One hundred and seven patients from 79 families were defined as having Leber's hereditary optic neuropathy (LHON) by the presence of one of the mitochondrial DNA (mtDNA) mutations at positions 11778 (60 families), 3460 (seven families) or 14484 (12 families). Only half of the 11778 index patients had a history of similarly affected relatives; this proportion was higher with the 3460 (71%) and 14484 (100%) mutations. The ratios of affected male to female patients were 2.5:1 (11778), 2:1 (3460), and 5.7:1 (14484). Detailed clinical data were available for 79 patients from 55 families. Visual loss developed between the ages of 11 and 30 years in 69%, with a range of 6-62 years, and no significant differences between mutation groups or males and females. It was bilateral in all but two patients, to a median of counting fingers with a central scotoma, developing simultaneously in 22% and sequentially in 78%, with a median inter-eye delay of 8 weeks, and progressing in each eye over a period of 4-6 weeks. Nineteen patients had pain in an affected eye or on eye movements, and four experienced Uhthoff's phenomenon. Retinal microangiopathy was uncommon after 6 months from onset and was not detected in 36% of patients examined within 3 months of visual loss; the microangiopathy was particularly uncommon in the 14484 group. There was no difference in the overall visual outcome between the 11778 and 3460 groups with median final visual acuities of 1/60 and 3/60, respectively. Particularly severe visual loss occurred in one-third of women with the 11778 mutation, to vague perception of light or no perception of light in at least one eye. A multiple sclerosis-like illness was observed in 45% of females with the 11778 mutation. Prognosis was substantially better in the 14484 patients, with recovery to a final visual acuity of at least 6/24, in 71% of patients. Good visual outcome was strongly correlated with age at onset, all those with onset before 20 years having a final visual acuity better than 6/24 as opposed to only 2 out of 6 with later onset. Improvement in vision occurred as long as 4 years after onset. High alcohol and tobacco consumption, cranial or ocular trauma, young or old age at presentation, co-existing neurological disease, and recent childbirth with post-partum haemorrhage, all contributed to diagnostic difficulties in this series, usually in the absence of a family history. These problems were resolved by mtDNA analysis.

SummaryBackgroundUnnecessary antibiotic prescribing contributes to antimicrobial resistance. In this trial, we aimed to reduce unnecessary prescriptions of antibiotics by general practitioners (GPs) in England.MethodsIn this randomised, 2 × 2 factorial trial, publicly available databases were used to identify GP practices whose prescribing rate for antibiotics was in the top 20% for their National Health Service (NHS) Local Area Team. Eligible practices were randomly assigned (1:1) into two groups by computer-generated allocation sequence, stratified by NHS Local Area Team. Participants, but not investigators, were blinded to group assignment. On Sept 29, 2014, every GP in the feedback intervention group was sent a letter from England's Chief Medical Officer and a leaflet on antibiotics for use with patients. The letter stated that the practice was prescribing antibiotics at a higher rate than 80% of practices in its NHS Local Area Team. GPs in the control group received no communication. The sample was re-randomised into two groups, and in December, 2014, GP practices were either sent patient-focused information that promoted reduced use of antibiotics or received no communication. The primary outcome measure was the rate of antibiotic items dispensed per 1000 weighted population, controlling for past prescribing. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN32349954, and has been completed.FindingsBetween Sept 8 and Sept 26, 2014, we recruited and assigned 1581 GP practices to feedback intervention (n=791) or control (n=790) groups. Letters were sent to 3227 GPs in the intervention group. Between October, 2014, and March, 2015, the rate of antibiotic items dispensed per 1000 population was 126·98 (95% CI 125·68–128·27) in the feedback intervention group and 131·25 (130·33–132·16) in the control group, a difference of 4·27 (3·3%; incidence rate ratio [IRR] 0·967 [95% CI 0·957–0·977]; p<0·0001), representing an estimated 73 406 fewer antibiotic items dispensed. In December, 2014, GP practices were re-assigned to patient-focused intervention (n=777) or control (n=804) groups. The patient-focused intervention did not significantly affect the primary outcome measure between December, 2014, and March, 2015 (antibiotic items dispensed per 1000 population: 135·00 [95% CI 133·77–136·22] in the patient-focused intervention group and 133·98 [133·06–134·90] in the control group; IRR for difference between groups 1·01, 95% CI 1·00–1·02; p=0·105).InterpretationSocial norm feedback from a high-profile messenger can substantially reduce antibiotic prescribing at low cost and at national scale; this outcome makes it a worthwhile addition to antimicrobial stewardship programmes.FundingPublic Health England.

Limited understanding of infant pain has led to its lack of recognition in clinical practice. While the network of brain regions that encode the affective and sensory aspects of adult pain are well described, the brain structures involved in infant nociceptive processing are less well known, meaning little can be inferred about the nature of the infant pain experience. Using fMRI we identified the network of brain regions that are active following acute noxious stimulation in newborn infants, and compared the activity to that observed in adults. Significant infant brain activity was observed in 18 of the 20 active adult brain regions but not in the infant amygdala or orbitofrontal cortex. Brain regions that encode sensory and affective components of pain are active in infants, suggesting that the infant pain experience closely resembles that seen in adults. This highlights the importance of developing effective pain management strategies in this vulnerable population.DOI: http://dx.doi.org/10.7554/eLife.06356.001

The use of behavioural sciences in government has expanded and matured in the last decade. Since the Behavioural Insights Team (BIT) has been part of this movement, we sketch out the history of the team and the current state of behavioural public policy, recognising that other works have already told this story in detail. We then set out two clusters of issues that have emerged from our work at BIT. The first cluster concerns current challenges facing behavioural public policy: the long-term effects of interventions; repeated exposure effects; problems with proxy measures; spillovers and general equilibrium effects and unintended consequences; cultural variation; 'reverse impact'; and the replication crisis. The second cluster concerns opportunities: influencing the behaviour of government itself; scaling interventions; social diffusion; nudging organisations; and dealing with thorny problems. We conclude that the field will need to address these challenges and take these opportunities in order to realise the full potential of behavioural public policy.

The Policy Research Working Paper Series disseminates the findings of work in progress to encourage the exchange of ideas about development issues. An objective of the series is to get the findings out quickly, even if the presentations are less than fully polished. The papers carry the names of the authors and should be cited accordingly. The findings, interpretations, and conclusions expressed in this paper are entirely those of the authors. They do not necessarily represent the views of the International Bank for Reconstruction and Development/World Bank and its affiliated organizations, or those of the Executive Directors of the World Bank or the governments they represent.

Firms are exposed to a variety of low-probability, high-impact risks that can disrupt their operations and supply chains. These risks are difficult to predict and quantify; therefore, they are difficult to manage. As a result, managers may suboptimally deploy countermeasures, leaving their firms exposed to some risks while wasting resources to mitigate other risks that would not cause significant damage. In a three-year research engagement with Ford Motor Company, we addressed this practical need by developing a novel risk-exposure model that assesses the impact of a disruption originating anywhere in a firm's supply chain. Our approach defers the need for a company to estimate the probability associated with any specific disruption risk until after it has learned the effect such a disruption will have on its operations. As a result, the company can make more informed decisions about where to focus its limited risk-management resources. We demonstrate how Ford applied this model to identify previously unrecognized risk exposures, evaluate predisruption riskmitigation actions, and develop optimal postdisruption contingency plans, including circumstances in which the duration of the disruption is unknown.

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We investigated the MRI appearance of the optic nerve and its cerebrospinal-fluid-containing sheath in 17 patients with benign intracranial hypertension (BIH) and 15 normal controls. Using phased-array local coils, 3-mm coronal T2-weighted fat-suppressed fast spin-echo images were obtained with an in-plane resolution of < 0.39 mm. The optic nerve and its sheath were clearly differentiated. An enlarged, elongated subarachnoid space around the optic nerve was demonstrated in patients with BIH. High-resolution MRI of the optic nerve offers additional information which may be of value for diagnosis and in planning and monitoring treatment.