ERGs on the brain: the benefits of simultaneous flash retinal and cortical responses in paediatric cerebral visual impairment

PURPOSE: To highlight the importance of simultaneous flash electroretinogram (ERG) and visual evoked potential (VEP) recording to differentiate a true flash VEP response from an artefact caused by the intrusion of the ERG on a mid-frontal reference electrode in cases of severe cerebral visual impairment (CVI). METHODS: We report an observational case series of four children with severe CVI who underwent simultaneous flash ERG and VEP recordings. Flash VEPs from Oz-Fz and lower lid skin ERGs referred to Fz were recorded simultaneously to Grass intensity setting 4 flash stimulation. RESULTS: In all cases, atypical, but reproducible VEPs were evident. Comparison of the timing and waveform of the VEPs and ERGs showed the occipital responses were inverted ERGs and no true flash VEP was evident. CONCLUSIONS: While ISCEV and neurophysiology standards do not require the simultaneous recording of the flash ERG with the VEP, these cases highlight the usefulness of this non-invasive technique particularly in suspected paediatric cerebral visual impairment to differentiate a true VEP from an artefact caused by ERG contamination

Is there a gap between recommended and ‘real world’ practice in the management of depression in young people? A medical file audit of practice

BACKGROUND: Literature has shown that dissemination of guidelines alone is insufficient to ensure that guideline recommendations are incorporated into every day clinical practice. METHODS: We aimed to investigate the gaps between guideline recommendations and clinical practice in the management of young people with depression by undertaking an audit of medical files in a catchment area public mental health service for 15 to 25 year olds in Melbourne, Australia. RESULTS: The results showed that the assessment and recording of depression severity to ensure appropriate treatment planning was not systematic nor consistent; that the majority of young people (74.5%) were prescribed an antidepressant before an adequate trial of psychotherapy was undertaken and that less than 50% were monitored for depression symptom improvement and antidepressant treatment emergent suicide related behaviours (35% and 30% respectively). Encouragingly 92% of first line prescriptions for those aged 18 years or under who were previously antidepressant-naïve was for fluoxetine as recommended. CONCLUSIONS: This research has highlighted the need for targeted strategies to ensure effective implementation. These strategies might include practice system tools that allow for systematic monitoring of depression symptoms and adverse side effects, particularly suicide related behaviours. Additionally, youth specific psychotherapy that incorporates the most effective components for this age group, delivered in a youth friendly way would likely aid effective implementation of guideline recommendations for engagement in an adequate trial of psychotherapy before medication is initiated

An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy.

BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood. The natural history of motor and language regression is used to monitor the efficacy of CNS treatments. Less is known about CLN2 retinopathy. Our aim is to elaborate the nature, age of onset, and symmetry of CLN2 retinopathy using visual electrophysiology and ophthalmic imaging. SUBJECTS AND METHODS: We reviewed 22 patients with genetically confirmed CLN2 disease; seventeen showing classical and five atypical disease. Flash electroretinograms (ERGs), flash and pattern reversal visual evoked potentials (VEPs), recorded from awake children were collated. Available fundus images were graded, optical coherence tomography (OCT) central subfoveal thickness (CST) measured, and genotype, age, clinical vision assessment and motor language grades assembled. RESULTS: ERGs show cone/rod system dysfunction preceded by localised macular ellipsoid zone disruption on OCT from 4.8 years. Electroencephalogram (EEG) time-locked spikes confounded both pattern 6/17 (35%) and flash VEPs 12/16 (75%). Paired right eye (RE) and left eye (LE) ERG amplitudes did not differ significantly for each flash stimulus at the p 0.001 level, Wilcoxon ranked signed test. Cone ERGs show a functional deficit before CST thinning in classical disease. Optomap hyper fundus autofluorescence (FAF) at the fovea was noted in three patients with normal ERGs. The oldest patient showed an ovoid aggregate above the external limiting membrane at the fovea, which did not affect the PERG. CONCLUSION: ERG findings in CLN2 retinopathy show symmetrical cone-rod dysfunction, from 4y10m in this series, but a broad range of ages when ERG function is preserved

7 Scoping review of homonymous hemianopia in childhood

Cerebral visual impairment (CVI) encompasses a heterogeneous group of disorders and a spectrum of types of visual impairments. Research is needed to characterise the different forms of CVI and identify the specific needs of these groups to inform individualised patient care. Homonymous hemianopia (HH) is a definable visual field defect that affect some children with CVI. As part of a new research programme, we conducted a scoping review of the literature on HH in children and young people to map current knowledge and identify evidence gaps.We used the PRISMA extension for Scoping Reviews methodology. Multiple online databases were searched using terms associated with 'homonymous hemianopia' and 'children'. This yielded 1588 papers which were screened by two reviewers. Of these 1001 were excluded at abstract screen and a further 415 excluded after full text review, with full text unavailable for 15. Data were extracted and charted from 157 studies and additional grey literature.Interim analysis shows reported studies are predominantly from high income countries with a paucity of higher-level evidence, and a preponderance of case reports. Most papers reported causative pathology and diagnosis of HH. There was minimal attention to or evidence relating to intervention. Child-specific grey literature on HH was limited.This review collates the current evidence-base for HH in children. It demonstrates the important evidence-gap relating to intervention in these cases that would help inform more individualised care. Similar scoping reviews may be prove useful in assessing the evidence relating to other definable groups within the CVI umbrella

Classification of neurological abnormalities in children with congenital melanocytic naevus syndrome identifies magnetic resonance imaging as the best predictor of clinical outcome

Background: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much wider variation in outcome. Objectives: To establish whether routine MRI of the CNS is a clinically relevant investigation in children with multiple CMN (more than one at birth), and to subclassify radiological abnormalities. Methods: Of 376 patients seen between 1991 and 2013, 289 fulfilled our criterion for a single screening CNS MRI, which since 2008 has been more than one CMN at birth, independent of size and site of the largest naevus. Cutaneous phenotyping and radiological variables were combined in a multiple regression model of long-term outcome measures (abnormal neurodevelopment, seizures, requirement for neurosurgery). Results: Twenty-one per cent of children with multiple CMN had an abnormal MRI. Abnormal MRI was the most significant predictor of all outcome measures. Abnormalities were subclassified into group 1 ‘intraparenchymal melanosis alone’ (n = 28) and group 2 ‘all other pathology’ (n = 18). Group 1 was not associated with malignancy or death during the study period, even when symptomatic with seizures or developmental delay, whereas group 2 showed a much more complex picture, requiring individual assessment. Conclusions: For screening for congenital neurological lesions a single MRI in multiple CMN is a clinically relevant strategy. Any child with a stepwise change in neurological/developmental symptoms or signs should have an MRI with contrast of the brain and spine to look for new CNS melanoma

20th Century Multivariate Indian Ocean Regional Sea Level Reconstruction

Despite having some of the world\u27s most densely populated and vulnerable coastlines, Indian Ocean sea level variability over the past century is poorly understood relative to other ocean basins primarily, due to the short and sparse observational records. In an attempt to overcome the limitations imposed by the lack of adequate observations, we have produced a 20th century Indian Ocean sea level reconstruction product using a new multivariate reconstruction technique. This technique uses sea level pressure and sea surface temperature in addition to sea level data to help constrain basin‐wide sea level variability by (1) the removal of large spurious signals caused as a result of insufficient tide gauge data specifically during the first half of the 20th century and (2) through its information on large‐scale climate modes such as El Niño‐Southern Oscillation and Indian Ocean Dipole. Basis functions generated by Cyclostationary Empirical Orthogonal Functions are used for the reconstruction. This new multivariate technique provides improved regional sea level variability estimates along with a longer record length in comparison to existing globally reconstructed sea level data. The biggest advantage of using this multivariate reconstruction technique lies in its ability to reconstruct Indian Ocean sea level for the first half of the 20th century, providing a long sea level record for the study of Indian Ocean internal climate variability. This will enable future studies to help improve the understanding of how sea level trends and variability can be modulated by internal climate variability in the Indian Ocean

High risk of unprecedented UK rainfall in the current climate

This is the final version. Available on open access from Springer Nature via the DOI in this recordIn winter 2013/14 a succession of storms hit the UK leading to record rainfall and flooding in many regions including south east England. In the Thames river valley there was widespread flooding, with clean-up costs of over £1 billion. There was no observational precedent for this level of rainfall. Here we present analysis of a large ensemble of high-resolution initialised climate simulations to show that this event could have been anticipated, and that in the current climate there remains a high chance of exceeding the observed record monthly rainfall totals in many regions of the UK. In south east England there is a 7% chance of exceeding the current rainfall record in at least one month in any given winter. Expanding our analysis to some other regions of England and Wales the risk increases to a 34% chance of breaking a regional record somewhere each winter.A succession of storms during the 2013-2014 winter led to record flooding in the UK. Here, the authors use high-resolution climate simulations to show that this event could have been anticipated and that there remains a high chance of exceeding observed record monthly rainfall totals in many parts of the UK.Development of the Met Office Hadley Centre’s decadal climate predictions, the innovative scientific research that contributed to the NFRR, has been resourced through the MOHCCP, the NCIC, the Newton Fund, and SPECS. Development of the methodology was supported by the Newton Fund

Developing predictive insight into changing water systems: use-inspired hydrologic science for the Anthropocene

Globally, many different kinds of water resources management issues call for policy- and infrastructure-based responses. Yet responsible decision-making about water resources management raises a fundamental challenge for hydrologists: making predictions about water resources on decadal - to century-long timescales. Obtaining insight into hydrologic futures over 100 yr timescales forces researchers to address internal and exogenous changes in the properties of hydrologic systems. To do this, new hydrologic research must identify, describe and model feedbacks between water and other changing, coupled environmental subsystems. These models must be constrained to yield useful insights, despite the many likely sources of uncertainty in their predictions. Chief among these uncertainties are the impacts of the increasing role of human intervention in the global water cycle – a defining challenge for hydrology in the Anthropocene. Here we present a research agenda that proposes a suite of strategies to address these challenges from the perspectives of hydrologic science research. The research agenda focuses on the development of co-evolutionary hydrologic modeling to explore coupling across systems, and to address the implications of this coupling on the long-time behavior of the coupled systems. Three research directions supportthe development of these models: hydrologic reconstruction, comparative hydrology and model-data learning. These strategies focus on understanding hydrologic processes and feedbacks over long timescales, across many locations, and through strategic coupling of observational and model data in specific systems. We highlight the value of use-inspired and team-based science that is motivated by real-world hydrologic problems but targets improvements in fundamental understanding to support decision-making and management. Fully realizing the potential of this approach will ultimately require detailed integration of social science and physical science understanding of water systems, and is a priority for the developing field of sociohydrology

Influenza transmission in a cohort of households with children: 2010-2011

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Identification of a new member of the phage shock protein response in Escherichia coli, the phage shock protein g (PspG)

The phage shock protein operon (pspABCDE) of Escherichia coli is strongly up-regulated in response to overexpression of the filamentous phage secretin protein IV (pIV) and by many other stress conditions including defects in protein export. PspA has an established role in maintenance of the proton-motive force of the cell under stress conditions. Here we present evidence for a new member of the phage shock response in E. coli. Using transcriptional profiling, we show that the synthesis of pIV in E. coli leads to a highly restricted response limited to the up-regulation of the psp operon genes and yjbO. The psp operon and yjbO are also up-regulated in response to pIV in Salmonella enterica serovar Typhimurium. yjbO is a highly conserved gene found exclusively in bacteria that contain a psp operon but is physically unlinked to the psp operon. yjbO encodes a putative inner membrane protein that is co-controlled with the psp operon genes and is predicted to be an effector of the psp response in E. coli. We present evidence that yjbO expression is driven by sigma(54)-RNA polymerase, activated by PspF and integration host factor, and negatively regulated by PspA. PspF specifically regulates only members of the PspF regulon: pspABCDE and yjbO. We found that increased expression of YjbO results in decreased motility of bacteria. Because yjbO is co-conserved and co-regulated with the psp operon and is a member of the phage shock protein F regulon, we propose that yjbO be renamed pspG