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Introduction:\ud Establishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable.\ud \ud Methods:\ud Herein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs).\ud \ud Results:\ud The gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects.\ud \ud Discussion:\ud Good quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating.

Aim To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome. What this paper adds Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.Estimates of impairment may be biased by intermediate to poor quality evidence., What this paper adds Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.Estimates of impairment may be biased by intermediate to poor quality evidence. Editor's Choice My Editor's Choice for the July 2019 issue is this systematic review. It highlights neurodevelopmental outcomes of children who had antenatal exposure to methadone given to their mother as maintenance treatment (as well as other, less documented risk factors). The surge in opiod dependence in the USA and other countries, particularly in young adults, raises specific concerns for the children's development. This article is commented on by Skranes on page 738 of this issue. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the abstract to view the translations. Video Podcast: https://www.youtube.com/watch?v=Ixo12Fg0FJs

PURPOSE:Visual evoked potentials (VEPs) can be used to measure visual resolution via a spatial frequency (SF) limit as an objective estimate of visual acuity. The aim of this systematic review is to collate descriptions of the VEP SF limit in humans, healthy and disordered, and to assess how accurately and precisely VEP SF limits reflect visual acuity. METHODS:The protocol methodology followed the PRISMA statement. Multiple databases were searched using "VEP" and "acuity" and associated terms, plus hand search: titles, abstracts or full text were reviewed for eligibility. Data extracted included VEP SF limits, stimulus protocols, VEP recording and analysis techniques and correspondence with behavioural acuity for normally sighted healthy adults, typically developing infants and children, healthy adults with artificially degraded vision and patients with ophthalmic or neurological conditions. RESULTS:A total of 155 studies are included. Commonly used stimulus, recording and analysis techniques are summarised. Average healthy adult VEP SF limits vary from 15 to 40 cpd, depend on stimulus, recording and analysis techniques and are often, but not always, poorer than behavioural acuity measured either psychophysically with an identical stimulus or with a clinical acuity test. The difference between VEP SF limit and behavioural acuity is variable and strongly dependent on the VEP stimulus and choice of acuity test. VEP SF limits mature rapidly, from 1.5 to 9 cpd by the end of the first month of life to 12-20 cpd by 8-12 months, with slower improvement to 20-40 cpd by 3-5 years. VEP SF limits are much better than behavioural thresholds in the youngest, typically developing infants. This difference lessens with age and reaches equivalence between 1 and 2 years; from around 3-5 years, behavioural acuity is better than the VEP SF limit, as for adults. Healthy, artificially blurred adults had slightly better behavioural acuity than VEP SF limits across a wide range of acuities, while adults with heterogeneous ophthalmic or neurological pathologies causing reduced acuity showed a much wider and less consistent relationship. For refractive error, ocular media opacity or pathology primarily affecting the retina, VEP SF limits and behavioural acuity had a fairly consistent relationship across a wide range of acuity. This relationship was much less consistent or close for primarily macular, optic nerve or neurological conditions such as amblyopia. VEP SF limits were almost always normal in patients with non-organic visual acuity loss. CONCLUSIONS:The VEP SF limit has great utility as an objective acuity estimator, especially in pre-verbal children or patients of any age with motor or learning impairments which prevent reliable measurement of behavioural acuity. Its diagnostic power depends heavily on adequate, age-stratified, reference data, age-stratified empirical calibration with behavioural acuity, and interpretation in the light of other electrophysiological and clinical findings. Future developments could encompass faster, more objective and robust techniques such as real-time, adaptive control. REGISTRATION:International prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), registration number CRD42018085666.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum protocol for clinical testing but encourages additional ERG testing when appropriate. This ISCEV extended protocol describes methods to record and evaluate a light-adapted (LA) ERG stimulus–response series with increasing flash strengths. The LA ERG stimulus–response series (also referred to as the luminance–response or intensity–response series in the published literature) can characterise generalised cone system function more comprehensively than the ISCEV standard LA ERGs alone. The amplitude of LA ERG a-waves, arising from cones and cone off-bipolar cells, typically shows a saturating function. The LA ERG b-wave amplitudes, which arise primarily from activity of retinal bipolar cells, show an amplitude peak followed by a nonzero plateau (the “photopic hill” phenomenon). This ISCEV extended protocol specifies a stimulus–response series suitable to evaluate generalised dysfunction affecting the LA retina, to aid in distinguishing between the on- and off-responses of the cone system and to monitor ERG changes in these characteristics. The LA ERG stimulus–response series for a- and b-waves is recorded to a sequence of nine flash stimuli ranging from 0.03 to 300 cd s m−2, superimposed on a standard background of 30 cd m−2. A shorter protocol is also presented to measure the mid-range of the function (the “photopic hill”) using 5 flash stimuli.

Only a very brave politician would broach the subject of local government boundary reform. Like the Council Tax, it is one of those subjects that everyone agrees is important, but probably just too difficult to do anything about. For sure, we can tinker at the margins and tweak this and that, but it is not going to win many votes. But we are not politicians, and we believe there is value in looking at the question of whether the boundaries we use to govern Scotland are a good fit. Therefore, this paper looks at the question of whether Scotland’s current Councils are the right political geography for governing Scotland and how they compare to those in other countries. We also set out two alternative administrative geographies. One of these is based on economic interactions, and the other is based on existing wards. However, these are not concrete proposals but are instead intended to prompt further reflection on the shape of local democracy in Scotland: a subject which spans economics, history, geography, identity, belonging and topography.

This report explores neighbourhood deprivation and disconnection at the neighbourhood level, focussing on the poorest neighbourhoods across the UK. It examines how and why these areas often remain disconnected from economic growth within their wider city regions.