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.

Meat quality is not only influenced by breed but also rearing environment. The aim of this study was to evaluate the influence of different housing environments on growth performance, carcase traits, meat quality, physiological response pre-slaughter and fatty acid composition in two pig breeds. A total of 120 growing pigs at 60-70 days of age were arranged in a 2 × 2 factorial design with the breeds (Duroc × Landrace × Large White [D × L × LW] and Duroc × Landrace × Min pig [D × L × M]) and environmental enrichment (barren concrete floor or enriched with straw bedding) as factors. Each treatment was performed in triplicate with ten pigs per replicate. The pigs housed in the enriched environment exhibited a higher average daily gain, average daily feed intake, saturated fatty acid percentage and backfat depth than the pigs reared in the barren environment. Plasma cortisol levels were lower and growth hormone higher in enriched compared to barren pens. The D × L × M pigs showed lower cooking loss compared with the D × L × LW pigs. Moreover, the D × L × M pigs exhibited poor growth performance but had a better water-holding capacity. Only carcase traits and meat quality interaction effects were observed. We concluded that an enriched environment can reduce preslaughter stress and improve the growth performance of pigs and modulate the fatty acid composition of pork products.

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.

We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (${\sim}60\%$), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.

Four complete platysiagid fish specimens are described from the Luoping Biota, Anisian (Middle Triassic), Yunnan Province, southwest China. They are small fishes with bones and scales covered with ganoine. All characters observed, such as nasals meeting in the midline, a keystone-like dermosphenotic, absence of post-rostral bone, two infraorbitals between dermosphenotic and jugal, large antorbital, and two postcleithra, suggest that the new materials belong to a single, new Platysiagum species, P. sinensis sp. nov. Three genera are ascribed to Platysiagidae: Platysiagum, Helmolepis and Caelatichthys. However, most specimens of the first two genera are imprints or fragmentary. The new, well-preserved specimens from the Luoping Biota provide more detailed anatomical information than before, and thus help amend the concept of the Platysiagidae. The Family Platysiagidae was previously classed in the Perleidiformes. Phylogenetic analysis indicates that the Platysiagidae is a member of basal Neopterygii, and its origin seems to predate that of Perleidiformes. Moreover, platysiagid fishes are known from the Middle Triassic of the western Tethys region. The newly found specimens of platysiagids from Luoping provide additional evidence that both eastern and western sides of the Tethys Ocean were biogeographically more connected than previously thought.

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.

Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (<3, 3–6, >6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future.

Co-infections of cystic echinococcosis (CE) and HIV/AIDS is rare. We report four CE cases that were HIV positive. Three out of the four patients underwent a surgical operation to remove the hydatid cysts in their livers. The operation confirmed that in two of the cases their cysts had ruptured. These patients were given 3 months of albendazole after the operation. Follow-up showed they were remarkably improved in term of their health, although they were still HIV antibody positive 6 months after surgical treatment. Interestingly, the treatment remarkably increased their CD4+ cell population. We showed that surgery is suitable for treating hepatic cystic echinococcosis with HIV/AIDS co-infection.

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.

MicroRNAs are endogenous ~22nt RNAs that negatively regulate gene expression at the posttranscriptional level via binding to the 3′-untranslated region (3′UTR) of target mRNAs. The microRNA miR-27a was reported to depress the expression of myostatin, a critical inhibitor of skeletal myogenesis, by binding to its 3′UTR in mouse. In this study, we cloned the full-length 3′UTR of porcine myostatin by rapid amplification of 3′-cDNA ends (3′-RACE) and demonstrated that the 3′UTR of porcine myostatin is targeted by miR-27a. The phenomenon that the level of myostatin inversely correlated with miR-27a was observed in fat and heart of pigs and also in proliferating porcine myoblasts. Besides, overexpression of miR-27a in porcine myoblasts promoted cell proliferation by reducing the expression of myostatin. Our data suggest that miR-27a positive regulates porcine myoblast proliferation via targeting myostatin.

A ‘pulsar timing array’ (PTA), in which observations of a large sample of pulsars spread across the celestial sphere are combined, allows investigation of ‘global’ phenomena such as a background of gravitational waves or instabilities in atomic timescales that produce correlated timing residuals in the pulsars of the array. The Parkes Pulsar Timing Array (PPTA) is an implementation of the PTA concept based on observations with the Parkes 64-m radio telescope. A sample of 20 ms pulsars is being observed at three radio-frequency bands, 50 cm (~700 MHz), 20 cm (~1400 MHz), and 10 cm (~3100 MHz), with observations at intervals of two to three weeks. Regular observations commenced in early 2005. This paper describes the systems used for the PPTA observations and data processing, including calibration and timing analysis. The strategy behind the choice of pulsars, observing parameters, and analysis methods is discussed. Results are presented for PPTA data in the three bands taken between 2005 March and 2011 March. For 10 of the 20 pulsars, rms timing residuals are less than 1 μs for the best band after fitting for pulse frequency and its first time derivative. Significant ‘red’ timing noise is detected in about half of the sample. We discuss the implications of these results on future projects including the International Pulsar Timing Array and a PTA based on the Square Kilometre Array. We also present an ‘extended PPTA’ data set that combines PPTA data with earlier Parkes timing data for these pulsars.

We are developing a purely commensal survey experiment for fast (<5 s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.

Heterosis breeding is a potential tool for developing coloured cotton hybrids, having good fibre yield and quality. The objective of the present study was to explore the extent of heterosis breeding for the modulation of fibre quality and biochemical traits during fibre development. The performance of 10 interspecific (Gossypium hirsutum L.×Gossypium barbadense L.) and four intraspecific (Gossypium hirsutum L.×Gossypium hirsutum L.) F1 coloured cotton hybrids and their parents was assessed under field conditions in 2008/9. Two interspecific, two intraspecific F1 coloured cotton hybrids and their parents were used to examine the role and changes in the amount of different biochemicals during the different stages of fibre development (2009). Among hybrids, interspecific brown cotton hybrids (ZUC × ZUA) and interspecific green cotton hybrids (ZUF × ZUA) showed high amounts of useful heterosis for yield, yield components and fibre quality attributes. Analysis of various biochemicals depicted a decline in fibre pH value and flavonoid contents among all hybrids and their parents, with maximum decrease in interspecific hybrids (ZUC × ZUA and ZUF × ZUA) at 15 days post anthesis (DPA). Similarly, a significant increase in the amount of cellulose, glucose and fructose was observed in all genotypes. However, the magnitude of increase was greatest in interspecific coloured cotton hybrids as compared to their parents and intraspecific hybrids. The negative correlation of fibre pH with flavonoid contents and the positive correlation of carbohydrates with cellulose contents (particularly at 15 DPA) suggested the significance of these biochemicals controlling fibre quality. In conclusion, heterosis breeding can be efficiently utilized to develop high-quality coloured cotton hybrids by modulating the synthesis of different biochemicals associated with fibre development and its quality.