Metacognitive processes accompanying the first stages of autobiographical retrieval in the self-memory system.

According to Conway's view, Autobiographical memory (AM) construction is accompanied by control processes. These processes range from filtering out relevant memories according to the current context, to generating or elaborating appropriate retrieval cues. These processes can be conceptualised as metacognition, the ability to control and monitor cognitive processes. Experimentally, little has been carried out to support the idea that metacognition is involved in AM. To assess this, we designed a task, the Feeling of Retrieval. Participants had to predict whether cue words would facilitate AM access (i.e., fluent access cues) or not (i.e., limited access cues) in a limited time (either 1 (Exp. 2) or 2 (Exp. 1) s). Later, they retrieved memories in response to both types of cues. Results show that cues judged as fluent access led to better AM generation, as illustrated by AM retrieval latency and a subjective measure of the ease with which the AMs were retrieved. These rapid predictions may rely on epistemic feelings and / or other mnemonic cues such as a partial retrieval of information. This metacognitive access to the earliest stages of AM retrieval illustrates the ability to monitor AM processes as proposed by Conway (2005).

Deductive automated pollen classification in environmental samples via exploratory deep learning and imaging flow cytometry.

Pollen and tracheophyte spores are ubiquitous environmental indicators at local and global scales. Palynology is typically performed manually by microscopic analysis; a specialised and time-consuming task limited in taxonomical precision and sampling frequency, therefore restricting data quality used to inform climate change and pollen forecasting models. We build on the growing work using AI (artificial intelligence) for automated pollen classification to design a flexible network that can deal with the uncertainty of broad-scale environmental applications. We combined imaging flow cytometry with Guided Deep Learning to identify and accurately categorise pollen in environmental samples; here, pollen grains captured within c. 5500 Cal yr BP old lake sediments. Our network discriminates not only pollen included in training libraries to the species level but, depending on the sample, can classify previously unseen pollen to the likely phylogenetic order, family and even genus. Our approach offers valuable insights into the development of a widely transferable, rapid and accurate exploratory tool for pollen classification in 'real-world' environmental samples with improved accuracy over pure deep learning techniques. This work has the potential to revolutionise many aspects of palynology, allowing a more detailed spatial and temporal understanding of pollen in the environment with improved taxonomical resolution.

Rapid Temperature-Dependent Rheological Measurements of Non-Newtonian Solutions Using a Machine-Learning Aided Microfluidic Rheometer.

Biofluids such as synovial fluid, blood plasma, and saliva contain several proteins which impart non-Newtonian properties to the biofluids. The concentration of such protein macromolecules in biofluids is regarded as an important biomarker for the diagnosis of several health conditions, including cardiovascular disorders, joint quality, and Alzheimer's. Existing technologies for the measurements of macromolecules in biofluids are limited; they require a long turnaround time, or require complex protocols, thus calling for alternative, more suitable, methodologies aimed at such measurements. According to the well-established relations for polymer solutions, the concentration of macromolecules in solutions can also be derived via measurement of rheological properties such as shear-viscosity and the longest relaxation time. We here introduce a microfluidic rheometer for rapid simultaneous measurement of shear viscosity and longest relaxation time of non-Newtonian solutions at different temperatures. At variance with previous technologies, our microfluidic rheometer provides a very short turnaround time of around 2 min or less thanks to the implementation of a machine-learning algorithm. We validated our platform on several aqueous solutions of poly(ethylene oxide). We also performed measurements on hyaluronic acid solutions in the clinical range for joint grade assessment. We observed monotonic behavior with the concentration for both rheological properties, thus speculating on their use as potential rheo-markers, i.e., rheological biomarkers, across several disease states.

Incidence and Prevalence of Paediatric Inflammatory Bowel Disease Continues to Increase in the South of England.

OBJECTIVE: The incidence of paediatric inflammatory bowel disease (IBD) has been increasing over 25 years; however, contemporary trends are not established and the impact of COVID-19 on case rates is unclear. METHODS: Data from Southampton Children's hospital prospective IBD database were retrieved for 2002-2021. Incidence rates were calculated based on referral area populations and temporal trends analysed. Disease prevalence for those aged <18 years was calculated for 2017-2021. Monoclonal prescriptions were reported. RESULTS: In total, 1150 patients were included (mean age at diagnosis 12.63 years, 40.5% female). An estimated 704 patients had Crohn's disease (61.2%), 385 had ulcerative colitis (33.5%), and 61 had IBD unclassified (5.3%). Overall IBD incidence increased, ß = 0.843, P = 3 × 10 -6 , driven by Crohn's disease, ß = 0.732, P = 0.00024 and ulcerative colitis, ß = 0.816, P = 0.000011. There was no change in IBDU incidence, ß = 0.230, P = 0.33. From 2002-2021, 51 patients were diagnosed <6 years of age, 160 patients aged 6 to <10 years and 939 patients aged 10 to <18 years of age. Increased incidence was observed in patients aged 10 to <18 years of age (ß = 0.888, P = 1.8 × 10 -7 ). There was no significant change in incidence of IBD in <6 years (ß = 0.124, P = 0.57), or 6 to <10 years (ß = 0.146, P = 0.54). IBD prevalence increased by an average of 1.71%/year from 2017 to 2021, ß = 0.979, P = 0.004. The number of new monoclonal prescriptions increased from 6 in 2007 to 111 in 2021. CONCLUSIONS: IBD incidence continues to increase in Southern England. Compounding prevalence and increased monoclonal usage has implications for service provision.

Inter-laboratory automation of the in vitro micronucleus assay using imaging flow cytometry and deep learning.

The in vitro micronucleus assay is a globally significant method for DNA damage quantification used for regulatory compound safety testing in addition to inter-individual monitoring of environmental, lifestyle and occupational factors. However, it relies on time-consuming and user-subjective manual scoring. Here we show that imaging flow cytometry and deep learning image classification represents a capable platform for automated, inter-laboratory operation. Images were captured for the cytokinesis-block micronucleus (CBMN) assay across three laboratories using methyl methanesulphonate (1.25-5.0 µg/mL) and/or carbendazim (0.8-1.6 µg/mL) exposures to TK6 cells. Human-scored image sets were assembled and used to train and test the classification abilities of the "DeepFlow" neural network in both intra- and inter-laboratory contexts. Harnessing image diversity across laboratories yielded a network able to score unseen data from an entirely new laboratory without any user configuration. Image classification accuracies of 98%, 95%, 82% and 85% were achieved for 'mononucleates', 'binucleates', 'mononucleates with MN' and 'binucleates with MN', respectively. Successful classifications of 'trinucleates' (90%) and 'tetranucleates' (88%) in addition to 'other or unscorable' phenotypes (96%) were also achieved. Attempts to classify extremely rare, tri- and tetranucleated cells with micronuclei into their own categories were less successful (≤ 57%). Benchmark dose analyses of human or automatically scored micronucleus frequency data yielded quantitation of the same equipotent concentration regardless of scoring method. We conclude that this automated approach offers significant potential to broaden the practical utility of the CBMN method across industry, research and clinical domains. We share our strategy using openly-accessible frameworks.

Image-Based Cell Profiling Enables Quantitative Tissue Microscopy in Gastroenterology.

Immunofluorescence microscopy is an essential tool for tissue-based research, yet data reporting is almost always qualitative. Quantification of images, at the per-cell level, enables "flow cytometry-type" analyses with intact locational data but achieving this is complex. Gastrointestinal tissue, for example, is highly diverse: from mixed-cell epithelial layers through to discrete lymphoid patches. Moreover, different species (e.g., rat, mouse, and humans) and tissue preparations (paraffin/frozen) are all commonly studied. Here, using field-relevant examples, we develop open, user-friendly methodology that can encompass these variables to provide quantitative tissue microscopy for the field. Antibody-independent cell labeling approaches, compatible across preparation types and species, were optimized. Per-cell data were extracted from routine confocal micrographs, with semantic machine learning employed to tackle densely packed lymphoid tissues. Data analysis was achieved by flow cytometry-type analyses alongside visualization and statistical definition of cell locations, interactions and established microenvironments. First, quantification of Escherichia coli passage into human small bowel tissue, following Ussing chamber incubations exemplified objective quantification of rare events in the context of lumen-tissue crosstalk. Second, in rat jejenum, precise histological context revealed distinct populations of intraepithelial lymphocytes between and directly below enterocytes enabling quantification in context of total epithelial cell numbers. Finally, mouse mononuclear phagocyte-T cell interactions, cell expression and significant spatial cell congregations were mapped to shed light on cell-cell communication in lymphoid Peyer's patch. Accessible, quantitative tissue microscopy provides a new window-of-insight to diverse questions in gastroenterology. It can also help combat some of the data reproducibility crisis associated with antibody technologies and over-reliance on qualitative microscopy. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC. on behalf of International Society for Advancement of Cytometry.

ISCEV extended protocol for the photopic On-Off ERG.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the photopic On-Off ERG, and outlines common clinical applications. A light stimulus duration of 150-200 ms is used in the presence of a rod-suppressing background to elicit cone-driven On- and Off-system ERG components. The On-response occurs after the stimulus onset and has a negative a-wave and positive b-wave. The Off d-wave is a positive component evoked by stimulus offset. Common diagnoses that may benefit from additional photopic On-Off ERG testing include retinal dystrophies and retinal disorders that cause dysfunction at a level that is post-phototransduction or post-receptoral. On-Off ERGs assess the relative involvement of On- and Off-systems and may be of use in the diagnosis of disorders such as complete and incomplete congenital stationary night blindness (complete and incomplete CSNB), melanoma-associated retinopathy, and some forms of autoimmune retinopathy. The photopic On-Off ERGs may also be useful in X-linked retinoschisis, Batten disease, Duchenne muscular dystrophy, spinocerebellar degeneration, quinine toxicity, and other retinal disorders.

Evaluation of telemedicine for screening of diabetic retinopathy in the Veterans Health Administration.

OBJECTIVE: To explore the cost-effectiveness of telemedicine for the screening of diabetic retinopathy (DR) and identify changes within the demographics of a patient population after telemedicine implementation. DESIGN: A retrospective medical chart review (cohort study) was conducted. PARTICIPANTS: A total of 900 type 1 and type 2 diabetic patients enrolled in a medical system with a telemedicine screening program for DR. METHODS: The cost-effectiveness of the DR telemedicine program was determined by using a finite-horizon, discrete time, discounted Markov decision process model populated by parameters and testing frequency obtained from patient records. The model estimated the progression of DR and determined average quality-adjusted life years (QALYs) saved and average additional cost incurred by the telemedicine screening program. MAIN OUTCOME MEASURES: Diabetic retinopathy, macular edema, blindness, and associated QALYs. RESULTS: The results indicate that telemedicine screening is cost-effective for DR under most conditions. On average, it is cost-effective for patient populations of >3500, patients aged <80 years, and all racial groups. Observable trends were identified in the screening population since the implementation of telemedicine screening: the number of known DR cases has increased, the overall age of patients receiving screenings has decreased, the percentage of nonwhites receiving screenings has increased, the average number of miles traveled by a patient to receive a screening has decreased, and the teleretinal screening participation is increasing. CONCLUSIONS: The current teleretinal screening program is effective in terms of being cost-effective and increasing population reach. Future screening policies should give consideration to the age of patients receiving screenings and the system's patient pool size because our results indicate it is not cost-effective to screen patients aged older than 80 years or in populations with <3500 patients.

The experience of patients with lung cancer during the COVID-19 pandemic and its importance for post-pandemic outpatient cancer care planning: A cross sectional study exploring the roles of age and frailty.

INTRODUCTION: The COVID-19 pandemic impacted the care and experiences of people with cancer, but it presented an opportunity to improve the delivery of outpatient care post-pandemic. MATERIALS AND METHODS: We performed an observational cross-sectional study with people with lung cancer throughout the COVID-19 pandemic. A survey investigated patients' experiences and preferences regarding the delivery of cancer care to plan for post-pandemic care, as well as the pandemic's impact on their functional status (physical and psycho-social), exploring the role of age and frailty. RESULTS: Amongst 282 eligible participants, 88%, 86%, and 59% of patients reported feeling appropriately supported during the pandemic by their cancer centre, friends/family, and primary care services, respectively. Remote oncology consultations were delivered to 90% of patients during the pandemic, of which 3% did not meet patients' expectations. Regarding post-pandemic outpatient care preferences, face-to-face appointments were preferred by 93% for the first appointment, by 64% when discussing imaging results, and by 60% for reviews during anti-cancer treatments. Older patients aged 70 years and above were more likely to favour face-to-face appointments (p = 0.007), regardless of their frailty status. Patient preferences changed over time, with the more recent participants preferring remote appointments during anti-cancer treatments (p = 0.0278). Regarding the pandemic's impact, abnormal levels of anxiety and depression were found in 16% and 17% of patients, respectively. Younger patients experienced higher abnormal levels of anxiety and depression (p = 0.036, p = 0.021). Amongst the older sub-group, those with frailty had higher levels of anxiety and depression (p < 0.001). Amongst all participants, 54% reported a considerable negative impact from the pandemic on different aspects of their daily life, particularly emotional and psychological health and sleep patterns, which were more marked in younger patients and the older sub-group with frailty. Older patients without frailty reported the least impact on their functional status. DISCUSSION: There is a need for more personalised outpatient consultation options during cancer care. Whilst there is a preference for face-to-face consultations for older patients, following the pandemic there is a growing acceptance of remote consultations particularly during anti-cancer treatment. Older patients with lung cancer without frailty were less affected by the pandemic than those with frailty and younger patients, requiring less support from healthcare services.

Label-free cell segmentation of diverse lymphoid tissues in 2D and 3D.

Unlocking and quantifying fundamental biological processes through tissue microscopy requires accurate, in situ segmentation of all cells imaged. Currently, achieving this is complex and requires exogenous fluorescent labels that occupy significant spectral bandwidth, increasing the duration and complexity of imaging experiments while limiting the number of channels remaining to address the study's objectives. We demonstrate that the excitation light reflected during routine confocal microscopy contains sufficient information to achieve accurate, label-free cell segmentation in 2D and 3D. This is achieved using a simple convolutional neural network trained to predict the probability that reflected light pixels belong to either nucleus, cytoskeleton, or background classifications. We demonstrate the approach across diverse lymphoid tissues and provide video tutorials demonstrating deployment in Python and MATLAB or via standalone software for Windows.

Negative electroretinograms in the pediatric and adult population.

Objective To assess the frequency of negative waveform electroretinograms (ERGs) in a tertiary referral center. Design Retrospective chart review. Participants All patients who had an ERG performed at the electrophysiology clinic at Emory University from January 1999 through March 2008 were included in the study. Methods Patients with b-wave amplitude ≤ a-wave amplitude during the dark-adapted bright flash recording, in at least one eye, were identified as having a "negative ERG". Clinical information, such as age, gender, symptoms, best corrected visual acuity, and diagnoses were recorded for these patients when available. Results A total of 1,837 patients underwent ERG testing during the study period. Of those, 73 patients had a negative ERG, for a frequency of 4.0%. Within the adult (≥ 18 years of age) and pediatric populations, the frequencies of a negative ERG were 2.5 and 7.2%, respectively. Among the 73 cases, negative ERGs were more common among male than female patients, 6.7% versus 1.8% (P < 0.0001). Negative ERGs were most common among male children and least common among female adults, 9.6% versus 1.1%, respectively, (P < 0.0001). Overall in this group of patients, the most common diagnoses associated with a negative ERG were congenital stationary night blindness (CSNB, n = 29) and X-linked retinoschisis (XLRS, n = 7). Conclusions The overall frequency of negative ERGs in this large retrospective review was 4.0%. Negative ERGs were most common among male children and least common among female adults. Despite the growing number of new diagnoses associated with negative ERGs, CSNB, and XLRS appear to be the most likely diagnoses for a pediatric patient who presents with a negative ERG.

Visual function and mobility after multifocal versus monofocal intraocular lens implantation.

Clinical relevance: Mobility and fall risk may be important considerations in choosing between intraocular lenses.Background: Fall risk in older adults increases when wearing multifocal spectacles, but little is known about mobility among individuals with different types of intraocular lenses. This study compared visual function, fall risk and balance control following bilateral implantation of monofocal or multifocal intraocular lenses.Methods: This was a non-randomised, cross-sectional study involving adults with bilateral intraocular lenses. Participants completed questionnaires concerning physical functioning, fall history and balance-related confidence. Binocular visual acuity, contrast sensitivity (Pelli-Robson chart and computerized testing), depth perception and glare sensitivity were assessed. Physical performance measures included the Sensory Organization Test, preferred gait speed, Dynamic Gait Index and wayfinding in a virtual environment.Results: Fifteen participants (mean ± standard deviation, 67.1 ± 6.8 years) had monofocal intraocular lenses and 14 participants (68.1 ± 6.1 years) had multifocal intraocular lenses. Contrast sensitivity in the monofocal group was significantly better than that in the multifocal group (p = 0.02) at intermediate and high spatial frequencies. Contrast sensitivity of the monofocal group also was less affected by glare than the contrast sensitivity of the multifocal group, at an intermediate spatial frequency (p = 0.02). However, the multifocal group had significantly better Dynamic Gait Index scores (p = 0.04), even after controlling for perceived physical function.Conclusions: The participants with monofocal intraocular lenses generally had better contrast sensitivity than did those with multifocal intraocular lenses. However, the scores on a mobility test that is associated with fall risk were worse for those with monofocal lenses.

Proximity-dependent biotin identification (BioID) reveals a dynamic LSD1-CoREST interactome during embryonic stem cell differentiation.

Lysine specific demethylase 1 (LSD1) regulates gene expression as part of the CoREST complex, along with co-repressor of REST (CoREST) and histone deacetylase 1 (HDAC1). CoREST is recruited to specific genomic loci by core components and numerous transient interactions with chromatin-associated factors and transcription factors. We hypothesise that many of these weaker and transient associations may be difficult to identify using traditional co-immunoprecipitation methods. We have therefore employed proximity-dependent biotin-identification (BioID) with four different members of the CoREST complex, in three different cell types, to identify a comprehensive network of LSD1/CoREST associated proteins. In HEK293T cells, we identified 302 CoREST-associated proteins. Among this group were 16 of 18 known CoREST components and numerous novel associations, including readers (CHD3, 4, 6, 7 and 8), writers (KMT2B and KMT2D) and erasers (KDM2B) of histone methylation. However, components of other HDAC1 containing complexes (e.g. Sin3) were largely absent. To examine the dynamic nature of the CoREST interactome in a primary cell type, we replaced endogenous LSD1 with BirA*-LSD1 in embryonic stem (ES) cells and performed BioID in pluripotent, early- and late-differentiating environments. We identified 156 LSD1-associated proteins of which 67 were constitutively associated across all three time-points (43%), including novel associations with the MMB and ChAHP complexes, implying that the majority of interactors are both dynamic and cell type dependent. In total, we have performed 16 independent BioID experiments for LSD1 in three different cell types, producing a definitive network of LSD1-assoicated proteins that should provide a major resource for the field.

A test of face discrimination ability in aging and vision loss.

PURPOSE: The ability to recognize faces is fundamental to social interactions but has not been studied extensively in visual disorders such as age-related macular degeneration (AMD). We report here the development of a face discrimination test, in which both response times (RTs) and accuracies are measured. Results are compared for young and older control subjects and older adults with AMD to determine the factors underlying performance on this test. METHODS: Subjects were 14 older controls, 11 young adult controls, and 34 individuals with binocular AMD. In the face discrimination test, colored reference photographs of eight people were presented continuously (male faces in the first half of the test, female faces in the second). On each trial, subjects reported which reference face matched the test face (shown with different poses and/or expressions). In addition, the older controls then identified the expression on the test face. RESULTS: The older controls showed generally small numbers of errors (0 to 9%) on the face identifications but more errors on expression identifications (up to 22%). They tended to show shorter RTs (but no changes in accuracy) with repeated presentations of the same face. The young controls responded more quickly, and they made almost no mistakes. Although performance varied, as a group, those with AMD were slower and showed more errors in identification than the older controls did. Across all subjects, both visual acuity and contrast sensitivity contributed significantly to the variances in RTs and accuracy. CONCLUSIONS: The group of older controls had poorer and more variable RTs and accuracies than the young controls. Difficulties in face matching, in terms of both accuracy and RT, were observed for subjects with AMD. Performance accuracy and RTs for this new test depended on both visual acuity and contrast sensitivity.

Deepometry, a framework for applying supervised and weakly supervised deep learning to imaging cytometry.

Deep learning offers the potential to extract more than meets the eye from images captured by imaging flow cytometry. This protocol describes the application of deep learning to single-cell images to perform supervised cell classification and weakly supervised learning, using example data from an experiment exploring red blood cell morphology. We describe how to acquire and transform suitable input data as well as the steps required for deep learning training and inference using an open-source web-based application. All steps of the protocol are provided as open-source Python as well as MATLAB runtime scripts, through both command-line and graphic user interfaces. The protocol enables a flexible and friendly environment for morphological phenotyping using supervised and weakly supervised learning and the subsequent exploration of the deep learning features using multi-dimensional visualization tools. The protocol requires 40 h when training from scratch and 1 h when using a pre-trained model.

Children and young people with inflammatory bowel disease attend less school than their healthy peers.

OBJECTIVE: Chronic diseases, such as inflammatory bowel disease (IBD), can impact negatively on education and social development. Examining the impact of IBD on school/college attendance for children and young people (CYP) is vital to provide targeted support to patients, families and schools. METHODS: We performed a cross-sectional survey to determine the school/college attendance rates, the reasons for absence related to IBD and facilitators or barriers to school/college attendance. In a subset of patients followed up locally, we performed a detailed review of hospital attendance data to assess healthcare burden. RESULTS: Two hundred and thirty-one questionnaires were given to CYP with IBD aged 5-17 years. Response rate was 74% (final sample 169). The median school/college attendance rate was 92.5%, significantly lower than all children in England (95.2%). 39.6% of children with IBD were persistently absent, defined nationally as missing 10% or more of school. Only five children (3%) had a 100% attendance record. Increasing age and use of monoclonal therapy were predictors of poor school attendance. Concerns about feeling unwell at school/college, access to toilets, keeping up with work and teachers' understanding of IBD are the main issues for CYP with IBD. There was a significant negative correlation between number of days in hospital and school attendance. CONCLUSION: IBD has a significant impact on school/college attendance, with hospital attendance, disease burden and school difficulties being major factors. Employing strategies to minimise healthcare burden and developing a partnership between health and education to support children with IBD will serve to facilitate school/college attendance.

Activity Mapping of Children in Play Using Multivariate Analysis of Movement Events.

PURPOSE: (i) To develop an automated measurement technique for the assessment of both the form and intensity of physical activity undertaken by children during play. (ii) To profile the varying activity across a cohort of children using a multivariate analysis of their movement patterns. METHODS: Ankle-worn accelerometers were used to record 40 min of activity during a school recess, for 24 children over five consecutive days. Activity events of 1.1 s duration were identified within the acceleration time trace and compared with a reference motif, consisting of a single walking stride acceleration trace, obtained on a treadmill operating at a speed of 4 km h. Dynamic time warping of motif and activity events provided metrics of comparative movement duration and intensity, which formed the data set for multivariate mapping of the cohort activity using a principal component analysis (PCA). RESULTS: The two-dimensional PCA plot provided clear differentiation of children displaying diverse activity profiles and clustering of those with similar movement patterns. The first component of the PCA correlated to the integrated intensity of movement over the 40-min period, whereas the second component informed on the temporal phasing of activity. CONCLUSIONS: By defining movement events and then quantifying them by reference to a motion-standard, meaningful assessment of highly varied activity within free play can be obtained. This allows detailed profiling of individual children's activity and provides an insight on social aspects of play through identification of matched activity time profiles for children participating in conjoined play.

A negative electroretinogram (ERG) in a case of probable multiple system atrophy (MSA).

Recent articles have described negative ERGs in a small number of patients with cerebellar degeneration. Five of the previously reported seven cases were hereditary (2/5 had spinocerebellar ataxia-1 (SCA-1) gene mutations) and the other two were sporadic. We report a negative ERG in a case of cerebellar degeneration that differs significantly from earlier cases. The 65-year-old man had a 5-year history of ataxia, unsteady gait, orthostatic hypotension, and bladder and erectile dysfunction, with no family history of neurological or retinal disease. Visual acuity was 20/30 OD, 20/40 OS, but reportedly was never 20/20. His fundus exam showed optic nerve pallor, but otherwise was normal. Visual fields had enlarged blind spots but no central scotomas. Autofluorescence was normal. Photopic flash and 30-Hz ERG responses were normal. Rod b-waves were reduced and delayed. Standard flash a-waves were normal, but the b-waves were smaller than the a-waves. Blood tests were negative for Leber's hereditary optic neuropathy, dominant optic atrophy, and for expansions in SCA genes including SCA-1. This is only the third reported case of sporadic ataxia with a negative ERG. The patient's prominent autonomic dysfunction differs from the previous cases, and meets the clinical criteria for probable multiple system atrophy (MSA). This introduces another possible diagnosis in cases of negative ERGs with ataxia, and suggests that the visual system may be affected in MSA.

Diagnosis and management of primary ciliary dyskinesia.

Primary ciliary dyskinesia is a rare inherited condition affecting the movement and structure of the cilia in various areas of the body, including sinuses, ears and airways. Since 2006, three centres for diagnosis and research in England have been raising awareness and funding for primary ciliary dyskinesia's diagnosis and treatment. Other areas in the UK have their own arrangements and can refer to one of the English centres. This article discusses the condition, introduces the centres and advises on where to get more information. The author concludes that paediatric nurses are in a unique position to learn about and increase awareness of the condition to help prevent unnecessary ear, nose and throat surgeries and permanent lung damage.

Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription.

Packaging the long and fragile genomes of eukaryotic species into nucleosomes is all well and good, but how do cells gain access to the DNA again after it has been bundled away? The solution, in every species from yeast to man, is to post-translationally modify histones, altering their chemical properties to either relax the chromatin, label it for remodelling or make it more compact still. Histones are subject to a myriad of modifications: acetylation, methylation, phosphorylation, ubiquitination etc. This review focuses on histone acylations, a diverse group of modifications which occur on the ε-amino group of Lysine residues and includes the well-characterised Lysine acetylation. Over the last 50 years, histone acetylation has been extensively characterised, with the discovery of histone acetyltransferases (HATs) and histone deacetylases (HDACs), and global mapping experiments, revealing an association of hyperacetylated histones with accessible, transcriptionally active chromatin. More recently, there has been an explosion in the number of unique short chain 'acylations' identified by MS, including: propionylation, butyrylation, crotonylation, succinylation, malonylation and 2-hydroxyisobutyrylation. These novel modifications add a range of chemical environments to histones, and similar to acetylation, appear to accumulate at transcriptional start sites and correlate with gene activity.