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Background: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking. Methods: Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12–24-year-old adolescent females: perinatally HIV-infected (group 1, n=40), behaviourally HIV-infected (group 2, n=10), and HIV-uninfected (group 3, n=10). Results: Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) (P

Abstract Objective Currently there is no parent administered scale for facial nerve function in children. We set out to assess the agreement between a newly developed parent‐administered modified version of the House‐Brackmann (HB) scale and the standard clinician‐administered HB scale in children with Bell's palsy. Study Design Secondary analysis of a triple‐blind, randomized, placebo‐controlled trial of corticosteroids to treat idiopathic facial paralysis (Bell's palsy) in children (6 months to

Abstract We sought to determine incidence, etiologies, and yield of genetic testing in infantile onset developmental and epileptic encephalopathies (DEEs) in a population isolate, with an intensive multistage approach. Infants born in Tasmania between 2011 and 2016, with seizure onset

Strong luminescence peaks were observed at 700 and 800 nm in undoped yttrium aluminum garnet (YAG) single crystals. They were attributed to low level of iron impurities as confirmed by Glow Discharge Mass Spectrometry analysis. The 800 nm was only excited by high energy band at 270 nm; the reason behind that was discussed. Photoluminescence measurements revealed a large number of luminescence peaks in all YAG crystals regardless of the growth conditions due to native defects and low-level impurities. These luminescence centers have significant effects on the optical properties of rare-earth doped YAG crystals and their performance in laser and scintillation applications. Excitons released in the lattice may be easily captured by iron ions instead of Ce3+ ions and the scintillation output is substantially decreased. Nevertheless, Undoped YAG crystals may have the potential to be developed into efficient scintillators.

OBJECTIVE. Our goals were to compare (1) single-channel amplitude-integrated electroencephalography alone, (2) 2-channel amplitude-integrated electroencephalography alone, and (3) amplitude-integrated electroencephalography plus 2-channel electroencephalography with simultaneous continuous conventional electroencephalography for seizure detection in term infants to check the accuracy of limited channels and compare the different modalities of bedside electroencephalography monitoring. METHODS. Infants referred to a tertiary center with clinical seizures underwent simultaneous continuous conventional electroencephalography and 2-channel (C3-P3 and C4-P4) bedside monitoring. Off-line analysis of the continuous conventional electroencephalographic results was performed independently by 2 neurologists. Two experienced neonatal readers reviewed results obtained with amplitude-integrated electroencephalography and 2-channel electroencephalography combined and single-channel and 2-channel amplitude-integrated electroencephalography. All readings were performed independently and then compared. RESULTS. Twenty-one term newborns were monitored. Seizures were detected in 7 patients who had up to 12 electrical seizures, with 1 infant in status epilepticus. Seizures were identified correctly in 6 of 7 patients with amplitude-integrated electroencephalograph,y plus 2-channel electroencephalography. The missed infant had an isolated 1 2-second seizure. With amplitude-integrated electroencephalography plus 2-channel electroencephalography, 31 of 41 non-status epilepticus seizures were correctly identified (sensitivity, 76%; specificity, 78%; positive predictive value, 78%; negative predictive value, 78%), with a substantial level of interrater agreement. The seizures missed were predominantly slow sharp waves of occipital origin from a single patient (7 of 10 seizures). Nine false-positive results were obtained in 351 hours of recording (1 false-positive result per 39 hours). These were thought to be related to muscle, electrode, and patting artifacts. Use of amplitude- integrated electroencephalography alone (1 or 2 channel) provided low sensitivity (27%-56%) and low interobserver agreement. CONCLUSIONS. Limited-channel bedside electroencephalography combining amplitude-integrated electroencephalography with 2-channel electroencephalography, interpreted by experienced neonatal readers, detected the majority of electrical seizures in at-risk newborn infants. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. Methods: Ninety-two participants with a Fontan circulation (aged 13–49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. Results: Forty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were −0.63 (SD = 1.07) and −0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF–III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis.Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (

Background: Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage., Aims: To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective., Method: We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14-35 years) presenting with a first episode of psychosis between May 2019 and July 2020 ( N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12-26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746., Results: Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP ( n = 652) versus sEIP alone ( n = 375) was 1.07 (95% CI 0.76-1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group., Conclusions: We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Introduction: Ethnic minorities (also called racialised groups) are more likely to experience severe mental illness (SMI). People with SMI are more likely to experience multimorbidity (MM), making psychosis among racialised groups more likely to lead to MM, poor outcomes, disability and premature mortality., Methods and Analysis: This National Institute for Health and Care Research-funded study (151887) seeks to use innovative participatory methods including photovoice and biographical narrative interviews in urban and rural areas of England to assemble experience data. These data will be subjected to polytextual thematic analysis, and alongside pictures and captions, will inform an experienced-based co-design of interventions, the implementation of which will be evaluated. There will be an economic analysis and a process evaluation of the implementation., Ethics and Dissemination: This programme of work has received ethical (IRAS 322421; Newcastle North Tyneside Research Ethics Committee 23/NE/0143) and sponsor approval. The findings will be disseminated in galleries showing the creative work, as lay and academic summaries and infographics; as practice briefings for practitioners, commissioners and policy makers; peer-reviewed publications., Trial Registration Number: https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/649c08111c037d0027b17d17/., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The Earned Income Tax Credit (EITC) is the largest cash-based means-tested transfer program in the United States. In 2021, 31 million households received $64 billion from the federal EITC. Twenty-eight states also offer eligible taxpayers a supplement to the federal program. An estimated one-fifth of eligible households fail to claim the federal credit, but little is known about take-up of these state programs. We use administrative data from California on the population of Supplemental Nutrition Assistance Program (SNAP) recipients linked to state tax records to estimate the number of households who are eligible for California's supplement to the federal EITC (CalEITC) but do not claim it. We find that over 400,000 households who received SNAP benefits and who were eligible for the state EITC in 2017 did not receive the credit. This includes approximately 40,000 eligible households who claimed the federal EITC but not the state credit; nearly 98,000 eligible households who filed a state tax return but did not claim the state or federal credit; and roughly 270,000 eligible households who did not file a state tax return. The corresponding take-up rate for the CalEITC among eligible SNAP-enrolled households was 54%. Altogether, these households left a total of $71 million in state EITC funds on the table. If received, these credits would have increased incomes among these households by 2.7% and increased total state EITC outlays by 20%., Competing Interests: Declaration of Interests None of the authors of this work, entitled “Measuring Take-up of the California EITC with State Administrative Data” have any financial and personal relationships with other people or organizations that could inappropriately influence or bias our work.

Background: New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneliness and thus improve health outcomes for people with TRD. Participants receive up to 10 individual meetings with a Community Navigator, who helps them to map their social world and set and enact goals to enhance their social connections and reduce loneliness. Participants may also access group meet-ups with others in the programme every 2 months, and may be offered modest financial support to enable activities to support social connections., Methods: A researcher-blind, multi-site, 1:1 randomised controlled trial with N = 306 participants will test the effectiveness of the Community Navigator programme for people with TRD in secondary community mental health teams (CMHTs). Our primary hypothesis is that people who are offered the Community Navigator programme as an addition to usual CMHT care will be less depressed, assessed using the PHQ-9 self-report measure, at 8-month, end-of-treatment follow-up, compared to a control group receiving usual CMHT care and a booklet with information about local social groups and activities. We will follow participants up at end-of-treatment and at 14 months, 6 months after end-of-treatment follow-up. Secondary outcomes include the following: loneliness, anxiety, personal recovery, self-efficacy, social network, social identities. We will collect data about health-related quality of life and service use to investigate the cost-effectiveness of the Community Navigator programme., Discussion: This trial will provide definitive evidence about the effectiveness and cost-effectiveness of the Community Navigator programme and whether it can be recommended for use in practice. The trial is due to finish in August 2025., Trial Registration: Prospectively registered on 8th July 2022 at: ISRCTN13205972., (© 2023. BioMed Central Ltd., part of Springer Nature.)

"Epistemic injustice" refers to how people from marginalized groups are denied opportunities to create knowledge and derive meaning from their experiences. In the mental health field, epistemic injustice occurs in both research and service delivery systems and particularly impacts people from racialized communities. Lived experience involvement and leadership are often proposed as methods of combatting epistemic injustice, a tool for ensuring the views of people at the center of an issue are heard and can inform decision-making. However, this approach is not without challenges. In this paper, we draw on our work as intermediary organizations that center lived experience perspectives to challenge epistemic injustice. We highlight two problems we have identified in working in the mental health research field: "elite capture" and "epistemic exploitation". We believe that these problems are barriers to the radical and structural change required for epistemic justice to occur. We propose a pragmatic approach to addressing these issues. Based on our work we suggest three considerations for researchers and our own organizations to consider when involving people with lived experience. These include reflecting on the purpose of creating knowledge, with a focus on impact. Embedding lived experience roles, with appropriate employment, support and remuneration, and acknowledging that it may be necessary to work alongside existing systems as a "critical friend" while developing new spaces and structures for alternative forms of knowledge. Finally, the mental health research system needs to change. We believe these three considerations will help us better move toward epistemic justice in mental health research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Okoroji, Mackay, Robotham, Beckford and Pinfold.)

Background: The connection between obstructive sleep apnea and secondary erythrocytosis is controversial. We hypothesised that there may be a higher prevalence of erythrocytosis in patients with obesity hypoventilation syndrome (OHS) due to persistent hypoxemia., Methods: The study was a retrospective, cross-sectional review of patients with OHS derived from an established cohort of "non-invasive ventilation" patients at the Department of Sleep Medicine at the Royal Infirmary Medical Centre, Edinburgh (2004-2017). Relevant clinical data were obtained from patient records., Results: The cohort comprised 74 patients with OHS, 44 men (60%), mean age at diagnosis 54 ± 10 years. The mean haematocrit level for the group overall was 0.44, in men 0.45, and in women 0.41. Of 11 patients with erythrocytosis (15%), 7 were men. Thirteen patients (18%) died during follow-up (2004-2017). There was a statistically significant increase in risk of death in patients with higher and lower haematocrit levels compared to that in patients with OHS who had normal haematocrits., Conclusions: This is the first study showing increased prevalence of erythrocytosis in OHS patients. There was a "U"-shaped correlation with mortality according to haematocrit levels., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Competing Interests: The authors report no conflicts of interest in relation to this study.

Attentional lapses occur commonly and are associated with mind wandering, where focus is turned to thoughts unrelated to ongoing tasks and environmental demands, or mind blanking, where the stream of consciousness itself comes to a halt. To understand the neural mechanisms underlying attentional lapses, we studied the behaviour, subjective experience and neural activity of healthy participants performing a task. Random interruptions prompted participants to indicate their mental states as task-focused, mind-wandering or mind-blanking. Using high-density electroencephalography, we report here that spatially and temporally localized slow waves, a pattern of neural activity characteristic of the transition toward sleep, accompany behavioural markers of lapses and preceded reports of mind wandering and mind blanking. The location of slow waves could distinguish between sluggish and impulsive behaviours, and between mind wandering and mind blanking. Our results suggest attentional lapses share a common physiological origin: the emergence of local sleep-like activity within the awake brain.

Background: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention., Method: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective., Discussion: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation., Trial Registration: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Drinking-water contaminants pose a risk to public health. When confronted with elevated levels of contaminants, individuals can take actions to reduce exposure. Yet, few studies address averting behavior due to impaired water, particularly in high-income countries. This is a problem of national interest, given that 9 million to 45 million people have been affected by water quality violations in each of the past 34 years. No national analysis has focused on the extent to which communities reduce exposure to contaminated drinking water. Here, we present an assessment that sheds light on how communities across the United States respond to violations of the Safe Drinking Water Act, using consumer purchases of bottled water. This study provides insight into how averting behavior differs across violation types and community demographics. We estimate the change in sales due to water quality violations, using a panel dataset of weekly sales and violation records in 2,151 counties from 2006 to 2015. Critical findings show that violations which pose an immediate health risk are associated with a 14% increase in bottled water sales. Generally, greater averting action is taken against contaminants that might pose a greater perceived health risk and that require more immediate public notification. Rural, low-income communities do not take significant averting action for elevated levels of nitrate, yet experience a higher prevalence of nitrate violations. Findings can inform improvements in public notification and targeting of technical assistance from state regulators and public health agencies in order to reduce community exposure to contaminants., Competing Interests: The authors declare no conflict of interest.

Purpose: Hispanics residing in rural areas are among those who are least likely to be screened for colorectal cancer (CRC) and more likely to present with late stage CRC than other racial or ethnic groups. We conducted a pilot study utilizing a mixed-method approach to explore perceptions of CRC and CRC screening among Hispanic adults residing in South Texas rural communities and to identify health literacy needs associated with CRC screening uptake., Methods: A convenience sample of 58 participants, aged 35-65, were recruited to complete questionnaires and participate in focus groups, ranging in size from 4 to 13 participants. Six focus groups were conducted across 3 adjacent rural counties. A semi-structured moderator's guide was designed to elicit discussion about participants' experiences, knowledge, and perceptions of CRC and CRC screening., Findings: Lack of knowledge of CRC and CRC screening as cancer prevention was a common theme across focus groups. A majority, 59%, reported never been screened. Thirty-nine percent reported they had been screened for colon cancer and 5% reported they did not know if they had been screened. Participants with lower educational levels perceived themselves at high risk for developing CRC polyps, would not want to know if they had CRC, and if they did have CRC, would not want to know until the very end. Limited information about CRC and CRC screening, a lack of specialized providers, limited transportation assistance, and compromised personal privacy in small-town medical facilities were perceived to be barriers to CRC screening., Conclusions: Low screening rates persist among rural Hispanics. Improving CRC screening literacy and addressing factors unique to rural Hispanics may be a beneficial strategy for reducing screening disparities in this at-risk population., Competing Interests: Conflict of interest: All authors declare no conflicts of interest in this paper.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Hereditary haemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is a rare autosomal dominant multisystem disorder, characterised by mucocutaneous telangiectases and arteriovenous malformations affecting any organ. The physiological changes in pregnancy pose significant obstetric and anaesthetic challenges for women affected by the disease. The optimal timing and mode of delivery requires careful consideration; and the benefits and risks of both regional and general anaesthetic techniques must be carefully considered, depending on the organs affected. This case report describes the successful management of a patient with this disease and severe pulmonary involvement, who received both regional and general anaesthesia as a result of a complication in the initial anaesthetic plan. The report demonstrates the benefits of a multidisciplinary approach to a complex case, achieved through providing care in a tertiary centre with appropriate expertise and resources., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Introduction: Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England's cancer survival rates through establishing effective routes to early diagnosis., Methods and Analysis: To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys., Ethics and Dissemination: The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Use of appropriate cardioprotective medication is a cornerstone of cardiovascular disease prevention, but less-than-optimal patient adherence is common. Thus, strategies for improving adherence are recommended to adopt a multifaceted approach., Objective: The objective of our study was to test a system comprising a biodegradable, ingestible sensor for direct measurement of medication ingestion in a group of patients at elevated cardiovascular risk attending a cardiac prevention and rehabilitation program., Methods: In this prospective intervention trial in a single group of 21 patients running from April 2014 to June 2015, we measured adherence by self-report and adherence determined objectively by the system. The sensor emits a signal when it encounters the acidic environment of the stomach, detectable by an externally worn patch and linked software app. Longitudinal adherence data in the form of daily progress charts for sensed dosing events as compared with scheduled dosing are visible to patients on their tablet computer's medication dosing app, thus providing patients with continuous medication adherence feedback. We sought feedback on patient acceptability by questionnaire assessment. Participants used the system for the 12-week period of their cardiac prevention and rehabilitation program., Results: Only 1 patient at initial assessment and 1 patient at end-of-program assessment reported often missing medication. The remaining patients reported never missing medication or had missing data. Only 12 (57%) of patients overall achieved system-determined adherence of 80% or more, and 3 patients had scores below 40%. Participants reported high levels of acceptability., Conclusions: This integrated system was well tolerated in a group of 21 patients over an appreciable time frame. Its ability to measure adherence reveals the sizeable disconnect between patient self-reported adherence and actual medication taking and has promising potential for clinical use as a tool to encourage better medication-taking behavior due to its ability to provide continuous patient-level feedback., (©David Thompson, Teresa Mackay, Maria Matthews, Judith Edwards, Nicholas Peters, Susan B Connolly. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 12.06.2017.)

Purpose: To evaluate the heritability of choroidal thickness and its relationship to age-related macular degeneration (AMD)., Design: Cohort study., Participants: Six hundred eighty-nine individuals from Amish families with early or intermediate AMD., Methods: Ocular coherence tomography was used to quantify choroidal thickness, and fundus photography was used to classify eyes into categories using a modified Clinical Age-Related Maculopathy Staging (CARMS) system. Repeatability and heritability of choroidal thickness and its phenotypic and genetic correlations with the AMD phenotype (CARMS category) were estimated using a generalized linear mixed model (GLMM) approach that accounted for relatedness, repeated measures (left and right eyes), and the effects of age, gender, and refraction., Main Outcome Measures: Heritability of choroidal thickness and its phenotypic and genetic correlation with the AMD phenotype (CARMS category)., Results: Phenotypic correlation between choroidal thickness and CARMS category was moderate (Spearman's rank correlation, r s  = -0.24; n = 1313 eyes) and significant (GLMM posterior mean, -4.27; 95% credible interval [CI], -7.88 to -0.79; P = 0.02) after controlling for relatedness, age, gender, and refraction. Eyes with advanced AMD had thinner choroids than eyes without AMD (posterior mean, -73.8; 95% CI, -94.7 to -54.6; P < 0.001; n = 1178 eyes). Choroidal thickness was highly repeatable within individuals (repeatability, 0.78; 95% CI, 0.68 to 0.89) and moderately heritable (heritability, 0.40; 95% CI, 0.14 to 0.51), but did not show significant genetic correlation with CARMS category, although the effect size was moderate (genetic correlation, -0.18; 95% CI, -0.49 to 0.16). Choroidal thickness also varied with age, gender, and refraction. The CARMS category showed moderate heritability (heritability, 0.49; 95% CI, 0.26 to 0.72)., Conclusions: We quantify the heritability of choroidal thickness for the first time, highlighting a heritable, quantitative trait that is measurable in all individuals regardless of AMD affection status, and moderately phenotypically correlated with AMD severity. Choroidal thickness therefore may capture variation not captured by the CARMS system. However, because the genetic correlation between choroidal thickness and AMD severity was not significant in our data set, genes associated with the 2 traits may not overlap substantially. Future studies should therefore test for genetic variation associated with choroidal thickness to determine the overlap in genetic basis with AMD., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Demonstration of the therapeutic utility of endobronchial valves in elderly high-risk patients unsuitable for surgery http://ow.ly/Y7eEx.

Purpose: Correlate OCT-derived measures of drusen and retinal pigment epithelium (RPE) atrophy areas (RAs) with demographic features in an elderly population., Patients and Methods: Subjects aged 50 years and older underwent Cirrus OCT scanning. Drusen area and volume were obtained from the macula within a central circle (CC) of 3 mm and a surrounding perifoveal ring (PR) of 3-5 mm, using the RPE analysis software (6.0). RA measurements were generated for the 6 × 6 mm(2) retinal area. Gender, age, smoking status, and systolic blood pressure (SBP) were considered., Results: A total of 434 eyes were included. RA was larger in women (0.63±0.16 vs 0.26±0.08 mm(2), P=0.05) and with increasing age. The PR drusen area increased with increasing age (P<0.001), whereas the CC drusen area remained stable after the age of 70 years (0.25±0.06 mm(2) for ages 70-79 years and 0.25±0.07 mm(2) for ages >80 years). Drusen volume in the CC was smaller after the age of 80 years (0.009±0.003 mm(3)) compared with the 70- to 79-year-old group (0.02±0.008 mm(3)). Drusen measurements were similar between smokers and nonsmokers, but the PR drusen area (0.29 mm(2), P=0.05) and volume (0.40 mm(3), P=0.005) were correlated with years smoked. RA (0.24 mm(2), P=0.10), PR drusen area (0.29 mm(2), P=0.05), and volume (0.40 mm(3), P=0.005) were found to be directly associated with SBP. There was a high correlation between the eyes of the same subject., Conclusion: OCT-based automated algorithms can be used to analyze and describe drusen and geographic atrophy burden in such population-based studies of elderly patients.

Background: Behaviourally HIV-infected adolescent females are at higher risk for abnormal cervical cytology and HPV infection compared to those who are uninfected, but data on perinatally HIV-infected adolescent females are lacking., Methods: Cervical cytology, HPV infection and E6/E7 mRNA were assessed in sexually active 12-24-year-old adolescent females: perinatally HIV-infected (group 1, n = 40), behaviourally HIV-infected (group 2, n = 10), and HIV-uninfected (group 3, n = 10)., Results: Median age was lower in group 1 (18 years) than in groups 2 (24 years) and 3 (20.5 years) ( P < 0.001), and median time since sexual debut was shorter: 2 vs 5 vs 4 years ( P < 0.001). More trial participants in group 1 than group 2 were on antiretrovirals (90% vs 70%; P <0.001). Abnormal cervical cytology (atypical squamous cells of undetermined significance and higher) was observed in 30% (group 1), 40% (group 2) and 30% (group 3) ( P = 0.92), whereas high-risk HPV infection was observed in 45%, 45% and 40%, respectively ( P = 1.00). Positive E6/E7 mRNA was found in 28% of group 1, but not in other groups. High-risk HPV infection predicted abnormal cytology in all groups [OR 6.77, 95% confidence interval (CI) 1.99-23.0; P = 0.001). Additionally, plasma HIV RNA ≥50 copies/mL (OR 13.3, 95% CI 1.16-153.06; P = 0.04) predicted abnormal cytology in HIV-infected adolescent females., Conclusions: Despite the younger age and shorter time since sexual debut, cervical cytological abnormalities and HPV infection were as common in perinatally HIV-infected as in behaviourally infected and uninfected adolescents. HPV vaccination, pre-cancer screening and antiretroviral treatment in HIV-infected female adolescents should be implemented to minimise the risk of cervical cancer.

Background: Phenotypic plasticity allows organisms to respond rapidly to changing environmental circumstances, and understanding its genomic basis can yield insights regarding the underlying genes and genetic networks affecting complex phenotypes. Female Drosophila melanogaster undergo dramatic physiological changes mediated by seminal fluid components transferred upon mating, including decreased longevity. Their physiological and behavioral effects have been well characterized, but little is known about resulting changes in regulation of gene expression or the extent to which mating-induced changes in gene expression are the same as those occurring during aging., Results: We assessed genome-wide mRNA, microRNA, and three common histone modifications implicated in gene activation for young and aged virgin and mated female D. melanogaster in a factorial design. We identified phenotypically plastic transcripts and epigenetic modifications associated with mating and aging. We used these data to derive phenotypically plastic regulatory networks associated with mating of young flies, and aging of virgin and mated flies. Many of the mRNAs, microRNAs and epigenetic modifications associated with mating of young flies also occur with age in virgin flies, which may reflect mating-induced accelerated aging. We functionally tested the plastic regulatory networks by overexpressing environmentally sensitive microRNAs. Overexpression resulted in altered expression of ~70% of candidate target genes, and in all cases affected oviposition., Conclusions: Our results implicate microRNAs as mediators of phenotypic plasticity associated with mating and provide a comprehensive documentation of the genomic and epigenomic changes that accompany mating- and aging-induced physiological changes in female D. melanogaster.

Background: Early diagnosis of autism spectrum disorders (ASD) is of crucial importance, but lengthy delays are common. We examined whether this issue could be reliably addressed by local teams trained by a specialist ASD assessment team., Method: Four local teams were trained in diagnostic assessment. Their assessments of 38 children and young people using the Autism Diagnostic Observation Schedule-Generic (ADOS-G) were video recorded and independently assessed by the specialist team., Results: There was a high level of correspondence between the diagnoses of the local teams and of the specialist team. The number of assessments carried out increased and there was a considerable reduction in waiting times., Conclusion: This study has demonstrated the potential feasibility of creating local, multi-agency ASD assessment teams, which will serve to reduce waiting times, improve clinical skills at a lower level of specialism and thereby improve the overall quality of ASD services.

Objectives: This epidemiological study aims to investigate the developmental enamel defects and dental caries among 9-year-old children resident in fluoridated and nonfluoridated regions in Auckland, New Zealand., Methods: A stratified, two-stage random selection design where strata were defined by fluoridation status, school size, and school decile. After informed consent was obtained, parents completed oral health questionnaires and children underwent dental examinations at school clinics., Results: 612 children from 38 schools participated in the study. Overall, 175 (29%) children had lived continuously in fluoridated areas, 149 (24%) had lived continuously in nonfluoridated areas, and 288 (47%) had resided intermittently in fluoridated areas. Diffuse opacities were present in 117 (19%) children and deciduous teeth dental caries was seen in 370 (60%) children. After adjustment for covariates, a strong dose-response relationship between diffuse opacity and fluoridation status was found, with children who lived continuously in fluoridated areas being 4.17 times as likely to have diffuse opacities as children who lived continuously in nonfluoridated areas (P < 0.001). Conversely, a strong protective dose-response relationship between caries experience and fluoridation status was seen, with children who lived continuously in fluoridated areas being 0.42 times as likely to have dental caries as children who lived continuously in nonfluoridated areas (P < 0.001)., Conclusions: Reticulated water fluoridation in Auckland reduces the risk of dental caries but increases the risk of diffuse opacities in 9-year-old children. Guidelines and health-promotion strategies that enable children to minimize their risk to diffuse opacities yet reduce their risk of dental caries should be reviewed.

Background: Difficulties with social interaction and understanding lie at the heart of the communication disorder that characterises the autism spectrum. This study sought to improve social communication for individuals with autism spectrum disorder (ASD) by means of a groupwork intervention focusing on social and emotional perspective-taking, conversation skills, and friendship skills. It also aimed to address some of the limitations of previous interventions, including a lack of generalisation to other settings, so as to maximise inclusion in the community., Method: A group of 46 high functioning children and adolescents with ASD (38 boys, 8 girls, age range 6-16 years) were allocated to one of 6 intervention groups. Each group met over a period of 12-16 weeks for a minimum of one 1(1/2)-hour weekly session aimed at promoting key areas of social interaction and understanding, supported by home-based practice., Results: Significant gains were achieved in comparison with a normative population, and individual parent ratings showed marked and sustained changes in the key areas targeted in the group sessions., Conclusion: Social communication in children and adolescents with ASD can be enhanced through the use of a groupwork intervention addressing social interaction and understanding.

Social interaction and understanding in autistic spectrum disorder (ASD) are key areas of concern to practitioners and researchers alike. However, there is a relative lack of information about the skills and competencies of children and young people with ASD who access ordinary community facilities including mainstream education. In particular, contributions by parents and their children have been under-utilized. Using two structured questionnaires, 19 children with ASD reported difficulties with social skills including social engagement and temper management and also reported difficulties with social competence, affecting both friendships and peer relationships. Parents rated the children's social skill and competence as significantly worse than did the children themselves, but there was considerable agreement about the areas that were problematic. Using an informal measure to highlight their children's difficulties, parents raised issues relating to conversation skills, social emotional reciprocity and peer relationships. The implications for assessment and intervention are discussed.

Investigation and treatment of sleep apnoea/hypopnoea syndrome (SAHS) is placing increasing demands on healthcare resources. This workload may be reduced by using split-night studies instead of the standard full-nights of diagnostic polysomnography and continuous positive airway pressure (CPAP) titration. Split-night studies involve polysomnography in the first half of the night followed, if there is an abnormal frequency of apnoeas and hypopneas, by CPAP titration for the remainder of the night. The authors' database of all patients prescribed a CPAP trial 1991-1997 was used to compare long-term outcomes in all 49 (46 accepting CPAP) patients prescribed split-night studies with those in full-night patients, matched 1:2 using an apnoea/ hypopnoea index (AHI) of +/-15% and Epworth score of +/-3 units. Classical symptoms of SAHS were the main reason for the split-night studies (n=27). There were no differences between the groups in long-term CPAP use, median nightly CPAP use (split-night 6.0 h x night-1, interquartile range (IQR) 3.8-7.4, full-night; 6.2 h x night-1, IQR 3.7-7.0, p=0.9), post-treatment Epworth scores and frequency of nursing interventions/clinic visits required. The median time from referral to treatment was less for the split-night patients (13 months, IQR 11-20 months) than for full-night patients (22 months, IQR 12-34 months; p=0.003). Split-night studies, in selected patients, result in equivalent long-term continuous positive airway pressure use to full-night studies with shorter treatment times and less healthcare utilization.

Doppler ultrasound detection of abnormally high-pitched signals within the arterial waveform offers a new method for diagnosis, and potentially for prediction, of embolic complications in at-risk patients. The nature of Doppler "microembolic" signals is of particular interest in patients with prosthetic heart valves, where a high prevalence of these signals is observed. Monitoring the middle cerebral artery with 2-MHz transcranial Doppler ultrasound (TC-2000, Nicolet Biomedical; Warwick, UK), we looked for microemboli signals in 150 patients (95 women and 55 men), and found 1 or more signals during a 30-min recording in 89% of 70 patients with Bjork-Shiley valves (principally monostrut), 54% of 50 patients with Medtronic-Hall valves, and 50% of 30 patients with Carpentier-Edwards valves (p < 0.001, chi 2). In the patients with Bjork-Shiley valves, the mean number of signals per hour was 59 (range, 42-86; 95% confidence interval), which was significantly higher than the mean in patients with Medtronic-Hall and Carpentier-Edwards valves (1.5[range, 0.5-2.5] and 1 [range, 0-5.3], respectively; both p < 0.04, multiple comparisons. Bonferroni correction). In the patients undergoing serial pre- and postoperative studies, the causative role of the valve implant was emphasized. There was no correlation between the number of emboli signals and a prior history of neurologic deficit, cardiac rhythm, previous cardiac surgery, or the intensity of oral anticoagulation, in patients with prosthetic heart valves. In Bjork-Shiley patients, dual (mitral and aortic) valves were associated with more signals than were single valves. In Medtronic-Hall patients, the signal count was greater for valves in the aortic position than it was for valves in the mitral position. Comparative studies of Doppler emboli signals in other clinical settings suggest a difference in composition or size of the underlying maternal between prosthetic valve patients and patients with carotid stenosis. These studies also suggest that the signals are of gaseous origin in valve patients. The clinical significance of continuing microembolism remains to be determined.

Transfusion practice and blood ordering policy for major joint replacement was studied during 1989-93. Existing practice requiring automatic preoperative cross-match was prospectively audited. A blood ordering policy rationalising transfusion practice, using the group and screen technique, was then introduced. This resulted in a decrease in the total number of units cross-matched and increased the transfusion fraction significantly. The percentage of blood returned to the blood bank decreased by 46% for knees and 41% for hip arthroplasty. After the introduction of low molecular weight heparin (LMWH) as routine deep vein thrombosis (DVT) prophylaxis for all major total joint arthroplasties, the total transfusion requirement did not increase. In fact, the average number of units transfused per case after its introduction was marginally less at 1.3 units per hip, and 0.9 units per knee.

1. To clarify the relationship between nocturnal oxygen desaturation and erythropoietin production in patients with chronic obstructive pulmonary disease, we determined arterial oxygen saturation and serum immunoreactive erythropoietin levels over 24 h in eight patients with chronic obstructive pulmonary disease and in nine normal subjects. 2. In the normal subjects, there was a significant circadian variation in serum erythropoietin levels with the highest mean deviation from the geometric mean at 22.00 hours and the nadir at 05.00 hours. 3. The three patients with chronic obstructive pulmonary disease with the most marked nocturnal desaturation (lowest arterial oxygen saturation < 57%) and most marked daytime hypoxaemia (daytime arterial partial pressure of oxygen < 6 kPa) had raised nocturnal serum erythropoietin levels. In two of these patients, the serum erythropoietin level was raised throughout the 24 h and erythrocyte mass was also raised. In the other patient, the serum erythropoietin level was not raised in five daytime samples and erythrocyte mass was normal. 4. The other five patients with chronic obstructive pulmonary disease with less severe nocturnal hypoxaemia (lowest arterial oxygen saturation range 78-86%) had serum erythropoietin levels (range 14-36 m-i.u./ml) which were indistinguishable from normal (range 12-44 m-i.u./ml) and showed circadian changes which were not significantly different (P = 0.35) from those in the normal subjects. 5. Thus, mild nocturnal oxygen desaturation is not associated with elevation of serum erythropoietin levels, whereas daytime hypoxaemia with associated severe nocturnal desaturation is associated with increased serum erythropoietin levels both by day and by night.

1. To investigate the role of mast cells and eosinophils in the pathogenesis of nocturnal asthma, the plasma methylhistamine concentration, serum eosinophil cationic protein level and peak expiratory flow rate were measured 2-hourly for 24 h in 10 patients with nocturnal asthma and in 10 healthy control subjects. Nocturnal asthma was defined as at least one nocturnal awakening per week due to cough, wheeze or breathlessness with an average overnight fall in peak expiratory flow rate of at least 15% during a 2-week run-in period. 2. The lowest peak expiratory flow rate occurred at 02.00-04.00 hours in the group with nocturnal asthma, whose overnight fall in peak expiratory flow rate was 29 +/- 5% in comparison with 5 +/- 1% (means +/- SEM) in the normal subjects. 3. Plasma methylhistamine levels at night (0.200-04.00 hours) were lower than during the day (10.00-20.00 hours) in both asthmatic patients and normal subjects (asthmatic patients: day, median 0.22 ng/ml, 95% confidence intervals 0.18-0.34 ng/ml; night, 0.17 ng/ml, 0.13-0.24 ng/ml; P < 0.01; normal subjects: day, 0.31 ng/ml, 0.24-0.41 ng/ml; night, 0.24 ng/ml, 0.21-0.33 ng/ml; P < 0.01). 4. The serum eosinophil cationic protein level was higher by day (30 ng/ml, 8-47 ng/ml) than by night (21 ng/ml, 5-34 ng/ml; P < 0.04) in the group with nocturnal asthma, but did not change significantly with the time of day in the normal subjects (day: 8 ng/ml, 4-14 ng/ml; night: 8 ng/ml, 5-21 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine whether inhaled salmeterol, a new long acting inhaled beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma., Design: Randomised, double blind, placebo controlled crossover study., Setting: Hospital outpatient clinics in Edinburgh., Subjects: Twenty clinically stable patients (13 women, seven men) with nocturnal asthma, median age 39 (range 18-60) years., Interventions: Salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run in and study periods., Main Outcome Measures: Improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography., Results: Salmeterol improved the lowest overnight peak flow rate at both 50 micrograms (difference in median values (95% confidence interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72 (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality, spending less time awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26 (6-34) min)., Conclusions: Salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality.