development.

The Bhutani Nomogram Reduces Incidence of Severe Hyperbilirubinaemia in Term and Near Term Infants.

Very high bilirubin levels can have devastating neurodevelopmental effects on infants including hearing loss and cerebral palsy. A previous study in our institution determined the rate of, and factors associated with, bilirubin values above exchange transfusion level. Since this study the Bhutani nomogram was introduced to help identify infants at risk of severe hyperbilirubinaemia. In our study we looked at the initial serum bilirubin taken in infants 36 weeks and 2.5 kgs. Our results show that since this nomogram was introduced there has been a significant reduction in the number of infants reaching exchange transfusion levels. We also showed that the Bhutani nomogram could successfully be used in a population of unknown direct Coombs status.

Mental health service users' experiences of mental health care: an integrative literature review.

A number of studies have highlighted issues around the relationship between service users and providers. The recovery model is predominant in mental health as is the recognition of the importance of person-centred practice. The authors completed an in-depth search of the literature to answer the question: What are service users' experiences of the mental health service? Three key themes emerged: acknowledging a mental health problem and seeking help; building relationships through participation in care; and working towards continuity of care. The review adds to the current body of knowledge by providing greater detail into the importance of relationships between service users and providers and how these may impact on the delivery of care in the mental health service. The overarching theme that emerged was the importance of the relationship between the service user and provider as a basis for interaction and support. This review has specific implications for mental health nursing. Despite the recognition made in policy documents for change, issues with stigma, poor attitudes and communication persist. There is a need for a fundamental shift in the provider-service user relationship to facilitate true service-user engagement in their care. The aim of this integrative literature review was to identify mental health service users' experiences of services. The rationale for this review was based on the growing emphasis and requirements for health services to deliver care and support, which recognizes the preferences of individuals. Contemporary models of mental health care strive to promote inclusion and empowerment. This review seeks to add to our current understanding of how service users experience care and support in order to determine to what extent the principles of contemporary models of mental health care are embedded in practice. A robust search of Web of Science, the Cochrane Database, Science Direct, EBSCO host (Academic Search Complete, MEDLINE, CINAHL Plus Full-Text), PsycINFO, PsycARTICLES, Social Sciences Full Text and the United Kingdom and Ireland Reference Centre for data published between 1 January 2008 and 31 December 2012 was completed. The initial search retrieved 272 609 papers. The authors used a staged approach and the application of predetermined inclusion/exclusion criteria, thus the numbers of papers for inclusion were reduced to 34. Data extraction, quality assessment and thematic analysis were completed for the included studies. Satisfaction with the mental health service was moderately good. However, accessing services could be difficult because of a lack of knowledge and the stigma surrounding mental health. Large surveys document moderate satisfaction ratings; however, feelings of fear regarding how services function and the lack of treatment choice remain. The main finding from this review is while people may express satisfaction with mental health services, there are still issues around three main themes: acknowledging a mental health problem and seeking help; building relationship through participation and care; and working towards continuity of care. Elements of the recovery model appear to be lacking in relation to user involvement, empowerment and decision making. There is a need for a fundamental shift in the context of the provider-service user relationship to fully facilitate service users' engagement in their care.

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration.

Focal adhesion turnover is a complex process required for cell migration. We have previously shown that the Ste20-like kinase (SLK) is required for cell migration and efficient focal adhesion (FA) turnover in a FA kinase (FAK)-dependent manner. However, the role of SLK in this process remains unclear. Using a candidate substrate approach, we show that SLK phosphorylates the adhesion adapter protein paxillin on serine 250. Serine 250 phosphorylation is required for paxillin redistribution and cell motility. Mutation of paxillin serine 250 prevents its phosphorylation by SLK in vitro and results in impaired migration in vivo as evidenced by an accumulation of phospho-FAK-Tyr397 and altered FA turnover rates. Together, our data suggest that SLK phosphorylation of paxillin on serine 250 is required for FAK-dependent FA dynamics.

A comparison of facial muscle squeezing versus non-facial muscle squeezing on the efficacy of botulinumtoxin-A injections for the treatment of facial dystonia.

BACKGROUND: This study was performed to address whether voluntary muscle squeezing post botulinum toxin-A treatment with increased neuronal activity translates into noticeable patient benefit in practice. METHODS: This was a prospective, consecutive, double crossover interventional study. Participants were receiving regular (3 monthly) botulinum toxin-A treatment for aberrant facial nerve regeneration (AFNR), benign essential blepharospasm (BEB) or hemifacial spasm (HFS). Twenty-six participants were recruited and these were randomised into two groups (A and B). Group A performed a program of intensive facial exercises for 5 minutes after their first and third treatment whereas after their second treatment, they were asked to rest in a seated position for 5 minutes, and instructed not to talk or perform any voluntary movements of their face. Conversely group B were only asked to perform squeezing exercises after their second treatment. Outcomes were evaluated objectively using video-recordings and subjectively by questionnaire and telephone interview of participants. RESULTS: Video-recording data was complete for 21 participants. There was a mean 40% reduction in the frequency of facial muscle spasms and a 33% lower severity score (video-recordings graded by 1 masked investigator) where intensive facial exercises were performed post-treatment. These findings did not reach statistical significance (Mann- Whitney two-tailed test; p = 0.367). CONCLUSION: Although statistical significance was not achievable, this study suggested a possible trend towards an increased efficacy of botulinum toxin-A, with facial muscle squeezing post BTX treatment. Future studies with a larger number and a better defined subset of subjects may lead to statistical significance.