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ObjectiveThis study aimed to describe the epidemiological and clinical features and potential factors related to the time to return negative reverse transcriptase (RT)-PCR in discharged paediatric patients with COVID-19.DesignRetrospective cohort study.SettingUnscheduled admissions to 12 tertiary hospitals in China.ParticipantsTwo hundred and thirty-three clinical charts of paediatric patients with confirmed diagnosis of COVID-19 admitted from 1 January 2020 to 17 April 2020.Primary and secondary outcome measuresPrimary outcome measures: factors associated with the time to return negative RT-PCR from COVID-19 in paediatric patients. Secondary outcome measures: epidemiological and clinical features and laboratory results in paediatric patients.ResultsThe median age of patients in our cohort was 7.50 (IQR: 2.92–12.17) years, and 133 (57.1%) patients were male. 42 (18.0%) patients were evaluated as asymptomatic, while 162 (69.5%) and 25 (10.7%) patients were classified as mild or moderate, respectively. In Cox regression analysis, longer time to negative RT-PCR was associated with the presence of confirmed infection in family members (HR (95% CI): 0.56 (0.41 to 0.79)). Paediatric patients with emesis symptom had a longer time to return negative (HR (95% CI): 0.33 (0.14 to 0.78)). During hospitalisation, the use of traditional Chinese medicine (TCM) and antiviral drugs at the same time is less conducive to return negative than antiviral drugs alone (HR (95% CI): 0.85 (0.64 to 1.13)).ConclusionsThe mode of transmission might be a critical factor determining the disease severity of COVID-19. Patients with emesis symptom, complications or confirmed infection in family members may have longer healing time than others. However, there were no significant favourable effects from TCM when the patients have received antiviral treatment.

To compare the addition of targeted agents to fulvestrant with fulvestrant alone in hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy; a meta-analysis of all relevant randomized controlled trials was performed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2016. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. Eight trials with a total of 2,470 patients were included in this meta-analysis. Compared with fulvestrant alone, combination therapy improved PFS (HR = 0.79; 95% CI 0.72-0.87; P = 0.00), increased ORR (RR = 1.70; 95% CI 1.30-2.21; P = 0.00), and showed a trend of increase in DCR (RR = 1.27; 95% CI 0.96-1.69, P = 0.09). In network analysis, only CD4/6 and PI3K/m-TOR inhibitors showed significant treatment effects with a P-score of 0.9999 and 0.7615, respectively. Patients treated with combination therapy developed more grade 3 or greater toxic effects (RR = 1.24; 95% CI 1.13-1.36; P = 0.00). Combining targeted agents with fulvestrant showed benefit but with increased toxicity in patients with advanced breast cancer compared with fulvestrant alone. Biomarkers for treatment optimization are lacking. The CD4/6 and PI3K/m-TOR pathways merit further investigation.

Background: The epidemic of disease due to SARS-CoV-2 has caused massive destruction to the world economy and overburdened health care systems worldwide. To date, information about the epidemiological features and potential factors related to the clinical recovery of pediatric COVID-19 patients is lacking. Methods: This retrospective study examined 233 pediatric cases confirmed COVID-19 admitted to 12 tertiary hospitals in China from January 1, 2020 to April 17, 2020. We retrieved the electronic medical records of these cases, including the patient epidemiological characteristics, laboratory results, and clinical information. Findings: The median age of the cohort was 7·50 (IQR: 2·92,12·17) years, and 133 (57·1%) patients were male. Forty-two patients were evaluated as asymptomatic, while 162 and 25 patients were classified as mild or moderate cases, respectively. The most common clinical symptoms were fever (40·8%), cough (35·6%), nausea (16·3%), and coughing productive of excess saliva (9·9%). In the Cox regression analysis, longer time to recovery was associated with having SARS-CoV-2-infected family members (HR [95%CI]: 0·56 [0·41–0·79]), and comorbidities (HR [95%CI]: 0·57 [0·37–0·89]). Regarding the clinical disease types, only severe disease was associated with longer recovery time (HR [95%CI]: 0·14 [0·03–0·59]). Interpretation: The transmission chain between adult and child COVID-19 patients is not one-way, and it is possible for the virus to transmit from adult patients to children in the household setting, and vice versa. The proportion of asymptomatic pediatric patients could be underestimated due to detection difficulties. Funding Statement: The Bill & Melinda Gates Foundation (Grant No. INV-006277). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the ethics committee of the National Children’s Medical Center, Children’s Hospital of Fudan University, and followed the Declaration of Helsinki. Written consent was obtained from the guardians of the patients.

To investigate the effects of angiogenesis inhibitors in the treatment of patients with advanced or recurrent ovarian cancer, a meta-analysis was performed and overall survival (OS), progression-free survival (PFS), and toxicity were assessed.The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for publications between January 2000 and June 2015. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.The 12 trials in this meta-analysis were divided into three groups: four trials with a VEGF inhibitor (the bevacizumab group), six trials with VEGFR inhibitors (the VEGFRIs group), and two trials with an angiopoietin inhibitor (the trebananib group). PFS improvement was seen in all groups (HR = 0.61, 95% CI 0.48 to 0.79, P 0.001 for bevacizumab; HR = 0.71, 95% CI 0.59 to 0.87, P = 0.001 for VEGFRIs; and HR = 0.67, 95% CI 0.62 to 0.72, P 0.001 for trebananib). Regarding OS, bevacizumab showed a trend of improvement (HR = 0.90, 95% CI 0.80 to 1.01, P = 0.079), VEGFRIs showed no improvement (HR = 0.92, 95% CI 0.75 to 1.11, P = 0.368), and trebananib demonstrated a significant prolongation (HR = 0.81, 95% CI 0.67 to 0.99, P = 0.036). Bevacizumab was associated with more class-specific adverse events (RR = 4.05, 95% CI 1.99 to 8.27, P 0.001). Although the toxicity profiles differed, VEGFRIs developed common higher incidences of hypertension, diarrhea, and fatigue. A higher incidence of edema was reported in the trebananib group (RR = 2.60, 95% CI 0.84 to 8.00, P = 0.097).Anti-angiogenic therapy showed clear PFS benefit with increased toxicity, but its role in OS was undefined for ovarian cancer which emphasized the need for patient selection.

Input variable selection (IVS) is one of the most important steps in the development of artificial neural network and other data driven environmental and water resources models. Partial mutual information (PMI) is one of the most promising approaches to IVS, but has the disadvantage of requiring kernel density estimates (KDEs) of the data to be obtained, which can become problematic when the data are non-normally distributed, as is often the case for environmental and water resources problems. In order to overcome this issue, preliminary guidelines for the selection of the most appropriate methods for obtaining the required KDEs are determined based on the results of 3780 trials using synthetic data with distributions of varying degrees of non-normality and six different KDE techniques. The validity of the guidelines is confirmed for two semi-real case studies developed based on the forecasting of river salinity and rainfall-runoff modelling problems.

Multi-layer perceptron artificial neural networks are used extensively in hydrological and water resources modelling. However, a significant limitation with their application is that it is difficult to determine the optimal model structure. General regression neural networks (GRNNs) overcome this limitation, as their model structure is fixed. However, there has been limited investigation into the best way to estimate the parameters of GRNNs within water resources applications. In order to address this shortcoming, the performance of nine different estimation methods for the GRNN smoothing parameter is assessed in terms of accuracy and computational efficiency for a number of synthetic and measured data sets with distinct properties. Of these methods, five are based on bandwidth estimators used in kernel density estimation, and four are based on single and multivariable calibration strategies. In total, 5674 GRNN models are developed and preliminary guidelines for the selection of GRNN parameter estimation methods are provided and tested.

To compare the effects of adding targeted agents to standard second-line chemotherapy with a single agent (pemetrexed or docetaxel) in patients with advanced NSCLC, a meta-analysis of all relevant randomized controlled trials was performed and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were assessed.The PubMed and Embase databases, and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and December 2013. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived.Fourteen trials with a total of 6922 patients were included in this meta-analysis. Compared with chemotherapy, combination therapy did not improve OS (HR = 0.95; 95% CI, 0.90-1.01; P = 0.081) but improved PFS (HR = 0.83; 95% CI, 0.78-0.87; P = 0.000). Survival outcomes did not differ significantly among trials. Combination therapy significantly increased ORR (RR = 1.83; 95% CI, 1.59-2.127; P = 0.000) and DCR (RR = 1.18; 95% CI, 1.13-1.23, P = 0.000). Sub-analysis indicated that adding targeted therapy to chemotherapy significantly prolonged OS in patients with non-squamous NSCLC (HR = 0.87; 95% CI, 0.87-0.97; P = 0.009). Patients treated with combination therapy had an increased incidence of grade 3 or greater diarrhea (RR = 1.96; 95% CI, 1.37-2.81; P = 0.000), neutropenia (RR = 1.27, 95% CI, 1.14-1.61; P = 0.000) and thrombocytopenia (RR = 4.21, 95% CI, 1.87-9.51; P = 0.001). This meta-analysis has the limitations of heterogeneity among the included trials and not using individual patient data.In the second-line treatment of advanced NSCLC, the combination of targeted therapy and chemotherapy significantly increased response rates and progression-free survival, but did not improve overall survival and was more toxic.

To compare the effects of an erlotinib-based targeted dual agent with erlotinib alone in previously treated patients with advanced non-small lung cancer (NSCLC).The PubMed and Embase databases and the Cochrane Central Register of Controlled Trials were searched for publications between January 2005 and March 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CIs were derived. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed.Thirteen trials with a total of 4509 patients were included in this meta-analysis. Compared with erlotinib alone, combination therapy showed no improvement in OS (HR = 0.95; 95% CI, 0.89-1.02; P = .132) though significantly prolonged PFS (HR = 0.82; 95% CI, 0.75-0.90; P .001). Combination therapy significantly increased ORR (RR = 1.32; 95% CI, 1.09-1.60; P = .005) and DCR (RR = 1.26; 95% CI, 1.17-1.36, P .001). Sub-analysis assessment failed to identify any sub-groups which could benefit from combination therapy in terms of OS. Combination therapy was associated with more grade 3 or higher toxic effects (RR = 1.54; 95% CI, 1.22-1.95; P .001). Patients treated with combination therapy had more grade 3 or greater fatigue (RR = 1.49; 95% CI, 1.16-1.91; P = .002), but did not develop more diarrhea (RR = 2.02; 95% CI, 0.86-4.77; P = .107) or rash (RR = 1.29, 95% CI, 0.90-1.85; P = .172). This study had limitations about heterogeneities among the included trials, and the analysis was not based on individual patient data.Compared with erlotinib alone, the erlotinib-based targeted dual agent showed a minimal magnitude of improvement in PFS but did not improve OS. The role of erlotinib-based combinations in previously treated patients with NSCLC seemed insignificant.

We performed a phase II trial of docetaxel in combination with capecitabine to evaluate the antitumor response, toxicity, and survival in pre-treated patients with advanced esophageal squamous cell carcinoma. Patients with advanced esophageal squamous cell carcinoma who had failed first-line chemotherapy with cisplatin and 5-fluorouracil were enrolled in this study. Treatment consisted of oral capecitabine (825 mg/m2 twice daily on days 1–14) plus 1-h intravenous docetaxel (60 mg/m2 on day 1) every 3 weeks for up to 6 cycles. Between June 2008 and August 2011, thirty eligible patients with a median age of 58 years (range 38–68 years) were enrolled. Patients received a median of three cycles of treatment (range 1–6). The median follow-up was 15.4 months (range 1.0–31.5 months). Intent-to-treat efficacy analysis demonstrated an overall response rate of 23.3 % (0 complete response and 7 partial response) and stable disease of 43.4 % (n = 13). The median time to progression was 3.0 months (95 % CI 1.9–4.1 months). The median survival was 8.3 months (95 % CI 6.8–9.8 months). Severe adverse events (grade 3/4) reported were as follows: neutropenia (33.3 %, n = 10, including febrile neutropenia 6.7 %, n = 2), anemia (16.7 %, n = 5), thrombocytopenia (10 %, n = 3), hand–foot syndrome (13.3 %, n = 4), and fatigue (10 %, n = 3). Docetaxel plus capecitabine had a manageable adverse event profile and promising activity in advance esophageal squamous cell carcinoma as a second-line treatment.

To compare the effects of gemcitabine-based chemotherapy and gemcitabine-free regimens, a meta-analysis of all relevant randomized controlled trials was performed to investigate the improvement in overall response rate (ORR), time to progression (TTP), and overall survival (OS). A subgroup of gemcitabine-based doublet compared with single agent was also analyzed.The PubMed and Embase databases were searched for relevant publications reporting randomized controlled trials comparing gemcitabine-based chemotherapy and gemcitabine-free regimens between January 1990 and December 2012. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived.Nine trials with a total of 2651 patients were included in this meta-analysis. Compared with gemcitabine-free chemotherapy, gemcitabine-based therapy demonstrated no improvement in terms of ORR (HR 1.09, 95% CI 0.73-1.62; P = 0.67), TTP (HR 0.91, 95% CI 0.72-1.15; P = 0.44) and OS (HR 1.05, 95% CI 0.88-1.25; P = 0.60). In a subgroup including patients who received adjuvant chemotherapy containing anthracyclines or taxanes, sub-analysis assessment revealed that gemcitabine-based doublets were superior to monotherapy in ORR (HR 1.64, 95% CI 1.26-2.12; P = 0.0002) and TTP (HR 0.71, 95% CI 0.62-0.81; P0.00001), but no benefit was observed for OS (HR 0.90, 95% CI 0.79-1.03; P = 0.14). The rates of grade 3 and 4 anemia (HR 2.02, 95% CI 1.35-3.02; P = 0.006), neutropenia (HR 2.33, 95% CI 1.37-3.63; P = 0.01), and thrombocytopenia (HR 8.31, 95% CI 5.00-13.82; P0.0001) were significantly higher in the gemcitabine-based arm.The present study suggests that gemcitabine-based chemotherapy was as effective as gemcitabine-free chemotherapy in patients with metastatic breast cancer with increased hematological toxicity. Subgroup analysis indicated that adding gemcitabine to monotherapy might be more effective.

A meta-analysis of all relevant randomized controlled trials (RCTs) was performed to assess the role of maintenance therapy with either a continuation or a switch strategy in the treatment of non-small-cell lung cancer and to investigate improvement in overall survival (OS) and progression-free survival (PFS). Depending on the tumor histologic type (squamous or nonsquamous), OS and PFS were also investigated. We used electronic databases to search for publications reporting RCTs comparing maintenance therapy and placebo or observation from January 1990 to March 2012. The primary endpoint of OS and the secondary endpoint of PFS were analyzed. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were derived. Eleven trials of 4790 patients were eligible for this analysis. A trend of improved OS was found in continuation maintenance therapy, despite a lack of statistical significance (HR 0.82; 95% CI, 0.66-1.01; P = .06). Improved OS with statistical significance was seen in switch maintenance therapy (HR, 0.80; 95% CI, 0.72-0.90; P = .0002). PFS benefit was found with both continuation (HR, 0.54; 95% CI, 0.46-0.63; P.00001) and switch maintenance therapy (HR, 0.64; 95% CI, 0.59-0.70; P.00001). The squamous subgroup analysis demonstrated no statistically significant differences in either OS (HR, 0.91; 95% CI, 0.63-1.30; P = .60) or PFS (HR, 0.80; 95% CI, 0.58-1.10; P = .17), whereas the nonsquamous subgroup analysis revealed an improvement in both OS (HR, 0.78; 95% CI, 0.64-0.94; P = .009) and PFS (HR, 0.56; 95% CI, 0.50-0.63; P.00001). Maintenance therapy was associated with higher drug-related grade 3 or greater toxic effects but without harming the patients' quality of life. Maintenance therapy with either a continuation or a switch strategy significantly increased PFS but OS was significantly improved only with the switch strategy. Patients with a nonsquamous histologic subgroup seemed to be more suitable for maintenance therapy.

Automated point layout plays an important pole in early phase nuclear emergency management which should take into account of nuke accidents source, weather condition, geography environment and other factors. However, owe to most of point selecting is done as manual work, there are some problems emerge as the too much of time cost, low efficiency in the course of working point layout etc. This paper proposes a kind of automatic technology framework which do points selecting based on forecast of pollutant diffuse model. Farther, the traditional method and its revised method are proposed, and point selecting achieve more scientifically and rationally. The experimental results show that our automated point layout could provide obvious improvements over previously methods, and the method could be widely used in emergency management of other kinds of accidents.