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The Asteroid Terrestrial impact Last Alert System (ATLAS) system consists of two 0.5 m Schmidt telescopes with cameras covering 29 square degrees at plate scale of 1.86 arcsec per pixel. Working in tandem, the telescopes routinely survey the whole sky visible from Hawaii (above δ > − 50 ° ) every two nights, exposing four times per night, typically reaching o < 19 magnitude per exposure when the moon is illuminated and c < 19.5 magnitude per exposure in dark skies. Construction is underway of two further units to be sited in Chile and South Africa which will result in an all-sky daily cadence from 2021. Initially designed for detecting potentially hazardous near earth objects, the ATLAS data enable a range of astrophysical time domain science. To extract transients from the data stream requires a computing system to process the data, assimilate detections in time and space and associate them with known astrophysical sources. Here we describe the hardware and software infrastructure to produce a stream of clean, real, astrophysical transients in real time. This involves machine learning and boosted decision tree algorithms to identify extragalactic and Galactic transients. Typically we detect 10-15 supernova candidates per night which we immediately announce publicly. The ATLAS discoveries not only enable rapid follow-up of interesting sources but will provide complete statistical samples within the local volume of 100 Mpc. A simple comparison of the detected supernova rate within 100 Mpc, with no corrections for completeness, is already significantly higher (factor 1.5 to 2) than the current accepted rates.

Objective: To test the effectiveness and long term safety of cannabinoids in multiple sclerosis (MS), in a follow up to the main Cannabinoids in Multiple Sclerosis (CAMS) study. Methods: In total, 630 patients with stable MS with muscle spasticity from 33 UK centres were randomised to receive oral Δ9-tetrahydrocannabinol (Δ9-THC), cannabis extract, or placebo in the main 15 week CAMS study. The primary outcome was change in the Ashworth spasticity scale. Secondary outcomes were the Rivermead Mobility Index, timed 10 metre walk, UK Neurological Disability Score, postal Barthel Index, General Health Questionnaire-30, and a series of nine category rating scales. Following the main study, patients were invited to continue medication, double blinded, for up to12 months in the follow up study reported here. Results: Intention to treat analysis of data from the 80% of patients followed up for 12 months showed evidence of a small treatment effect on muscle spasticity as measured by change in Ashworth score from baseline to 12 months (Δ9-THC mean reduction 1·82 (n = 154, 95% confidence interval (CI) 0.53 to 3.12), cannabis extract 0.10 (n = 172, 95% CI −0.99 to 1.19), placebo −0.23 (n = 176, 95% CI −1.41 to 0.94); p = 0.04 unadjusted for ambulatory status and centre, p = 0.01 adjusted). There was suggestive evidence for treatment effects of Δ9-THC on some aspects of disability. There were no major safety concerns. Overall, patients felt that these drugs were helpful in treating their disease. Conclusions: These data provide limited evidence for a longer term treatment effect of cannabinoids. A long term placebo controlled study is now needed to establish whether cannabinoids may have a role beyond symptom amelioration in MS.

Aims/hypothesis Diabetic peripheral neuropathy (DN) is a common complication of diabetes; however, the mechanisms producing positive or negative symptoms are not well understood. The enzyme glyoxalase I (GLO1) detoxifies reactive dicarbonyls that form AGEs and may affect the way sensory neurons respond to heightened AGE levels in DN. We hypothesised that differential GLO1 levels in sensory neurons may lead to differences in AGE formation and modulate the phenotype of DN. Methods Inbred strains of mice were used to assess the variability of Glo1 expression by quantitative RT-PCR. Non-diabetic C57BL/6 mice were used to characterise the distribution of GLO1 in neural tissues by immunofluorescence. Behavioural assessments were conducted in diabetic A/J and C57BL/6 mice to determine mechanical sensitivity, and GLO1 abundance was determined by western blot. Results GLO1immunoreactivity was found throughout the nervous system, but selectively in small, unmyelinated peptidergic dorsal root ganglia (DRG) neurons that are involved in pain transmission. GLO1 protein was present at various levels in DRG from different inbred mice strains. Diabetic A/J and C57BL/6 mice, two mouse strains with different levels of GLO1, displayed dramatically different behavioural responses to mechanical stimuli. Diabetic C57BL/6 mice also had a reduced abundance of GLO1 following diabetes induction. Conclusions/interpretation These findings reveal that the abundance of GLO1 varies between different murine strains and within different sensory neuron populations. These differences could lead to different responses of sensory neurons to the toxic effects of hyperglycaemia and reactive dicarbonyls associated with diabetes.

Hematopoietic stem cells (HSCs) reside predominantly in bone marrow, but low numbers of HSCs are also found in peripheral blood. We examined the fate of blood-borne HSCs using genetically marked parabiotic mice, which are surgically conjoined and share a common circulation. Parabionts rapidly established stable, functional cross engraftment of partner-derived HSCs and maintained partner-derived hematopoiesis after surgical separation. Determination of the residence time of injected blood-borne progenitor cells suggests that circulating HSCs/progenitors are cleared quickly from the blood. These data demonstrate that HSCs rapidly and constitutively migrate through the blood and play a physiological role in, at least, the functional reengraftment of unconditioned bone marrow.

Observations and modelling of an optical transient counterpart to a gravitational-wave event and γ-ray burst reveal that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a source of heavy elements. When neutron stars collide Merging neutron stars are potential sources of gravitational waves and have long been predicted to produce jets of material as part of a low-luminosity transient known as a 'kilonova'. There is growing evidence that neutron-star mergers also give rise to short, hard gamma-ray bursts. A group of papers in this issue report observations of a transient associated with the gravitational-wave event GW170817—a signature of two neutron stars merging and a gamma-ray flash—that was detected in August 2017. The observed gamma-ray, X-ray, optical and infrared radiation signatures support the predictions of an outflow of matter from double neutron-star mergers and present a clear origin for gamma-ray bursts. Previous predictions differ over whether the jet material would combine to form light or heavy elements. These papers now show that the early part of the outflow was associated with lighter elements whereas the later observations can be explained by heavier elements, the origins of which have been uncertain. However, one paper (by Stephen Smartt and colleagues) argues that only light elements are needed for the entire event. Additionally, Eleonora Troja and colleagues report X-ray observations and radio emissions that suggest that the 'kilonova' jet was observed off-axis, which could explain why gamma-ray-burst detections are seen as dim. Gravitational waves were discovered with the detection of binary black-hole mergers 1 and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova 2 , 3 , 4 , 5 . The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate 6 . Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst 7 , 8 . The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of −1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90–140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

Background: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate. Methods: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol. Results: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure. Conclusions: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

In Smith et al. we published estimates of the volumetric rate of supernovae within 100 Mpc. These were incorrect and we present the correct values in this corrigendum.

Routinely collected weight measurements from 4665 Plymouth children born 1996–97 were compared with the British Growth Reference Charts (BGRC). The children were 0.33 SDS heavier on average than the reference population at 24–30 months, an actual excess of 460 g.

Insight in schizophrenia tends to be assessed as the degree to which one possesses specific knowledge. It therefore often fails to account for the fact that awareness of illness is an inextricable part of a personal narrative and may be incoherent or incomplete for many different narrative reasons. Accordingly, we have developed a means of eliciting narratives of illness: the Indiana Psychiatric Illness Interview, and a method for rating the coherence of those narratives: the Narrative Coherence Rating Scale. In this article we describe these methods and present data on their reliability and validity in a study of the illness narratives of 33 outpatients with schizophrenia or schizoaffective disorder. Results suggest our measures possess sufficient internal consistency and good to excellent interrater reliability. Additionally, as predicted, our measures of narrative coherence were significantly correlated with traditional measures of insight and with measures of cognitive impairment and hopelessness gathered earlier.

While at Glasgow he met Nessie, who was studying languages, and, instead of joining the Royal Army Veterinary Corps after graduation in 1950 as he'd originally planned, he married Nessie and settled in Bromyard.