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Introduction: Many cardiac arrest survivors die later due to hemorrhage or thromboembolism, thought to be caused by acquired coagulopathy in post-cardiac arrest syndrome (PCAS) from shock and reperfusion injury. Understanding PCAS is a priority identified by the AHA for the prevention of complications in cardiac arrest survivors. Shock dysregulates both coagulation and fibrinolysis. The key effector enzyme thrombin (Th), is responsible for both up- and down-regulating coagulation and fibrinolysis. Measuring early Th activity may allow for predicting PCAS coagulopathy, and early medical intervention in the ED. Therefore, we aimed to characterize the time-course profile of early coagulation using an established pig model of cardiac arrest. Methods: Yorkshire pigs were anaesthetised and intubated, had VF-arrest induced by pacing, and were resuscitated per ACLS. Rotational thromboelastometry (ROTEM) was performed on whole blood at four times: baseline, intra-arrest, post-arrest, and death, using the fibrin-based test with tissue factor to initiate clotting in the presence of a platelet inhibitor cytochalasin D (FIBTEM). Clot time (CT), clot formation time (CFT), alpha-angle during clot formation (Alpha), clot amplitude at 10 min (A10), maximum clot firmness (MCF), and maximum lysis as total percentage (ML%) were quantified. The primary outcome is the overall coagulation initiation measured by CFT, while secondary outcomes include ROTEM parameters reflecting Th activity. Parameters are compared over time in SPSS using repeated measures ANOVA and Bonferroni correction. Results: Pilot data from one experiment show that cardiac arrest causes immediate early changes to coagulation that subsequently normalized with ROSC (Figure 1). CFT was impaired immediately upon cardiac arrest (2.3-fold increase), normalized with ROSC, and impaired again at death when compared with baseline. Consistent with clotting impairment, A10, Alpha, and MCF were all reduced with cardiac arrest, normalized with ROSC, and impaired again at death. Conclusion: Higher initial indices of coagulopathy in patients with cardiac arrest appear to correlate with death and thromboembolism. In this pilot, CFT is acutely modified by cardiac arrest. Since CFT is affected by overall Th activity, early Th dysregulation may be a critical driver of coagulopathy. Th may therefore be a lead target that is modifiable in the emergency post-arrest setting to decrease morbidity and mortality from PCAS in cardiac arrest survivors.
To compare efficacy and medical costs of typital and atypical antipsychotics in treating schizophrenic patients.
250 in patients in general hospital and psychiatric hospital were randomly allocated to one of the two groups, one treated with typital antipsychotics as chlorpromazine, haloperidol and so on with a mean daily dose of 500∼800 mg in chlorpromazine equivalents, and the other with atypical agents in cluding clozapine (mean daily dose of 400∼800mg ), risperidone of 6 mg, or olanzapine of 20 mg.
The total costs of the treatment were (3157±253) Yuan RMB for patients treated with typical agents in general hospital, and (3673±294) Yuan RMB for patients treated with typical agents in psychiatric hospital respectively. the costs for medicine were (774±903) Yuan RMB, (1061±903) Yuan RMB respectively. the costs in atypical group were(1120±390) Yuan RMB and (1637±325) Yuan RMB, and (108±157) Yuan RMB and (240±317) Yuan RMB respectively. the duration of patients treated with typical agents in hospital is longer than that with atypical agents.
It indicates that atypical antipsychotics have similar efficacy to typical agents in treating schizophrenic patients with less costs.
rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS. In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.
Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.
Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.
Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.
Jumping to conclusions (JTC) is a reasoning bias where individuals make hasty decisions based on insufficient data. It is commonly observed among patients with delusions and is a risk factor for developing delusions. Several task paradigms have been developed to test JTC, but their convergence in measuring JTC remains unexplored.
This is a pilot test to examine the consistencies between three JTC tasks with a student sample. The relationships between JTC and cognitive abilities were also explored.
Forty-six university students completed the Beads Task, Fish Task and Box Task, as well as assessment of memory, intellectual functioning, executive function, impulsivity and need for closure.
There was a moderate correlation between the beads task and fish task on various measures of JTC (draws to decision [DTD], r=.50, p<.01; confidence, r=.47, p<.01; dichotomous JTC bias, ×2=16.14, p<.001). There was a mild correlation between DTD on the fish task and box task (r=.30, p<.05). General intelligence was associated with DTD and JTC bias (but not confidence) on the beads and fish tasks. Confidence in decision was associated with a higher level of impulsivity and a lower level of set-shifting ability.
Despite differences in materials and design of the three probability-based tasks, results of JTC measured by the beads task and box task were individually consistent with the fish task, and were not correlated between the two. The data-gathering process and the confidence in decision are associated with different cognitive abilities. Further study including a clinical sample is needed.
In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.
At GE Research, we are combining “physics” with artificial intelligence and machine learning to advance manufacturing design, processing, and inspection, turning innovative technologies into real products and solutions across our industrial portfolio. This article provides a snapshot of how this physical plus digital transformation is evolving at GE.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Few studies have evaluated the relationships between intake of sugar-sweetened beverages (SSB) and intermediate biomarkers of cardiometabolic risk. Associations between artificially sweetened beverages (ASB) and fruit juice with cardiometabolic biomarkers are also unclear. We investigated habitual SSB, ASB and fruit juice intake in relation to biomarkers of hepatic function, lipid metabolism, inflammation and glucose metabolism. We analysed cross-sectional data from 8492 participants in the Nurses’ Health Study who were free of diabetes and CVD. Multivariate linear regression was used to assess the associations of SSB, ASB and fruit juice intake with concentrations of fetuin-A, alanine transaminase, γ-glutamyl transferase, TAG, HDL-cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein (CRP), intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1, adiponectin, insulin and HbA1c as well as total cholesterol:HDL-cholesterol ratio. More frequent intake of SSB was significantly associated with higher concentrations of fetuin-A, TAG, CRP, ICAM-1, adiponectin and insulin, a higher total cholesterol:HDL-cholesterol ratio, and a lower concentration of HDL-cholesterol (Ptrend ranges from <0·0001 to 0·04) after adjusting for demographic, medical, dietary and lifestyle variables. ASB intake was marginally associated with increased concentrations of CRP (Ptrend=0·04) and adiponectin (Ptrend=0·01). Fruit juice intake was associated with increased concentrations of TAG and HbA1c and a lower concentration of adiponectin (Ptrend ranges from <0·0001 to 0·01). In conclusion, habitual intake of SSB was associated with adverse levels of multiple cardiometabolic biomarkers. Associations between ASB and fruit juice with cardiometabolic risk markers warrant further exploration.
The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Fatigue cracking in polycrystalline NiTi was investigated using a multiscale experimental framework for average grain sizes (GS) from 10 to 1500 nm for the first time. Macroscopic fatigue crack growth rates, measured by optical digital image correlation, were connected to microscopic crack opening and closing displacements, measured by scanning electron microscope DIC (SEM-DIC) using a high-precision external SEM scan controller. Among all grain sizes, the 1500 nm GS sample exhibited the slowest crack growth rate at the macroscale, and the largest crack opening level (stress intensity at first crack opening) and minimum crack opening displacements at the microscale. Smaller GS samples (10, 18, 42, and 80 nm) exhibited nonmonotonic trends in their fatigue performance, yet the correlation was strong between macroscale and microscale behaviors for each GS. The samples that exhibited the fastest crack growth rates (42 and 80 nm GS) showed a small crack opening level and the largest crack opening displacements. The irregular trends in fatigue performance across the nanocrystalline GS samples were consistent with nonmonotonic values in the elastic modulus reported previously, both of which may be related to the presence of residual martensite only evident in the small GS samples (10 and 18 nm).
The effects of soluble fiber inclusion in gestation diets with varying fermentation characteristics (fermentation kinetics and short-chain fatty acids (SCFA)-profile) on lactational feed intake of sows and their piglet growth over two parities were investigated using an in vitro–in vivo methodology. After breeding, 90 multiparous Landrace sows were randomized to one of three experimental diets: the control (CON) diet, konjac flour (KF) diet or sugar beet pulp (SBP) diet. All diets had similar levels of net energy, CP, insoluble fiber and NDF, but KF and SBP diets had higher soluble fiber levels than the CON diet. During gestation, the sows were restrictively fed with three different diets, but during lactation, all the sows were similarly fed ad libitum. The three gestation diets were enzymatically hydrolyzed using pepsin and pancreatin, and enzymolyzed residues were used in in vitro fermentation. Gas and SCFA production were monitored during fermentation. After fermentation, enzymolyzed residues of KF or SBP diets resulted in higher final asymptotic gas volume than those of the CON diet. The enzymolyzed residues of KF diet were mainly part of rapidly fermented fractions, whereas those of SBP diet were mainly part of slowly fermented fractions. In addition, the acetic acid, butyric acid and total SCFA concentrations of enzymolyzed residues of KF diet were higher (P<0.01) than the control and SBP diets. In the in vivo studies, on day 90 of gestation, the KF diet sows had higher plasma SCFA concentration (P<0.05) at 4 h after feeding than the CON diet sows. Furthermore, the KF diet sows had lower plasma free fatty acid (FFA) concentration (P<0.01) at 4 h after feeding, and a lower value of homeostasis model assessment (HOMA)-insulin resistance (P<0.05), but a higher value of HOMA-insulin sensitivity (P<0.01). The KF diet sows also consumed more feed during lactation (P<0.01) and weaned significantly heavier pigs (P<0.01) than the CON diet sows. The overall results showed that the high fermentation capacity KF diet contributed to an increased lactational feed intake and improved performance of piglets in the second reproductive cycle.
Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.
Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.
Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.
In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.