Spatial-temporal evolution of production-living-ecological space and layout optimization strategy in eco-sensitive areas: a case study of typical area on the Qinghai-Tibetan Plateau, China.

To achieve sustainable development goals and to solve environmental problems, land resources in eco-sensitive areas should be used and optimized. Qinghai, which is an important eco-sensitive area in China, represents a typical ecological vulnerable region on the Qinghai-Tibetan Plateau. Using land use/cover data for 2000, 2010 and 2020, this study applied a series of quantitative methods to analyze the spatial pattern and structure of the production-living-ecological space (PLES) in Qinghai. The results indicated that the spatial pattern of the PLES in Qinghai was stable over time, but the spatial distribution was very different. The structure of the PLES in Qinghai was stable, and the proportion of each space from high to low was ecological (81.01%), production (18.13%) and living (0.86%). We found that the proportion of ecological space in both the Qilian Mountains and the Three River Headwaters Region was lower than the rest of the study area, except for the Yellow River-Huangshui River Valley. Our study objectively and credibly presented the characteristics of the PLES in an important eco-sensitive area in China. This study further formulated targeted policy suggestions to provide a basis for regional sustainable development, ecological environment protection, and land and space optimization in Qinghai.

Economic evaluation of intravenous alteplase for stroke with the time of onset between 4.5 and 9 hours.

BACKGROUND: A clinical trial proved the clinical effectiveness of perfusion imaging-guided intravenous thrombolysis with alteplase for patients with acute ischemic stroke (AIS) with the time of onset between 4.5 and 9 hours. This study aimed to assess the lifetime cost-effectiveness of alteplase versus placebo from the perspective of Chinese and United States (US) healthcare payers. METHODS: A decision-analytic model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) associated with alteplase or placebo. Model inputs were extracted from published sources. Incremental costs, incremental QALYs, and incremental cost-effectiveness ratio (ICER) were calculated to evaluate the base-case scenario. One-way and probabilistic sensitivity analysis were performed to evaluate uncertainty in the results. RESULTS: In China, alteplase yielded an additional lifetime QALY of 0.126 with an additional cost of Chinese Yuan (¥) ¥9552 compared with placebo, and the ICER was ¥83 950 (US$12 157)/QALY. In the US, alteplase had a higher QALY (difference: 0.193) with a lower cost (difference: US$-2024) compared with placebo. In probabilistic sensitivity analyses, alteplase had a 42.54% to 78.3% probability of being cost-effective compared with placebo in China when the willingness-to-pay (WTP) threshold ranged from ¥72 447/QALY to ¥217 341/QALY. In the US, alteplase had a 93.47% to 93.57% probability of being cost-effective under the WTP threshold of US$100 000/QALY to US$150 000/QALY. These findings remained robust under one-way sensitivity analysis. CONCLUSION: For patients with AIS with a time of onset between 4.5 and 9 hours, perfusion imaging-guided intravenous alteplase was likely to be cost-effective in China and was cost-effective in the US when compared with placebo.

Health economic evaluation on population-based Helicobacter pylori eradication and endoscopic screening for gastric cancer prevention.

Gastric cancer is a global public health burden, nearly one million new cases are diagnosed per year worldwide, of which 44% of cases occur in China. The prognosis of gastric cancer varies remarkably by the stage of cancer, and most of the patients in China are diagnosed at advanced stages, resulting in poor prognoses. Effective strategies to reduce the burden of gastric cancer include primary prevention through testing and treatment of Helicobacter pylori (H. pylori) and secondary prevention by screening and early detection. Although many countries have issued management guidelines and consensus reports concerning these strategies, the limited availability of healthcare resources often precludes their widespread implementation. Therefore, assessing the costs, benefits, and harms of population-based intervention measures through health economic evaluation is necessary for informed health policy decisions. Accordingly, we synthesize management approaches from different countries on H. pylori eradication and endoscopic screening, and also summarize recent advancements in health economic evaluations on population-based preventive strategies. The goal of the review is to provide empirical evidence supporting optimal resource allocation, maximizing benefits for the population, and ultimately reducing the burden of gastric cancer.

Energy consumption in China: Spatial effects of industrial concentration, localization, and diversity.

This paper discusses the effects of industrial agglomeration on electrical energy consumption from a spatial perspective by highlighting multiple agglomeration types. It is argued that different types of industry agglomeration may exert differentiated effects on energy consumption and their possible spatial interactions. With city sector panel data of China's 285 prefecture-level cities for the period 2003-2013, we adopted the Spatial Durbin Model (SDM) with fixed effects to examine the spatial effects of industrial agglomeration types on energy consumption. The model found that all types of industrial agglomeration play significant and different roles in explaining overall local energy consumption. Second, geographical proximity, diversity, and related variety show the spatial spillover effects on surrounding areas. Third, the spatial energy effects of industrial agglomeration across regions are evidently heterogeneous. Diversity and one of its sub-forms-related variety maintains consumption-saving effects in regions with the initial or intermediate stage of an industry life cycle, while unrelated variety changes over different phases. The results suggest that policymakers scientifically discriminate regional features and guide the agglomerated types of industries in order to balance economic growth with energy conservation.

Few-Shot Learning by a Cascaded Framework With Shape-Constrained Pseudo Label Assessment for Whole Heart Segmentation.

Automatic and accurate 3D cardiac image segmentation plays a crucial role in cardiac disease diagnosis and treatment. Even though CNN based techniques have achieved great success in medical image segmentation, the expensive annotation, large memory consumption, and insufficient generalization ability still pose challenges to their application in clinical practice, especially in the case of 3D segmentation from high-resolution and large-dimension volumetric imaging. In this paper, we propose a few-shot learning framework by combining ideas of semi-supervised learning and self-training for whole heart segmentation and achieve promising accuracy with a Dice score of 0.890 and a Hausdorff distance of 18.539 mm with only four labeled data for training. When more labeled data provided, the model can generalize better across institutions. The key to success lies in the selection and evolution of high-quality pseudo labels in cascaded learning. A shape-constrained network is built to assess the quality of pseudo labels, and the self-training stages with alternative global-local perspectives are employed to improve the pseudo labels. We evaluate our method on the CTA dataset of the MM-WHS 2017 Challenge and a larger multi-center dataset. In the experiments, our method outperforms the state-of-the-art methods significantly and has great generalization ability on the unseen data. We also demonstrate, by a study of two 4D (3D+T) CTA data, the potential of our method to be applied in clinical practice.

Pricing Constraint and the Complexity of IPO Timing in the Stock Market: A Dynamic Game Analysis.

The timing of an initial public offering (IPO) is a complex dynamic game in the stock market. Based on a dynamic game model with the real option, this paper investigates the relationship between pricing constraint and the complexity of IPO timing in the stock market, and further discusses its mechanism. The model shows that the IPO pricing constraint reduced the exercise value of the real option of IPO timing, thus restricting the enterprise's independent timing and promoting an earlier listing. The IPO price limit has a stronger effect on high-trait enterprises, such as technology enterprises. Lowering the upper limit of the pricing constraint increases the probability that enterprises are bound by this restriction during IPO. A high discount cost and stock-market volatility are also reasons for early listing. This paper suggests a theoretical explanation for the mechanism of the pricing constraint on IPO timing in the complex market environment, which is an extension of IPO timing theory, itself an interpretation of the IPO behavior of Chinese enterprises. These findings provide new insights in understanding the complexity of IPOs in relation to the Chinese stock market.

Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection.

Cerebral ventricular infection (CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques (NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery (NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I (n = 3), Grade II (n = 13), Grade III (n = 10), and Grade IV (n = 6) CVI. The three patients with grade I CVI underwent one NES, the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two (n = 3) or three (n = 3) NESs. The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures. Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus, 18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6- to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.

CAGI SickKids challenges: Assessment of phenotype and variant predictions derived from clinical and genomic data of children with undiagnosed diseases.

Whole-genome sequencing (WGS) holds great potential as a diagnostic test. However, the majority of patients currently undergoing WGS lack a molecular diagnosis, largely due to the vast number of undiscovered disease genes and our inability to assess the pathogenicity of most genomic variants. The CAGI SickKids challenges attempted to address this knowledge gap by assessing state-of-the-art methods for clinical phenotype prediction from genomes. CAGI4 and CAGI5 participants were provided with WGS data and clinical descriptions of 25 and 24 undiagnosed patients from the SickKids Genome Clinic Project, respectively. Predictors were asked to identify primary and secondary causal variants. In addition, for CAGI5, groups had to match each genome to one of three disorder categories (neurologic, ophthalmologic, and connective), and separately to each patient. The performance of matching genomes to categories was no better than random but two groups performed significantly better than chance in matching genomes to patients. Two of the ten variants proposed by two groups in CAGI4 were deemed to be diagnostic, and several proposed pathogenic variants in CAGI5 are good candidates for phenotype expansion. We discuss implications for improving in silico assessment of genomic variants and identifying new disease genes.

Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016.

The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies in NAGLU activity lead to a rare, monogenic, recessive lysosomal storage disorder, Sanfilippo syndrome type B (MPS type IIIB). This challenge attracted 17 submissions from 10 groups. We observed that top models were able to predict the impact of missense mutations on enzymatic activity with Pearson's correlation coefficients of up to .61. We also observed that top methods were significantly more correlated with each other than they were with observed enzymatic activity values, which we believe speaks to the importance of sequence conservation across the different methods. Improved functional predictions on the VUS will help population-scale analysis of disease epidemiology and rare variant association analysis.

Assessment of patient clinical descriptions and pathogenic variants from gene panel sequences in the CAGI-5 intellectual disability challenge.

The Critical Assessment of Genome Interpretation-5 intellectual disability challenge asked to use computational methods to predict patient clinical phenotypes and the causal variant(s) based on an analysis of their gene panel sequence data. Sequence data for 74 genes associated with intellectual disability (ID) and/or autism spectrum disorders (ASD) from a cohort of 150 patients with a range of neurodevelopmental manifestations (i.e. ID, autism, epilepsy, microcephaly, macrocephaly, hypotonia, ataxia) have been made available for this challenge. For each patient, predictors had to report the causative variants and which of the seven phenotypes were present. Since neurodevelopmental disorders are characterized by strong comorbidity, tested individuals often present more than one pathological condition. Considering the overall clinical manifestation of each patient, the correct phenotype has been predicted by at least one group for 93 individuals (62%). ID and ASD were the best predicted among the seven phenotypic traits. Also, causative or potentially pathogenic variants were predicted correctly by at least one group. However, the prediction of the correct causative variant seems to be insufficient to predict the correct phenotype. In some cases, the correct prediction has been supported by rare or common variants in genes different from the causative one.

Cisplatin for testicular germ cell tumors: a rapid review.

OBJECTIVE: Cisplatin is one of efficacious medicines for TGCT, but is not in 18th WHO EML now. The Union for International Cancer Control recommended cisplatin to the 19th WHO EML for TGCT. To evaluate the effectiveness, safety and cost of cisplatin for TGCT according to the requirements of WHO EML Expert Committee, and to provide the evidence whether cisplatin should be included in WHO EML. METHOD: We searched The Cochrane Library, PubMed, EMbase, NHS EED, US National Guideline Clearinghouse (NGC) and WHO guidelines. Guidelines and systematic reviews (SRs) on cisplatin for TGCT were included. Two reviewers selected studies and extracted relevant information independently. Quality of SRs was appraised through AMSTAR. RESULTS: Seven guidelines and four SRs were included in this rapid review. Quality of SRs was moderate according to AMSTAR. The results showed that: (a) effectiveness: cisplatin-based chemotherapy significantly improved in response rates and overall survival for more advanced disease (stage II and stage III). Bleomycin, etoposide, and cisplatin (BEP)-one of the most widely used of cisplatin-based chemotherapy regimens should be considered as the standard treatment of good-prognosis patients with survival rates of 90% and as the best option for intermediate- or poor-prognosis patients with survival rates of 75% and 50%, respectively. (b) Safety: nephrotoxicity, ototoxicity and peripheral neuropathy are common adverse effects of cisplatin. (c) Cost: there was no relevant study about cost of cisplatin for TGCT. But the affordability of cispaltin is good for Chinese patients, due to it is in health insurance directory of China. CONCLUSIONS: We recommend cisplatin to be listed in 19th WHO EML for TGCT, due to adequate evidence of effectiveness and good affordability.

Exploration and practice of methods and processes of evidence-based rapid review on peer review of WHO EML application.

OBJECTIVE: After 38 years of development, the procedure of selection and evaluation of the World Health Organization Essential Medicine List (WHO EML) is increasingly scientific and formal. However, peer review for the applications of World Health Organization Essential Medicine List is always required in a short period. It is necessary to build up a set of methods and processes for rapid review. METHOD: We identified the process of evidenced-based rapid review on WHO EML application for peer reviews according to 11 items which were required during reporting of the peer review results of the proposals. RESULTS: The most important items for the rapid review of World Health Organization Essential Medicine List peer reviewers are (1) to confirm the requirements and identify the purposes; (2) to establish the research questions and translate the questions into the 'Participants, Interventions, Comparators, Outcomes, Study design' (PICOS) format; (3) to search and screen available evidence, for which high-level evidence is preferred, such as systematic reviews or meta-analyses, health technology assessment, clinical guidelines; (4) to extract data, where we extract primary information based on the purposes; (5) to synthesize data by qualitative methods, assess the quality of evidence, and compare the results; (6) to provide the answers to the applications, quality of evidences and strength of recommendations. CONCLUSIONS: Our study established a set of methods and processes for the rapid review of World Health Organization Essential Medicine List peer review, and our findings were used to guide the reviewers to fulfill the 19(th) World Health Organization Essential Medicine List peer review. The methods and processes were feasible and met the necessary requirements in terms of time and quality. Continuous improvement and evaluation in practice are warranted.

Toward the development of microbial indicators for wetland assessment.

Wetland assessment tools are being developed and employed in wetland monitoring and conservation based on physical, chemical and biological characterization. In wetland biological assessment, various ecological functions have been described by biological traits of an entire species pool that adapts to different types of wetland environments. Since microorganisms play a key role in wetland biogeochemical processes and respond quickly to environmental disturbances, this review paper describes the different macro indicators used in wetland biological monitoring and expands the potential use of microbial indicators in wetland assessment and management. Application of molecular microbial technologies paves the path to an integrated measure of wetland health conditions. For example, the ratio of ammonia-oxidizing archaeal and bacterial populations has been proposed to serve as a microbial indicator of wetland nutrient conditions. The microbial indicators coupled with physical, chemical and other biological parameters are vital to the development of multi-metric index for measuring wetland health conditions. Inclusion of microbial indicators will lead to a more comprehensive wetland assessment for wetland restoration and management practices.

An improved method for the synthesis of gamma-DDB.

A mild and efficient method for the synthesis gamma-DDB has been developed through anhydride-linker assisted intramolecular Ullmann reaction. Highly regioselective bromination of differentially protected gallate was realized by virtue of the introduction of NBS.