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.

The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.

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.

Posttraumtic stress disorder (PTSD) is an anxiety disorder caused by traumatic experience, exhibiting three major clinical symptoms: re-experience, avoidance and numbing, and hyperarousal (APA,DSM-IV, 1994). It is thought to involve a dysregulation of medial prefrontal cortex (mPFC) activity in response to fear. The mPFC plays an important role in regulating the stress response (RJ. Ursano et al, Textbook of Disaster Psychiatry). Studies have reported that the calcium signal in the brain cell of PTSD rats is disordered (BING XIAO et al, 2009). Calreticulin, helping to deal with misfolded proteins during the endoplasmic reticulum stress (ERS) response as molecular chaperone, is a calcium binding protein.In this study,detection of the expression level of calreticulin in mPFC of rats with PTSD provides experimental evidence reveled part pathogenesis of PTSD and Single prolonged stress (SPS) method as an established animal model for PTSD was used. A total of 75 male Wistar rats were divided randomly into five groups: SPS1d,SPS4d,SPS7d,SPS14d, and the control group. The calreticulin expression in mPFC was examined using immunohistochemistry, western boltting and reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry showed calreticulin widely distributed throughout the mPFC, mainly in the cytoplasm, appeared as buffy particle. Protein level of calreticulin of SPS group gradually increased and peaked at SPS 7d. The mRNA expression of calreticulin was upward trend and peaked at SPS4d. ERS induced by SPS stimulation made misfolded protein accumulation increase, which made calreticulin separate from calcium and increase to deal with misfolded protein. Then intracellular free calcium r increased, which exacerbated ERS and induced cell apoptosis. Expression change of calreticulin caused cell apoptosis, which may be closely related to changes of emotion,cognition of PTSD rats.

Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5–98) ml at 18 months of age and 111 (interquartile range 57–198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.

The mechanical properties of thin-walled plate with close-packed film cooling holes are studied based on the equivalent solid material concept. The equivalent principals of the method of equivalent strain energy, homogenization theory and uniform static deformation are considered. A simplification method of square penetration pattern for pitch and diagonal direction loading is presented. The goodness of fit is calculated to determine the optimal method. The tensile deformation, bending deflection, rotation displacement and maximum Mises equivalent stress of simplification plate models are in good agreement with plate models with close-packed film cooling holes. For square penetration pattern for pitch direction loading, the equivalent errors of Mises equivalent stress are all less than 10% when the ligament efficiency is more than 0.6.

Superior and inferior rice grains have different weights and are located on the upper primary branch and lower secondary branches of the panicle, respectively. To study differences in germination vigour of these two types of grain, a number of factors were investigated from 0 to 48 h of germination. The present study demonstrated that in inferior grains the starch granule structure was looser at 0 h, with full water absorption at 48 h, while in superior grains the structure was tight and dense. Relative water content increased, and dry matter decreased, more rapidly in inferior grains than in superior ones. Abscisic acid and gibberellin levels, as well as α-amylase activity, also changed more rapidly in inferior grains, while soluble sugar content and amylase coding gene expression increased more rapidly in inferior than superior grains during early germination. The expression of OsGAMYB was higher in inferior grains at 24 h but higher in superior grains at 48 h. The phenotypic index of seedlings was higher in seedlings from superior grains at the two-leaf stage. However, the thousand-grain weight and yield per plant in superior and inferior plants showed no significant difference at harvest. The present study indicates that inferior grains germinate faster than superior ones in the early germination stage. Although inferior grains produced weaker seedlings, it is worthwhile using them in rice production due to their comparative yield potential over that of superior grains.

In this study, the biomass of winter wheat was estimated by using hyperspectral data obtained from a hyperspectral camera on an Unmanned Aerial Vehicle (UAV). Every two bands from the hyperspectral data were selected to calculate two kinds of vegetation indexes: the Normalized Difference Vegetation Index (NDVI) and Ratio Vegetation Index (RVI). Linear models were established between winter wheat biomass and those indexes, and coefficient of determination R2 was used to draw the two-dimensional distribution of R2 values. The comparison between NDVI and RVI for pixel covered by soil and wheat showed that RVI is more efficient to mask the influence from soil than NDVI. For calculating the NDVI, optimal bands are located mainly around 820 nm and 725 nm to 750 nm. For assessing RVI, the wavelength range from 820 to 832 nm, 794 to 808 nm, 770 to 788 nm, 725 nm to 750 nm and 890 nm for RVI are most suitable. Those optimal bands can achieve a coefficient of determination R2 higher than 0.88 by using the linear regression model in the study.

Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.

To understand the clinical epidemiology and molecular characteristics of human bocavirus (HBoV) infection in children with diarrhoea in Guangzhou, South China, we collected 1128 faecal specimens from children with diarrhoea from July 2010 to December 2012. HBoV and five other major enteric viruses were examined using real-time polymerase chain reaction. Human rotavirus (HRV) was the most prevalent pathogen, detected in 250 (22·2%) cases, followed by enteric adenovirus (EADV) in 76 (6·7%) cases, human astrovirus (HAstV) in 38 (3·4%) cases, HBoV in 17 (1·5%) cases, sapovirus (SaV) in 14 (1·2%) cases, and norovirus (NoV) in 9 (0·8%) cases. Co-infections were identified in 3·7% of the study population and 23·5% of HBoV-positive specimens. Phylogenetic analysis revealed 14 HBoV strains to be clustered into species HBoV1 with only minor variations among them. Overall, the detection of HBoV appears to partially contribute to the overall detection gap for enteric infections, single HBoV infection rarely results in severe clinical outcomes, and HBoV sequencing data appears to support conserved genomes across strains identified in this study.

A numerical study is undertaken to simulate failure of solder joint caused by cyclic shear deformation. A progressive ductile damage model is incorporated into the rate-dependent elastic-viscoplastic finite element analysis, resulting in the capability of simulating damage evolution and eventual failure through crack formation. It is demonstrated that quantitative information of fatigue life, as well as the temporal and spatial evolution of fatigue cracks, can be explicitly obtained.

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

Three ELISA assays, based on hyperimmune rabbit serum raised against adult cestode somatic antigen, were applied in this study for the detection of Taenia- and Echinococcus-specific antigens in host faeces. The first assay, using an antiserum against Taenia pisiformis antigen extract, was used in a time-course of T. pisiformis experimental infection in dogs. The assay was shown to be considerably more sensitive than microscopical detection of eggs in faeces. Antigen was present in faeces before patency and antigen levels were independent of T. pisiformis egg output. The second assay, involving a test for human taeniasis based on antibodies against T. solium, was applied in two field studies carried out in China and Guatemala. The test was highly specific, no false positive reactions occurred with human faecal samples and the test was capable of diagnosing individuals who would not have been detected by coproscopy or treatment to recover the tapeworm. A third assay was designed for E. granulosus and demonstrated 87·5% sensitivity and 96·5% specificity with samples from naturally and experimentally infected dogs with Echinococcus or Taenia infections. In both the human Taenia and canine Echinococcus studies antigen could be detected in faecal samples from infected hosts stored in 5% formalin for 6 months. Further refinements to these tests for field application are discussed.

The microstructure, hardness, elastic modulus, and indentation creep of Ag/Cu multilayers prepared by magnetron sputtering were investigated by x-ray diffraction, transmission electron microscopy, and nanoindentation. The hardness values obey the Hall–Petch relationship as the periodicity decreases to 20 nm. For multilayers with periodicity smaller than 20 nm, the Hall–Petch relationship breaks down and the hardness values saturate at about 4.6 GPa; moreover, there are shear bands formed around their indents and strain bursts occurring during the load-holding process of indentation creep. These results imply that there is a transition of the deformation mechanism in the region where the periodicity is equal to 20 nm. This transition of the deformation mechanism can be ascribed to grain-size-dependent competition between the dislocations-mediated plasticity and grain-boundary sliding-mediated plasticity.

Extended abstract of a paper presented at Microscopy and Microanalysis 2005 in Honolulu, Hawaii, USA, July 31--August 4, 2005

Conventionally, the wetting of metallic substrates by liquid metals involves undermining of the substrate–oxide layer by the liquid. Evidence is presented here for an alternative wetting process involving spreading of liquid copper along the exterior of the oxide layer on Ti–48 at.% Al–2 at.% Cr–2 at.% Nb substrates. A mechanism is presented that involves compositional changes in the liquid, which in turn allow a wetting-promoting reaction between the (initially unreactive) liquid and the exterior layer of the substrate oxide.

A (110)-oriented diamond film was deposited by hot filament chemical vapor deposition with H2 and CH4 separately introduced into the reactive zone. The film with a degree of orientation I(220)/I(111) of more than 200% and deposition rate of 2–3 μm/h was obtained for a deposition time of 17 h. The long deposition time enlarged the grain size and enhanced the degree of orientation, but too long a deposition time resulted in random growth. The temperature field was measured and also calculated using a simple model. Both results showed that a temperature field existed with varied gradients along the normal of substrate surface. The (110)-oriented diamond film was deposited in the zone with negative temperature gradient. The change in orientation occurring for long deposition times was ascribed to the change of temperature gradient.

The distribution of glycine-immunoreactive (glycine-IR) neurons and their associated axon terminals in the rat cuneate nucleus was studied using antiglycine postembedding immunoperoxidase labelling and immunogold staining, respectively. The immunoperoxidase-labelled glycine-IR neurons were widely distributed in the entire rostrocaudal extent of the nucleus. They made up 30.8% (9671/31368) of the neurons surveyed. Quantitative evaluation showed that the percentage of glycine-IR neurons in the caudal level was significantly higher than that in the middle and rostral levels. The glycine-IR neurons were small cells (mean area=198±1.9 μm2, n=2862) with ovoid or spindle-shaped somata. Statistical analysis showed that the size of the glycine-IR neurons in the rostral level was significantly smaller than that in the middle and caudal levels. Immunogold labelled glycine-IR terminals which contained predominantly pleomorphic synaptic vesicles were mostly small (mean area=1.24±0.03 μm2, n=286) and they constituted 24.7% (286/1158) of the total terminals surveyed. They formed axodendritic, axosomatic and axoaxonic synapses with unlabelled elements. It is suggested from this study that glycine is one of the major neurotransmitters involved in the depression of synaptic transmission in the cuneate nucleus.