Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

Although research has demonstrated the positive nutritional value and environmental benefits associated with edible insect consumption, several factors challenge the growth and development of the edible insect industry for human consumption in the US and Canada. Cultural and psychological factors account for much of the aversion US and Canadian consumers display. The absence of specific regulation also constitutes a structural barrier to more widespread production and sale of edible insects. Compared to the US, the European Union has a more developed edible insect industry and has enacted legislation that removes some of the barriers. As consumer awareness of the putative health benefits of edible insects increases, more comprehensive regulations may emerge to keep pace with the growth of this industry. Overall, a multi-disciplinary approach that addresses both benefits and barriers to consumption is needed to facilitate a robust market for edible insects in the US and Canada.

Nucleobases are nitrogenous bases composed of monomers that are a major constituent of RNA and DNA, which are an essential part of any cellular life on the Earth. The search for nucleobases in the interstellar medium remains a major challenge, however, the recent detection of nucleobases in meteorite samples and laboratory synthesis in simulated analogue experiments have confirmed their abiotic origin and a possible route for their delivery to the Earth. Nevertheless, cellular life is based on the interacting network of complex structures, and there is substantial lack of information on the possible routes by which such ordered structures may be formed in the prebiotic environment. In the current study, we present the evidence for the synthesis of complex structures due to shock processing of nucleobases. The nucleobases were subjected to the reflected shock temperature of 3500–7000 K (estimated) and pressure of about 15–34 bar for over ~2 ms timescale. Under such extreme thermodynamic conditions, the nucleobases sample experiences superheating and subsequent cooling. Electron microscopic studies of shock processed residue show that nucleobases result in spontaneous formation of complex structures when subjected to extreme conditions of shock. These results suggest that impact shock processes might have contributed to the self-assembly of biologically relevant structures and the origin of life.

Major, minor, and trace elements were measured with electron and ion microprobes for eighteen anorthoclase megacrysts from five locations. Comparisons with concentration ranges tabulated by Smith (1974) show excellent agreement except for consistently lower values of Mg and B. The discrepancy for Mg probably reflects Mg-rich impurities contaminating samples analysed by bulk methods. The cause of the discrepancy for B is unknown and deserves further study. Samples from Mt. Erebus, Antarctica, contain glass inclusions from which the following crystal/liquid partition coefficients ensue: Mg, 0.008; P, 0.04; Ti, 0.08; Fe, 0.04; Ba, 5.2; Sr, 8; Rb, 0.27.

A combination of ion-microprobe (for Li) and electron-microprobe (for other major elements including F) methods has been used to analyse Li-rich micas from the S.W. England batholith (mainly the St Austell granite) and the Massif Central, France. Rocks showing various degrees of hydrothermal alteration were studied in order to separate the original compositional trends from alteration trends. The original compositional trend is essentially one of increasing Li with increasing degree of evolution. The main atomic substitution in the original micas is 3Li substituting for A1 and 2 vacancies in octahedral sites; substitution of Li for R2+ (Fe, Mn, Mg) in octahedral co-ordination is generally subordinate. Alteration trends involve a loss of Li, Fe, F, Rb and Cs, and a gain in A1. The effects of volatile elements on phase relations of granites are reviewed and it is concluded that the original Li-micas were primary, i.e. crystallized from the melt. It is suggested that the late-magmatic stage passed transitionally into the hydrothermal stage leading inevitably to subsolidus recrystallization (autometasomatism) of the primary minerals, so introducing further textural and mineralogical complexities to the rocks.

A large measles outbreak occurred in South Wales in 2012/2013. The outbreak has been attributed to low take-up of measles-mumps-rubella (MMR) immunization in the early 2000s. To understand better the factors that led to this outbreak we present the findings of a case-control study carried out in the outbreak area in 2001 to investigate parents' decision on whether to accept MMR. Parents who decided not to take-up MMR at the time were more likely to be older and better educated, more likely to report being influenced by newspapers [adjusted odds ratio (aOR) 3·07, 95% confidence interval (CI) 1·62–5·80], television (aOR 3·30, 95% CI 1·70–6·43), the internet (aOR 7·23, 3·26–16·06) and vaccine pressure groups (aOR 5·20, 95% CI 2·22–12·16), and less likely to be influenced by a health visitor (aOR 0·30, 95% CI 0·16–0·57). In this area of Wales, daily English-language regional newspapers, UK news programmes and the internet appeared to have a powerful negative influence. We consider the relevance of these findings to the epidemiology of the outbreak and the subsequent public health response.

We investigated an international outbreak of Salmonella Agona with a distinct PFGE pattern associated with an Irish Food company (company X) producing pre-cooked meat products sold in various food outlet chains in Europe. The outbreak was first detected in Ireland. We undertook national and international case-finding, food traceback and microbiological investigation of human, food and environmental samples. We undertook a matched case-control study on Irish cases. In total, 163 cases in seven European countries were laboratory-confirmed. Consumption of food from food outlet chains supplied by company X was significantly associated with being a confirmed case (mOR 18·3, 95% CI 2·2–149·2) in the case-control study. The outbreak strain was isolated from the company's pre-cooked meat products and production premises. Sufficient evidence was gathered to infer the vehicles of infection and sources of the outbreak and to justify the control measures taken, which were plant closure and food recall.

In summer 2008, we investigated an outbreak of diarrhoeal illness in participants of a mountain-bike event in Wales (UK) which had been affected by heavy rain. We conducted a retrospective cohort study to investigate the cause using an internet-based questionnaire. Fifty-three percent of those contacted responded, and 161 (46·5%) out of the 347 responders, reported gastrointestinal symptoms. Median day of onset was 3 days following the event. Ten riders reported receiving a laboratory-confirmed diagnosis of Campylobacter. Multivariate logistic regression analysis identified the inadvertent ingestion of mud (OR 2·5, 95% CI 1·5–4·2, P<0·001) and eating ‘other’ food during the event (OR 2·1, 95% CI 1·2–3·6, P=0·01) as significant risk factors for illness. We concluded that the outbreak was caused by Campylobacter, spread to the riders by the inadvertent ingestion of mud which had been contaminated with sheep faeces from the rural course. Mountain-bike race organizers should consider microbiological hazards when risk-assessing potential race courses. The internet is an efficient tool for the investigation of outbreaks in computer-literate populations.

BOOMERanG has recently resolved structures on the last scattering surface at redshift ˜ 1100 with high signal to noise ratio. We review the technical advances which made this possible, and we focus on the current results for maps and power spectra, with special attention to the determination of the total mass-energy density in the Universe and of other cosmological parameters.

In the 1998-99 flight, BOOMERanG has produced maps of ∼4% of the sky at high Galactic latitudes, at frequencies of 90, 150, 240 and 410 GHz, with resolution ≳ 10'. The faint structure of the Cosmic Microwave Background at horizon and sub-horizon scales is evident in these maps. These maps compare well to the maps recently obtained at lower frequencies by the WMAP experiment. Here we compare the amplitude and morphology of the structures observed in the two sets of maps. We also outline the polarization sensitive version of BOOMERanG, which was flown early this year to measure the linear polarization of the microwave sky at 150, 240 and 350 GHz.

The Cosmic Background Imager (CBI) is an instrument designed to make images of the cosmic microwave background radiation and to measure its statistical properties on angular scales from about 3 arc minutes to one degree (spherical harmonic scales from l ˜ 4250 down to l ˜ 400). The CBI is a 13-element interferometer mounted on a 6 meter platform operating in ten 1-GHz frequency bands from 26 GHz to 36 GHz. The instantaneous field of view of the instrument is 45 arcmin (FWHM) and its resolution ranges from 3 to 10 arcmin; larger fields can be imaged by mosaicing. At this frequency and resolution, the primary foreground is due to discrete extragalactic sources, which are monitored at the Owens Valley Radio Observatory and subtracted from the CBI visibility measurements.

The instrument has been making observations since late 1999 of both primordial CMB fluctuations and the Sunyaev-Zeldovich effect in clusters of galaxies from its site at an altitude of 5080 meters near San Pedro de Atacama, in northern Chile. Observations will continue until August 2001 or later. We present preliminary results from the first few months of observations.

Our current knowledge of the basic characteristics of CVs, such as their distance and luminosity, are largely based on observations of optically bright (V < 16 mag) systems. This has tended to favour the more luminous members (Mv ~ 7 … 10 mag) lying nearby in the Galactic plane (z < 400 pc;). In order to alleviate this bias, Howell & Szkody (1990) compiled a list of ~90 CVs that were faint enough and were at high galactic latitude to potentially place them well outside the Galactic plane, in the halo. We have obtained infrared J and K band images of a number of the CVs listed by Howell & Szkody (1990) in order to establish whether these systems are truely at large distances, or are instead a population of intrinsically faint objects lying relatively nearby. The distances were determined using Bailey’s method (1982) and incorporated the recent SK calibrations by Ramseyer (1994).