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.

Haiti has the highest human rabies burden in the Western Hemisphere. There is no published literature describing the public's perceptions of rabies in Haiti, information that is critical to developing effective interventions and government policies. We conducted a knowledge, attitudes and practices survey of 550 community members and 116 health professionals in Pétionville, Haiti in 2013 to understand the perception of rabies in these populations. The majority of respondents (85%) knew that dogs were the primary reservoir for rabies, yet only 1% were aware that bats and mongooses could transmit rabies. Animal bites were recognized as a mechanism of rabies transmission by 77% of the population and 76% were aware that the disease could be prevented by vaccination. Of 172 persons reporting a bite, only 37% sought medical treatment. The annual bite incidence rate in respondents was 0·9%. Only 31% of bite victims reported that they started the rabies vaccination series. Only 38% of respondents reported that their dog had been vaccinated against rabies. The majority of medical professionals recognized that dogs were the main reservoir for rabies (98%), but only 28% reported bats and 14% reported mongooses as posing a risk for rabies infection. Bites were reported as a mechanism of rabies transmission by 73% of respondents; exposure to saliva was reported by 20%. Thirty-four percent of medical professionals reported they would wash a bite wound with soap and water and 2·8% specifically mentioned rabies vaccination as a component of post-bite treatment. The majority of healthcare professionals recommended some form of rabies assessment for biting animals; 68·9% recommended a 14-day observation period, 60·4% recommended a veterinary consultation, and 13·2% recommended checking the vaccination status of the animal. Fewer than 15% of healthcare professionals had ever received training on rabies prevention and 77% did not know where to go to procure rabies vaccine for bite victims. Both study populations had a high level of knowledge about the primary reservoir for rabies and the mode of transmission. However, there is a need to improve the level of knowledge regarding the importance of seeking medical care for dog bites and additional training on rabies prevention for healthcare professionals. Distribution channels for rabies vaccines should be evaluated, as the majority of healthcare providers did not know where rabies vaccines could be obtained. Canine rabies vaccination is the primary intervention for rabies control programmes, yet most owned dogs in this population were not vaccinated.

The superheating that usually occurs when a solid is melted by volumetric heating can produce irregular solid–liquid interfaces. Such interfaces can be visualised in ice, where they are sometimes known as Tyndall stars. This paper describes some of the experimental observations of Tyndall stars and a mathematical model for the early stages of their evolution. The modelling is complicated by the strong crystalline anisotropy, which results in an anisotropic kinetic undercooling at the interface; it leads to an interesting class of free boundary problems that treat the melt region as infinitesimally thin.

Influenza causes severe illness and deaths, and global surveillance systems use different clinical case definitions to identify patients for diagnostic testing. We used data collected during January 2007–July 2010 at hospital-based influenza surveillance sites in western Kenya to calculate sensitivity, specificity, positive predictive value, and negative predictive value for eight clinical sign/symptom combinations in hospitalized patients with acute respiratory illnesses, including severe acute respiratory illness (SARI) (persons aged 2–59 months: cough or difficulty breathing with an elevated respiratory rate or a danger sign; persons aged ⩾5 years: temperature ⩾38 °C, difficulty breathing, and cough or sore throat) and influenza-like illness (ILI) (all ages: temperature ⩾38 °C and cough or sore throat). Overall, 4800 persons aged ⩾2 months were tested for influenza; 416 (9%) had laboratory-confirmed influenza infections. The symptom combination of cough with fever (subjective or measured ⩾38 °C) had high sensitivity [87·0%, 95% confidence interval (CI) 83·3–88·9], and ILI had high specificity (70·0%, 95% CI 68·6–71·3). The case definition combining cough and any fever is a simple, sensitive case definition for influenza in hospitalized persons of all age groups, whereas the ILI case definition is the most specific. The SARI case definition did not maximize sensitivity or specificity.

The use of chemotherapy on a mass scale in endemic areas may lead to the appearance of resistant isolates through the mechanism of selective drug pressure. Studies have demonstrated that praziquantel (PZQ) is able to inhibit the excretory activity and to cause tegumental damage in Schistosoma mansoni adult worms. The use of the probe resorufin to evaluate excretory activity, as well as the probe Hoechst 33258 to detect tegumental damage in adult worms, may represent a method to identify resistant (or less susceptible) isolates. The purpose of the present work was to compare the changes caused by PZQ in the function of the excretory system and in the integrity of the tegument of adult worms from the LE isolate (susceptible to PZQ) and the LE-PZQ isolate (less susceptible to PZQ). Worms from the isolate LE-PZQ showed less severe tegumental lesions, in both in vitro and in vivo experiments, detected by labelling with Hoechst 33258 and continued to have a functional excretory system as shown by labelling with resorufin in vitro.

Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 μg retinol equivalents of preformed vitamin A or 42 mg of β-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006–2008, we revisited and assessed 13,118 children aged 9–13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or β-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal.

Approximately 12%–27% of cerebrovascular disease in women of childbearing age is associated with pregnancy. The reported incidence of stroke in pregnancy ranges from 0.01%–0.05%. While these events are uncommon, they are often clinically devastating. The Center for Disease Control's (CDC) review of death certificates in all 50 states and the District of Columbia found that neurologic or neurovascular problems are one of the leading causes of mortality in pregnancy.

We have chosen the name of GYES, one of the mythological giants with one hundred arms,offspring of Gaia and Uranus, for our instrument study of a multifibre spectrograph forthe prime focus of the Canada-France-Hawaii Telescope. Such an instrument could provide anexcellent ground-based complement for the Gaia mission and a northern complement to theHERMES project on the AAT. The CFHT is well known for providing a stable prime focusenvironment, with a large field of view, which has hosted several imaging instruments, buthas never hosted a multifibre spectrograph. Building upon the experience gained at GÉPIwith FLAMES-Giraffe and X-Shooter, we are investigating the feasibility of a highmultiplex spectrograph (about 500 fibres) over a field of view one degree in diameter. Weare investigating an instrument with resolution in the range 15 000 to 30 000, whichshould provide accurate chemical abundances for stars down to 16th magnitude and radialvelocities, accurate to 1 km s-1 for fainter stars. The study is led byGÉPI-Observatoire de Paris with a contribution from Oxford for the study of thepositioner. The financing for the study comes from INSU CSAA and Observatoire de Paris.The conceptual study will be delivered to CFHT for review by October 1st 2010.

During the five years of the mission, the Gaia spectrograph, the Radial VelocitySpectrometer (RVS) will repeatedly survey the celestial sphere down to magnitudeV ~ 17–18. This talk presents: (i) the system which is currently developed withinthe Gaia Data Processing and Analysis Consortium (DPAC) to reduce and calibrate thespectra and to derive the radial and rotational velocities, (ii) the RVS expectedperformances and (iii) scientific returns.

Gaia is an ambitious space astrometry mission of ESA with a main objective to map the sky in astrometry and photometry down to a magnitude 20 by the end of the next decade. While the mission is built and operated by ESA and an industrial consortium, the data processing is entrusted to a consortium formed by the scientific community, which was formed in 2006 and formally selected by ESA one year later. The satellite will downlink around 100 TB of raw telemetry data over a mission duration of 5 years from which a very complex iterative processing will lead to the final science output: astrometry with a final accuracy of a few tens of microarcseconds, epoch photometry in wide and narrow bands, radial velocity and spectra for the stars brighter than 17 mag. We discuss the general principles and main difficulties of this very large data processing and present the organization of the European Consortium responsible for its design and implementation.