A shared accretion instability for black holes and neutron stars.

Accretion disks around compact objects are expected to enter an unstable phase at high luminosity1. One instability may occur when the radiation pressure generated by accretion modifies the disk viscosity, resulting in the cyclic depletion and refilling of the inner disk on short timescales2. Such a scenario, however, has only been quantitatively verified for a single stellar-mass black hole3-5. Although there are hints of these cycles in a few isolated cases6-10, their apparent absence in the variable emission of most bright accreting neutron stars and black holes has been a continuing puzzle11. Here we report the presence of the same multiwavelength instability around an accreting neutron star. Moreover, we show that the variability across the electromagnetic spectrum-from radio to X-ray-of both black holes and neutron stars at high accretion rates can be explained consistently if the accretion disks are unstable, producing relativistic ejections during transitions that deplete or refill the inner disk. Such a new association allows us to identify the main physical components responsible for the fast multiwavelength variability of highly accreting compact objects.

A persistent ultraviolet outflow from an accreting neutron star binary transient.

All disc-accreting astrophysical objects produce powerful disc winds. In compact binaries containing neutron stars or black holes, accretion often takes place during violent outbursts. The main disc wind signatures during these eruptions are blue-shifted X-ray absorption lines, which are preferentially seen in disc-dominated 'soft states'1,2. By contrast, optical wind-formed lines have recently been detected in 'hard states', when a hot corona dominates the luminosity3. The relationship between these signatures is unknown, and no erupting system has as yet revealed wind-formed lines between the X-ray and optical bands, despite the many strong resonance transitions in this ultraviolet (UV) region4. Here we report that the transient neutron star binary Swift J1858.6-0814 exhibits wind-formed, blue-shifted absorption lines associated with C IV, N V and He II in time-resolved UV spectroscopy during a luminous hard state, which we interpret as a warm, moderately ionized outflow component in this state. Simultaneously observed optical lines also display transient blue-shifted absorption. Decomposing the UV data into constant and variable components, the blue-shifted absorption is associated with the former. This implies that the outflow is not associated with the luminous flares in the data. The joint presence of UV and optical wind features reveals a multi-phase and/or spatially stratified evaporative outflow from the outer disc5. This type of persistent mass loss across all accretion states has been predicted by radiation-hydrodynamic simulations6 and helps to explain the shorter-than-expected duration of outbursts7.

CD19 occupancy with tafasitamab increases therapeutic index of CART19 cell therapy and diminishes severity of CRS.

ABSTRACT: In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.

Yak miR-2285o-3p attenuates hypoxia-induced apoptosis by targeting caspase-3.

miRNAs are a class of hairpin-derived RNAs, 21-24 nucleotides in length, which are involved in a range of biological processes. The bta-miR-2285 family has over 40 members spanning the entire bovine genome. We previously found that bta-miR-2285o-3p was highly expressed in yak heart and lung when compared with cattle, which prompted us to investigate its potential function in high-altitude adaptation of yaks. In this study, we detected wide-spread high expression of bta-miR-2285o-3p in yak tissues. Further experiments revealed that the protein tyrosine phosphatase receptor type M (PTPRM) gene was the host gene of bta-miR-2285o-3p and that two linked SNPs in bta-mir-2285o precursor affected the biogenesis of mature miRNA (bta-miR-2285o-3p). Functional analysis in vitro indicated that bta-miR-2285o-3p attenuated hypoxia-induced apoptosis by targeting very low-density lipoprotein receptor (VLDLR), phosphatase and tensin homolog (PTEN) and caspase-3. Expression level analysis in vivo revealed the high negative Pearson's correlation between bta-miR-2285o-3p and caspase3 in yak, highlighting the potential important roles of bta-miR-2285o-3p in yak high-altitude adaptation. Our study provides a typical model for deciphering the function of miRNAs in environmental adaptation.

[Efficacy and safety of percutaneous transluminal pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension].

Objective: To explore the efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: This prospective single arm study included 19 CTEPH patients (7 male, age(56.3±12.5)years) admitted to Wuhan Asia Heart Hospital from January 2017 to June 2019 and received PTPA interventional therapy. Baseline data, including age, sex, WHO functional class, 6-minute walk distance (6MWD), NT-proBNP, right heart catheterization values, were collected. Patients received single or repeated PTPA. Number of dilated vessels from each patient was analyzed, patients were followed up for 24 weeks and right heart catheterization was repeated at 24 weeks post initial PTPA. All-cause death, perioperative complications, and reperfusion pulmonary edema were reported. WHO functional class, 6MWD, NT-proBNP, right heart catheterization values were compared between baseline and at 24 weeks follow up. Results: Nineteen CTEPH patients received a total of 56 PTPA treatments. The pulmonary artery pressure (mPAP) decreased from (40.11±7.55) mmHg (1 mmHg=0.133 kPa) to (27.53±4.75) mmHg (P<0.001), and the total pulmonary resistance (TPR) decreased from (13.00±3.56) Wood U to (5.48±1.56) Wood U (P<0.001), cardiac output increased from (3.19±0.63) L/min to (5.23±0.94) L/minutes (P<0.01) at 24 weeks post PTPA. The WHO functional class improved significantly (P<0.001), 6MWD increased from (307.08±129.51) m to (428.00±112.64) m (P=0.002), the NT-proBNP decreased at 24 weeks post PTPA (P=0.002). During the follow-up period, there was no death; hemoptysis occurred in 4 patients during the operation, none of which resulted in serious adverse clinical consequences. One patient developed reperfusion pulmonary edema and recovered after treatment. Conclusion: PTPA treatment is safe and can significantly improve the hemodynamics and WHO functional class of patients with CTEPH.

Secondhand smoke in public places in Vietnam: An assessment 5 years after implementation of the tobacco control law.

OBJECTIVES: This study quantified the secondhand smoke (SHS) concentration in a sample of public places in Vietnam to determine changes in SHS levels 5 years after a public smoking ban was implemented. METHODS: Two monitoring campaigns, one in 2013 (before the tobacco control law was implemented) and another in 2018 (5 years after the implementation of the law) were conducted in around 30 restaurants, cafeterias and coffee shops in major cities of Vietnam. Concentrations of PM2.5, as an indicator of SHS, were measured by portable particulate matter monitors (TSI SidePak AM510 and Air Visual Pro). RESULTS: The geometric mean PM2.5 concentration of all monitored venues was 87.7 µg/m3 (83.7-91.9) in the first campaign and 55.2 µg/m3 (53.7-56.7) in the second campaign. Pairwise comparison showed the PM2.5 concentrations in the smoking observed area was triple and double those in the non-smoking area and the outdoor environment. After adjusting for sampling locations and times, the SHS concentration 5 years after the implementation of the tobacco control law reduced roughly 45%. CONCLUSION: The study results indicate an improvement in air quality in public places in Vietnam via both the reduction in PM2.5 levels and the number of people observed smoking. However, greater enforcement of the free-smoke legislation is needed to eliminate SHS in public places in Vietnam.

Health-related quality of life, service utilization and costs of low language: A systematic review.

BACKGROUND: Low language (LL) is a common childhood condition affecting 7-17% of children. It is associated with life-long adverse outcomes and can affect various aspects of a child's life. However, the literature on its impact on health-related quality of life (HRQoL), service use and costs are limited. To date, there has been no systematic review of the overall economic burden of LL. A systematic review regarding the economic burden of LL is important for clinical, educational, policy decision-making and theoretical aspects. We adopted the term 'low language' to refer to children whose language performance falls below well-recognized cut-points regardless of known or unknown aetiology. AIMS: To review the literature systematically on how LL is associated with HRQoL, service utilization and costs. METHODS & PROCEDURES: A systematic search was conducted across various databases, including MEDLINE, Embase, PsycINFO, CINAHL, up to July 2017. Data on study design, population and outcomes were extracted and screened by two pairs of reviewers with the revision of other experts in the panel on any discrepancies. The Effective Public Health Practice Project tool was used to assess the risk of bias of the included studies. The findings of the included studies were summarized in a narrative synthesis. OUTCOMES & RESULTS: We identified 22 relevant articles, of which 12 reported HRQoL and 11 reported service utilization and costs associated with LL. Preference-based instruments, which include the relative importance attached to different aspects of HRQoL, were less employed in the literature. Most studies found poorer HRQoL in children with LL compared with their peers. About half the families having children with LL did not actively seek professional help, and many families felt they did not receive sufficient services when needed. Healthcare costs associated with LL were substantial. Non-healthcare costs were largely unexplored. CONCLUSIONS & IMPLICATIONS: LL was associated with reduced children's HRQoL, higher service use and costs. Under-servicing was evident in children with LL. LL also imposed large costs on the healthcare system. Further research is required to examine (1) the overall HRQoL of children with LL, in particular studies using and testing the performance of preference-based instruments; and (2) the service use and costs specific to LL, especially non-healthcare costs.

Monitoring the levels of brominated and organophosphate flame retardants in passenger cars: Utilisation of car air filters as active samplers.

Filters in residential and office air conditioning (A/C) systems have been used as sampling devices for monitoring different pollutants. However, cabin air filters (CAFs) in the A/C system of passenger cars have not been utilised for this purpose. In this study, we collected 22 used CAFs from passenger cars in Hanoi, Vietnam to analyse for 8 polybrominated diphenyl ethers (PBDEs) and 10 organophosphate esters (OPEs). All the analytes were detected in more than 50% of samples with the exception of BDE153 and BDE154. The average concentrations of ∑10OPEs and ∑8BDEs in the captured dust were 2600 and 40 ng/g, respectively with Tris (1-chloro-2-propyl) phosphate (TCIPP) and BDE209 as the dominant congener in OPE and BDE groups, respectively. CAFs are a potential tool to qualitatively assess the levels of semi-volatile chemicals in suspended dust in cars as a screening step for exposure assessment of those chemicals.

Environmental seasonality on predator-prey systems under nutrient and toxicant constraints.

Bioaccumulation of toxicants in aquatic food webs can pose risks to ecosystem function and human health. Toxicant models of aquatic ecosystems can be improved by incorporating realistic environmental impacts such as nutrient availability and seasonality. It is well known that the carrying capacity of predator-prey systems can vary seasonally due to environmental cycles resulting from natural and human activities. As such, incorporating seasonal variation in the carrying capacity of a predator-prey system provides a better understanding of the underlying population dynamics bioaccumulation of toxicants. Here, we develop a seasonally varied predator-prey model subject to concurrent nutrient and toxicant stressors. We investigate the effects of seasonality on population dynamics to increase understanding of the complex governing processes of the trophic transfer of nutrients, energy, and toxicants. We observe that the strength of seasonality can shift solutions from periodic to quasi-periodic and models that neglect environmental seasonality may be under-predicting adverse effects of toxicity.

Including internal mammary lymph nodes in radiation therapy for synchronous bilateral breast cancer: an international survey of treatment technique and clinical priorities.

PURPOSE: The aim of this study was to understand the international standard practice for radiation therapy treatment techniques and clinical priorities for institutions including the internal mammary lymph nodes (IMLNs) in the target volume for patients with synchronous bilateral breast cancer. METHODS: An international survey was developed to include questions that would provide awareness of favored treatment techniques, treatment planning and delivery resource requirements, and the clinical priorities that may lead to the utilization of preferred treatment techniques. RESULTS: Of the 135 respondents, 82 indicated that IMLNs are regularly included in the target volume for radiation therapy (IMLN-inclusion) when the patient is otherwise generally indicated for regional nodal irradiation. Of the 82 respondents that regularly include IMLNs, five were removed as those respondents do not treat this population synchronously. Of the 77 respondents, institutional standard of care varied significantly, though VMAT (34%) and combined static photon and electron fields (21%) were the most commonly utilized techniques. Respondents did preferentially select target volume coverage (70%) as the most important clinical priority, followed by normal tissue sparing (25%). CONCLUSION: The results of the survey indicate that the IMLN-inclusion for radiation therapy has not yet been comprehensively adopted. As well, no consensus on best practice for radiation therapy treatment techniques has been reached.

Experimental and DFT Studies of the Electron-Withdrawing Ability of Perfluoroalkyl (RF ) Groups: Electron Affinities of PAH(RF )n Increase Significantly with Increasing RF Chain Length.

Two series of aromatic compounds with perfluoroalkyl (RF ) groups of increasing length, 1,3,5,7-naphthalene(RF )4 and 1,3,5,7,9-corannulene(RF )5 , have been prepared and their electronic properties studied by low-temperature photoelectron spectroscopy (PES) (for gas-phase electron affinity measurements). These and many related compounds were also studied by DFT calculations. The data demonstrate unambiguously that the electron-withdrawing ability of RF substituents increases significantly and uniformly from CF3 to C2 F5 to n-C3 F7 to n-C4 F9 .

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

OBJECTIVE: To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. METHODS: Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. RESULTS: Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. CONCLUSION: This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children.

Association between serum vitamin D, retinol and zinc status, and acute respiratory infections in underweight and normal-weight children aged 6-24 months living in an urban slum in Bangladesh.

We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6-24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23-25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4-2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0-1·5) times higher risk of URI and 1·9 (95% CI 1·4-2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.

Corannulene Molecular Rotor with Flexible Perfluorobenzyl Blades: Synthesis, Structure and Properties.

Two members of a new class of organic-acceptor perfluorobenzyl corannulenes were prepared by gas-phase and highly-selective solution-phase reactions at elevated temperatures. The peculiar single-crystal X-ray structure of C5-C20H5(CF2C6F5)5 revealed two high-energy conformers with drastically different bowl depths and orientations of perfluorobenzyl blades; the conformers are alternating in columnar packing arrangements and every pair is sandwiched by toluene molecules.

Longitudinal trajectories of post-traumatic stress disorder symptoms among adolescents after the Wenchuan earthquake in China.

BACKGROUND: This study examines the patterns and predictors of post-traumatic stress disorder (PTSD) symptom trajectories among adolescent survivors following the Wenchuan earthquake in China. METHOD: A total of 1573 adolescent survivors were followed up at 6, 12, 18 and 24 months post-earthquake. Participants completed the Posttraumatic Stress Disorder Self-Rating Scale (PTSD-SS), Adolescent Self-Rating Life Events Checklist, Social Support Rate Scale, and the Simplified Coping Style Questionnaire. Distinct patterns of PTSD symptom trajectories were established through grouping participants based on time-varying changes of developing PTSD (i.e. reaching the clinical cut-off on the PTSD-SS). Multivariate logistic regressions were used to examine predictors for trajectory membership. RESULTS: PTSD prevalence rates at 6, 12, 18 and 24 months were 21.0, 23.3, 13.5 and 14.7%, respectively. Five PTSD symptom trajectories were observed: resistance (65.3% of the sample), recovery (20.0%), relapsing/remitting (3.3%), delayed dysfunction (4.2%) and chronic dysfunction (7.2%). Female gender and senior grade were related to higher risk of developing PTSD symptoms in at least one time point, whereas being an only child increased the possibility of recovery relative to chronic dysfunction. Family members' injury/loss and witness of traumatic scenes could also cause PTSD chronicity. More negative life events, less social support, more negative coping and less positive coping were also common predictors for not developing resistance or recovery. CONCLUSIONS: Adolescents' PTSD symptoms showed an anniversary reaction. Although many adolescents remain euthymic or recover over time, some adolescents, especially those with the risk factors noted above, exhibit chronic, delayed or relapsing symptoms. Thus, the need for individualized intervention with these adolescents is indicated.

Hypoxia-related gene expression in porcine skeletal muscle tissues at different altitude.

Hypoxia influences many physiological processes, such as respiration, cardiovascular, neurophysiology, and digestion. Skeletal muscle is an important motor organ, which relies on oxygen of oxidation; however, the study of hypoxia in skeletal muscle is lacking. In order to understand the effect of hypoxia on skeletal muscle, we determined the expression level of four hypoxia-related genes (ADAM17, ARG2, MMP, and HIF1A) in two distinct skeletal muscle tissues from Tibetan pigs that live at different altitudes (500 and 3650 m). Consistent with the well-characterized role of four hypoxia-related genes in the adaptation to high altitude, we found that, compared with the plain pigs, the plateau pigs had higher mRNA abundances of the four genes and lower myofiber ratio in skeletal muscle. The negative correlation between the myofiber ratio and mRNA abundance of the four hypoxia-related genes highlights their critical roles in skeletal muscle. These findings may be important for understanding skeletal muscle adaptation to high altitude and hypoxia-related muscle diseases in humans.

Effectiveness of microsatellite and single nucleotide polymorphism markers for parentage analysis in European domestic pigs.

Parentage analysis and individual identification are recent, promising methods that have been applied to evolutionary and ecological studies, as well as conservation management. Parental exclusion relying on polymorphic microsatellites has been used worldwide in parentage determination, while the low mutation rate and genotyping error rate of single nucleotide polymorphisms (SNPs) make them another important marker for pedigree tracing. Here, we compared the effectiveness of microsatellites and SNP markers in European pigs. We also measured and presented the minimum and optimal criteria for SNP markers to be used in paternity and identity analysis. Our findings may contribute to the development of techniques for future molecular evolution and conservation studies, as well as breeding programs.

Identification of conserved microRNAs in peripheral blood from giant panda: expression of mammary gland-related microRNAs during late pregnancy and early lactation.

The giant panda (Ailuropoda melanoleuca) is one of the world's most endangered mammals, and it has evolved several unusual biological and behavioral traits. During puberty, pregnancy, lactation, and involution, the mammary gland undergoes profound morphological and functional changes. A large number of microRNAs (miRNAs) have been identified to be involved in mammary gland development and lactation. In this study, we identified 202 conserved mature miRNAs, corresponding to 147 pre-miRNAs, in giant panda peripheral blood using a small RNA-sequencing approach. In addition, 27 miRNA families and 29 miRNA clusters were identified. We analyzed the arm selection preference of pre-miRNAs and found that: 1) most giant panda pre-miRNAs generated one-strand miRNAs, and the 5p-arm only miRNAs have a higher expression level than 3p-arm only miRNAs; 2) there were more 5p-arm dominant miRNAs than 3p-arm dominant miRNAs; and 3) 5p-arm dominant miRNAs have a larger fold change within miRNA pairs than 3p-arm dominant miRNAs. Expression of 12 lactation-related miRNAs was detected across late pregnancy and early lactation stages by qPCR, and seven miRNAs were identified as clustered in one significant model. Most of these clustered miRNAs exhibited inhibitory roles in proliferation and differentiation of mammary epithelial cells. Functional analysis highlighted important roles of the seven as signed miRNAs in mammary development and metabolic changes, including blood vessel morphogenesis, macromolecule biosynthesis, cell cycle regulation, and protein transport.

Promoter and first exon methylation regulate porcine FASN gene expression.

DNA methylation is a stable epigenetic mark mediating gene expression. Methylation is crucial for diverse biological processes, including aging and embryo development. FASN (fatty acid synthase) plays an important role in de novo lipogenesis, through catalyzing the reductive synthesis of long-chain fatty acids. In this study, we investigated the FASN gene expression pattern and corresponding DNA methylation status in the inner layer of backfat from Jinhua pigs at different developmental stages. Our results showed that FASN gene expression increases with age and is positively associated with adipocyte volume (r = 0.98, P < 0.01). In addition, the DNA methylation level for the first exon (0.11, CGI 3) of the FASN gene is approximately 8-fold lower than levels for its promoter (0.94, CGI 1&2) (two-way ANOVA, PCGI < 0.01). The association analysis revealed that both promoter (r = -0.944, P < 0.01) and first exon methylation (r = -0.774, P < 0.01) are significantly and negatively correlated with FASN gene expression. Our results will benefit future investigations of the epigenetic mechanism underlying FASN gene expression.

Single-step gas-phase polyperfluoroalkylation of naphthalene leads to thermodynamic products.

High-temperature gas-phase, solvent- and catalyst-free reaction of naphthalene with an excess of RF I reagent (RF CF3 , C2 F5 , n-C3 F7 , and n-C4 F9 ) was used for the first time to produce a series of highly perfluoroalkylated naphthalene products NAPH(RF )n with n=2-5. Four 95+ % pure 1,3,5,7-NAPH(RF )4 with RF CF3 , C2 F5 , n-C3 F7 , and n-C4 F9 were isolated using a simple chromatography-free procedure. These new compounds were fully characterized by (19) F and (1) H NMR spectroscopy, X-ray crystallography (for RF CF3 and C2 F5 ), atmospheric-pressure chemical ionization mass spectrometry, and cyclic and square-wave voltammetry. DFT calculations confirm that the proposed synthesis yields the most stable isomers that have not been accessed by alternative preparation techniques.