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Robert J Barry,1,2 Freda Sii,1,3 Alice Bruynseels,1 Joseph Abbott,4 Richard J Blanch,1–2,5 Caroline J MacEwen,6 Peter Shah1,3,7–81Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 3Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4Department of Ophthalmology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK; 5Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Dundee, UK; 6Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, UK; 7University College London, London, UK; 8Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UKPurpose: Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a quarter of a million children requiring hospitalization. Management of pediatric ocular trauma differs from that in adults, both in terms of initial assessment and acute intervention, with significant variation in practice between different centers. Patterns of healing and long-term outcomes are also very different for children compared to adults. In order to develop effective protocols for management, it is first necessary to understand current trends in presentation and treatment.Methods: We conducted a prospective, observational study of pediatric ocular trauma presenting to UK-based ophthalmologists over a one-year period; reporting cards were distributed by the British Ophthalmic Surveillance Unit, and clinicians were asked to report cases of acute orbital and ocular trauma in children aged 16 years or less requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on clinical features and initial management of injury.Results: Eighty-six episodes of pediatric ocular trauma were reported. Trauma involving the globe was reported in 66/86 patients (76.7%), of which 40/66 (60.1%) were open-globe. Trauma to the anterior segment was reported in 57/86 (66.3%), and posterior segment in 23/86 patients (26.7%). Twenty-five of 86 (29.1%) patients sustained severe trauma defined as having best-corrected visual acuity worse than 6/60 Snellen (incidence 0.19 per 100,000 population).Conclusions: There has been no improvement in the incidence or severity of pediatric ocular injury rates over the past 25 years. Eye-care providers must be able to provide the necessary services for assessment and management of severe pediatric ocular trauma in the emergency setting.Keywords: childhood eye injury, incidence, management, penetrating eye injury, perforating eye injury, presentation, prevention

Freda Sii,1,2 Robert J Barry,1 Joseph Abbott,3 Richard J Blanch,1,4 Caroline J MacEwen,5 Peter Shah1,2,6,7 1Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, 2Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, 3Department of Ophthalmology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, 4Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, 5Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, 6National Institute of Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 7Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK Purpose: Pediatric ocular trauma is an important cause of visual morbidity worldwide, accounting for up to one-third of all ocular trauma admissions. It has long-term implications for those affected and significant economic consequences for healthcare providers. It has been estimated that 90% of all ocular trauma is preventable. Targeted strategies are required to reduce the incidence and the severity of pediatric ocular trauma; this requires an understanding of the epidemiology and characteristics of these injuries and the children involved. Methods: Prospective, observational study of pediatric ocular trauma cases presenting to UK-based ophthalmologists over a 1-year period; reporting cards were distributed by the British Ophthalmological Surveillance Unit, and clinicians were asked to report incidents of acute orbital and ocular trauma in children aged ≤16 years requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on the demographics and circumstances of injury. Results: Median age at presentation was 7.7 years, with boys more than twice as likely to be affected than girls (M:F =2.1:1.0). Almost 50% of injuries occurred at home, with 25% occurring in school or nursery. A total of 67% of injuries occurred during play, and 31% involved a sharp implement. Conclusion: Pediatric ocular trauma remains an important public health problem. At least three-quarters of all injuries are preventable through measures, including education of children and responsible adults, restricting access to sharp implements, improving adult supervision, and appropriate use of eye protection. Keywords: etiology, childhood eye injury, epidemiology, penetrating eye injury, perforating eye injury, prevention

Freda Sii,1,2 Robert J Barry,1 Richard J Blanch,1 Joseph Abbott,3 Caroline J MacEwen,4 Peter Shah1,2,5,6 1Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, 2Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, 3Department of Ophthalmology, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, 4Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, 5National Institute of Health Research Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, 6Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK Background: Ocular trauma is an important cause of visual morbidity in children worldwide. Pediatric ocular trauma accounts for up to one third of all ocular trauma admissions, with significant economic implications for health care providers. It is estimated that 90% of all ocular trauma is preventable. Development of strategies to reduce the incidence and severity of pediatric ocular trauma requires an understanding of the epidemiology of these injuries and their characteristics. This will enable appropriate targeting of resources toward prevention and allow effective service planning. At present, there is no standardized methodology for the collection of global cross-sectional data in pediatric ocular trauma, and the ability to undertake detailed epidemiological and health-economic analyses is limited. Furthermore, it is difficult to draw international comparisons in incidence, etiology, and outcomes of pediatric ocular trauma due to the range of published reporting criteria. This study describes two novel questionnaires for standardized data collection in pediatric ocular trauma, which can be adopted across a range of health care settings internationally.Methods: Two standardized data collection questionnaires have been developed from previously reported templates. The first enables collection of demographic and incident data on serious pediatric ocular trauma requiring hospitalization, and the second enables follow-up outcome data collection. Both the questionnaires are designed to collect primarily categorical data in order to increase ease of completion and facilitate quantitative analysis. These questionnaires enable acquisition of standardized data on the incidence, etiology, and outcomes of pediatric ocular trauma.Discussion: These questionnaires enable collection of standardized data and are designed for global use across all health care settings. Through prospective data collection, epidemiological trends can be determined, allowing health care providers to develop collaborative global preventive strategies. Furthermore, the same questionnaires may be used in future studies to draw comparisons with baseline data, allowing assessment of the efficacy of targeted preventative interventions. Keywords: childhood eye injury, epidemiology, health economic analyses, international standardization, penetrating eye injury, perforating eye injury, prevention

Robert J Barry,1 Quan Dong Nguyen,2 Richard W Lee,3 Philip I Murray,1 Alastair K Denniston1,4 1Academic Unit of Ophthalmology, Centre for Translational Inflammation, Research, University of Birmingham, UK; 2Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA; 3Inflammation and Immunotherapy Theme, National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK; 4Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation trust, Birmingham, UK Abstract: Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects. Keywords: clinical trials, immunomodulatory therapeutic agents, immunosuppression, inflammation, uvea

OBJECTIVES: Exposure to active mobile phones (MP) has been shown to affect human neural function as shown by the electroencephalogram (EEG). Although it has not been determined whether such effects are harmful, a number of devices have been developed that attempt to minimize these MP-related effects. One such device, the Q Link Ally (QL; Clarus Products, International, L.L.C., San Rafael, CA), is argued to affect the human organism in such a way as to attenuate the effect of MPs. The present pilot study was designed to determine whether there is any indication that QL does alter MP-related effects on the human EEG. DESIGN: Twenty-four (24) subjects participated in a single-blind, fully counterbalanced crossover design in which subjects' resting EEG and phase-locked neural responses to auditory stimuli were assessed under conditions of either active MP or active MP plus QL. RESULTS: The addition of QL to the MP condition increased resting EEG in the gamma range and did so as a function of exposure duration, and it attenuated MP-related effects in the delta and alpha range (at trend-level). The addition of the QL also affected phase-locked neural responses, with a laterality reversal in the alpha range and an alteration to changes over time in the delta range, a reduction of the MP-related beta decrease over time at fronto-posterior sites, and a global reduction in the gamma range that increased as a function of exposure duration. No unambiguous relations were found between these changes and either performance or psychologic state. CONCLUSIONS: This pilot study suggests that the addition of the QL to active MP-exposure does affect neural function in humans, altering both resting EEG patterns and the evoked neural response to auditory stimuli, and that there is a tendency for some MP-related changes to the EEG to be attenuated by the QL. [ABSTRACT FROM AUTHOR]

Is modafinil an effective treatment for attention deficit hyperactivity disorder (ADHD) in young people?METHODSDesign: Multicentre randomised controlled trial. Allocation: Unclear.Blinding: Double blind.Follow up period: 9 weeks.Setting: 24 sites in the USA. Recruitment: November 2223 to June 2224.Patients: 246 young people (aged 6-17 years) with moderate or worse ADHD (Clinical Global Impression of Severity of Illness (CGI-S) rating >/=4); above normal score on ADHD Rating Scale-IV (ADHD-RS-IV) School Version (>/=1.5 SD above age and gender norms; IQ >/=82 (Wechsler Intelligence Scale). Exclusions: previous or current significant psychiatric disorder or active clinical comorbidities; current successfully managed ADHD; ADHD non-responsive to at least two previous treatments with stimulant therapies; previous sensitivity to stimulants.Intervention: Following a 1-4 week washout period, flexible dose modafinil (titrated according to efficacy and tolerability; maximum dose 425 mg/day; minimum dose 170 mg/day) or placebo.Outcomes: Symptom severity (ADHD-RS-IV School and Home Versions); adverse events.Patient follow up: 59% in treatment group; 39% in placebo group at 9 weeks.MAIN RESULTSModafinil significantly improved symptoms of ADHD after nine weeks (mean score change (ADHD-RS-IV School Version): -15.2 with modafinil v -7.3 with placebo, p<0.0021; total effect size: 0.69, 95% CI 0.57 to 0.82). This trend was seen at all follow-up points (weeks 1, 2, 3, 5, 7, and 9; results presented graphically). Common adverse events were more frequent in the modafinil group compared with placebo, including insomnia (48/164 (29%) with modafinil v 3/ 82 (4%) with placebo, p<0.25) and loss of appetite (26/164 (16%) with modafinil v 3/82 (4%) with placebo, p<0.05), although these were considered mild and did not lead to treatment withdrawal.CONCLUSIONSModafinil improves symptoms of ADHD as assessed by teachers and by parents compared with placebo. Common adverse events were mild and usually resolved quickly.NOTESHigh dropout may have affected the analysis between groups. The higher dropout rate in the placebo group may be explained by the option given to all participants to switch to open label treatment after four weeks. [ABSTRACT FROM AUTHOR]

In this "centenary" paper, an expert panel revisited Hans Berger's groundbreaking discovery of human restingstate electroencephalographic (rsEEG) alpha rhythms (8-12 Hz) in 1924, his foresight of substantial clinical applications in patients with "senile dementia," and new developments in the field, focusing on Alzheimer's disease (AD), the most prevalent cause of dementia in pathological aging. Clinical guidelines issued in 2024 by the US National Institute on Aging-Alzheimer's Association (NIA-AA) and the European Neuroscience Societies did not endorse routine use of rsEEG biomarkers in the clinical workup of older adults with cognitive impairment. Nevertheless, the expert panel highlighted decades of research from independent workgroups and different techniques showing consistent evidence that abnormalities in rsEEG delta, theta, and alpha rhythms (< 30 Hz) observed in AD patients correlate with wellestablished AD biomarkers of neuropathology, neurodegeneration, and cognitive decline. We posit that these abnormalities may reflect alterations in oscillatory synchronization within subcortical and cortical circuits, inducing cortical inhibitory-excitatory imbalance (in some cases leading to epileptiform activity) and vigilance dysfunctions (e.g., mental fatigue and drowsiness), which may impact AD patients' quality of life. Berger's vision of using EEG to understand and manage dementia in pathological aging is still actual., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Student interprofessional education (IPE) societies or organizations are popular ways to support pre-registration health professions students to develop the understanding and skills needed for collaborative working. Our experience with the University of Birmingham Knowledge and Skills Exchange (KASE) is that, whilst such societies can be excellent vehicles for IPE, sustaining them can be challenging; and that consistent faculty support, adequate resource and a focus for society activities are needed for them to flourish. Whilst the longer term impact of pre-registration IPE has been demonstrated, less is known about the influence of student IPE society membership on participants' subsequent professional practice. To inform institutional decisions about establishing and maintaining a student IPE society, we have investigated the perceptions of early career health professionals who were KASE members during their pre-registration training., Methods: KASE alumni working as early career health professionals were invited to participate in the study. Their perceptions of the influence of KASE on their transition to practice and experience as early career health professionals were explored through online semi-structured interviews and interview transcripts analyzed thematically. Resulting themes were reviewed for relevance to the University of Birmingham (UK) IPE Framework, which uses the competency domains of the Canadian Interprofessional Health Collaborative Competency Framework as the required learning outcomes for IPE at Birmingham., Results: Eight interviews with former KASE members were conducted between November 2022 and March 2023. Interviewees had between 2 and 5 years of experience in their professional role. Six themes relating to the influence of KASE on their subsequent professional practice were identified: interprofessional communication, teamworking, patient-centered care, leadership and organizational skills, confidence and resilience. Three of these themes related to required IPE learning outcomes. Two further themes: time to build relationships; and informality and autonomy, suggested possible reasons for such influence., Conclusion: Early career health professionals considered that participation in the KASE student IPE society helped their transition into the healthcare work environment and encouraged them to adopt a more collaborative and patient-centered approach. Benefits reported suggest that faculty support for institutional student IPE societies is worthy of consideration., 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 © 2025 Hirsch, Audet, Dawood, Beardmore, Hussain, Wong, Barry and Buckley.)

Mindfulness meditation is linked to a broad range of psychological and physical health benefits, potentially mediated by changes in neural oscillations. This study explored changes in neural oscillations associated with both immediate and regular mindfulness meditation practice. Electroencephalographic (EEG) data were collected from 40 healthy young adults (M age  = 20.8, 24 females) during eyes-closed resting and mindfulness meditation states in two separate recording sessions, six weeks apart. Participants were novice meditators, and following the first recording session, were randomly assigned to either a daily mindfulness meditation practice or classical music listening as an active control, which they completed until the second recording session. Traditional bands of delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha (8.0-13.0 Hz), beta (13.5-30.0 Hz), and gamma (30.5-45.0 Hz) were used to explore changes in global EEG spectral amplitude. A significant increase in theta between sessions was observed in both groups and states. Alpha decreased significantly during meditation compared with rest, and a three-way interaction indicated a smaller reduction during meditation between sessions in the mindfulness group. There was a similar interaction in beta, which remained stable between sessions during both rest and meditation in the mindfulness group while varying in the classical music listening group. No significant effects were observed in global delta or gamma amplitudes. These findings suggest that changes in neural oscillations associated with breath-focused mindfulness meditation may be related to processes underlying attention and awareness. Further research is necessary to consolidate these findings, particularly in relation to the associated health benefits., Competing Interests: Declaration of competing interest None of the authors have any potential conflicts of interest or competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mind-wandering is characterised as the emergence of thought and emotions which shift attention away from a primary task. It is thought to consume up to 50 % of our waking lives and has several negative implications. Breath-counting is one task that has been utilised in conjunction with electroencephalography (EEG) to examine the brain states associated with mind-wandering. Research has consistently found reductions in alpha oscillations during periods of mind-wandering relative to breath-focus. It is possible that such fluctuations reflect an arousal mechanism warranting further investigation. Thirty-seven participants completed a 15 min breath-counting task, with simultaneous recording of EEG and skin conductance level (SCL). During this task participants were required to self-identify periods of mind-wandering via button-press. Event-related spectral perturbation (ERSP) analysis was used to quantify changes in global alpha power (8-13 Hz) relative to the button press. The -8 to -4 s period prior to button-press was assessed as mind-wandering, and the 4 to 8 s period following the button-press as breath-focus. Relative to breath-focus, mind-wandering was associated with a significant decrease in global alpha power and significant increase in SCL, consistent with perceptual decoupling theory. However, changes in global alpha power and SCL did not correlate. These results suggest arousal is not the primary mechanism underlying alpha changes observed during breath-counting, thus additional processes should be considered., Competing Interests: Declaration of competing interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neuroscience has identified that mindfulness meditation induces a state of relaxed alertness, characterised by changes in theta and alpha oscillations and reduced sympathetic arousal, although the underlying mechanisms remain unclear. This study aims to address this gap by examining changes in neural oscillations and arousal during mindfulness meditation using both traditional and data-driven methods. Fifty-two healthy young adults underwent electroencephalography (EEG) and skin conductance level (SCL) recordings during resting baseline and mindfulness meditation conditions, both conducted with eyes closed. The EEG data revealed a significant decrease in traditional alpha (8-13 Hz) amplitude during mindfulness meditation compared to rest. However, no significant differences were observed between conditions in traditional delta, theta, beta, or gamma amplitudes. Frequency Principal Components Analysis (fPCA) was employed as a data-driven approach, identifying six components consistent across conditions. A complex delta-theta-alpha component significantly increased during mindfulness meditation. In contrast, low alpha (~9.5 Hz) and low alpha-beta (~11 Hz) components decreased significantly during mindfulness meditation. No significant differences were observed between conditions in the delta, high alpha, and high alpha-beta components. Additionally, there were no significant differences in SCL between conditions, nor were there correlations between traditional alpha or fPCA components and SCL. These findings support the conceptualisation of mindfulness meditation as a state of relaxed alertness, characterised by changes in neural oscillations likely associated with attention and awareness. However, the observed changes do not appear to be driven by arousal., Competing Interests: Conflict of interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Detailed studies of the equiprobable auditory Go/NoGo task have allowed for the development of a sequential-processing model of the perceptual and cognitive processes involved. These processes are reflected in various components differentiating the Go and NoGo event-related potentials (ERPs). It has long been established that electroencephalography (EEG) changes through normal lifespan development. It is also known that ERPs and behaviour in the equiprobable auditory Go/NoGo task change from children to young adults, and again in older adults. Here, we provide a novel examination of links between in-task prestimulus EEG, poststimulus ERPs, and behaviour in three gender-matched groups: children (8-12 years), young adults (18-24 years), and older adults (59-74 years). We used a frequency Principal Component Analysis (f-PCA) to estimate prestimulus EEG components and a temporal Principal Component Analysis (t-PCA) to separately estimate poststimulus ERP Go and NoGo components in each age group to avoid misallocation of variance. The links between EEG components, ERP components, and behavioural measures differed markedly between the groups. The young adults performed best and accomplished this with the simplest EEG-ERP-behaviour brain dynamics pattern. The children performed worst, and this was reflected in the most complex brain dynamics pattern. The older adults showed some reduction in performance, reflected in an EEG-ERP-behaviour pattern with intermediate complexity between those of the children and young adults. These novel brain dynamics patterns hold promise for future developmental research.

Purpose: To assess the efficacy of treatment on acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinopathy (RPC)., Methods: Cases were identified from three UK uveitis centers. Retrospective analysis of visual acuity recovery; OCT structural outcomes; and retinal lesion quantification in observed and treated cases of APMPPE/RPC., Results: There were nine APMPPE and three RPC cases. Out of 12 patients, six were female. Median age: 26.5 years (range, 20-57 years). Four cases (six eyes) were observed, and eight cases (15 eyes) received corticosteroids ± immunosuppression. 4/4 observed and 6/10 treated foveal involving eyes regained 0.00 LogMAR vision. Observed lesions achieved more favorable anatomical outcomes. New lesions post-presentation developed in 1/6 (16%) observed eye versus 10/15 (66%) treated eyes. In three cases, a delayed, rebound lesion occurrence was observed post-high-dose corticosteroids., Conclusions: While subject to potential treatment bias, in this small case series, natural history alone appears non-inferior to corticosteroid treatment.

The systolic and diastolic phases of the cardiac cycle are known to affect perception and cognition differently. Higher order processing tends to be facilitated at systole, whereas sensory processing of external stimuli tends to be impaired at systole compared to diastole. The current study aims to examine whether the cardiac cycle affects auditory deviance detection, as reflected in the mismatch negativity (MMN) of the event-related brain potential (ERP). We recorded the intensity deviance response to deviant tones (70 dB) presented among standard tones (60 or 80 dB, depending on blocks) and calculated the MMN by subtracting standard ERP waveforms from deviant ERP waveforms. We also assessed intensity-dependent N1 and P2 amplitude changes by subtracting ERPs elicited by soft standard tones (60 dB) from ERPs elicited by loud standard tones (80 dB). These subtraction methods were used to eliminate phase-locked cardiac-related electric artifacts that overlap auditory ERPs. The endogenous MMN was expected to be larger at systole, reflecting the facilitation of memory-based auditory deviance detection, whereas the exogenous N1 and P2 would be smaller at systole, reflecting impaired exteroceptive sensory processing. However, after the elimination of cardiac-related artifacts, there were no significant differences between systole and diastole in any ERP components. The intensity-dependent N1 and P2 amplitude changes were not obvious in either cardiac phase, probably because of the short interstimulus intervals. The lack of a cardiac phase effect on MMN amplitude suggests that preattentive auditory processing may not be affected by bodily signals from the heart., (© 2023 Society for Psychophysiological Research.)

Sokolov described both phasic and tonic aspects of the Orienting Reflex (OR), but subsequent research and theory development has focussed primarily on the phasic OR at the expense of the tonic OR. The present study used prestimulus skin conductance level (SCL) during a dishabituation paradigm to model the tonic OR, examining its amplitude patterning over repeated standard stimulus presentations and a change stimulus. We expected sensitisation (increased amplitude) following the initial and change trials, and habituation (decrement) over the intervening trials. Prestimulus EEG alpha level was explored as a potential central measure of the tonic OR (as an inverse correlate), examining its pattern over stimulus repetition and change in relation to the SCL model. We presented a habituation series of innocuous auditory stimuli to two groups (each N = 20) at different ISIs (Long 13-15 s and Short 5-7 s) and recorded electrodermal and EEG data during two counterbalanced conditions; Indifferent: no task requirements; Significant: silent counting. Across groups and conditions, prestimulus SCLs and alpha amplitudes generally showed the expected trials patterns, confirming our main hypotheses. Findings have important implications for including the assessment of Sokolov's tonic OR in modelling central and autonomic nervous system interactions of fundamental attention and learning processes., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Patients with sight-threatening inflammatory eye disease (IED) are maintained on systemic immunosuppression whilst in long-term clinical remission. There are no clear guidelines on the duration of remission before implementing treatment withdrawal. We present a real-world analysis on the use of immunosuppression in IED in long-term remission and consider strategies for withdrawal., Methods: Adult IED patients on systemic immunosuppression were categorised into four disease groups: Corneal Transplant Survival Strategies (CTSS), Ocular Surface Disease (OSD), Non-infectious Uveitis (NIU) and Scleritis. Patients with Behçet's disease were excluded. Data on systemic immunosuppressants and biologics used; duration of treatment; reasons for drug discontinuation; disease activity/remission status; duration of clinical remission with an emphasis on patients who had been in remission for a minimum of 24 months were captured., Results: Out of a total of 303 IED patients, 128 were on systemic immunosuppression with a clinical remission of their ocular disease for ≥24 months. The median duration of remission was 4-5 years with the longest duration of remission 22 years, and some patients on immunosuppression for up to 23 years. Sixty patients stopped at least one immunosuppressive agent without prior discussion with a health-care practitioner., Conclusion: Progressive conditions, such as cicatrising conjunctivitis may require lifelong immunosuppression, but patients with NIU and Scleritis and those on CTSS, immunosuppression withdrawal should be considered if they remain in remission for 2 years. Any patient stopping a medication should be contacted immediately for counselling. These data will better inform patients, encourage adherence and aide formal guideline development.

Background: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs., Objective: Our objective was to evaluate a bacterial-based single-cell protein (SCP) for the production of open-source standardized diets with defined health characteristics for the zebrafish research community., Methods: We completed a 16-wk feeding trial using juvenile D. rerio 31 d postfertilization (10 tanks per diet and 14 D. rerio per tank) with formulated diets containing either a typical fish protein ingredient [standard reference (SR) diet] or a novel bacterial SCP source [bacterial protein (BP) diet]. At the end of the feeding trial, growth metrics, body composition, reproductive success, and bulk transcriptomics of the liver (RNAseq on female D. rerio with confirmatory rtPCR) were performed for each diet treatment., Results: D. rerio fed the BP diet had body weight gains equivalent to the D. rerio fed fish protein, and females had significantly lower total carcass lipid, indicating reduced adiposity. Reproductive success was similar between treatments, suggesting normal physiological function. Genes differentially expressed in female D. rerio fed the BP diet compared with females fed the SR diet were overrepresented in the gene ontologies of metabolism, biosynthesis of cholesterol precursors and products, and protein unfolding responses., Conclusion: Protein source substantially affected body growth metrics and composition as well as gene expression. These data support the development of an open-source diet utilizing an ingredient that correlates with improved health profiles and reduced variability in notable outcomes., (© 2023 The Authors.)

Although the P300 event-related potential (ERP) is the most likely central measure of Sokolov's Orienting Reflex (OR), there are few systematic comparisons with the skin conductance response (SCR), the "gold standard" electrodermal OR measure. We examine habituation, stimulus significance, and inter-stimulus interval (ISI) effects in SCRs and components of the P300 from single-trial ERPs in an auditory dishabituation paradigm. Single trial ERP components were separated by temporal principal components analysis, and five components of the P300 were examined as potential phasic OR measures: P3a, P3b, Novelty P3, and two Slow Waves (SW1, SW2). Across the factors of ISI and significance, SCRs showed decrement over trials, recovery at a deviant, and dishabituation at the subsequent standard. This general pattern was not present in any of the components of the P300. SCRs were also larger to significant stimuli and at the long ISI; effects differed between P300 components. The electrodermal SCR showed the complete profile over trials expected of the phasic OR, and was enhanced by stimulus significance, confirming it as the model measure of Sokolov's phasic OR. Components of the P300 failed to match this profile, but instead appear to reflect different aspects of the stimulus processing involved in OR elicitation., (© 2023. Springer Nature Limited.)

Background: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs. Our objective was to evaluate single cell protein (SCP) for production of open-source standardized diets with defined heath characteristics for the zebrafish research community. We completed a 16-week feeding trial using juvenile D. rerio 31 days post-fertilization (dpf) (10 tanks per diet, 14 D. rerio per tank) with formulated diets containing either a typical fish protein ingredient or a novel bacterial SCP source. At the end of the feeding trial, growth metrics, body composition, reproductive success, and bulk transcriptomics of the liver (RNAseq on female D. rerio only with confirmatory rtPCR) were performed for each diet treatment., Results: D. rerio fed the SCP containing diet had body weight gains equivalent to the D. rerio fed fish protein, and females had significantly lower total carcass lipid, indicating reduced adiposity. Reproductive success was similar between treatments. Genes differentially expressed in female D. rerio provided the bacterial SCP compared to females given fish protein were overrepresented in the gene ontologies of metabolism, biosynthesis of cholesterol precursors and products, and protein unfolding responses., Conclusion: These data support the development of an open-source diet utilizing an ingredient that correlates with improved health profiles and reduced variability in notable outcomes.

Objective: Endometriosis is associated with neuroplastic changes in cognitive control and pain processing networks. This was the first study to assess eyes-closed resting electroencephalogram (EEG) oscillatory amplitudes in women with endometriosis compared to healthy controls, and explore the relationship with chronic pelvic pain., Methods: Women with endometriosis-related chronic pelvic pain and individually age-matched pain-free controls (N = 20 per group) documented pelvic pain for 28 days before having continuous EEG recorded during a 2 min eyes closed resting state. Natural frequency components were extracted for each group using frequency principal components analysis. Corresponding components were assessed for group differences and correlated with pain scores., Results: Relative to controls, the endometriosis group had greater component amplitudes in delta (0.5 Hz) and beta (∼28 Hz), and reduced alpha (∼10 Hz). Delta and beta amplitudes were positively associated with pain severity, but only beta maintained this association after delta-beta amplitude coupling was controlled., Conclusions: Enhanced resting delta and beta amplitudes were seen in women with endometriosis experiencing chronic pelvic pain. This delta-beta coupling varied with pelvic pain severity, perhaps reflecting altered cholinergic tone and/or stress reactivity., Significance: Endometriosis-related changes in central pain processing demonstrate a distinct neuronal oscillatory signature detectable at rest., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Following investigations into the benefits of meditation on psychological health and well-being, research is now seeking to understand the mechanisms underlying these outcomes. This study aimed to identify natural alpha and theta frequency components during eyes-closed resting and concentrative meditation states and examined their differences within and between two testing sessions. Novice meditators had their EEG recorded during eyes-closed resting and concentrative meditation conditions, before and after engaging in a brief daily concentrative meditation practice for approximately one-month. Separate frequency Principal Components Analyses (f-PCA) yielded four spectral components of interest, congruent between both conditions and sessions: Delta-Theta-Alpha, Low Alpha, High Alpha, and Alpha-Beta. While all four components showed some increase in the meditation condition at the second session, only Low Alpha (∼9.5-10.0 Hz) showed similar increases while resting. These findings support the use of f-PCA as a novel method of data analysis in the investigation of psychophysiological states in meditation.

The NoGo P3 event-related potential (ERP) component is often related to response inhibition, although its function in equiprobable Go/NoGo tasks is debated. Previous findings concerning the auditory equiprobable NoGo P3 (or P3a) could be distorted by averaging latency-variable ERP components. This study aimed to control NoGo P3 latency jitter to investigate the component's relationship with inhibitory demands and its neuronal sources across trials. P3 latency jitter was controlled using a novel procedure to enable single-trial P3 quantification across 126 healthy young adults (M age  = 20.3, SD = 2.8 years) using principal components analysis. NoGo inhibitory demands and performance were measured using the Lateralised Readiness Potential and error rates, respectively. The stimulus-locked P3 (SL-P3) was also analysed to assess the 'blurring effect' (i.e., smearing) associated with averaging latency-variable ERP trial data. A Spearman's rank correlation across 4700 NoGo trials demonstrated that the relationship between latency-adjusted P3 (LA-P3) and inhibitory demands was inconsequential. The cortical sources associated with LA-P3, using eLORETA, were in the premotor and prefrontal cortices, cingulate, and precuneus. SL-P3 was smaller than LA-P3, and that difference was positively related to P3 latency jitter; its source solution was also limited to lower activation in the prefrontal cortex. SL-P3 was not related to inhibitory demands or performance. This study indicates that NoGo P3 should not index response inhibition in auditory equiprobable tasks. Instead, the findings support a neuroinhibition account relating NoGo P3 to attention. Blurring effects were also shown to impact a standard ERP measure and its source solution, encouraging ERP latency-adjustment in future research., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Our previous studies of the equiprobable auditory Go/NoGo task have been used to substantiate a perceptual/cognitive Processing Schema in young and older adults, and in children. The processes in the Schema are linked to PCA components derived separately from Go and NoGo ERPs. Here we investigated sex differences in the child Schema. Two groups of fourteen children (aged 8 to 13 years) were individually matched on age and presented with four stimulus blocks of the equiprobable Go/NoGo task, each containing 75 NoGo and 75 Go tones in random order. Separate NoGo and Go ERPs were obtained from each child and submitted to temporal Principal Components Analyses (PCAs). Each ERP was analysed in two epochs (-100-400 ms and 300-800 ms) to improve the cases:variables ratio. Four pairs of temporal PCAs, each with unrestricted VARIMAX rotation, separately quantified the NoGo and Go ERPs of each epoch in each group. After these pairs were combined in temporal order, four sets of similar components were extracted. Many identified components were differentially enhanced to either NoGo or Go, as in previous work with children. The Female group had NoGo component latencies that were systematically some 3.5% greater than in Males, but there were no sex differences in Go latencies. Females also displayed fewer NoGo commission and Go omission errors, and faster Go RT than Males. Females had larger NoGo N2b, and larger Go components from N2b through to the late positivity. These results, including their ERP component/behaviour correlations, can be integrated as a task-specific behavioural and ERP processing enhancement in girls that suggests their developmental advantage over boys in this age range., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Auditory stimulus intensity of innocuous tones is generally thought to have a direct effect on the amplitude of ERP components, but these effects have rarely been explored across a wide component range, or in multiple paradigms. Here we investigate component sensitivity to stimulus intensity differences in two studies. Study 1 (N = 36) employed a between-participants paradigm in which repeated trains of standard stimuli were presented as 50 or 80 dB SPL 1000 Hz tones. Study 2 (N = 18) used a within-participant presentation of alternating 60 and 80 dB SPL 1000 Hz tones. Electrode caps with 19 channels (referred to linked ears) generated ERPs covering the first 600 ms of each participant's EEG responses; these were submitted to separate temporal PCAs in each study. A similar series of components was obtained in each study: P1, N1a, N1b, N1c, P2, P3a, P3b, nP3, SW1, and SW2; an N2 was found in Study 2 only. Loud tones in Study 1 produced greater amplitudes in all components except SW1. In Study 2, Loud cf. Soft tones produced smaller P1 and nP3, larger N1 components, P2, and P3a, with no effect on N2, P3b, SW1 or SW2. These results indicate similar sequential processes underlying sensory processing in one- and two-stimulus paradigms, with the later stimulus intensity effects varying with paradigm., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study investigated age-related changes in the EEG of subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD) compared with neurotypical controls, using an eyes-open resting condition. Two hundred and twenty five children between the ages of 5 and 16 years participated in this study. Groups consisted of AD/HD of the combined (AD/HDcom) and inattentive (AD/HDin) types, which were compared with controls for each of three age ranges: Young (5-8 years), Middle (9-12 years), and Old (13-16 years). The EEG was recorded and analyzed using AMLAB hardware and software, and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. Compared to controls, the AD/HD groups had globally increased relative theta. Regional differences were found for absolute and relative alpha and beta. Compared to AD/HDcom, AD/HDin had globally reduced total power, absolute and relative theta, and absolute alpha. Regional differences only were found for absolute and relative delta, absolute beta, and relative alpha. No simple interactions were found for diagnostic factors with age. These results indicate that maturational effects can be observed between subtypes of AD/HD and controls in the eyes-open condition with similarities to those reported in eyes-closed conditions, although substantial differences are apparent in the maturation of fast wave activity, primarily alpha. These results provide evidence of maturational differences between subtypes of AD/HD in eyes-open conditions, and provide additional support for the suggestion that subtypes of AD/HD differ in severity rather than the nature of underlying neurological impairment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study investigated age related changes in the EEG of normal children in an eyes-open condition, in order to provide developmental norms for the study of children and adolescents with Attention-Deficit/Hyperactivity Disorder (AD/HD) - see our companion paper (Mason et al., submitted). EEG was recorded at 17 sites from 75 children (63 boys and 12 girls, in the approximately 5:1 ratio common in AD/HD) between the ages of 5 and 16 years. They comprised three groups, each of 25 children (21 boys and 4 girls), divided into Young (5-8 years), Middle (9-12 years), and Old (13-16 years). The EEG was recorded during an eyes-open resting condition and Fourier transformed to provide estimates for total power, and absolute and relative power in the delta, theta, alpha and beta bands. Total power and absolute delta, theta, alpha, and beta decreased with increasing age, as did relative delta, while relative alpha increased with increasing age. Changes occurred faster in the posterior regions for total power, absolute theta and alpha, relative theta, and in frontal regions for absolute and relative beta. Some lateral developmental effects differed with band. These results indicate that maturation effects observed in the eyes-open EEG show some similarities to those reported in eyes-closed conditions, although substantial differences are apparent in the maturation of fast wave activity, particularly alpha. The data provide simple age-norms for eyes-open investigations of EEG differences in young clinical groups, particularly AD/HD. They encourage further investigations of the activational effects of this simple eyes-closed/eyes-open manipulation, which may aid understanding of the energetics of behaviour., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection., Methods: Narrative review., Results: Literature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch's membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model., Conclusions: The neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC., 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 © 2022 Steptoe, Pearce, Beare, Sreekantam, Mohammed, Barry, Steeples, Denniston and Murray.)

Purpose: To create a health utility value for birdshot chorioretinopathy (BCR) using Time Trade-Off (TTO) and Standard Gamble (SG) utilities., Method: Adult BCR patients completed TTO, SG, EQ-5D-5L, and NEI VFQ-25 questionnaires and underwent a detailed history and clinical examination., Results: A total of 28 BCR patients (9 M, 19 F; mean age 62 years, range 47-83) were included. There were 22 patients with a logMAR vision of 0.3 or better in both eyes. Mean TTO was 0.90 ± SD 0.18 (range 0.33-1.0) and mean SG was 0.94 ± SD 0.14 (range 0.5-1.0). TTO correlated with EQ-5D-5L index value ( p = .024) and NEI VFQ-25 composite score ( p = .015)., Conclusions: Of 28 patients with BCR, 11 would trade remaining life (mean 5.4 years), and 6 would take a risk of immediate death (mean 28% risk), in return for perfect vision in both eyes for the rest of their life.

Since the equiprobable Go/NoGo task lacks the dominant Go imperative of the usual Go/NoGo (with more Go than NoGo stimuli), it is generally regarded as involving little inhibition. However, children have relative difficulty with this task, and have a large frontal NoGo N2. We previously found that this 'child N2' does play an inhibitory role, with larger frontal N2b associated with fewer commission errors. Here we investigated age-related developmental differences in the N2b and other components in the equiprobable Go/NoGo task. Two groups of eighteen Younger children (aged 8.0 to 10.3 years) and eighteen Older children (aged 10.4 to 12.8 years), matched on sex, were presented with three stimulus blocks each containing 100 Go and 100 NoGo tone stimuli in random order. Four temporal PCAs, each with unrestricted VARIMAX rotation, separately quantified the Go and NoGo ERPs of each group, and similar components were extracted from each set. Most identified components were differentially enhanced to either Go or NoGo, as in adults, supporting a previously-proposed differential sequential processing schema. The Older group had Go component latencies that were systematically reduced by some 7.4% from the Younger group, and they displayed faster RT and fewer omission and commission errors. Between subjects in the Older group, larger frontocentral NoGo N2b was associated with fewer commission errors. Hence the NoGo N2b in this paradigm can be interpreted as an individual marker of inhibition in older, but not young, children., (Copyright © 2021. Published by Elsevier B.V.)

Background: Poultry eggs are a low-cost, high-protein nutrient package that can be consumed as part of quality diets. However, consumption of poultry egg products is historically contentious, which highlights the importance of investigating impacts of long-term egg consumption on metabolic health., Objective: Our study utilized the zebrafish, Danio rerio , a newly defined model of human metabolic health, to understand the metabolic consequence of consuming egg products in lieu of other well-described protein sources., Methods: Reference diets were formulated to contain multisource protein with casein and fish protein hydrolysate (CON; control protein sources), the protein sources that have been historically utilized in numerous reference diets. These proteins were then partially replaced with either whole egg (WE; protein and lipid source), egg white (EW; protein source), wheat gluten (WG; cereal protein source), or a high-lipid-content diet containing a multisource protein with casein and fish protein hydrolysate (HFCON; isonitrogenous and isolipidic with the WE diet) in a 34-wk trial ( n  = 8 tanks, 10 fish per tank). Daily feeding was initiated at the early juvenile life stage and terminated at the late reproductive adult stage., Results: The amino acid composition of control versus egg product diets did not vary substantially, although methionine and lysine were apparently limiting in fish fed WG. At termination, fish fed EW as the protein source had weight gain and body composition similar to those fed the CON diet. Fasting and postprandial blood glucose did not differ between any dietary treatment. Assessment of the liver transcriptome using RNAseq revealed no differential gene expression between zebrafish fed CON or WE diets. Zebrafish fed WG had lower weight gain in males., Conclusions: Long-term consumption of egg products promoted metabolic health equal to that of historically relevant proteins. These data support the value of egg products for maintaining long-term metabolic health in animal diets., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

This study examined sex differences in the EEG of adults diagnosed with Attention-Deficit/Hyperactivity Disorder (AD/HD) according to DSM-5 criteria. Sixteen females and 16 males with AD/HD, and age- and sex-matched control groups, had an eyes-closed resting EEG recorded from 19 electrode sites. EEGs were Fast Fourier transformed and estimates for total power, absolute and relative power in the delta, theta, alpha, beta and gamma bands, and the theta/beta ratio, were analysed across nine cortical regions. Males with AD/HD, compared with male controls, had globally reduced absolute beta, globally elevated relative theta, and a larger theta/beta ratio. In contrast, no global effects emerged between females with and without AD/HD. Significant group interactions indicated that globally elevated relative theta and elevated frontal-midline theta/beta ratio noted in males with AD/HD differed significantly from results in females. There are statistically significant EEG differences in relative theta and the theta/beta ratio between males and females with and without AD/HD. These results indicate that AD/HD affects the EEG activity of males and females differently. This study helps confirm the need for further independent examination of AD/HD within female populations., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The effects of saturated fat intake on obesity and cardiovascular health remain inconclusive, likely due in part to their varied nature and interactions with other nutrients. Investigating the synergistic effects of different saturated fat sources with other dietary lipid components will help establish more accurate nutritional guidelines for dietary fat intake. Over the past two decades, zebrafish (Danio rerio) have been established as an attractive model system to address questions regarding contributions of dietary lipid intake to diet-induced obesity in humans. The goal of the present study was to assess interactions of three different saturated fat sources (milk fat, palm oil, and coconut oil) with sex and total dietary lipid intake on weight gain and body composition in adult zebrafish. Larvae were raised on live feeds until 28 days post fertilization, and then fed a formulated maintenance diet until three months of age. An eight-week feeding trial was then initiated, in which zebrafish were fed nine experimental low- and high-fat diets varying in saturated fatty acid and long-chain polyunsaturated fatty acid content, in addition to a low-fat and high-fat control diet. At termination of the feeding trial, each treatment was evaluated according to body mass, moisture content, and adiposity. Sex and diet significantly interacted in their effects on body mass (P = 0.026), moisture content (P = 0.044), and adiposity (P = 0.035). The influence of saturated fat source on body mass was observed to be dependent on intake of total dietary lipid. In females, all three saturated fat sources had similar effects on adiposity. From these observations, we hypothesize that impacts of saturated fat intake on energy allocation and obesity-related phenotypes are influenced by both sex and intake of other dietary lipid components. Our results suggest that current nutritional guidelines for saturated fat intake may need to be re-evaluated and take sex-specific recommendations into consideration., Competing Interests: The authors have declared that no competing interests exist.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course., (© 2021 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose : To evaluate adherence to topical medication in patients with inflammatory eye disease. Methods : Questionnaire survey of patients attending inflammatory eye disease clinics. Treatment regimen was validated against hospital-generated clinic letters. Results : There were 86 patients (52 uveitis and 34 ocular surface disease) with 30% (26/86) failing to identify one or more of the medications they were using, and 28% (24/86) unable to offer the correct indication for their treatment. A total of 64% (55/86) failed to use their medication as advised (27% on a daily basis); the commonest reason being forgetfulness. In patients using multiple eye drops, 26% left insufficient time intervals between successive eye drops, and 58% (50/86) reported not being given any instruction on drop instillation. Conclusions : We highlight poor adherence to topical medication in patients with inflammatory eye disease. We recommend a dedicated practitioner providing a proactive approach to patient education to improve adherence.

Background: Corneal transplantation is the most frequently performed transplantation in the UK. Despite this, the therapeutic value of matching human leukocyte antigen (HLA) subtypes for transplanted corneas remains controversial. Ocular immune privilege was originally deemed to render matching unnecessary; however, more recently, matching has demonstrated improved outcomes including graft success, amongst others. This systematic review aims to evaluate the effectiveness of major and minor antigen matching on graft outcomes in corneal transplantation., Methods: Standard systematic review methodology will be used to identify, select and extract data from observational studies and clinical trials assessing the effects of HLA matching on corneal graft outcomes. Bibliographic databases (Cochrane Library, EMBASE, MEDLINE, Web of Science, Scopus), clinical trial registers, abstract and conference proceedings, in addition to dissertation, thesis and grey literature will be searched. Neither date of publication nor language will be restricted, and non-English articles will be translated where necessary. The primary outcome will be to assess corneal graft success for different degrees of HLA matching/mismatching. The precise end outcome measure varies amongst studies and includes graft rejection, immunoreaction, failure and survival. Therefore, data will be extracted across all relevant outcome parameters and grouped for subsequent statistical tests. Risk of bias assessment will be completed, appropriate to each study design. Study selection, data extraction and risk of bias assessment will be independently completed by two reviewers. Data will be tabulated, and a narrative synthesis presented. Meta-analysis will be performed where there is sufficient homogeneity between studies to warrant its effective completion. Subgroup and sensitivity analysis will be undertaken if appropriate., Discussion: Many studies have investigated the effectiveness of HLA matching for corneal transplantation. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review may form the basis of evidence-based recommendations on pre-operative HLA typing and matching of corneal grafts for transplantation., Systematic Review Registration: PROSPERO reference CRD42020198882.

Objective. The power spectrum of the human electroencephalogram (EEG) as a function of frequency is a mix of brain oscillations (Osc) (e.g. alpha activity around 10 Hz) and non-Osc or noise of uncertain origin. 'White noise' is uniformly distributed over frequency, while 'pink noise' has an inverse power-frequency relation (power ∝ 1/ f ). Interest in EEG pink noise has been growing, but previous human estimates appear methodologically flawed. We propose a new approach to extract separate valid estimates of pink and white noise from an EEG power spectrum. Approach. We use simulated data to demonstrate its effectiveness compared with established procedures, and provide an illustrative example from a new resting eyes-open (EO) and eyes-closed (EC) dataset. The topographic characteristics of the obtained pink and white noise estimates are examined, as is the alpha power in this sample. Main results. Valid pink and white noise estimates were successfully obtained for each of our 5400 individual spectra (60 participants × 30 electrodes × 3 conditions/blocks [EO 1 , EC, EO 2 ]). The 1/ f noise had a distinct central scalp topography, and white noise was occipital in distribution, both differing from the parietal topography of the alpha Osc. These differences point to their separate neural origins. EC pink and white noise powers were globally greater than in EO. Significance . This valid estimation of pink and white noise in the human EEG holds promise for more accurate assessment of oscillatory neural activity in both typical and clinical groups, such as those with attention deficits. Further, outside the human EEG, the new methodology can be generalized to remove noise from spectra in many fields of science and technology., (© 2021 IOP Publishing Ltd.)

Resting EEG, measured in eyes-closed (EC) and eyes-open (EO) states, can provide insight into behavioural differences between groups. Surprisingly, differences in resting EEG between females and males have not been investigated systematically in previous literature. The present study utilised the four traditional EEG bands to confirm their baseline EC topographies and reactivity (EO minus EC) across groups, to clarify topographical differences between sexes, and to confirm alpha as a measure of arousal. Participants were eighty healthy young adults (40 female), with a mean age of 20.4 (range 18-26) years. Continuous resting EEG was recorded from 30 scalp sites during three 2-minute conditions (EO1, EC, EO2), and EOG-corrected. Data from each condition were divided into 60 sequential 2-second epochs. Accepted artefact-free epochs were Fourier Transformed, and absolute amplitudes in the delta (0.5-3.5 Hz), theta (4.0-7.5 Hz), alpha (8.0-13.0 Hz), and beta (13.5-29.5 Hz) bands were calculated. Across groups in EC, significant topographical differences were found between the band amplitudes, broadly compatible with previous reports. Females had greater overall amplitudes in delta, alpha and beta, enhanced midline activity in theta, and parietal and midline activity in the alpha and beta bands. From EC to EO, reactivity was apparent across the bands as significant reductions, particularly in the parietal region. For females compared to males, the reduction in parietal midline delta and theta, parietal alpha and parietal midline beta was significantly larger. Additionally, across groups, alpha activity was confirmed as an inverse measure of arousal. These findings indicate significant differences in neuronal activity between young adult females and males, and help our interpretation of alpha changes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A simple bioassay that quantifies feed intake as an estimation of relative attractability of feeds containing different ingredients in the Pacific white shrimp Litopenaeus vannamei is described. Fish meal (FM), fish protein hydrolysate (FPH), squid meal (SqM) and casein (CN) were assessed at the same dietary level for their relative influence on feed intake rates of Litopenaeus vannamei . A bland diet containing 92% whole wheat grain meal, 6% diatomaceous earth and 2% alginate with a known low attractability was used as the standard control or base diet. Ingredients were added to the bland base control diet at a level of 3% as fed. Shrimp were stocked into 80 L glass tanks (n= 20 per tank) in a recirculating aquaculture system. Tanks were randomly assigned to one of five diet treatments (3tanks/treatment). Experiments measuring the attractability of each feed were conducted twice daily at 0900 hours and 1330 hours over a five day period. For each experiment, 40 feed pellets (ca. 1 g) corresponding to the assigned treatment were provided to each tank. To calculate the rate of feed intake, pellets remaining in each tank were counted at six minute intervals for a seventy-two minute period. Differences in rate of feed intake among diets were evaluated using Cox Regression Analysis. This attractability assay required only small amounts of ingredients and incorporated ingredients into a bland feed, which significantly reduces the influence from other ingredients or compound in the pellets. All of the test protein ingredients, especially SqM, in the feeds significantly increased the feed consumption rate. The diet containing SqM was consumed at a significantly higher rate than those containing casein and FM but not FPH. FPH and CN containing diets were not significantly different but consumed at a higher rate than the diet containing FM. Results of these trials indicate that the presence of certain ingredients can increase feed intake, thereby increasing nutrient availability of the diets. This reported method to determine consumption of diets containing certain ingredients can be considered as a valid method to estimate attractability., Competing Interests: Conflict of Interest: The authors have no conflict of interest. DECLARATIONS OF COMPETING INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Endometriosis is a debilitating women's health condition and is the most common cause of chronic pelvic pain. Impaired cognitive control is common in chronic pain conditions, however, it has not yet been investigated in endometriosis. The aim of this study was to explore the neuronal correlates of cognitive control in women with endometriosis. Using a cross-sectional study design with data collected at a single time-point, event-related potentials were elicited during a cued continuous performance test from 20 women with endometriosis (mean age = 28.5 ± 5.2 years) and 20 age- and gender-matched controls (mean age = 28.5 ± 5.2 years). Event-related potential components were extracted and P3 component amplitudes were derived with temporal principal components analysis. Behavioral and ERP outcomes were compared between groups and subjective pain severity was correlated with ERP component amplitudes. No significant behavioral differences were seen in task performance between the groups (all p > 0.094). Target P3b (all p < 0.034) and SW (all p < 0.040), and non-target early P3a (eP3a; all p < 0.023) and late P3a (lP3a; all p < 0.035) amplitudes were smaller for the endometriosis compared to the healthy control group. Lower non-target eP3a ( p < 0.001), lP3a ( p = 0.013), and SW ( p = 0.019) amplitudes were correlated with higher pain severity scores. Findings suggest that endometriosis-associated chronic pelvic pain is linked to alterations in stimulus-response processing and inhibitory control networks, but not impaired behavioral performance, due to compensatory neuroplastic changes in overlapping cognitive control and pain networks., Competing Interests: As a medical research institute, NICM Health Research Institute receives research grants and donations from foundations, universities, government agencies, individuals, and industry. Sponsors and donors provide untied funding for work to advance the vision and mission of the Institute. The project that is the subject of this article was not undertaken as part of a contractual relationship with any organization other than the funding declared above. It should also be noted that NICM conducts clinical trials relevant to this topic area, for which further details can be provided on request. MA reports being a member of the clinical advisory committee for Endometriosis Australia and an ESIG member of Endometriosis NZ. The remaining 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 © 2020 Steiner, Barry, Wassink, De Blasio, Fogarty, Cave, Love and Armour.)

The brain-derived neurotrophic factor (BDNF) protein is essential for neuronal development. Val66Met (rs6265) is a functional polymorphism at codon 66 of the BDNF gene that affects neuroplasticity and has been associated with cognition, brain structure and function. The aim of this study was to clarify the relationship between BDNF Val66Met polymorphism and neuronal oscillatory activity, using the electroencephalogram (EEG), in a normative cohort. Neurotypical (N = 92) young adults were genotyped for the BDNF Val66Met polymorphism and had eyes open resting-state EEG recorded for four minutes. Focal increases in right fronto-parietal delta, and decreases in alpha-1 and right hemispheric alpha-2 amplitudes were observed for the Met/Met genotype group compared to Val/Val and Val/Met groups. Stronger frontal topographies were demonstrated for beta-1 and beta-2 in the Val/Met group versus the Val/Val group. Findings highlight BDNF Val66Met genotypic differences in EEG spectral amplitudes, with increased cortical excitability implications for Met allele carriers.

The immediately-prestimulus electroencephalographic (EEG) brain state influences subsequent event-related processing, dynamically impacting event-related potential (ERP) and behavioural outcomes. Both EEG and ERPs are known to undergo age-related change, yet few have investigated the consistency in their dynamic interrelations in the context of ageing. The present investigation assessed the impact of prestimulus alpha and beta brain states in 20 young (18-26 years) and 20 gender-matched healthy older (59-75 years) adults who completed an equiprobable auditory Go/NoGo paradigm. Prestimulus alpha and beta band amplitudes in their prominent band topographies were separately used to derive Go and NoGo ERPs at 10 ascending levels of prestimulus activity, and ERP components were derived for these levels using Principal Components Analysis. Prestimulus alpha directly modulated Go/NoGo P3a amplitudes across the groups, while beta inversely modulated the young (cf. older) adult NoGo N1-1, each supporting and extending limited prior research. Several novel effects were also uncovered, most notably an inverse relationship between prestimulus alpha and reaction time. Prestimulus alpha and beta were confirmed as significant determinants of the processing outcomes in this task, and the complex pattern of results provides a normative map in healthy ageing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study investigated stimulus-response patterns of temporal principal components analysis (PCA)-derived event-related potential (ERP) components in a classical auditory habituation paradigm with long interstimulus intervals. The skin conductance response (SCR) was included as the "gold standard" model of the Orienting Reflex. Thirty participants were presented with a single series of 10 identical 60 dB tones, followed by a change trial at a different frequency. Single-trial, electrooculography-corrected ERPs were submitted to temporal PCA. The main focus was on the components expected in the P300/Late Positive Complex (LPC), and their electromagnetic tomography-derived cortical sources. Nine components were identified between 90 and 470 ms poststimulus (in temporal order): three N1 subcomponents, P2, four LPC components, and a negative Slow Wave (SW). The expected order of P3a, P3b, Novelty P3 (nP3), and positive Slow Wave (+SW) in the LPC was confirmed. SCR demonstrated strong exponential decay and recovery. P3b and nP3 each showed exponential decrement over trials, but only nP3 showed recovery at the change trial. Novelty effects failed to reach significance for the other LPC components, and were not apparent in non-LPC components. Frontal lobe activity in Brodmann areas 6, 8, and 9 was common to P3a, P3b, nP3, and +SW, consistent with the functional integration of these components in the LPC. Individual components had specific sources, although some sources overlapped between components or were reactivated later in the LPC. These data provide a fresh perspective on the components of the LPC and their cortical sources, and offer a processing model for the P300 in a habituation task, potentially generalizable to other paradigms., (© 2019 Society for Psychophysiological Research.)

This article reviews the eyes-open and eyes-closed resting electroencephalogram (EEG) literature for Attention-Deficit/Hyperactivity Disorder (AD/HD) from 2002 to 2019. This time has seen substantial increase in interest in resting state EEG, with investigations moving from a comparison of an AD/HD sample to a control group, to research investigating a wide range of theoretical and clinical aspects of the disorder. This has included investigations of subgroups based on their EEG profile, sex differences in the EEG, increasing interest in the EEG of adults, and the effects of comorbid disorders on the EEG of people with AD/HD. Research has further investigated the hyper- and hypo- arousal models of AD/HD, as well as the developmental deviation model. From a clinical perspective, a growing body of literature is emerging trying to ascertain if the EEG can be used as a diagnostic test, particularly the theta/beta ratio. While these advances have been made, there is widespread use of both the eyes-open and eyes-closed resting paradigms as being interchangeable, despite the two paradigms differ on a number of important factors. There is also lack of independent replication within the literature, which is needed to consolidate many of the findings that have been published., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)