Incidental Findings from 16,400 Brain MRI Examinations of Research Volunteers.

BACKGROUND AND PURPOSE: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation. MATERIALS AND METHODS: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan. RESULTS: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings (P < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation. CONCLUSIONS: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols.

Overview and first measurements of the MAST Upgrade bolometer diagnostic.

A suite of multi-channel resistive bolometers has been implemented to measure the total radiation from Mega Amp Spherical Tokamak Upgrade plasmas, with cameras covering the core plasma and lower divertor chamber. Data are digitized and processed using novel field-programmable gate array-based electronics, offering improved compactness and new operational capabilities. A synthetic diagnostic has been developed to explore the quality of 2D reconstructions available from the system and to quantify the uncertainty on quantities such as the total radiated power. Measurements in the first campaign have demonstrated correct functioning of the diagnostic while also highlighting issues with electrical noise and some failure mechanisms of the detectors, as well as significant neutral beam fast-particle losses.

Comparing pedestal structure in JET-ILW H-mode plasmas with a model for stiff ETG turbulent heat transport.

A predictive model for the electron temperature profile of the H-mode pedestal is described, and its results are compared with the pedestal structure of JET-ILW plasmas. The model is based on a scaling for the gyro-Bohm normalized, turbulent electron heat flux [Formula: see text] resulting from electron temperature gradient (ETG) turbulence, derived from results of nonlinear gyrokinetic (GK) calculations for the steep gradient region. By using the local temperature gradient scale length [Formula: see text] in the normalization, the dependence of [Formula: see text] on the normalized gradients [Formula: see text] and [Formula: see text] can be represented by a unified scaling with the parameter [Formula: see text], to which the linear stability of ETG turbulence is sensitive when the density gradient is sufficiently steep. For a prescribed density profile, the value of [Formula: see text] determined from this scaling, required to maintain a constant electron heat flux [Formula: see text] across the pedestal, is used to calculate the temperature profile. Reasonable agreement with measurements is found for different cases, the model providing an explanation of the relative widths and shifts of the [Formula: see text] and [Formula: see text] profiles, as well as highlighting the importance of the separatrix boundary conditions. Other cases showing disagreement indicate conditions where other branches of turbulence might dominate. This article is part of a discussion meeting issue 'H-mode transition and pedestal studies in fusion plasmas'.

Peripartum cardiomyopathy: a global effort to find the cause and cure for the rare and little understood disease.

In this review, we present our current understanding of peripartum cardiomyopathy (PPCM) based on reports of the incidence, diagnosis and current treatment options. We summarise opinions on whether PPCM is triggered by vascular and/or hormonal causes and examine the influence of comorbidities such as preeclampsia. Two articles published in 2021 strongly support the hypothesis that PPCM may be a familial disease. Using large cohorts of PPCM patients, they summarised the available genomic DNA sequence data that are expressed in human cardiomyocytes. While PPCM is considered a disease predominately affecting the left ventricle, there are data to suggest that some cases also involve right ventricular failure. Finally, we conclude that there is sufficient evidence to warrant an RNAseq investigation and that this would be most informative if performed at the cardiomyocytes level rather than analysing genomic DNA from the peripheral circulation. Given the rarity of PPCM, the combined resources of international human heart tissue biobanks have assembled 30 ventricular tissue samples from PPCM patients, and we are actively seeking to enlarge this patient base by collaborating with human heart tissue banks and research laboratories who would like to join this endeavour.

Controlled before-after intervention study of suburb-wide street changes to increase walking and cycling: Te Ara Mua-Future Streets study design.

BACKGROUND: Achieving a shift from car use to walking, cycling and public transport in cities is a crucial part of healthier, more environmentally sustainable human habitats. Creating supportive active travel environments is an important precursor to this shift. The longevity of urban infrastructure necessitates retrofitting existing suburban neighbourhoods. Previous studies of the effects of street changes have generally relied on natural experiments, have included few outcomes, and have seldom attempted to understand the equity impacts of such interventions. METHODS: In this paper we describe the design of Te Ara Mua - Future Streets, a mixed-methods, controlled before-after intervention study to assess the effect of retrofitting street changes at the suburb scale on multiple health, social and environmental outcomes. The study has a particular focus on identifying factors that improve walking and cycling to local destinations in low-income neighbourhoods and on reducing social and health inequities experienced by Maori (Indigenous New Zealanders) and Pacific people. Qualitative system dynamics modelling was used to develop a causal theory for the relationships between active travel, and walking and cycling infrastructure. On this basis we selected outcomes of interest. Together with the transport funder, we triangulated best evidence from the literature, transport policy makers, urban design professionals and community knowledge to develop interventions that were contextually and culturally appropriate. Using a combination of direct observation and random sample face to face surveys, we are measuring outcomes in these domains of wellbeing: road-user behaviour, changes to travel mode for short trips, physical activity, air quality, road traffic injuries, greenhouse gas emissions, and perceptions of neighbourhood social connection, safety, and walking and cycling infrastructure . DISCUSSION: While building on previous natural experiments, Te Ara Mua - Future Streets is unique in testing an intervention designed by the research team, community and transport investors together; including a wide range of objective outcome measures; and having an equity focus. When undertaking integrated intervention studies of this kind, a careful balance is needed between epidemiological imperatives, the constraints of transport funding and implementation and community priorities, while retaining the ability to contribute new evidence for healthy, equitable transport policy. The study was retrospectively registered as a clinical trial on 21 June 2018 in the ISCRTN registry: ISRCTN89845334 http://www.isrctn.com/ISRCTN89845334.

Synthetic MRI for Clinical Neuroimaging: Results of the Magnetic Resonance Image Compilation (MAGiC) Prospective, Multicenter, Multireader Trial.

BACKGROUND AND PURPOSE: Synthetic MR imaging enables reconstruction of various image contrasts from 1 scan, reducing scan times and potentially providing novel information. This study is the first large, prospective comparison of synthetic-versus-conventional MR imaging for routine neuroimaging. MATERIALS AND METHODS: A prospective multireader, multicase noninferiority trial of 1526 images read by 7 blinded neuroradiologists was performed with prospectively acquired synthetic and conventional brain MR imaging case-control pairs from 109 subjects (mean, 53.0 ± 18.5 years of age; range, 19-89 years of age) with neuroimaging indications. Each case included conventional T1- and T2-weighted, T1 and T2 FLAIR, and STIR and/or proton density and synthetic reconstructions from multiple-dynamic multiple-echo imaging. Images were randomized and independently assessed for diagnostic quality, morphologic legibility, radiologic findings indicative of diagnosis, and artifacts. RESULTS: Clinical MR imaging studies revealed 46 healthy and 63 pathologic cases. Overall diagnostic quality of synthetic MR images was noninferior to conventional imaging on a 5-level Likert scale (P < .001; mean synthetic-conventional, -0.335 ± 0.352; Δ = 0.5; lower limit of the 95% CI, -0.402). Legibility of synthetic and conventional morphology agreed in >95%, except in the posterior limb of the internal capsule for T1, T1 FLAIR, and proton-density views (all, >80%). Synthetic T2 FLAIR had more pronounced artifacts, including +24.1% of cases with flow artifacts and +17.6% cases with white noise artifacts. CONCLUSIONS: Overall synthetic MR imaging quality was similar to that of conventional proton-density, STIR, and T1- and T2-weighted contrast views across neurologic conditions. While artifacts were more common in synthetic T2 FLAIR, these were readily recognizable and did not mimic pathology but could necessitate additional conventional T2 FLAIR to confirm the diagnosis.

Body mass index, new modes of TV viewing and active video games.

BACKGROUND: Recent technologies have changed screen time. TV can be viewed anywhere, anytime. Content can be collected via digital recorders and online streaming and viewed on smartphones. Video games are no longer strictly sedentary. OBJECTIVES: We sought to assess the unknown relations between new modes of TV viewing - recorded, online, downloaded and on hand-held devices - and active video games with body mass index (BMI). METHODS: Cross-sectional analysis of the 2011 wave of the Growing Up Today Study 2 cohort. We used gender-specific generalized estimating equations to examine screen time and BMI among 3071 women and 2050 men aged 16-24 years. RESULTS: Among women, each hour/day of online TV (0.47; confidence interval [CI]: 0.12, 0.82) and total non-broadcast TV (0.37; CI: 0.14, 0.61) was associated with higher BMI, as was watching ≥ 1/2 h week-1 of TV on hand-held devices (1.04; CI: 0.32-1.77). Active video games were associated with BMI among women, but not after restricting to those not trying to lose/maintain weight. Broadcast TV was associated with higher BMI (kg m-2 ) among women and men (P < 0.05). CONCLUSIONS: Among women, online TV, TV viewed on hand-held devices and the sum of non-broadcast TV time were associated with higher BMI. Broadcast TV was also associated with BMI in women and men.

Eating disorder behaviours amongst adolescents: investigating classification, persistence and prospective associations with adverse outcomes using latent class models.

Diagnostic criteria for eating disorders (ED) remain largely based on clinical presentations, but do not capture the full range of behaviours in the population. We aimed to derive an empirically based ED behaviour classification using behavioural and body mass index (BMI) indicators at three time-points in adolescence, and to validate classes investigating prospective associations with adverse outcomes. Adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) provided data on ED at age 14 (n = 6615), 16 (n = 5888), and 18 years (n = 5100), and had weight and height measured. Psychological and behavioural outcomes were assessed at 15.5/16 and 17.5/18 years. We fit gender- and age-stratified latent class models, and employed logistic regression to investigate associations between classes and later outcomes. One asymptomatic and two symptomatic (largely representing higher and lower frequency ED behaviours) classes were observed at each time-point, although their relative prevalence varied by age and gender. The majority of girls in symptomatic classes remained symptomatic at subsequent assessments. Girls in symptomatic classes had higher odds of subsequent anxiety and depressive disorders, binge drinking, drug use, and deliberate self-harm. Data analyses were underpowered amongst boys. The presence of two symptomatic classes (characterised by different ED behaviour frequency) and their prospective association with adverse outcomes suggest a need to refine diagnostic thresholds based on empirical data. Despite some instability of classes, particularly in mid-adolescence, evidence that half of girls in symptomatic classes remained symptomatic suggests persistence of ED behaviours in adolescence, and highlights a need for early identification to reduce chronicity.

Faecal occult blood testing screening for colorectal cancer and 'missed' interval cancers: are we ignoring the elephant in the room? Results of a multicentre study.

AIM: Biennial faecal occult blood testing (FOBT) is used to screen for colorectal cancer throughout the UK. Interval cancers are tumours that develop in patients between screening rounds who have had a negative FOBT. Through a multicentre study, we compared the demographics of patients with interval cancers, FOBT screen detected cancers and cancers that developed in patients who chose not to participate in the screening programme. METHOD: Five hundred and sixteen colorectal cancers were detected in the screening age group (60-74 years) population in three UK National Health Service hospitals over 2 years. One hundred and twenty seven (25%) were interval cancers, 161 (31%) were screen detected and 228 (44%) were cancers that developed in patients who had declined FOBT. The interval cancer group had a higher incidence of right-sided cancers (38% vs 29% and 24%), a higher proportion of high tumour stages (Dukes C and D) (70% vs 53% and 33%) and a shorter time from diagnosis to death (10 months vs 13 months and 24 months) compared to patients who had declined the FOBT and the FOBT screen detected cancers. Of all the patients studied, those with right-sided interval cancers had the worst outcome. CONCLUSION: A quarter of the colorectal cancers diagnosed in our study were interval cancers. Patients with right-sided interval cancers had the highest proportion of Dukes C and D tumours coupled with the shortest survival time after diagnosis compared with the other groups.

Tackling Complexity in High Performance Computing Applications.

We present a software framework that supports the specification of user-definable configuration options in HPC applications independently of the application code itself. Such options include model parameter values, the selection of numerical algorithm, target platform etc. and additional constraints that prevent invalid combinations of options from being made. Such constraints, which are capable of describing complex cross-domain dependencies, are often crucial to the correct functioning of the application and are typically either completely absent from the code or a hard to recover from it. The framework uses a combination of functional workflows and constraint solvers. Application workflows are built from a combination of functional components: higher-order co-ordination forms and first-order data processing components which can be either concrete or abstract, i.e. without a specified implementation at the outset. A repository provides alternative implementations for these abstract components. A constraint solver, written in Prolog, guides a user in making valid choices of parameters, implementations, machines etc. for any given context. Partial designs can be stored and shared providing a systematic means of handling application use and maintenance. We describe our methodology and illustrate its application in two classes of application: a data intensive commercial video transcoding example and a numerically intensive incompressible Navier-Stokes solver.

Training for cytotechnologists and cytopathologists in the developing world.

Currently there is a major challenge to train sufficient cytopathologists and cytotechnicians in developing countries that have poor medical and pathology infrastructure. Cytology requires well trained pathologists and laboratory staff but it needs only minimal laboratory resources. Cytology can provide the material for rapid, accurate and inexpensive diagnoses of infections such as tuberculosis and of benign and malignant palpable and impalpable lesions. Cytology can achieve this in the developing world by utilizing fine needle aspiration biopsy cytology, general fluids cytology and cervical cytology, in the same manner as is currently done in the developed world where cytology specimens are used to make cytomorphological diagnoses and increasingly to provide material for the full range of ancillary testing including molecular pathology. There are a number of ways to develop sustainable training in cytology in developing countries, especially in fine needle aspiration biopsy cytology, and these are presented and discussed.

Longitudinal Associations Among Posttraumatic Stress Disorder, Disordered Eating, and Weight Gain in Military Men and Women.

Obesity is a major health problem in the United States and a growing concern among members of the military. Posttraumatic stress disorder (PTSD) has been associated with overweight and obesity and may increase the risk of those conditions among military service members. Disordered eating behaviors have also been associated with PTSD and weight gain. However, eating disorders remain understudied in military samples. We investigated longitudinal associations among PTSD, disordered eating, and weight gain in the Millennium Cohort Study, which includes a nationally representative sample of male (n = 27,741) and female (n = 6,196) service members. PTSD at baseline (time 1; 2001-2003) was associated with disordered eating behaviors at time 2 (2004-2006), as well as weight change from time 2 to time 3 (2007-2008). Structural equation modeling results revealed that the association between PTSD and weight change from time 2 to time 3 was mediated by disordered eating symptoms. The association between PTSD and weight gain resulting from compensatory behaviors (vomiting, laxative use, fasting, overexercise) was significant for white participants only and for men but not women. PTSD was both directly and indirectly (through disordered eating) associated with weight change. These results highlight potentially important demographic differences in these associations and emphasize the need for further investigation of eating disorders in military service members.

Adherence to the Mediterranean dietary pattern and BMI change among US adolescents.

BACKGROUND: Among adults, the Mediterranean dietary pattern (MDP) is inversely related to body mass index (BMI). Data are lacking on adherence to the MDP among youth in the United States and whether the MDP is related to weight change in that group. OBJECTIVE: To assess whether adherence to the MDP was associated with BMI change among adolescents. To examine temporality, we studied the association between baseline and 2-3-year changes in adherence to the MDP with concurrent changes in BMI, as well as subsequent changes in BMI over a 7-year period. METHODS: We prospectively followed 6002 females and 4916 males in the Growing Up Today Study II, aged 8-15 years in 2004, living across United States. Data were collected by questionnaire in 2004, 2006, 2008 and 2011. Dietary intake was assessed by the Youth/Adolescent Questionnaire. The KidMed Index was derived to measure the adherence to the MDP. We used generalized estimating equations with repeated measures within subjects to assess the association between MDP and BMI change. RESULTS: A two-point increment in the KidMed Index was independently associated with a lower gain in BMI (-0.04 kg m(-2); P=0.001). A greater increase in adherence to the KidMed Index was independently related to a lower gain in BMI in both the concurrent (P-for-trend<0.001) and the subsequent period (P-for-trend=0.002). CONCLUSIONS: Adherence to MDP was inversely associated with change in BMI among adolescents. Two-year improvement in adherence to MDP was independently associated with less steep gain in the BMI in both the concurrent and the subsequent period.

Longitudinal study of maternal body mass index, gestational weight gain, and offspring asthma.

BACKGROUND: Sparse data are available on the relationship between prenatal exposures and asthma during later childhood. In a longitudinal study of adolescents and their mothers, we examined the association of (i) maternal prepregnancy body mass index (BMI) and (ii) gestational weight gain (GWG), with incidence of allergic and nonallergic asthma in offspring. METHODS: Analyses were conducted using data from 12 963 children aged 9-14 years at enrolment in the Growing Up Today Study, and their mothers, who are participants in the Nurses' Health Study II. Physician-diagnosed asthma and allergies were assessed by questionnaires sent regularly to participants and their mothers. Logistic regression was used to evaluate associations of maternal BMI and GWG with offspring asthma, overall and by subtype. RESULTS: Physician-diagnosed asthma during childhood or adolescence was reported by 2694 children (21%). Maternal prepregnancy overweight (OR: 1.19, 95% CI: 1.03-1.38) and obesity (1.34, 1.08-1.68) were associated with offspring asthma. In asthma subtype analyses, the association was seen only for asthma onset before age 12 years. Moreover, the association of maternal obesity with nonallergic asthma was observed in boys (2.39, 1.40-4.09) and not in girls (0.96, 0.50-1.85; Pinteraction = 0.03); the opposite pattern was suggested for allergic asthma. With regard to GWG, an association was suggested between gains of <15 lb and higher risk of offspring asthma (1.28, 0.98-1.66), without clear allergy- or sex-related patterns. CONCLUSION: The relation of several prenatal factors to risk of childhood asthma supports the early origins hypothesis for asthma. The observed allergy- and sex-specific patterns suggest multiple etiologic pathways.