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Background: Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy.Methods and analysis: This is a monocentric, prospective, randomized, double-blind clinical trial. A total of 90 pediatric patients will be randomized to receive remimazolam-based total intravenous anesthesia (remimazolam group, n = 45) or sevoflurane-based inhalation anesthesia (sevoflurane group, n = 45). The primary outcome will be the incidence of emergence delirium, which will be evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes include the extubation time, recovery time, behavior change using the post-hospitalization behavior questionnaire for ambulatory surgery (PHBQ-AS), and adverse events.Ethics and dissemination: This study has been approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (2023-K-262-02).Clinical trial registration:ClinicalTrials.gov, identifier NCT06214117.

Summary: There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine’s analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p

Objective/purpose: Previously patient reported quality of life (QOL) was reported in men with prostate cancer a mean 2 and 6 years post treatment with open radical prostatectomy (RP), 3D conformal radiation therapy (3D CRT), or 125I low dose rate (LDR) brachytherapy (BT). Herein we update the results 15 years post-treatment QOL. Materials/methods: The Expanded Prostate Cancer Index (EPIC) domains were scored with differences evaluated at a median 15.8 years follow up based upon mean EPIC summary domains by ANOVA with pairwise post-hoc comparisons adjusted for age. Patient differences of current survey from first cross-section are reported as median change in summary score for each treatment group at median of 2.2 and 6.0, and 15.8 years. Results: Among men still alive response rate was 52% in BT, 60% in 3D CRT, and 62% in RP resulting in 30, 41, and 330 QOL questionnaires to evaluate for each corresponding modality at median follow up of 15.8 years. Men were a mean 75.3, 83.6, and 79.3 years of age after RP, 3DCRT, and BT, respectively.At a median of 15.8 years, there were largely persistent differences in EPIC domains without substantial evolution in QoL from middle time points. Persistent worsening in urinary irritative and bowel domain with 3DRT or BT compared to RP. Trend towards worse urinary incontinence with RP were noted without statistical differences within radiotherapy options. Conclusion: As the EPIC patient reported outcomes with the longest follow-up, these data uniquely reveal temporal trends from 2 to 15 years post treatment. However, the treatment modalities of open RP, 3D CRT without image guidance or intensity modulation, and BT without peripheral loading or MRI guidance may not reflect modern techniques.

Abstract Background Fetal growth restriction (FGR) is associated with increased risks for complications before, during, and after birth, in addition to risk of disease through to adulthood. Although placental insufficiency, failure to supply the fetus with adequate nutrients, underlies most cases of FGR, its causes are diverse and not fully understood. One of the few diagnosable causes of placental insufficiency in ongoing pregnancies is the presence of large chromosomal imbalances such as trisomy confined to the placenta; however, the impact of smaller copy number variants (CNVs) has not yet been adequately addressed. In this study, we confirm the importance of placental aneuploidy, and assess the potential contribution of CNVs to fetal growth. Methods We used molecular-cytogenetic approaches to identify aneuploidy in placentas from 101 infants born small-for-gestational age (SGA), typically used as a surrogate for FGR, and from 173 non-SGA controls from uncomplicated pregnancies. We confirmed aneuploidies and assessed mosaicism by microsatellite genotyping. We then profiled CNVs using high-resolution microarrays in a subset of 53 SGA and 61 control euploid placentas, and compared the load, impact, gene enrichment and clinical relevance of CNVs between groups. Candidate CNVs were confirmed using quantitative PCR. Results Aneuploidy was over tenfold more frequent in SGA-associated placentas compared to controls (11.9% vs. 1.1%; p = 0.0002, OR = 11.4, 95% CI 2.5–107.4), was confined to the placenta, and typically involved autosomes, whereas only sex chromosome abnormalities were observed in controls. We found no significant difference in CNV load or number of placental-expressed or imprinted genes in CNVs between SGA and controls, however, a rare and likely clinically-relevant germline CNV was identified in 5.7% of SGA cases. These CNVs involved candidate genes INHBB, HSD11B2, CTCF, and CSMD3. Conclusions We conclude that placental genomic imbalances at the cytogenetic and submicroscopic level may underlie up to ~ 18% of SGA cases in our population. This work contributes to the understanding of the underlying causes of placental insufficiency and FGR, which is important for counselling and prediction of long term outcomes for affected cases.

Background and purpose — Up to 20% of patients are dissatisfied after total knee arthroplasty (TKA), mainly because of pain and restricted physical function. We developed a prediction model for 6-month knee range of motion, knee pain, and walking limitations in patients undergoing TKA surgery. Patients and methods — We performed a prospective cohort study of 4,026 patients who underwent elective, primary TKA between July 2013 and July 2017. Candidate predictors included demographic, clinical, psychosocial, and preoperative outcome measures. The outcomes of interest were (i) knee extension and flexion range of motion, (ii) knee pain rated on a 5-point ordinal scale, and (iii) self-reported maximum walk time at 6 months post TKA. For each outcome, we fitted a multivariable proportional odds regression model with bootstrap internal validation. Results — At 6 months post TKA, around 5% to 20% of patients had a flexion contracture ³ 10°, range of motion

This investigation studies the impact of mutual fund herding on the returns achieved by contrarian strategy from 1990 to 2015 in the Chinese stock market. The relationship between the profit gained by the contrarian strategy and the macroeconomic environment is also examined. First, the returns of the contrarian strategy in China’s stock market are found to be significant. Second, most loser stocks with a high degree of mutual fund herding outperform loser stocks with a low degree of mutual fund herding, revealing that the profitability of an investment portfolio depends on the degree of mutual fund herding. Third, investors should buy loser stocks with a high degree of herding and sell winner stocks with a low degree of herding during a two-year formation period, over which zero-cost contrarian strategies yield the significantly highest return. Finally, the payoff of contrarian strategies is positively related to the herding effect and negatively related to macroeconomic variables.

Abstract Background Schizophrenia is a severe psychiatric disorder associated with IQ deficits. Rare copy number variations (CNVs) have been established to play an important role in the etiology of schizophrenia. Several of the large rare CNVs associated with schizophrenia have been shown to negatively affect IQ in population-based controls where no major neuropsychiatric disorder is reported. The aim of this study was to examine the diagnostic yield of microarray testing and the functional impact of genome-wide rare CNVs in a community ascertained cohort of adults with schizophrenia and low (

Genome-wide copy-number association studies offer new opportunities to identify the mechanisms underlying complex diseases, including chronic inflammatory, psychiatric disorders and others. We have used genotyping microarrays to analyse the copy-number variants (CNVs) from 243 Caucasian individuals with Inflammatory Bowel Disease (IBD). The CNV data was obtained by using multiple quality control measures and merging the results of three different CNV detection algorithms: PennCNV, iPattern, and QuantiSNP. The final dataset contains 4,402 CNVs detected by two or three algorithms independently with high confidence. This paper provides a detailed description of the data generation and quality control steps. For further interpretation of the data presented in this article, please see the research article entitled ‘Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease’.

BackgroundInflammatory bowel disease (IBD) is an idiopathic, chronic disorder of unclear etiology with an underlying genetic predisposition. Recent genome-wide association studies have identified more than 200 IBD susceptibility loci, but the causes of IBD remain poorly defined. We hypothesized that rare (MethodsDNA samples from 243 individuals with IBD from the Manitoba IBD Cohort Study and 2988 healthy controls were analyzed using genome-wide SNP microarray technology. Three CNV calling algorithms were applied to maximize sensitivity and specificity of CNV detection. We identified IBD-associated genes affected by rare CNV from comparing the number of overlapping CNVs in IBD samples with the number of overlapping CNVs in controls for each gene.Results4,402 CNVs detected by two or three algorithms intersected 7,061 genes, in at least one analyzed sample. Four genes (e.g. DUSP22 and IP6K3) intersected by rare deletions and fourteen genes (e.g. SLC25A10, PSPN, GTF2F1) intersected by rare duplications demonstrated significant association with IBD (FDR-adjusted p-value < 0.01). Of these, ten genes were functionally related to immune response and intracellular signalling pathways. Some of these genes were also identified in other IBD related genome-wide association studies. These suggested that the identified genes may play a role in the risk of IBD.ConclusionOur results revealed new genomic loci associated with IBD, which suggested the role of rare CNVs in IBD risk.

Long noncoding RNAs (lncRNAs) are an emerging class of oncogenic molecules implicated in a diverse range of human malignancies. We recently identified SChLAP1 as a novel lncRNA that demonstrates outlier expression in a subset of prostate cancers, promotes tumor cell invasion and metastasis, and associates with lethal disease. Based on these findings, we sought to develop an RNA in situ hybridization (ISH) assay for SChLAP1 to 1) investigate the spectrum of SChLAP1 expression from benign prostatic tissue to metastatic castration-resistant prostate cancer and 2) to determine whether SChLAP1 expression by ISH is associated with outcome after radical prostatectomy in patients with clinically localized disease. The results from our current study demonstrate that SChLAP1 expression increases with prostate cancer progression, and high SChLAP1 expression by ISH is associated with poor outcome after radical prostatectomy in patients with clinically localized prostate cancer by both univariate (hazard ratio = 2.343, P = .005) and multivariate (hazard ratio = 1.99, P = .032) Cox regression analyses. This study highlights a potential clinical utility for SChLAP1 ISH as a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy.

We employ the DEMATEL-based analytic network process (D-ANP) to evaluate the weight of various factors on S&P 500 index futures. The general regression method is employed to prove the result. We then employed grey relational analysis (GRA) to examine predictive power of determinants suggested by 13 experts for fluctuations in S&P 500 index futures. This study yields a number of empirical results. (1) The explanatory power of macroeconomic factors for S&P 500 index futures outperforms that of technical indicators, as found in most of previous research papers; (2) The D-ANP revealed that five core factors (US dollar index, ISM manufacturing purchasing managers’ index (PMI), interest rate, volatility index, and unemployment rate) affect fluctuations in S&P 500 index futures, of which the US dollar index is the most important; (3) A casual diagram shows that the US dollar index and interest rate have mutual effects, and the US dollar index unilaterally affects ISM manufacturing PMI, unemployment rate, and the volatility index; (4) Granger causality test results confirmed some similar results obtained via the D-ANP that the US dollar index, interest rate, and the PMI have major impacts on the S&P 500 index futures; (5) The general regression results confirmed that four of five factors selected via the D-ANP (US dollar index, interest rate, volatility index, and unemployment rate) have strong explanatory power in forecasting the rate of return on S&P 500 index futures; (6) The GRA revealed that the explanatory power of various factors selected via the D-ANP was better for S&P 500 than for Dow Jones Industrial Average (DJIA) and Nasdaq 100 index futures; (7) The explanatory power is better for S&P 500 Industrial than for S&P 500 transportation, utility, and financial index futures.

Superhero fan fiction is increasingly popular in the Chinese boys' love (BL) community. An exploration of the fan fic Gangtiexia: Zhongdu Yilai (Iron Man: Overly attached) investigates how the Hollywood cultural icon Iron Man/Tony Stark is reimagined in Chinese BL culture and to what degree this kind of rendition both echoes and extends as well as challenges and deviates from our current insights into BL fandoms. Through the lenses of queerness and technological human transformation, I explore the fresh contribution of Iron Man fan fiction to both local BL cultures and global superhero fandoms.

The aim of this paper is to examine the impact of temperature shock on both near-month and far-month natural gas and heating oil futures returns by extending the weather and storage models of the previous study. Several notable findings from the empirical studies are presented. First, the expected temperature shock significantly and positively affects both the near-month and far-month natural gas and heating oil futures returns. Next, significant temperature shock has effect on both the conditional mean and volatility of natural gas and heating oil prices. The results indicate that expected inventory surprises significantly and negatively affects the far-month natural gas futures returns. Moreover, volatility of natural gas futures returns is higher on Thursdays and that of near-month heating oil futures returns is higher on Wednesdays than other days. Finally, it is found that storage announcement for natural gas significantly affects near-month and far-month natural gas futures returns. Furthermore, both natural gas and heating oil futures returns are affected more by the weighted average temperature reported by multiple weather reporting stations than that reported by a single weather reporting station.

Lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, has been shown to have a strong adjuvant effect towards inhaled antigens contributing to airway inflammation. Isoflavones are anti-inflammatory molecules present in abundant quantities in soybeans. We investigated the effect of isoflavones on human dendritic cell (DC) activation via LPS stimulation and subsequent DC-mediated effector cell function both in vitro and in a mouse model of upper airway inflammation. Human monocyte-derived DCs (MDDC) were matured with LPS (or TNF-α) +/- isoflavones (genistein or daidzein). The surface expression levels of DC activation markers were analyzed by flow cytometry. Mature DCs +/- isoflavones were washed and cultured with freshly-isolated allogenic naïve CD4⁺ T cells for 5 days or with autologous natural killer (NK) cells for 2 hours. The percentages of proliferating IFN-γ⁺ CD4⁺ T cells and cytokine levels in culture supernatants were assessed. NK cell degranulation and DC cytotoxicity were measured by flow cytometry. Isoflavones significantly suppressed the activation-induced expression of DC maturation markers (CD83, CD80, CD86) and MHC class I but not MHC class II molecules in vitro. Isoflavone treatment inhibited the ability of LPS-DCs to induce IFN-γ in CD4⁺ T cells. NK cell degranulation and the percentage of dead DCs were significantly increased in isoflavone-treated DC-NK co-culture experiments. Dietary isoflavones suppressed the mucosal immune response to intra-nasal sensitization of mice to ovalbumin. Similar results were obtained when isoflavones were co-administered during sensitization. These results demonstrate that soybean isoflavones suppress immune sensitization by suppressing DC-maturation and its subsequent DC-mediated effector cell functions.

Summary Introduction Methods Results Discussion Remimazolam is an ultra‐short‐acting benzodiazepine sedative drug. This study aimed to compare the efficacy and safety of remimazolam with propofol for induction and maintenance of general anaesthesia in children undergoing elective surgery.Children (aged 3–6 y, ASA physical status 1 or 2, BMI 14–25 kg.m‐2) undergoing elective surgery under general anaesthesia with tracheal intubation were eligible for inclusion. Children were allocated randomly using a web‐based system to receive either remimazolam or propofol in a 3:1 ratio. After receiving fentanyl 3 μg.kg‐1, children received their allocated drug for both induction and maintenance of general anaesthesia. Induction doses were remimazolam 0.3 mg.kg‐1 or propofol 2.5 mg.kg‐1, with a second dose given should they not achieve loss of consciousness. After neuromuscular blockade and tracheal intubation, maintenance anaesthesia was achieved with an infusion either remimazolam 1–3 mg.kg‐1.h‐1 or propofol 4–12 mg.kg‐1.h‐1, alongside a remifentanil infusion (0.1–0.5 μg.kg‐1.min‐1) titrated to surgical stimulus and haemodynamic parameters. Primary outcomes were the incidence of successful induction and maintenance of anaesthesia. Secondary outcomes included: time to loss of consciousness, awakening and tracheal extubation; incidence of emergence delirium and moderate or severe pain in post‐anaesthesia care unit; incidence of negative behaviour change after surgery at postoperative day 3; and incidence of adverse events.A total of 187 children were analysed (140 allocated to remimazolam and 47 to propofol). All children achieved successful induction of anaesthesia. Successful maintenance of anaesthesia was achieved in 139 (99%) children who received remimazolam compared with 46 (98%) who received propofol (rate difference 1.4%, 95%CI ‐2.9–5.8%, p = 0.441). Adverse events occurred in 27 (19%) children who received remimazolam and 23 (49%) who received propofol.Remimazolam was well tolerated for the induction and maintenance of general anaesthesia in pre‐school‐age children and was non‐inferior to propofol. [ABSTRACT FROM AUTHOR]

Aims: Limited knee range-of-motion (ROM) is common following total knee arthroplasty (TKA). It is associated with functional limitations and patient dissatisfaction. Regular knee ROM assessment is important but accurate testing traditionally requires timely access to trained healthcare professionals. Although accelerometer-based smartphone goniometry has shown to provide reliable and valid joint angles, current evidence of its use still positions healthcare providers as end users instead of patients themselves. Therefore, to maximize the impact of smartphone goniometry on post-TKA care, our study aimed to examine the feasibility, reliability, and validity of patients' self-measurement of knee ROM using an accelerometer-based smartphone goniometry application. Methods: Patients were given standard instructions with a practice trial before the actual measurements. Passive knee flexion and extension ROM was measured on 2 sessions in 30 patients with TKA using 4 block-randomized methods: (i) smartphone self-assessment, (ii) long-arm goniometry by physiotherapist, (iii) smartphone assessment by physiotherapist, and (iv) extendable-arm goniometry by physiotherapist with placement adjudication. Feasibility was assessed by the number of participants who could independently perform the self-measurement. To assess intra- and inter-session reliability, we computed intraclass correlation coefficients (ICCs) from random-effects models. To assess intra- and inter-session agreement, we computed mean absolute differences (MADs) and minimum detectable change (MDC). To assess concurrent validity, we designated extendable-arm goniometry as the "gold standard" and compared other methods against it using ICCs and MADs. Results: All patients were able to comprehend and execute the assessment. 87% (n = 26) found the application easy to administer. Smartphone goniometry by patients showed excellent intra- and inter-session reliability (ICCs>0.97) and minimum variability (MAD = 0.9°-3.9°; MDC95 = 3.1°–9.0°). Smartphone or long-arm goniometry by physiotherapists did not outperform patients' self-assessment (ICC = 0.96–0.99, MAD = 0.7°-3.1°; MDC95 = 2.2°-8.0°). Compared against extendable-arm goniometry, smartphone goniometry by patients measured knee flexion and extension ROM with a MAD of 4.5° (ICC, 0.97) and 2.2° (ICC = 0.98), respectively. Conclusion: Our study demonstrates that smartphone goniometry is feasible, reliable and accurate, and can be used with confidence in the self-assessment of knee ROM post-TKA. Future studies should further explore its utility in telemonitored rehabilitation, and its possible integration into mobile health applications to enhance accessibility to care following TKA. [ABSTRACT FROM AUTHOR]

We replicate 469 anomaly variables similar to those studied by Hou et al. (2020) using Chinese A-share data and a reliable testing procedure with mainboard breakpoints and value-weighted returns. We find that 83.37% of the anomaly variables do not generate significant high-minus-low quintile raw return spreads. Further adjusting risk increases the failure rate slightly to 84.22% based on CAPM alphas and 86.99% based on Fama–French three-factor alphas. We show that the conventional procedure using all A-share breakpoints with equal-weighted returns for the anomaly test is indeed problematic as it assigns too much weight to microcaps and has a very limited investment capacity. The CH3-factor, CH4-factor, and q-factor models show the best performance over the whole sample period. The q-factor model is the best performer in the post-2007 subsample period after significant improvements occurred in China's financial market environment, such as the completion of the split-share structure reform and the implementation of new accounting standards conforming to the International Financial Reporting Standards. The non–state-owned enterprise subsample in the post-2007 period is a cleaner sample in which the CH4-factor and q-factor models are the best performers. This paper was accepted by Lukas Schmid, finance. Funding: Z. Li acknowledges financial support from the National Natural Science Foundation of China [Grant 72103043] and the Fundamental Research Funds for the Central Universities in UIBE [Grants 19QN01 and 22PY053-72103043]. L. X. Liu acknowledges financial support from the National Natural Science Foundation of China [Grants 71872006 and 72273006]. L. X. Liu and X. Liu acknowledge financial support from the Guanghua Thought Leadership Platform of Peking University. K. C. J. Wei acknowledges partial financial support from the Research Grants Council of the Hong Kong Special Administrative Region, China [Grant 15507320]. The authors acknowledge financial support from the Guanghua School of Management, Peking University; the School of Banking and Finance, University of International Business and Economics; and the Non-PAIR Research Centre "Research Centre for Quantitative Finance" at Hong Kong Polytechnic University. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4904. [ABSTRACT FROM AUTHOR]