Background: Wolfram syndrome (WFS) is a genetic disorder clinically characterized by optic atrophy (OA), diabetes mellitus, sensorineural deafness, and diabetes insipidus. It is caused by mutations in WFS1 (mono- or biallelic) or CISD2 (biallelic) genes. Neuroradiological features include cerebellar and/or brainstem atrophy with visual pathway and white matter involvement. We report two subjects with WFS in which multifocal, progressive, and contrast-enhancing white matter abnormalities (WMA) led to the consideration of multiple sclerosis (MS). Methods: We retrospectively analyzed the clinical, genetic, and radiological data from two unrelated subjects with genetically confirmed WFS and multifocal WMA. Results: Subject I: a 43-year-old woman, heterozygous for a known WFS1 variant, had a history of congenital deafness and OA. The brain MRI documented progressive multifocal WMA including pericallosal lesions. Subject II: a 28-year-old woman, compound heterozygous for two WFS1 variants, was known for OA and diabetes mellitus. The brain MRI revealed multifocal periventricular, callosal, subcortical, and juxtacortical WMA, with some enhancing after gadolinium injection. Conclusions: Our report expands the WFS spectrum of white matter involvement to include progressive, seemingly inflammatory lesions. Although we cannot exclude a dual diagnosis, the roles of WFS1 and CISD2 in myelination suggest a selective white matter vulnerability in WFS.

Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.

Many popular books and articles that purport to explain how people, companies, orideas succeed highlight a few successes chosen to fit a particular narrative. Weinvestigate what effect these highly selected “success narratives”have on readers’ beliefs and decisions. We conducted a large, randomized,pre-registered experiment, showing participants successful firms with foundersthat all either dropped out of or graduated college, and asked them to makeincentive-compatible bets on a new firm. Despite acknowledging biases in theexamples, participants’ decisions were very strongly influenced by them.People shown dropout founders were 55 percentage points more likely to bet on adropout-founded company than people who were shown graduate founders. Mostreported medium to high confidence in their bets, and many wrote causalexplanations justifying their decision. In light of recent concerns about falseinformation, our findings demonstrate how true but biased information canstrongly alter beliefs and decisions.

A terrestrial (lacustrine and fluvial) palaeoclimate record from Hoxne (Suffolk, UK) shows two temperate phases separated by a cold episode, correlated with MIS 11 subdivisions corresponding to isotopic events 11.3 (Hoxnian interglacial period), 11.24 (Stratum C cold interval), and 11.23 (warm interval with evidence of human presence). A robust, reproducible multiproxy consensus approach validates and combines quantitative palaeotemperature reconstructions from three invertebrate groups (beetles, chironomids, and ostracods) and plant indicator taxa with qualitative implications of molluscs and small vertebrates. Compared with the present, interglacial mean monthly air temperatures were similar or up to 4.0°C higher in summer, but similar or as much as 3.0°C lower in winter; the Stratum C cold interval, following prolonged nondeposition or erosion of the lake bed, experienced summers 2.5°C cooler and winters between 5°C and 10°C cooler than at present. Possible reworking of fossils into Stratum C from underlying interglacial assemblages is taken into account. Oxygen and carbon isotopes from ostracod shells indicate evaporatively enriched lake water during Stratum C deposition. Comparative evaluation shows that proxy-based palaeoclimate reconstruction methods are best tested against each other and, if validated, can be used to generate more refined and robust results through multiproxy consensus.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

We highlight the advances and difficulties in understanding PSR B1828-11, which undergoes long-term periodic modulations in its timing and pulse shape over several years. A model comparison of precession and magnetospheric switching models based on the long-term modulation data favours the former; we discuss the implications of this in the context of short timescale switching observed in this pulsar. Furthermore, we highlight the difficulties this pulsar poses for our understanding of pulsars due to the increasing rate of the modulation period and its behaviour during a recent glitch.

Tomato (Lycopersicon esculentum Mill. ‘Fireball’), white bean (Phaseolus vulgaris L. ‘Seaway’), and tobacco (Nicotiana tabacum L. ‘Delhi 34’ and ‘White Gold’) were pretreated with herbicides at one of three rates prior to fumigation with ozone at 0, 7.5, 15, or 30 pphm (parts per hundred million) for two 1.5-hr period. The plants were harvested 5 to 7 days after ozone fumigation, dried, and weighed. The natural logarithms of the dry weight data were subjected to multiple regression analysis to test for synergistic or antagonistic interactions between ozone and the various herbicides. Synergistic phytotoxicity was definitely observed for pebulate (S-propyl butylethylthiocarbamate) and possibly for chloramben (3-amino-2,5-dichlorobenzoic acid) in combination with ozone on tobacco ‘White Gold’ and ‘Delhi 34’, respectively. For most of the other combinations (chloramben, trifluralin α,α,α-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine) or monolinuron (3-(p-chlorophenyl)-1-methoxy-1-methylurea) on white bean, diphenamid (N,N-dimethyl-2,2-diphenylacetamide) or trifluralin on tomato, chloramben on tobacco ‘White Gold’, and pebulate on tobacco ‘Delhi 34’) the phytotoxicity in the presence of ozone was additive and no interaction was indicated. An antagonistic interaction between ozone and benefin (N-butyl-N-ethyl-α,α,α-trifluoro-2,6-dinitro-p-toluidine) was indicated on the two cultivars of tobacco.

Most of the recent advances in X-ray astronomy have resulted from satellite observations in the low energy (< 20 keV) range. The Einstein X-ray Observatory in particular has been responsible for a dramatic increase in our knowledge of the X-ray sky, in that all major classes of astronomical objects have been detected.

In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0–38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.

A community outbreak of legionellosis occurred in Barrow-in-Furness, Cumbria, during July and August 2002. A descriptive study and active case-finding were instigated and all known wet cooling systems and other potential sources were investigated. Genotypic and phenotypic analysis, and amplified fragment length polymorphism of clinical human and environmental isolates confirmed the air-conditioning unit of a council-owned arts and leisure centre to be the source of infection. Subsequent sequence-based typing confirmed this link. One hundred and seventy-nine cases, including seven deaths [case fatality rate (CFR) 3·9%] were attributed to the outbreak. Timely recognition and management of the incident very likely led to the low CFR compared to other outbreaks. The outbreak highlights the responsibility associated with managing an aerosol-producing system, with the potential to expose and infect a large proportion of the local population and the consequent legal ramifications and human cost.

This paper describes virological and epidemiological features of an infection which killed two of three affected cheetahs at Whipsnade Park in 1977. Two animals had profuse skin lesions and the third had an acute haemorrhagic pneumonia. The outbreak was shown to be caused by cowpox virus. Cowpox virus is believed to circulate in small wild animals, but the source of infection was not traced despite virological and serological tests on 93 captive and 102 wild animals.

Sub-clinical infections did not occur in susceptible contact cheetahs. Immune globulin did not influence the outcome and smallpox vaccine does not take in cheetahs. Management of any future outbreak will rely on prompt diagnosis and segregation of infected animals.

Skeletal muscle is a highly dynamic and malleable tissue that is able to adapt to different stimuli placed upon it, both during gestation and after birth, ultimately resulting in anatomical changes to muscle fibre composition. Variation in nutrient supply throughout gestation is common, whether in livestock or in the human. The specific effects of maternal nutrition on foetal development are at the forefront of scientific research. However, results describing how different maternal feeding strategies affect skeletal muscle fibre development in the offspring are not fully consistent, even where the same time windows during gestation have been examined. The aim of this study is to determine the effects of increased maternal nutrition (above the recommended levels) on the Musculus semitendinosus phenotype of progeny. In all, 24 pregnant sows were assigned to one of four feeding regimes during gestation; T1 (control group): 30 MJ digestible energy per day (MJ DE/day) throughout gestation, T2: same as that for T1 but increased to 60 MJ DE/day from 25 to 50 days of gestation (dg), T3: same as that for T1 but increased to 60 MJ DE/day from 50 to 80 dg, T4: same as that for T1 but increased nutrition to 60 MJ DE/day from 25 to 80 dg. Light- and heavy-weight littermate pairs of the same sex were selected at birth and individually fed to slaughter (c. 158 days). Histochemical and immunohistochemical staining were used to identify the predominantly oxidative (deep) and less oxidative (superficial) regions of the M. semitendinosus, and to determine total fibre number and proportions of fibre types. The results demonstrate that increased maternal nutrition alters skeletal muscle phenotype in the offspring by changing fibre-type proportions, leading to an increased oxidative capacity due to an increase in Type IIA fibres. No change in total muscle area, total muscle fibre number, or fibre cross-sectional area is observed. The precise molecular mechanism(s) by which these findings occur is being investigated.

Serum samples from 1963 Merino sheep were examined for serum transferrin type. Two of the five transferrin alleles previously described in British breeds of sheep, viz. T fA and T fc, were found, but T fB, T fD and T fE were absent. Evidence for seven further transferrin alleles was obtained. These alleles were coded T fF, T fG, T fH, T fJ, T fN, T fK and T fL in decreasing order of mobility of the zones they produce in starch gel.

Gene frequency data is presented for the populations studied.