Perception of patient habitus and the influence on exposure factor selection and resultant imparted dose.

INTRODUCTION: Exposure factor selection influences ionising radiation dose and image quality in projection radiography. Radiographers have a duty to comply with legislation, ensuring doses (resulting from exposure factor selection) are kept ALARP. Hence, this paper aims to explore variation in patient habitus perceptions among final-year student radiographers and any influence on imparted dose due to exposure factor selection. METHODS: Institutional ethics was granted. Student radiographers engaged in a 2-stage primary research study. Students were asked to select exposure factors (kVp and mAs values) and the most appropriate BMI category for several models undergoing a routine anteroposterior abdomen projection. Monte-Carlo simulation software was utilised to establish the absorbed and effective dose for these exposures. SPSS software was used to conduct statistical analysis of this data. RESULTS: A response rate of 19% (n = 14) was recorded. The findings identified variation in habitus perception with greater variation among female models. (p = 0.002). There was significant variation in exposure factor selection and ionising radiation dose, particularly between the male and female models. There was a significant difference between the healthy, overweight, and obese female models for absorbed (p = 0.032) and effective dose (p = 0.032) but not for the male models. CONCLUSION: There was a distinct difficulty recognising overweight and obese models and inconsistency regarding the selection of exposure factors. It was concluded that male models were more likely to receive a greater dose than females due to higher proposed exposure factors. IMPLICATIONS FOR PRACTICE: This study adds to the existing evidence base, providing insight into the perceptions of radiography students and the effect on exposure factor selection. This study will likely stand as a baseline for further investigation into competency levels among qualified radiographers to improve radiation protection.

I'll be there for you: The effects of exercise engagement on social support provision within undergraduate students' personal networks.

Objective: To use social network analysis to examine exercise participation relative to health and wellness support provision within students' networks. Participants: 513 undergraduates from a large private university completed online surveys. Methods: Multilevel modeling assessed exercise engagement at the individual and dyadic level and support provision from network members. Results: More support was perceived by first and second-year students and individuals who reported more exercise engagement. Significant others, roommates, siblings, female network members, and those who exercised often provided greater support. Greater support was reported when both the participant and their social tie were involved in the campus group-exercise program. Conclusion: This study suggests individual and dyadic-level exercise was related to undergraduates feeling more supported. Findings support campus group exercise programs as opportunities to create reciprocal supportive ties for college students. Future research could further explore ways exercise and social support, particularly in group settings, affect health and well-being.

N-acetyl-L-leucine for Niemann-Pick type C: a multinational double-blind randomized placebo-controlled crossover study.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as progressive cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded phase IIb clinical trial. Here, we describe the development of a study protocol (Sponsor Code "IB1001-301") for the chronic treatment of symptoms in adult and pediatric patients with NPC. METHODS: This multinational double-blind randomized placebo-controlled crossover phase III study will enroll patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites. Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments. DISCUSSION: Pre-clinical as well as observational and phase IIb clinical trials have previously demonstrated that IB1001 rapidly improved symptoms, functioning, and quality of life for pediatric and adult NPC patients and is safe and well tolerated. In this placebo-controlled cross-over trial, the risk/benefit profile of IB1001 for NPC will be evaluated. It will also give information about the applicability of IB1001 as a therapeutic paradigm for other rare and common neurological disorders. TRIAL REGISTRATIONS: The trial (IB1001-301) has been registered at www. CLINICALTRIALS: gov (NCT05163288) and www.clinicaltrialsregister.eu (EudraCT: 2021-005356-10). Registered on 20 December 2021.

Assessment of university policies for service animals and emotional support animals.

OBJECTIVE: Assess administrative responsibilities and experiential effects of emotional support animal (ESA) and service animal (SA) policies on college campuses. PARTICIPANTS: Students at two four-year universities participated in an emotional support animals and service animals survey. Selected students and professional personnel participated in interviews and focus groups. METHODS: This mixed-methods study included quantitative survey data from 1,363 students, qualitative individual interviews (3) and a focus group (1) regarding emotional support animal (ESA) and service animal (SA). RESULTS: Seventy-one students reported having ESAs, 18 had SAs. Barriers for ESAs on campus included no ESAs outside of dorms, while SA-owners reported fewer barriers. University administrators followed federal guidelines for SAs but lacked clear guidelines for ESAs. Qualitative themes included lack of awareness, education, support for SA, and ESA accommodations. CONCLUSIONS: ESA and SA accommodations continue to rise, on university campuses. Clear guidelines and implementation processes are imperative for future improvements.

Egocentric network composition and structure relative to violence victimization among a sample of college students.

ObjectiveTo use egocentric network analysis to understand how composition and structure of egonetworks relate to violence victimization among college students. Participants: 697 students from a large southeastern university completed online surveys. Methods: Hierarchical logistic regression analyses assessed the relationship between egocentric network variables and a history of violence victimization. Results: Being connected to others with a history of violence victimization increased a student's odds of indicating their own history of physical, emotional, and sexual violence victimization. Having less dense egonetworks was related to sexual violence victimization, while being connected to less people of the same gender was related to emotional violence victimization. Conclusion: The way college students' networks are composed and structured could help in understanding violence victimization in this population, and should be considered in prevention and reactionary efforts on campuses. These findings add to the current literature largely focused on individual-level risk factors related to violence.

Establishing the shadowline: the border between legally acceptable and unacceptable standards of surgical practice.

INTRODUCTION: Our study investigated how the standard of surgical care is assessed within the English and Welsh litigation process. The 'shadowline' represents the dividing line between acceptable and unacceptable standards of care. Our hypothesis was that different assessors risk adopting materially different interpretations regarding the acceptable standard of care. Any variation in the interpretation of where the shadowline falls will create uncertainty and unfairness to surgeons and patients alike. METHODS: We summarised the legal literature and suggested the factors affecting the assessment of surgical standards. We illustrated our findings on distribution curves. RESULTS: There was a risk that the shape of the curve and the location of the shadowline may vary according to the assessor. Importantly, a gap may have developed between the legal and clinical shadowlines in respect of the consenting process. DISCUSSION AND CONCLUSION: We suggested how a gap between the surgical and legal shadow lines could be narrowed. Clinical governance, balanced literature and realistic expert assessments were all part of the solution.

How do you develop systems leadership in public health? Insights from a scoping study.

OBJECTIVES: Systems leadership is widely acknowledged to be needed to address the many 'wicked issues' challenging public health systems. However, there is a lack of evidence on how to develop public health professionals into effective systems leaders. This study scoped the possibilities for developing the systems leadership capacity of public health specialists in England. STUDY DESIGN: This was a mixed-methods qualitative scoping study design. METHODS: The study involved three stages. In the first, a rapid literature review mapped key documents in three relevant areas: systems leadership theory and practice, the changing context of public health in the UK, and training and development for UK public health professionals. In the second, 29 stakeholders were consulted to understand the context and needs for systems leadership development in public health. A third phase involved stakeholders codesigning a potential development framework for the project commissioners. RESULTS: Four main themes were identified: the nature and purpose of systems leadership; development needs and opportunities for public health specialists; the enabling environment; and wider contextual factors impacting public health. CONCLUSIONS: Key principles of, and a framework for, a systems leadership development approach are identified, which could be applied to any public health system.

A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia.

BACKGROUND: The lack of approved treatments for the majority of rare diseases is reflective of the unique challenges of orphan drug development. Novel methodologies, including new functionally relevant endpoints, are needed to render the development process more feasible and appropriate for these rare populations and thereby expedite the approval of promising treatments to address patients' high unmet medical need. Here, we describe the development of an innovative master protocol and primary outcome assessment to investigate the modified amino acid N-acetyl-L-leucine (Sponsor Code: IB1001) in three separate, multinational, phase II trials for three ultra-rare, autosomal-recessive, neurodegenerative disorders: Niemann-Pick disease type C (NPC), GM2 gangliosidoses (Tay-Sachs and Sandhoff disease; "GM2"), and ataxia telangiectasia (A-T). METHODS/DESIGN: The innovative IB1001 master protocol and novel CI-CS primary endpoints were developed through a close collaboration between the Industry Sponsor, Key Opinion Leaders, representatives of the Patient Communities, and National Regulatory Authorities. As a result, the open-label, rater-blinded study design is considerate of the practical limitations of recruitment and retention of subjects in these ultra-orphan populations. The novel primary endpoint, the Clinical Impression of Change in Severity© (CI-CS), accommodates the heterogenous clinical presentation of NPC, GM2, and A-T: at screening, the principal investigator appoints for each patient a primary anchor test (either the 8-m walk test (8MWT) or 9-hole peg test of the dominant hand (9HPT-D)) based on his/her unique clinical symptoms. The anchor tests are videoed in a standardized manner at each visit to capture all aspects related to the patient's functional performance. The CI-CS assessment is ultimately performed by independent, blinded raters who compare videos of the primary anchor test from three periods: baseline, the end of treatment, and the end of a post-treatment washout. Blinded to the time point of each video, the raters make an objective comparison scored on a 7-point Likert scale of the change in the severity of the patient's neurological signs and symptoms from video A to video B. To investigate both the symptomatic and disease-modifying effects of treatment, N-acetyl-L-leucine is assessed during two treatment sequences: a 6-week parent study and 1-year extension phase. DISCUSSION: The novel CI-CS assessment, developed through a collaboration of all stakeholders, is advantageous in that it better ensures the primary endpoint is functionally relevant for each patient, is able to capture small but meaningful clinical changes critical to the patients' quality of life (fine-motor skills; gait), and blinds the primary outcome assessment. The results of these three trials will inform whether N-acetyl-L-leucine is an effective treatment for NPC, GM2, and A-T and can also serve as a new therapeutic paradigm for the development of future treatments for other orphan diseases. TRIAL REGISTRATION: The three trials (IB1001-201 for Niemann-Pick disease type C (NPC), IB1001-202 for GM2 gangliosidoses (Tay-Sachs and Sandhoff), IB1001-203 for ataxia telangiectasia (A-T)) have been registered at www.clinicaltrials.gov (NCT03759639; NCT03759665; NCT03759678), www.clinicaltrialsregister.eu (EudraCT: 2018-004331-71; 2018-004406-25; 2018-004407-39), and https://www.germanctr.de (DR KS-ID: DRKS00016567; DRKS00017539; DRKS00020511).

Patient, family and carer experiences of nutritional screening: a systematic review.

BACKGROUND: Despite recommendations for nutritional risk screening of all inpatients, outpatients and care home residents, as well as work to assess clinician's experiences and the validity of tools, little attention has been paid to the experiences of patients undergoing nutritional screening. This review aims to synthesise systematically the current evidence regarding nutritional risk screening with respect to the experiences and views of patients, their families and carers. METHODS: A systematic search was performed in MEDLINE, Embase, PsychINFO, CINAHL, Web of Science and British Nursing Database (inception - July 2019); with screening terms related to malnutrition, screening tools and experience. Titles, abstracts and full-text papers were independently reviewed by two reviewers and then quality-appraised. Qualitative papers and quantitative surveys were included. A narrative review of surveys and a thematic framework synthesis of interviews were used to identify themes. RESULTS: Nine studies, including five qualitative interview papers, were included. Qualitative and quantitative study results were combined using a matrix chart to allow comparison. Surveyed participants reported processes of nutritional screening as acceptable. Three key themes emerged from qualitative data: (i) experience of nutritional screening; (ii) misunderstanding of malnutrition: of causes, role of screening and poor self-perception of risk; and (iii) barriers to and opportunities for change. CONCLUSIONS: Although the screening process is acceptable, patients' misunderstanding and poor knowledge regarding causes and consequences of malnutrition result in reduced risk perception and disbelief or disregard of nutritional screening results. Findings should inform policy and clinical practice, as well as highlight the known paucity of data regarding the effectiveness of screening on clinical outcomes.

Social networks, group exercise, and anxiety among college students.

OBJECTIVE: This study aimed to evaluate the relationship between group exercise membership, social network characteristics, and general state anxiety in a sample of college students. Participants: 490 undergraduates from a private university in the southern US participated in the study. Methods: An egocentric network analysis was conducted to test whether demographic variables, leisure-time physical activity, group exercise membership, flourishing scores, and network variables were related to anxiety. Results: Regression analyses (R2 = .174, F = 7.650, p < .0001) suggest group exercise membership (ß = -.105, p = .034) and flourishing scores (ß = -.342, p < .0001) were related to lower anxiety scores, while being a racial/ethnic minority (ß = .094, p = .036), and having personal networks composed of more people who exercise often (ß = .100, p = .025), were related to higher anxiety scores in this sample. Conclusions: Findings suggest a connection between group exercise membership, activity habits of peers, and anxiety. Encouraging group exercise participation could be an effective way of combating anxiety for college students.

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study.

Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada.Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut.Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27-78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47-35.30).Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut.

Inhibition of fatty acid amide hydrolase by chlorpyrifos in juvenile rats results in altered exploratory and social behavior as adolescents.

The organophosphorus insecticide chlorpyrifos (CPF) is suspected to cause developmental neurotoxicity in children leading to long term effects. Developmental exposure of rat pups to CPF at low levels disrupts degradation of the brain endocannabinoids through the inhibition of fatty acid amide hydrolase (FAAH) and decreases the reactivity of juvenile rats in an emergence test. In this study, we further investigated the effects of developmental CPF exposure on behavior but also included exposure to PF-04457845, a specific inhibitor of FAAH, for comparison of behavior altered by FAAH inhibition with behavior altered by CPF. Ten day old rat pups were exposed orally either to 0.5, 0.75, or 1.0 mg/kg CPF or 0.02 mg/kg PF-04457845 daily for 7 days. In an open field (day 23), the high CPF and PF-04457845 groups exhibited increased motor activity but no differences in the time spent in the field's center. In an elevated plus maze (day 29), all treatment groups had increased open arm activity but ethological behaviors associated with anxiety were not altered. Behaviors in the maze associated with increased general activity and exploratory drive were increased. Social interactions (day 36) were measured and all treatment groups exhibited increased levels of play behavior. The similarities in behavior between PF-04457845 and CPF suggest that enhanced endocannabinoid signaling during the exposure period plays a role in the persistent alteration of behavior observed following developmental CPF exposure.

The amplitude and origin of sea-level variability during the Pliocene epoch.

Earth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'1, when atmospheric carbon dioxide concentrations were about 400 parts per million, global sea level oscillated in response to orbital forcing2,3 and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value4,5. For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 ± 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy3 (as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession6 between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere3,6. Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century.

SleepNet: automated sleep analysis via dense convolutional neural network using physiological time series.

OBJECTIVE: In this work, a dense recurrent convolutional neural network (DRCNN) was constructed to detect sleep disorders including arousal, apnea and hypopnea using polysomnography (PSG) measurement channels provided in the 2018 PhysioNet Challenge database. APPROACH: Our model structure is composed of multiple dense convolutional units (DCU) followed by a bidirectional long-short term memory (LSTM) layer followed by a softmax output layer. The sleep events, including sleep stages, arousal regions and multiple types of apnea and hypopnea, are manually annotated by experts, which enables us to train our proposed network using a multi-task learning mechanism. Three binary cross-entropy loss functions, corresponding to sleep/wake, target arousal and apnea-hypopnea/normal detection tasks, are summed up to generate our overall network loss function that is optimized using the Adam method. Our model performance was evaluated using two metrics: the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC). To measure our model generalization, 4-fold cross-validation was also performed. For training, our model was applied to full night recording data. MAIN RESULTS: Finally, the average AUPRC and AUROC values associated with the arousal detection task were 0.505 and 0.922, respectively, on our testing dataset. An ensemble of four models trained on different data folds improved the AUPRC and AUROC to 0.543 and 0.931, respectively. SIGNIFICANCE: Our proposed algorithm achieved the first place in the official stage of the 2018 PhysioNet Challenge for detecting sleep arousals with an AUPRC of 0.54 on the blind testing dataset.

Five-year results of the complete versus culprit vessel percutaneous coronary intervention in multivessel disease using drug-eluting stents II (CORRECT II) study: a prospective, randomised controlled trial.

OBJECTIVES/BACKGROUND: In patients with multivessel coronary artery disease (MVD) the decision whether to treat a single culprit vessel or to perform multivessel revascularisation may be challenging. The purpose of this study was to evaluate the long-term outcome of multivessel percutaneous coronary intervention (MV-PCI) versus culprit vessel only (CV-PCI) in patients with stable coronary artery disease or non-ST elevation acute coronary syndrome. METHODS: In this dual-centre, prospective, randomised study a total 215 patients with MVD were randomly assigned to MV-PCI or CV-PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE) including death, myocardial infarction (MI), and repeat revascularisation. Secondary endpoints were the combined endpoint of death or MI, the individual components of the primary endpoint, and the occurrence of stent thrombosis. Patients were followed up to 5 years after enrolment. RESULTS: The occurrence of the primary endpoint was similar at 28% versus 31% in the MV-PCI and CV-PCI group, respectively (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.53-1.44, p = 0.59). The rate of repeat revascularisation was 15% versus 24% (HR 0.59, 95% CI 0.32 to 1.11, p = 0.11), whereas definite or probable stent thrombosis occurred in 2% versus 0% (p = 0.44). CONCLUSIONS: In this randomised study comparing the strategies for MV-PCI and CV-PCI in patients with MVD, no difference was found in the occurrence of MACE after 5 years. We observed a numerically higher rate of death or MI and a lower rate of repeat revascularisation after MV-PCI, although these findings were not statistically significant.

Addressing tuberculosis among Inuit in Canada.

The average annual rate of tuberculosis (TB) among Inuit in Canada is now more than 290 times higher than Canadian born non-Indigenous people. How did this happen? Using the Territory of Nunavut as a case example, the roots of this situation can largely be traced back to social determinants of health and challenges in access to health care. Half (52%) of all Nunavut residents live in social housing, often under overcrowded conditions. Many experience food insecurity, with food prices in Nunavut that are twice those in southern Canada. Sixty percent of Nunavut residents smoke. Challenges in health care delivery include the small isolated communities, with few roads and difficult weather conditions during the long winters, which impede the ability to reach or provide healthcare, staff that arrive with little TB experience or cultural knowledge, multiple competing health care demands, limited resources and high staff turnover. The housing shortage is not only a social determinant of health, it also impacts the ability to hire new staff or mount an effective response in the event of an outbreak. Yet despite these challenges, progress has been made. Tuberculosis care in Nunavut includes active case finding, contact tracing for all cases of infectious TB, and screening of school age children. Rapid testing with the GeneXpert© platform has resulted in a quicker diagnosis of active TB, earlier treatment (preventing progression of disease) and less transmission. Progressively, there has been a switch from plain film to digital x-rays reducing x-ray turnaround time from as long as two to three weeks to one or two days. Standard treatment protocols include quadruple therapy until sensitivities are known, the use of home isolation for active cases and directly observed treatment (DOT) for both latent and active TB. Special access to rifapentine (Priftin), and its use in combination therapy (3HP), requires only once weekly treatments that can be completed in 12 visits instead of 78 visits for isoniazid (INH) or 120 visits for rifampin, which increases adherence and greatly reduces the health care resources needed to treat TB. In October 2017, the Honourable Jane Philpott, then Minister of Health and now Minister of Indigenous Services, and Natan Obed, president of Inuit Tapiriit Kanatami (ITK) announced the establishment of a Task Force to develop an Inuit TB Elimination Action Framework, accompanied by regional action plans. It is hoped that the task force, and current efforts in Nunavut, will lead to the long term changes needed to ultimately eliminate TB among Inuit in Canada.

Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading.

Sedimentation, nutrients and metal loading to coastal environments are increasing, associated with urbanization and global warming, hence there is a growing need to predict ecological responses to such change. Using a regression technique we predicted how maximum abundance of 20 macrobenthic taxa and 22 functional traits separately and interactively responded to these key stressors. The abundance of most taxa declined in response to sedimentation and metal loading while a unimodal response was often associated with nutrient loading. Optimum abundances for both taxa and traits occurred at relatively low stressor levels, highlighting the vulnerability of estuaries to increasing stressor loads. Individual taxa were more susceptible to stress than traits, suggesting that functional traits may be less sensitive for detecting changes in ecosystem health. Multiplicative effects were more common than additive interactions. The observed sensitivity of most taxa to increasing sedimentation and metal loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

Genetic influences on hormonal markers of chronic hypothalamic-pituitary-adrenal function in human hair.

BACKGROUND: Cortisol is the primary output of the hypothalamic-pituitary-adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function. METHOD: In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80-19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type. RESULTS: Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone. CONCLUSIONS: Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.

Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The 'wait a day' approach might be safer.

BACKGROUND: The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTE-ACS, long-term outcomes are essential. METHODS: Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. RESULTS: No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73-4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21-16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. CONCLUSION: There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI.